RxPG News : Cancer

Interferon-stimulated gene 15 (ISG15), a ubiquitin like protein, is a new therapeutic target for breast cancer

Thu, 12 Jan 2012 01:44:02 PST

( from http://www.rxpgnews.com ) In a study published in the January 2012 issue of Experimental Biology and Medicine, Dr. Shyamal Desai and her co-investigators report that gene knock-down studies demonstrate that elevated ISG15 pathway results in disruption of the cytoskeletal architecture of breast cancer cells. ISG15 also inhibits degradation of cellular proteins involved in cell motility, invasion, and metastasis, promoting breast cancer cell migration. Interferon-stimulated gene 15 (ISG15), a ubiquitin like protein, is highly elevated in a variety of cancers including breast cancer.

Dr. Desai said "Using ISG15 and UbcH8 gene knocked-down approach, our recent published and unpublished results explicitly demonstrated that the ISG15 pathway inhibits the ubiquitin-mediated proteasome-dependent protein degradation in breast cancer cells. We were the first to recognize this antagonizing effect of ISG15 in cancer cells"; however, others are increasingly coming to the same conclusion in their observations that ISG15 conjugation stabilizes cellular proteins.

Dr. Arthur Haas said "Given the crucial role of the ubiquitin/26S proteasome pathway in normal cell homeostasis, one expects that ISG15-induced downregulation of the ubiquitin pathway must contribute to breast tumor cell viability. Concurrently, in this manuscript we demonstrate that ISG15 promotes breast cancer cell migration by inhibiting ubiquitin-mediated degradation of cellular proteins associated with cell motility, invasion and metastasis".

The authors report that the elevated ISG15 pathway results in disruption of the cytoskeletal architecture effecting actin polymerization and formation of focal adhesions in breast cancer cells. Targeted knockdown of both ISG15 and UbcH8 resulted in reconstitution of the cytoskeletal architecture. Dr. Desai said "Disruption of cellular architecture is a hallmark of cancer. The ISG15 pathway is also elevated in a variety of tumors. Our results therefore reveal that the ISG15 pathway which is aberrantly elevated in tumors could disrupt cell architecture and contribute to breast cancer cell motility". "Because the cellular architecture is conserved and the ISG15 pathway is constitutively activated in tumor cells of different lineages, our observations in breast cancer must hold true for many other tumors".

If ISG15 confers motility to tumor cells in vivo, as suggested in this manuscript, then Dr. Desai concludes that "strategies to decrease ISGylation could provide a therapeutic advantage for patients diagnosed with metastatic tumors overexpressing the ISG15 pathway".

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said that "these intriguing studies by Desai and colleagues suggests that modulation of the ISG15 pathway may provide future therapeutic targets for breast cancer and other metastatic tumors".

Tapping the body's own defenses, researchers look to cutting-edge gene therapy for bladder cancer

Tue, 10 Jan 2012 05:00:00 PST

( from http://www.rxpgnews.com ) CLEVELAND -- Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in menand women in the U.S. More than 70 percent of bladder cancers are diagnosed in stage T1 or less and have not invaded the muscle layer. At these early stages, standard treatment is surgery (transurethral resection) and the burning away of tumors with high energy electricity (fulguration). Many patients also may receive subsequent intravesical chemotherapy because there is often a high-risk for cancer recurrence.

The prognosis for recurrent cancer is poor, which drives clinician-scientists like William Larchian, MD, Urologic Oncologist, University Hospitals Urology Institute at University Hospitals Case Medical Center, and Associate Professor of Surgery, Case Western Reserve University School of Medicine, and his colleagues to develop an immunotherapy for bladder cancer that will stimulate the body's own natural defense mechanisms to cure the disease and prevent recurrence.

What is interesting is that our bodies are capable of identifying, responding to and killing tumor cells naturally, explained Dr. Larchian. We are developing a vaccination system to enhance this response and drive an effective immune response against existing and future bladder tumor cells in patients diagnosed with bladder cancer.

IL-2, a cytokine-signaling molecule, stimulates the T-cell immune response to cancer cells in the bladder. Dr. Larchian and his colleagues have developed a system that reliably introduces multiple copies of IL-2 DNA into bladder cancer cells.

This method allows for more gene copies to enter the cells, he said, and we are able to see higher rates of transfection compared to retroviral methods.

The enhanced IL-2 protein expression has been shown to successfully stimulate T-cell response and eliminate bladder tumors in a mouse model, particularly when followed by transfection with B7.1 gene. The addition of the B7.1 gene, which encodes an immuneco-stimulatory molecule, enhanced T-cell production logarithmically and produced a 70 percent cure rate. Rechallenge with new cancer cells was also prevented. Clinical translation of this research has been submitted for Institutional Review Board approval at UH Case Medical Center.

Other research by Dr. Larchian and his colleagues aims to leverage this work to develop a gene-therapy system that can be utilized to deliver other key defense genes.

Our future pursuits, he said, will include using this system with very specific biological response modifiers, including anti-angiogenesis factors, and with the tumor suppressor gene, MCP3. Dr. Larchian also is developing a targeted drug delivery system using nanoparticles for bladder cancer treatment.

Personalized gene therapies may increase survival in brain cancer patients

Mon, 09 Jan 2012 05:00:00 PST

( from http://www.rxpgnews.com ) Personalized prognostic tools and gene-based therapies may improve the survival and quality of life of patients suffering from glioblastoma, an aggressive and deadly form of brain cancer, reports a new University of Illinois study funded by the NIH National Cancer Institute.

We confirmed known biomarkers of glioblastoma survival and discovered new general and clinical-dependent gene profiles, said Nicola Serao, a U of I Ph.D. candidate in animal sciences with a focus in statistical genomics. We were able to compare biomarkers across three glioblastoma phases that helped us gain insight into the roles of genes associated with cancer survival.

Glioblastoma is a complex, multifactorial disease that has swift and devastating consequences, Serao said. Although some genes have been associated with the presence of glioblastoma, few have been identified as prognostic biomarkers of glioblastoma survival and fewer have been confirmed in independent reports.

You can't just find one gene that is related to this cancer and fix it, he said. This is one of the aspects of our research that makes it unique. We were able to look at several genes at the same time and relate our findings to this cancer.

Using genomic information from more than 22,000 genes, Serao took this huge piece of information and began slicing away at it, one gene at a time, until he ended up with a group of genes related to brain cancer.

He studied different survival variables, including length of survival from birth to death, from diagnosis to death, and from diagnosis to progression of the cancer.

We studied different variables, but they were complementary, and allowed us to learn more about those genes, he said. We understand that some genes have much more impact in cancer than others. And we also discovered that some genes only appeared in one variable, so they were specific for a given phase of cancer.

This study not only evaluated genes influencing survival, but also took into consideration clinical factors such as age, race and gender.

Our research suggests you can't treat all patients the same, Serao said. For example, we found gene expression patterns that have different, and sometimes opposite, relationships with survival in males and females and concluded that treatments affecting these genes will not be equally effective. Personalized therapy dependent on gender, race and age is something that is possible today with our advanced genomic tools.

Recognizing that genes seldom act alone, this team of researchers took several genes into consideration at the same time and uncovered networks of genes related to glioblastoma survival.

Sandra Rodriguez Zas, co-researcher and U of I professor of animal science and bioinformatics, said they looked at commonalities between the genes linked to glioblastoma survival and progression, too.

If a large number of genes linked to survival belong to a particular pathway, this pathway is considered enriched, Rodriguez Zas said. Depending on whether the pathway and genes have tumor suppressor or oncogenic characteristics, we should be able to use that information to support or attack that pathway with targeted therapies.

Gaining a deeper understanding of the biological meaning, or roles, for these genes will provide researchers with even more ammunition to fight this deadly form of brain cancer.

Because of the innovative approach we used, we believe we can more confidently predict whether a patient will have a shorter or longer survival rate and select the most adequate therapies, she said.

This study, Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival, was published in

Estrogen-targeting drug combo may help prevent lung cancer

Mon, 09 Jan 2012 05:00:00 PST

( from http://www.rxpgnews.com ) SAN DIEGO -- A combination of drugs that target estrogen production significantly reduced the number of tobacco carcinogen-induced lung tumors in mice, according to results from a preclinical study.

Antiestrogens have been shown to prevent breast cancer in some women, said Jill M. Siegfried, Ph.D., professor in the department of pharmacology and chemical biology at University of Pittsburgh Cancer Institute. If antiestrogens can prevent lung cancer as well, this would be a major advance, because these drugs are safe to give for long periods and there are no approved ways to prevent lung cancer.

Siegfried presented the results at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012.

Most lung cancers are positive for a type of estrogen receptor that makes lung tumors grow when exposed to estrogen. In addition, an enzyme in the lung called aromatase produces estrogen. Siegfried and colleagues hoped that by blocking this estrogen receptor and the aromatase enzyme, they might be able to prevent estrogen-sensitive lung tumors.

To test this theory, they conducted a study on two groups of female mice: one group that was currently being exposed to a tobacco carcinogen and one that had past exposure to a tobacco carcinogen and in which some precancerous cells had already formed. The mice were assigned to treatment with a placebo, the aromatase inhibitor anastrozole, the antiestrogen fulvestrant or a combination of anastrozole and fulvestrant.

The first model asks whether the treatments inhibit the process by which cancer is first started before it is even detectable under the microscope, and the second asks whether the treatments inhibit the process by which microscopic precancers develop into visible tumors, Siegfried said.

In the first model, the combination treatment given during carcinogen exposure resulted in significantly fewer lung cancer tumors compared with placebo or either treatment alone. The tobacco carcinogen was stopped once treatment began to maximize its ability to halt lung cancer development. Combination treatment also resulted in maximum antitumor effects in the second model, where precancerous cells were already present.

According to Siegfried, these results suggest that antiestrogen treatment combined with an aromatase inhibitor prevents lung cancer development during tobacco carcinogen exposure and after carcinogen damage to the airways has already occurred.

Siegfried said that ultimately, the hope is that this research could lead to an approved treatment that could greatly reduce the risk for an ex-smoker to develop lung cancer.

We may be able to prevent lung cancer in people who have been previously exposed to tobacco carcinogens using some of the same antiestrogen drugs that can prevent breast cancer, Siegfried said. A lot of work needs to be done to determine who would benefit from this therapy, and these drugs would need to be tested in clinical trials in those at high risk for lung cancer.

Abiraterone has been approved for men with metastatic prostate cancer that is no longer responsive to therapy with hormones and docetaxel

Sun, 08 Jan 2012 18:23:00 PST

( from http://www.rxpgnews.com ) Abiraterone (trade name: Zytiga®) has been approved since September 2011 for men with metastatic prostate cancer that is no longer responsive to hormone therapy and progresses further during or after therapy with the cytostatic drug docetaxel. In an early benefit assessment pursuant to the "Act on the Reform of the Market for Medicinal Products" (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether abiraterone offers an added benefit compared with the present standard therapy.

IQWiG finds an indication of a considerable added benefit of abiraterone in patients who are not eligible for further treatment with docetaxel. In contrast, an added benefit is not proven in patients who can still be treated with docetaxel, as the dossier submitted by the drug manufacturer provides inadequate information for this group of patients.

Separate assessment for two groups of patients

In accordance with the specifications of the Federal Joint Committee (G-BA), IQWiG separately assessed abiraterone in two groups of patients. The G-BA has specified different appropriate comparator therapies for the two groups.

The "best supportive care population" contains patients who are not eligible for further treatment with docetaxel. The appropriate comparator therapy for this group is palliative treatment with dexamethasone, prednisone, prednisolone or methylprednisolone, as well as "best supportive care".

"Best supportive care" means the therapy that provides the patient with the best possible individually optimized supportive treatment to alleviate symptoms (e.g. adequate pain therapy) and improve quality of life.

The "docetaxel-retherapy population" comprises patients who are still eligible for further treatment with docetaxel. The appropriate comparator therapy for this patient population is docetaxel in combination with prednisone or prednisolone.

Indication of increase in survival and delay in consequences of disease

One study (COU-AA-301), which considers patient-relevant outcomes and provides relevant data, was included in the assessment of added benefit in the "best supportive care population". This study compared treatment with abiraterone versus placebo, in each case combined with prednisone and "best supportive care".

IQWiG finds an indication of an added benefit in patients treated with abiraterone: the above study provides indications that abiraterone can prolong survival and delay consequences of prostate cancer, such as fractures or operations due to bone metastases. In addition, the "time to pain progression" was prolonged in study participants receiving abiraterone.

IQWiG classifies the extent of this added benefit as "considerable". The corresponding legal ordinance has specified three grades to determine the extent of added benefit: "minor", "considerable" and "major".

The study data presented on health-related quality of life assessments cannot be used; an added benefit of abiraterone is therefore not proven for this outcome.

The indications of advantages for abiraterone are not accompanied by proof of greater harm.

Added benefit in the docetaxel-retherapy population not proven

The manufacturer presented inadequate data for the "docetaxel-retherapy population". The required search in trial registries was missing in the dossier. Moreover, studies presented by the manufacturer, such as indirect comparisons and one-arm studies, cannot be used due to deficits in methods and content. An added benefit in this patient group is therefore not proven.

G-BA decides on the extent of added benefit

The procedure for inferring the overall conclusion on the extent of added benefit is a proposal from IQWiG. The G-BA, which has opened a formal commenting procedure, decides on the extent of added benefit.

A new sensor to detect lung cancer from exhaled breath

Fri, 30 Dec 2011 23:00:00 PST

( from http://www.rxpgnews.com ) Some illnesses such as lung and stomach cancer or liver diseases which, due to the difficulty of diagnosis, have symptoms that are often confused with routine disorders. Therefore, in most cases, the disease is only detected at an advanced stage. New methods for early detection are being investigated as an urgent need.

Tecnalia, through the Interreg project Medisen, is contributing to develop biosensors capable of detecting the presence of tumour markers of lung cancer in exhaled breath. This is possible because of the changes produced within the organism of an ill person, changes reflected in the exhaled breath of the patient and which enable determining the presence of this type of marker during the initial stages of the disease.

Patients with lung cancer, treated in the Section of Medical Oncology of the Institute of Onco-Haemathology of the Donostia Hospital (IDOH) have collaborated in this phase of the project. For that, the Ethic Committee of the Clinical Research of Euskadi (CEIC) gave the authorization to the Instituto Biodonostia for the clinical trials

Human breath, whether from a healthy or ill person, is comprised of a hundreds of organic compounds: acetone, methanol, butanol, hydrocarbons, amongst others. There is not a single specific component in the exhaled breath capable of acting as a marker for the diagnosis of lung cancer. A range of biomarkers and its combination should be selected. The compounds of interest are generally to be found at 1-20 parts per billion (ppb) in healthy human breath but can be increased 10-100-fold in the breath of sick patients. In order to be able to detect these changes the development of novel materials was required.

During the first phase of the project, breath samples were collected by the hospital staff by a breath collecting device. A detailed analysis of the most representative compounds present in the breath samples has been carried out and the family or families of compounds required to act as markers for the presence of lung cancer selected. Organic compounds have been analysed using gas chromatograph/mass spectrometry analysis (GC/MS). Then, the GC/MS results of breath tests have been analysed by statistical and structural algorithms to discriminate and identify "healthy and "cancerous" patterns that really provide information for the design of the sensor.

In parallel, novel materials for the detection of the selected organic compounds have been developed by Tecnalia in order to increase the sensitivity of the devices. Participating together with Tecnalia in this project were the Instituto de Tecnologías Químicas Emergentes de La Rioja (Inter-Química) designing the sensor device and the University of Perpignan (France) testing the novel materials.

As a conclusion, the biosensors will facilitate the diagnosis of certain diseases; mainly those located in the lungs, at the initial stages of the illness, which could increase considerably the chances of survival.

Northwestern scientist gets mentoring award at White House

Fri, 16 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- Teresa Woodruff, the Thomas J. Watkins Professor of Obstetrics and Gynecology at Northwestern University Feinberg School of Medicine, received the prestigious Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring at the White House from President Barack Obama Monday, Dec. 12.

The award was for a Northwestern Medicine program called the Women's Health Science Program for High School Girls and Beyond. The program mentors urban minority high-school girls for college and careers in science and health.

Meeting President Obama in the Oval Office was a true honor and humbling event, said Woodruff, also director of the Institute for Women's Health Research. In his remarks, the president affirmed his deep commitment to science and engineering and the role that basic science plays in the health of our nation. He made time to congratulate us on our efforts and comment on the critical role that science mentorship plays in the development of the next generation of innovators on whom we count to solve our world's most pressing needs.

This award is for the hundreds of faculty, staff and students throughout Northwestern University and Northwestern Memorial Hospital who donate their time to mentorship, Woodruff added. Our program focuses on the next generation of female leaders. Our goal is to ensure that the future is filled with a diverse group of problem solvers ready to meet the world's challenges.

The Women's Health Science Program for High School Girls and Beyond (WHSP), a four-year-old program, targets primarily African American and Latina girls from disadvantaged backgrounds in Chicago. The young women can study at four different Northwestern academies: cardiology, physical science, infectious disease and oncofertility. The science program is part of the Institute for Women's Health Research at the Feinberg School.

Carole LaBonne, an associate professor of molecular biosciences at Northwestern and faculty member in the mentoring program, emphasized the importance of increasing the representation of women and minorities in the STEM disciplines.

The program developed by Dr. Woodruff has had amazing impact and is truly transformative, said LaBonne, a member of Northwestern's diversity committee. It should be used as a model for how universities across the country can address the pipeline problem by helping to educate and excite students from underrepresented groups about science from an early age.

Of the 90 students who have participated in the Women's Health Science Program from the Young Women's Leadership Charter School in Chicago, 18 are seniors in high school, 70 are attending college and two have received undergraduate degrees. Of those attending college, 51 percent are pursuing science majors.

WSHP has grown beyond Chicago through Woodruff's efforts. Similar informal education programs based on the Chicago model have been running in San Diego, Oregon and Philadelphia. Plans also are underway to expand the program to other Chicago high schools.

Woodruff, a reproductive endocrinologist, researches female reproductive health and infertility and is chief of the division of fertility preservation at the Feinberg School. She also leads the Oncofertility Consortium, a national a team of oncologists, fertility specialists, social scientists, educators and policymakers to translate her research to the clinical care of women who will lose their fertility due to cancer treatment. In addition, she has been an advocate for sex and gender inclusivity and study in basic science, translational studies and clinical trials.

President Obama honored nine individuals and eight organizations as recipients of the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.

Through their commitment to education and innovation, these individuals and organizations are playing a crucial role in the development of our 21st century workforce, President Obama said when the award was first announced. Our nation owes them a debt of gratitude for helping ensure that America remains the global leader in science and engineering for years to come.

The White House award recognizes the crucial role mentoring plays in the academic and personal development of students studying science and engineering -- particularly those who belong to groups underrepresented in these fields. By offering their expertise and encouragement, mentors help prepare the next generation of scientists and engineers, while ensuring that tomorrow's innovators reflect and benefit from the diverse talent of the United States.

RTOG activates study to determine best treatment strategies for patients with glioma brain tumors

Thu, 15 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Treatment remains controversial for patients diagnosed with a low-risk, low-grade glioma (LGG) brain tumor. These patients have significantly better prognosis than patients diagnosed with more aggressive high-grade glioma, and their clinical care often involves ongoing observation for tumor changes with imaging studies. Because low-risk LGG are slow growing tumors, concerns about the potential adverse effects of early treatment on patients' neurocognitive function (NCF) and quality of life (QOL) may outweigh treatment benefits in patients who are frequently young and highly functional.

Although a low-grade tumor, LGG has a significant potential for transforming into a high-grade glioma. Currently there is no consensus on when and how best to treat this tumor, says RTOG 0925 principal investigator Ali K. Choucair, M.D., Director of Neuro-oncology and Co-director of the Brain Tumor Center at the Neuroscience Institute, Norton Healthcare System, Louisville, KY. The RTOG 0925 study was designed with compilation of best available data from both prospective as well as retrospective studies in an effort to identify early clinical and neurocognitive changes that could precede changes observed on imaging scans and could trigger early and timely treatment, Choucair explains.

The study's goal is to better understand the affects of tumor progression on patients with low-risk LGG. The phase II trial will enroll 170 study participants with newly diagnosed LGG who are undergoing observation alone for clinical care. The study will compare NCF, QOL, and seizure control over time in patients who have evidence of tumor progression versus patients who have no evidence of progression as determined by magnetic imaging resonance (MRI) scans. Standardized and clinically meaningful definitions of tumor progression in low-risk LGG are clearly needed to further the examination and understanding of these tumors, says Walter J. Curran, Jr., MD, RTOG Group Chair, and Executive Director of the Winship Cancer Institute of Emory University in Atlanta, It is hoped the study's findings will help guide future treatment decisions for these patients, Curran concludes.

The study also has an important translational research component that is expected to contribute much needed information to current limited knowledge about the role molecular markers in predicting LGG tumor progression. Tumor tissue from consenting study participants will be used to evaluate molecular correlates of NCF, QOL, seizure control, and progression-free survival. Such information has the potential to aid clinical decision-making and further the identification of individualized patient therapy approaches.

Patients who have disease progression while enrolled on RTOG 0925 may be eligible for entry on a trial available to RTOG members through the NCI Clinical Trials Support Unit (CTSU) sponsored by ECOG, E3F05/RTOG 1072, Phase III Randomized Study of Radiotherapy With Versus Without Temozolomide in Patients With Symptomatic or Progressive Low-Grade Gliomas.

U.S. Supreme Court petitioned to review AMP, et al. lawsuit on gene patents

Thu, 15 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON, DC -- The American Civil Liberties Union and the Public Patent Foundation have petitioned the U.S. Supreme Court to hear Association for Molecular Pathology v. U.S. Patent and Trademark Office, a case that challenges the validity of patents on two human genes associated with hereditary breast and ovarian cancer.

The American Civil Liberties Union and the Public Patent Foundation originally filed the lawsuit on behalf of a coalition of professional organizations led by the Association for Molecular Pathology (AMP), and representing over 150,000 physicians and scientists, against licensees and patent holders Myriad Genetics and the University of Utah Research Foundation, as well as the U.S. Patent and Trademark Office. Other plaintiffs included individual physicians and scientists, genetic counselors, women's groups and patients.

The lawsuit argued that as products of nature, genes are ineligible for patenting under Section 101 of the U.S. Patent Act. In addition, the suit asserted that process claims involving comparison of mutated and normal sequences are also invalid. Finally, the plaintiffs challenged the issuance of the patents on Constitutional grounds, contending that the encumbrances placed by the patents on scientific inquiry and medical care violate Article I, Section 8, Clause 8 and the First Amendment.

In March, 2010 a district court granted summary judgment for the plaintiffs, ruling that human genes and the sequence comparison claims are not patent eligible under Section 101. A divided Court of Appeals for the Federal Circuit last July reversed in part, holding that the gene sequences at issue are patent eligible as isolated human DNA. However, the Appeals Court affirmed the lower court's finding of invalidity of the comparison, or correlation, claims as unpatentable mental processes.

The patents granted to Myriad give the company the right to exclude others from sequencing the genes or performing other diagnostic tests on BRCA1 and BRCA2. In effect they grant Myriad a monopoly on both medical and research testing for familial breast and ovarian cancer caused by these genes.

That pathologists can be excluded from 'looking at' or 'reading' a patient's DNA sequence to characterize or assess the risk for disease is akin to prohibiting a physician from taking a patient's pulse to see if his or her heart is beating, said Mary Steele Williams, Executive Director of the Association for Molecular Pathology. I think that the fact that patients can be prevented from accessing the information contained in their DNA would offend most people's conceptions of individual rights and personal liberty.

AMP is optimistic the Supreme Court will follow its precedents that render natural products, natural laws, and natural phenomena ineligible for patent protection. Only by upholding the prohibition on patenting laws of nature can the patent system foster competition and advancement in test development, and thereby usher in the era of personalized medicine.

Gene patents are a barrier to innovation in molecular testing because they grant monopolies in diagnostic testing for key biologic relationships in inherited diseases and cancer, said Roger D. Klein, MD, JD, AMP Professional Relations Committee Chair. One cannot invent around gene patents. Excluding medical practitioners from independently accessing the information contained within the genes of their patients, and the subsequent loss of competition this implies, results in higher test prices, decreased patient access, and diminished innovation in the development of new test methods. The overall effects on patient care are resoundingly negative.

AMP is deeply concerned about potential restrictions on physician and patient access to information that could inform care, and the chilling effect gene patents have on medical research.

Because information about gene sequences is so fundamental to elucidating the cause, progression and treatment of disease, patent holders can essentially gain ownership of the understanding of some diseases and of certain areas of patient care itself, said Iris Schrijver, AMP President. Even the possibility of enforcement by a patent holder creates a chilling effect, as pathologist s become reluctant to perform testing procedures that could benefit patients.

New test to indicate likely spread or recurrence of breast cancer

Tue, 13 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) A Queensland University of Technology (QUT) PhD student has developed a potential breakthrough test for predicting the likelihood of the spread or return of breast cancer.

While in recent years there have been fantastic advances in the treatment of breast cancer there has been no way of predicting its progress, said Helen McCosker, a PhD student at the Institute of Health and Biomedical Innovation (IHBI).

Ms McCosker's research found that a breast cancer's interaction with its surrounding environment held the key to predicting whether it would grow, become dormant or spread to other organs.

The ability to predict its progress is a huge step forward as it will ultimately enable doctors to select the most appropriate treatments for individual patients, she said.

This test should identify those patients who need their cancer removed but require no further treatment, those who need the tumour removed but also require additional treatment, for example, chemotherapy, and those who need more vigorous treatments.

That will mean that patients should neither receive unnecessary treatments nor be undertreated when a more aggressive medical response is required.

Ms McCosker said the new test would use the tissue surrounding the cancer cells, which were collected for biopsy purposes, but were currently not examined.

The test makes better use of tissue that's already being collected anyway, so from the patient's point of view there would be no change; no new test, she said.

She said the next step was to develop an easy-to-use, accurate online program that doctors would use to diagnose cancer progression.

Ultimately, doctors should be able to key the results of the examination of tissue samples into an online program with built-in mathematical models and be presented with a clear answer as to the likelihood of cancer progression.

She said the test would offer solutions for a wide range of patients, particularly those with more advanced, aggressive, disease that could spread to other organs as well as those in rural and remote areas with limited access to advanced medical services.

The next step is to seek financial backing to fine-tune and commercialise the current prototype. It's expected our models will be trialled in pathology laboratories over the coming years and if successful rolled out over the next five to 10 years, Ms McCosker said.

Ms McCosker said the test, which is being funded by the Wesley Research Institute, should ultimately be applicable to other forms of cancer.

She said breast cancer accounted for 28 per cent of diagnosed cancers in Australian women and 16 per cent of cancer associated deaths.

Circulating tumor cells not linked to survival in newly diagnosed inflammatory breast cancer

Fri, 09 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) SAN ANTONIO, TX -- The presence of circulating tumor cells in the blood appears to have no relationship to survival in women who have just been diagnosed with inflammatory breast cancer, according to new research from Fox Chase Cancer Center. However, the research shows that these stray tumor cells may signal that the disease has spread to other parts of the body, even before imaging reveals any metastases. The results will be presented on Friday, December 9 at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

If a woman is diagnosed with inflammatory breast cancer, a particularly fast-growing form of the disease, doctors should consider close imaging to monitor and possibly continue aggressive treatment if she also has circulating tumor cells (CTCs), regardless of what imaging shows, recommends study author Massimo Cristofanilli, M.D., F.A.C.P., chair of the department of medical oncology at Fox Chase. You should be carful before stopping treatment in someone who has evidence of circulating cells, particularly when dealing with a disease like inflammatory breast cancer, which can progress rapidly.

Previous research by Cristofanilli and his colleagues found that the number of stray cancer cells circulating in the blood is the best predictor of both how long a woman with metastatic breast cancer will live and the amount of time until her cancer progresses. But the researchers have also found that the presence or lack of CTCs has little to say about prognosis in women with metastatic inflammatory breast cancer, an aggressive disease with extremely poor outcomes in spite of multidisciplinary modality treatment.

During the current study, Cristofanilli and his team reviewed the records of 84 women who had just learned they have inflammatory breast cancer, either in stage III or stage IV. A total of 64 (76.2%) women had at least 1 CTC and 29 (34.5%) had at least 5. The researchers found that women with no CTCs had comparable survival and spent the same amount of time progression-free as women with one or more CTCs. The results suggest that there is little prognostic value in measuring CTCs in women newly diagnosed with inflammatory breast cancer.

It's not clear why CTCs appear to be linked to prognosis in some forms of cancer but not others, says Cristofanilli. Inflammatory breast cancer is already an aggressive disease, he says, so compared to other forms of breast cancer whether or not cells have broken off and entered the blood may say little more about an otherwise already aggressive disease.

Inflammatory breast tumors are typically fast-growing, and travel quickly to lymph nodes and the brain. During follow-up in the current study, which lasted more than 22 months for half of patients, more than 30% of the entire group had died.

Perhaps the most important finding from the study, says Cristofanilli, is that more than three-quarters of women who just learned they have inflammatory breast cancer had CTCs that can be detected in the blood. In comparison, he adds, only 15% of women with non-inflammatory breast cancer typically have CTCs. So there is a huge difference in inflammatory breast cancer and other forms of breast cancer. These stray tumor cells, therefore, may indicate something about inflammatory breast cancer, he reasons, perhaps serving as an early sign that it has already spread. Indeed, only approximately one-third of women with inflammatory breast cancer have detectable metastases at diagnosis, but 60% will eventually develop them.

Why women quit breast cancer drugs early

Fri, 09 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- Why do so many postmenopausal women who are treated for estrogen-sensitive breast cancer quit using drugs that help prevent the disease from recurring?

The first study to actually ask the women themselves -- as well as the largest, most scientifically rigorous study to examine the question -- reports 36 percent of women quit early because of the medications' side effects, which are more severe and widespread than previously known. The Northwestern Medicine research also reveals a big gap between what women tell their doctors about side effects and what they actually experience.

Clinicians consistently underestimate the side effects associated with treatment, said lead investigator Lynne Wagner, an associate professor in medical social sciences at Northwestern University Feinberg School of Medicine and a clinical psychologist at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. They give patients a drug they hope will help them, so they have a motivation to underrate the negative effects. Patients don't want to be complainers and don't want their doctor to discontinue treatment. So no one knew how bad it really was for patients.

The symptom most likely to cause women to stop using the drugs was joint pain. Other side effects women reported as compromising their quality of life were hot flashes, decreased libido, weight gain, feeling bloated, breast sensitivity, mood swings, irritability and nausea.

Wagner's research will be presented Dec. 9 at the 34th Annual San Antonio Breast Cancer Symposium.

The drugs, aromatase inhibitors, stop the production of estrogen in postmenopausal women, whose breast cancer cells are stimulated by estrogen. About two-thirds of breast cancers are estrogen sensitive, and aromatase inhibitors reduce the recurrence of cancer in postmenopausal women.

The women at highest risk for quitting the medications before the recommended five years are those who still are experiencing residual side effects from recent chemotherapy or radiation therapy when they start the aromatase therapy, according to the study. Women who had surgery for breast cancer but not chemotherapy or radiation therapy, or who weren't taking many other medications, were more likely to keep taking the aromatase medication.

The more miserable they were before they started, the more likely they were to quit, Wagner said. By the time they get through chemotherapy or radiation, they have to face five more years of another medication that will make them feel lousy. They feel like they already lost enough time to cancer and have reached their threshold for feeling bad.

This is a wake-up call to physicians that says if your patient is feeling really beaten up by treatment, the risk of her quitting early is high, Wagner said. We need to be better at managing the symptoms of our patients to improve their quality of life.

The new research exposes the disparity between clinicians' reporting of side effects and women's actual experiences. In a previous study, clinicians reported 5 percent of their patients experienced moderate to severe symptoms as a result of taking aromatase inhibitors. The new Northwestern study surveyed 686 women with a detailed questionnaire about their symptoms before treatment and at three, six, 12 and 24 months after starting treatment. The researchers found after three months of treatment that 33 to 35 percent of women had severe joint pain, 28 to 29 percent had hot flashes, 24 percent had decreased libido, 15 to 24 percent had fatigue, 16 to 17 percent had night sweats and 14 to 17 percent had anxiety. These numbers increased as women were on treatment longer.

Earlier studies also asked women to recall their symptoms after treatment ended, which is less accurate than reporting them at regular intervals while taking the drugs.

As a result of the side effects, 36 percent of women ended treatment before an average of 4.1 years. After two years, 10 percent had quit; the remainder quit between 25 months and the 4.1 years.

These findings can help us identify women at risk for quitting the therapy, counsel them about the importance of staying on it and provide treatment for troubling side effects, Wagner noted.

Weight gain can be addressed with nutritional counseling, while mood swings and irritability can be treated with cognitive behavioral therapy or mind-body techniques, Wagner said. Joint pain can be tempered with nonsteroidal anti-inflammatory drugs, or women may be switched to a different hormonal medication. Nausea can be reduced with medication.

For the study, patients who had postmenopausal breast cancer filled out a 46-question survey rating their quality of life and symptoms associated with breast cancer and endocrine treatment. The survey included an item asking how much they were bothered by side effects of treatment from zero (not bothered) to four (severely bothered). For each additional one-point increase on this item, the patient's risk of quitting treatment early rose 29 percent. The patients were randomized to take one of two hormonal treatments (anastrozole or exemestane) daily for five years.

Breast cancer patients face increasing number of imaging visits before surgery

Fri, 09 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) SAN ANTONIO, TX -- Breast cancer patients frequently undergo imaging like mammograms or ultrasounds between their first breast cancer-related doctor visit and surgery to remove the tumor. Evaluations of these scans help physicians understand a person's disease and determine the best course of action. In recent years, however, imaging has increased in dramatic and significant ways, say researchers from Fox Chase Cancer Center. More patients have repeat visits for imaging than they did 20 years ago, and single imaging appointments increasingly include multiple types of imaging.

The researchers, led by Richard Bleicher, M.D., surgical oncologist at Fox Chase, found that between 1992 and 2005, the percentage of patients who had multiple (2+) imaging visits nearly quadrupled. Bleicher says additional visits present a burden to patients, many of whom are elderly, but the stress may be alleviated through better coordination and evaluation by physicians. Bleicher will present his group's findings on Friday, December 9 at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

The burden to the patient is increasing substantially, Bleicher says. The number of days patients are having mammograms, MRIs, and ultrasounds is going up steadily year by year. They're having imaging done more frequently on separate dates during the preoperative interval than ever before. It's surprising.

The preoperative interval begins when a patient first reports to a doctor with a breast complaint and ends when the patient undergoes therapeutic surgery to resect a tumor. For the more than 65,000 patients involved in the study, the preoperative interval lasted 37 days on average. The Fox Chase researchers found that in 1992, roughly one in 20 cancer patients (4.9 percent) diagnosed with invasive, non-metastatic cancer underwent imaging twice or more during the preoperative interval. By 2005, that portion had climbed to about one in 5 (19.4 percent). In the extreme case, a small subset of 20 patients underwent mammograms on five or more visits during the preoperative interval.

The researchers also found that a single imaging visit increasingly includes multiple imaging types. In 1992, 4.3 percent of patients underwent multiple types of imaging; in 2005, that rate rose to 27.1 percent.

With the increased use of imaging, Bleicher says that for physicians, the question becomes, 'How are we affecting patients overall with what we're ordering nowadays?'

Previous studies have examined patient burden in terms of cost, but Bleicher says he hasn't seen studies that focus on the patient burden in terms of the patient's time. I wanted to take a look at how things have been changing for patients and how many times they have to travel back and forth to get more imaging, he says. Physicians need to keep in mind that it's hard enough for working people to take off from work and trek back and forth to appointments, but older people have infirmities, and it's harder to get around. The coordination of care is very important. We need to focus more on the burden to the patient.

Gene inheritance patterns influence age of diagnosis in BRCA families

Fri, 09 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) LAKE SUCCESS, NY -- Women who inherit the cancer genes BRCA1 or BRCA2 from their paternal lineage may get a diagnosis a decade earlier than those women who carry the cancer genes from their mother and her ancestors, according to a new study by researchers at the North Shore-LIJ Health System's Monter Cancer Center in Lake Success, NY. The findings were reported on Thursday, Dec. 8, at the San Antonio Breast Cancer Symposium.

Iuliana Shapira, MD, North director of cancer genetics, and her colleagues conducted a retrospective review of 130 breast or ovarian cancer patients with the BRCA1 or BRCA2 mutations. They chose only those patients who knew the parent of origin. In other words, they could follow along their family tree to see where the breast cancer gene originated from. Some of their families had their own genetic tests done. For others, it was a matter of following the family pedigree.

As expected, a person had a 50-50 chance of getting a mutant BRCA gene from their mother or their father's branch that carried the mutation. It is an autosomal dominant mutation. Looking at the family maps revealed some surprising findings. Contrary to the notion that the BRCA mutations are associated more commonly with Ashkenazi Jews, the scientists found that the BRCA mutations were also in families of Irish and Jamaican descent. No one had ever conducted a study to look at the parent-of-origin effects, said Dr. Shapira. Genetic diseases may display parent-of-origin effects. In such cases, the risk depends on the specific parent or origin allele. Cancer penetrance in mutations carriers may be determined by the parent origin of BRCA mutation.

They analyzed 1,889 consecutive (136 ovarian + 1753 breast) breast (BrCa) or ovarian cancer (OvCa) patients presenting for treatment at the Monter Cancer Center between 2007 and 2010. In 130 patients with BRCA 1 or 2 mutations the parent of origin for the mutation was known. Of the 130 patients, two had both BRCA1 and BRCA2 mutated paternally inherited disease and were excluded from this analysis. Of the breast cancer patients: 28 patients had paternal and 29 had maternal BRCA1 mutations, 24 had paternal and 21 had maternal BRCA 2 mutations. Of the ovarian cancer patients, six had paternal and 10 had maternal BRCA1 mutations; seven had paternal and three had maternal BRCA2 mutations.

In carriers of BRCA mutations, the mean age at diagnosis for ovarian cancer was 51 (range 21-70) and for breast cancer was 43 (range 24-78). But when they compared the mean age at diagnosis in the maternal versus paternal inheritance, they were surprised to find that breast cancer patients with a BRCA1 maternal inheritance, the age of diagnosis was on average around 45. By comparison, women with BRCA1 paternal inheritance were diagnosed around 38. For breast cancer BRCA2 maternal inheritance, the average age of diagnosis was 50 compared to 41 years old for those with a BRCA2 paternal inheritance.

There was no significant difference between paternal and maternal age of ovarian cancer diagnosis of BRCA1 or BRCA2 mutations.

If this observation is duplicated in larger cohorts the results will have important implications for recommendation of surgical risk reduction in BRCA mutation carriers, said Dr. Shapira. That would mean that doctors might think about watching and waiting in young woman with BRCA mutations inherited from her mother's family and being more aggressive in young women who inherited the mutation from their father's side.

Novel approach to treating breast cancer shows great promise

Wed, 07 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) MAYWOOD, Il. -- In a novel therapeutic approach to treating breast cancer, Loyola University Medical Center researchers are reporting positive results from a clinical trial of a drug that targets tumor stem cells.

Existing cancer drugs are effective in killing mature cancer cells. But a handful of cancer stem cells are resistant to such drugs. They survive and go on to develop into new tumor cells.

A pilot study at Loyola found that an experimental drug known as a notch inhibitor appears to block this process by turning off key genes. Kathy Albain, MD, who led the study, presented findings Dec. 7 during the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

Albain collaborated with scientists from Loyola, University of Mississippi Cancer Center, Baylor Breast Center and Merck Oncology.

Our results suggest a potential role that notch inhibitors could play in optimizing existing therapies and in overcoming resistance to cancer drugs, Albain said.

The so-called notch protein promotes tumor growth and survival. The protein is present on the surface of cancer stem cells. The protein latches on to other cells, and the resulting molecular handshake activates various genes in the stem cells. Activating these genes, in effect, makes the stem cells resistant to common cancer drugs.

The study included 20 patients who finished all therapy. The women all had early-stage, estrogen-receptor-positive breast cancer.

Prior to surgery, the patients received one of two commonly used drugs, tamoxifen or letrozole. These drugs work by blocking estrogen stimulation of breast cancer cells. In addition to tamoxifen or letrozole, patients also received the experimental notch-inhibitor drug, MK-0752.

Following treatment with the notch inhibitor, patients underwent biopsies to provide tumor specimens. Researchers found that the drug turned off the key genes that in effect would have kept the tumor stem cells resistant to conventional drugs.

The notch inhibitor appears to be doing what it is intended to do, said Clodia Osipo, PhD, a breast cancer scientist in Loyola's Cardinal Bernardin Cancer Center.

There were minimal side effects from either the notch inhibitor or the estrogen-blocking drugs. One patient experienced puffy eyes and coughing and four patients experienced facial acne. No patients experienced diarrhea or surgical complications

The purpose of the study was to determine how well the notch inhibitor is tolerated and how it affects the expression of critical genes in cancer stem cells. The next step is to determine how effective the drug would be in treating breast cancer.

Researchers proposed a randomized clinical trial, in which patients who received estrogen-blocking drugs before surgery would be compared to patients who received estrogen-blocking drugs plus a notch inhibitor.

Study finds side effects, complications, mastectomy more likely after partial breast irradiation

Tue, 06 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) San Antonio, TX - Accelerated partial breast irradiation (APBI) brachytherapy, the localized form of radiation therapy growing increasingly popular as a treatment choice for women with early-stage breast cancer, is associated with higher rate of later mastectomy, increased radiation-related toxicities and post-operative complications, compared to traditional whole breast irradiation (WBI), according to researchers from The University of Texas MD Anderson Cancer Center.

The retrospective study was presented in the CTRC-AACR San Antonio Breast Cancer Symposium's press briefing by Benjamin Smith, M.D., assistant professor in the Department of Radiation Oncology, and in the meeting's scientific session by Grace Smith, M.D., Ph.D., a resident in MD Anderson's Department of Radiation Oncology and the study's first author.

Our study compared the two radiation therapy techniques available to women with early-stage breast cancer. We found that women treated with accelerated partial breast irradiation therapy have a two-fold increased risk for subsequent mastectomy, most likely because of tumor recurrence or local complications, as well as an increased risk for post-operative and radiation-related complications, said Ben Smith, the study's senior author.

There are numerous types of APBI; the MD Anderson study only looked at the brachytherapy technique, in which a form of radiation treatment involving insertion of a catheter containing a radioactive source to kill breast cancer cells that may remain after lumpectomy surgery. A specialized catheter is surgically inserted into the cavity left behind after tumor removal. APBI brachytherapy is performed a few weeks after a lumpectomy, twice daily over a course of five to seven days.

APBI brachytherapy has grown in popularity over the past decade, since earlier studies showed generally low cancer recurrence rates, though most prior studies have not directly compared the outcomes of APBI brachytherapy to traditional radiation therapy, explained Ben Smith.

The first commercially-available single catheter to deliver partial breast irradiation was approved by the FDA in 2002, escalating APBI's use, said Ben Smith.

The MD Anderson study was based on analysis of claim forms filed by 130,535 Medicare beneficiaries nationwide, who were diagnosed with cancer between 2000 and 2007.

In our study of Medicare patients, we found a consistent increase in APBI brachytherapy, from less than 1 percent in 2000 to 13 percent in 2007. It's our guess that this trend has continued, said Smith.

There are benefits to the practicality APBI offers women, noted Ben Smith.

For whole breast irradiation, the standard treatment time is between five and seven weeks, but studies have shown that some women experience delays or have obstacles completing their course of radiation. Treatment delays and incompletion are known to increase the risk of cancer recurrence in the breast. APBI brachytherapy is attractive because it has the potential to address those issues, because treatment only lasts one week.

However, it's also an invasive procedure with the greater potential for side-effects that are not associated with a non-invasive therapy, such as WBI, noted Smith.

For the retrospective population-based study, the MD Anderson team used Medicare claims to examine the treatment history of 130,535 women age 66 and older diagnosed with early-stage, invasive breast cancer between 2000 and 2007. All of the women were treated with breast-conserving surgery followed by either APBI, delivered by brachytherapy, or traditional radiation therapy.

The researchers analyzed for effectiveness of radiation (defined as the need for a later mastectomy), post-operative complications (infectious and non-infectious), and post-radiation complications (breast pain, fat necrosis and rib fracture).

At five years, the incidence of mastectomy was statistically significantly higher in the APBI brachytherapy-treatment group compared to that of the WBI, 4 percent and 2.2 percent, respectively. APBI brachytherapy was also found to be associated with a higher incidence of acute and late toxicities, compared to those of WBI - infectious complications, 16 and 10 percent, respectively; non-infectious complications, 16 percent and 8 percent, respectively; - and post-radiation complications - five-year incidence of rib fracture, 4 and 4 percent, respectively; fat necrosis, 9 and 4 percent, respectively; and breast pain, 15 percent and 12 percent, respectively.

The researchers note the study's limits, including that it was not randomized, the relatively-short follow up of patients and limited details regarding tumor characteristics were available.

Given the findings, communication between the patient and her physician is paramount so that a woman with breast cancer can make an informed, personalized decision, said Thomas A. Buchholz, M.D., professor and head of the Division of Radiation Oncology at MD Anderson.

This is a very important, well-designed study in a large cohort of patients and provides the first comparison of these two popular radiation techniques after breast-conserving surgery, said Buchholz, also an author on the study. It's important to note that in both groups, we found a relatively low risk of recurrence. Still, we have a responsibility to discuss potential risks and benefits with our patients, while we await definitive results from randomized trials.

National randomized trials comparing APBI brachytherapy to WBI are ongoing. MD Anderson will continue offering APBI to interested patients in the context of ongoing institutional and multi-institutional clinical protocols, says Buchholz.

Researchers discover patterns of genes associated with timing of breast cancer recurrences

Tue, 06 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) SAN ANTONIO -- An international research team led by Georgetown Lombardi Comprehensive Cancer Center has found biological differences in hormone-receptor positive breast cancer that are linked to the timing of recurrence despite endocrine therapy.

They say their findings, presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, may help oncologists find ways to individualize systemic therapy to delay or prevent recurrences, and to avoid excessive treatment of patients who will never recur.

We found that, at the time of diagnosis, there are clear biological differences within the supposedly uniform group of hormone receptor positive breast cancers, and these differences distinguish subtypes relative to the time at which they recur, says Minetta Liu, M.D., director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center.

We need to exploit these differences and use our data to figure out what drives a tumor to never metastasize. Then we will try to manipulate the cancers that are programmed to recur to act like that of the non-recurrences, she says.

Tamoxifen is credited with saving the lives of thousands of women with estrogen receptor-positive (ER+) breast cancer, which accounts for two-thirds of all diagnoses of invasive breast cancer in the United States. As the world's leading breast cancer treatment and prevention drug, tamoxifen can stave off cancer recurrences for more than 10 years in some patients, but for others, the cancer returns much earlier.

To determine why some ER+ cancers treated with tamoxifen recur earlier rather than later, if at all, Liu and her Georgetown team collaborated with researchers at the University of Edinburgh and with engineers at Virginia Tech.

The Scottish collaborators shared high quality tumor biopsies collected from patients with different stages of breast cancer before they had started tamoxifen therapy. Critical clinical information was available to determine whether or not patients developed metastatic disease, and when the recurrence (if any) was found. The samples were processed and analyzed at Georgetown. Then scientists at Virginia Tech examined the gene expression patterns generated from the tumor biopsies relative to the known clinical outcomes to develop a predictive model of early, late or no disease recurrence.

The final analysis revealed distinct patterns in cancers that recurred early (up to three years from diagnosis) or late (more than ten years from diagnosis). Liu says that some of the genes that were identified were expected and reassuring, but others were unexpected and novel. Work is ongoing to validate selected genes as biological drivers of metastasis.

Endocrine therapy and chemotherapy are not without toxicity, Liu says. The ability to predict which patients will recur early in their treatment course can lead to more appropriate recommendations for adjuvant chemotherapy. It might also identify those women who would benefit most from studies using investigational agents to enhance the effects of tamoxifen or aromatase inhibitors.

University of Kentucky researchers awarded CDC grant to study cancer survival in Appalachia

Mon, 05 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) LEXINGTON, Ky. -- University of Kentucky researchers recently received a $225,000 grant to study the differences in cancer survival in Appalachia.

The grant gives the team $225,000 for the first year, with potential funding for two additional years that could total $675,000. It is funded by the Centers for Disease Control and Prevention through the UK-based Rural Cancer Prevention Center.

Published studies have shown a high incidence of cancer incidence and mortality and insufficient cancer care in Appalachia. However, differences in relative survival and avoidable death within sub-regions of Appalachia, and between Appalachian and non-Appalachian areas, have not yet been studied.

The project will collect cancer incidence data from the 13 cancer registries in Appalachian states to identify differences in relative survival and avoidable death within sub-regions of Appalachia, and between Appalachian and non-Appalachian areas for lung, colorectal, female breast, prostate, ovarian and cervical cancer.

Bin Huang, director of Population-Based Cancer Research at the Kentucky Cancer Registry, will serve as a principle investigator for the project. The findings from the project will provide valuable information needed to develop and target effective evidence-based cancer control interventions for the Appalachian population, says Huang.

Population-based survival is arguably the best single measure of the overall effectiveness of health service, Huang said. Results of the study will have direct impact in cancer prevention research here at Markey as the Appalachian population is the focus of our research. With combined knowledge of cancer incidence, mortality, survival and health behavior, more effective or novel intervention strategies could be developed and conducted for this special population.

Thomas Tucker, director of the Kentucky Cancer Registry, will serve as a co-principal investigator for the project, and Robin Vanderpool, deputy director of the Rural Cancer Prevention Center, will join as a co-principal investigator for the third year of the study and lead the efforts to disseminate study findings.

Findings from this project have implications for multiple stakeholders, including state comprehensive cancer control coalitions; healthcare providers, including primary care and oncology specialists; hospitals and cancer centers; public and private insurers; cancer advocacy organizations; and policymakers, Vanderpool said. It is important we disseminate our findings to state and local-level constituents, researchers, and organizations across Appalachia in order to improve cancer prevention, screening, treatment and survivorship services in this region of the country.

Bringing all of the 13 states with Appalachian counties together for a study of this magnitude is a significant undertaking, Tucker said. Cancer survival has never been studied across the entire Appalachian area. Yet, the results of this important research will help to identify the areas in greatest need for cancer prevention and control interventions.

National experts from the John Theurer Cancer Center will present 31 studies at the 2011 ASH Meeting

Thu, 01 Dec 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Hackensack, N.J. (December 1, 2011) - The John Theurer Cancer Center at Hackensack University Medical Center, one of the nation's top 50 best hospitals for cancer, will present research updates and clinical trial results of 31 cutting-edge studies at the 2011 American Society of Hematology (ASH) Annual Meeting in San Diego from December 10-13.

More than half of the John Theurer Cancer Center presentations showcased at the ASH Annual Meeting have been considered exceptionally significant and will be presented orally, including Phase I and Phase II studies, multi-center, international trials in collaboration with leading cancer institutions such as the National Cancer Institute, MD Anderson, Dana-Farber, Mayo Clinic, and Memorial Sloan-Kettering.

Personalizing therapies will certainly play a growing role in the practice of oncology, said Andre Goy, M.D., M.S., chairman and director, chief of lymphoma, and director, clinical and translational cancer research. Our center is part of many studies researching novel therapies as well as the identification of biomarkers predictive of outcomes in cancer.

ASH is the world's largest professional society concerned with the causes and treatments of blood disorders. The research presented by the John Theurer Cancer Center will include advancements made in research and clinical trials in lymphoma, multiple myeloma, blood and marrow stem cell transplantation and leukemia.

Seven John Theurer Cancer Center physicians are first or senior authors, including Dr. Goy; Michele Donato, M.D., collection facility medical director, blood and marrow transplantation; Anthony Mato, M.D., oncologist, lymphoma; Joshua Richter, M.D., oncologist, multiple myeloma; Scott Rowley, M.D., chief, blood and marrow transplantation; David Siegel, M.D., Ph.D., chief, multiple myeloma; and David Vesole, M.D., Ph.D., co-chief and director of research, multiple myeloma.

John Theurer Cancer Center experts will also participate in panel discussions and moderate sessions. Dr. Siegel will present a complicated case at the International Hematologic Oncology Tumor Board during the Friday Satellite Symposium preceding the ASH Annual Meeting. In addition, Dr. Goy will moderate an oral and poster session featuring lymphoma chemotherapy.

We are proud to contribute such a significant body of scientific research, said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., chief innovation officer, professor and vice president of cancer services, John Theurer Cancer Center. We are thankful to the patients who entrust us and participate in our clinical trials, the physicians who lead this research at our institution, and the institutions we collaborate with to help us accelerate the development of novel and combination therapies.

For those attending the ASH annual meeting, visit the John Theurer Cancer Center at Booth 1923. The following are abstracts and presentations at ASH annual meeting from the John Theurer Cancer Center. For ongoing updates, please visit

Taccalonolides from bat plants selectively kill cancer cells

Tue, 22 Nov 2011 18:29:24 PST

( from http://www.rxpgnews.com ) In a new study published this month in the Journal of the American Chemical Society, researchers with The University of Texas Health Science Center at San Antonio have pinpointed the cancer-fighting potential in the bat plant, or Tacca chantrieri.

Susan Mooberry, Ph.D., leader of the Experimental Development Therapeutics Program at the Cancer Therapy & Research Center and a professor of pharmacology in the School of Medicine at the UT Health Science Center, has been working to isolate substances in the plant, looking for a plant-derived cancer drug with the potential of Taxol.

Taxol, the first microtubule stabilizer derived from the Yew family, has been an effective chemotherapy drug, but patients eventually develop problems with resistance over time and toxicity at higher doses. Researchers have long been seeking alternatives.

“We’ve been working with these for years with some good results, but never with the potency of Taxol,” said Dr. Mooberry, lead author of the study. “Now we have that potency, and we also show for the first time the taccalonolides’ cellular binding site.”

Microtubules are structures in the cells that act as conveyer belts. They help maintain cell shape and help guide chromosones in cell division to ensure that every new cell, including every new cancer cell, gets a full complement of genetic material. When microtubules are stabilized — essentially held still so they can’t do their jobs — this disrupts numerous cellular processes, and the cell can die.

The taccalonolides stabilize microtubules in cancer cells, but they do not attack healthy cells, Dr. Mooberry said. “We’ve run normal prostate cells and normal breast cells through these tests, and they don’t die. The taccalonolides selectively kill cancer cells.”

Until now, how they did this was unknown. The isolation of these highly potent taccalonolides for the first time by Dr. Mooberry’s team shows how they interact directly with microtubules.

Derivative of the agent zileuton has proteasome inhibiting properties

Tue, 22 Nov 2011 17:48:06 PST

( from http://www.rxpgnews.com ) Biochemists at the Technische Universitaet Muenchen (TUM) have now identified the lead structure of a new class of drugs that attacks the proteasome in an unusual way. New medication could be developed on the basis of this previously unknown binding mechanism. The scientists report their results in the scientific journal Angewandte Chemie.

The proteasome, a large protein complex, carries out a vitally important function in the cells of the body. Similar to a recycling plant, it decomposes unneeded proteins into short pieces and recycles them. In this way it controls a number of functions in the cell. It regulates cell growth and division, decomposes damaged proteins and also acts as a key partner of the immune system in immune defense and inflammatory reactions. Because it is involved in so many important mechanisms within the cell, the proteasome is also associated with many diseases such as cancer, mucoviscidosis and a whole series of neurodegenerative disorders such as Parkinson's or Alzheimer's disease.

Due to its significant role in the growth of cancer cells, in recent years the proteasome has taken center stage in pharmacological research as a starting point for cancer medication. When it becomes inhibited, the growth of cancer cells slows down. Bortezomib, the first drug to apply this strategy, generates revenues of over one billion US dollars per year in the meantime. It is used against multiple myeloma, a cancer disease of the bone marrow. Yet in spite of all its successes, the proteasome inhibitors currently in use often have severe disadvantages. As a result of their high reactivity they attack other proteins, too, thereby damaging not only cancer cells but also other healthy cells.

The search for alternatives conducted by a group of scientists headed by Professor Michael Groll, who holds the Chair of Biochemistry in the Department of Chemistry at the TU München, in collaboration with Professor Robert Huber, Director Emeritus at the Max-Plank Institute of Biochemistry and Dr. Stefan Hillebrand from Bayer CropScience, has now borne fruit: In a high throughput screening, the scientists examined a substance library of 200,000 potential agents in their quest to identify proteasome inhibitors – and they were successful. They identified a new structure with the so-called N-hydroxyurea motif, which reacts not only reversibly but above all specifically with the active nucleus of the proteasome. The structure inhibits the function of particular subunits of the protein complexes, which are catalytically active, and thus incapacitates the enzyme. Because of this property, the newly discovered hydroxyurea structures work more specifically than other proteasome inhibitors and are thus expected to lead to less severe adverse side effects.

The scientists were already familiar with the basic hydroxyurea structure, albeit in a completely different context. The substance in question is a derivative of the agent zileuton, which is used to treat asthma. Zileuton itself does not influence the proteasome, but its derivative, which had so far received little attention, does. "We have now found a completely new application for this previously known class of substances," explains Michael Groll. "This is of great advantage, because there are already clinical trials that give us first indications of how this class of substances behaves in the human body."

The initial structure originally discovered in the database inhibited the proteasome very specifically, but not terribly effectively. In order to modify the substance in such a way that it also works in lower concentrations – such as those required for medication – it was an important next step to understand how exactly the structure attacks the proteasome. To shed further light on this, the scientists conducted a crystal structure analysis. The outcome was that the hydroxyurea motif attacked the proteasome in a completely different manner than all other previously known inhibitors. It reacts via hitherto unknown binding pockets that may serve as starting points for the development of the new medication agents.

Starting from preliminary modeling studies, the researchers synthesized a series of different derivatives of the agent, which were then examined using X-ray crystallography and activity tests to optimize the effectiveness of the structure. The results showed that the proteasome inhibiting activity of the hydroxyurea derivatives depends on the two side chains attached to the basic structure.

Because the proteasome is contained in every cell and involved in numerous cellular functions the new inhibiting structure offers a whole range of applications, not only in the field of oncology. In the context of autoimmune diseases, an inhibition of the immunoproteasome, a derivative of the proteasome, might play an important role. In the case of autoimmune diseases, including some forms of rheumatism, the immune system attacks the body's own tissue. If the immunoproteasome is inhibited such over-reactions might be weakened. In future studies Professor Groll's team plans to improve the effectiveness of the hydroxyurea structure via experiments on cell cultures.

New service brings power of genomics to patient care

Tue, 22 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Physicians can now take advantage of a new genetics test -- one of the first of its kind to be offered in the United States -- that can help determine the best treatment for cancer patients.

Genomics and Pathology Services at Washington University School of Medicine in St. Louis (GPS@WUSTL) is now offering a test for mutations in 28 genes associated with cancer. The genes in the test affect a variety of different types of tumors, including blood, lymph, lung, brain, bladder, kidney, skin, stomach, prostate and breast cancers.

Identifying specific mutations in these genes can help doctors decide which treatments are most likely to benefit individual patients, which is the goal of genomic (or personalized) medicine.

All of these genes already can be tested individually for mutations. But using GPS@WUSTL, physicians throughout the country can order the new test to simultaneously examine the genes most likely to influence treatment of a patient's tumor.

According to GPS@WUSTL organizers, sequencing multiple genes at once is less expensive than sequencing the genes separately. The next-generation sequencing technique and the novel bioinformatics platform used to produce the data also will significantly improve the sensitivity and accuracy of the results.

Scientists envision the cancer genetics test as the first of many disease panels to be offered by GPS@WUSTL. Work is under way on similar panels that will influence the diagnosis and treatment of other disorders, including autism and kidney disease.

GPS@WUSTL is bringing the promise of human genomics to the clinic, says Karen Seibert, PhD, director of GPS@WUSTL. We use the latest gene sequencing technology and cross-reference the results to known treatment options for the patient's particular mutations. In addition to patient care, our labs will support clinical trials aimed at identifying new ways to diagnose and treat disease.

While costs for sequencing a patient's entire genome are decreasing, it's still not economically feasible to perform whole-genome sequencing for clinical treatment of patients. Sequencing of multiple genes known to influence a disease will produce the information physicians need to guide treatment decisions.

The services provided by GPS@WUSTL will be paid for by a mixture of revenue streams, including health-care insurers, hospitals, patients and federal research grants, and through partnerships with companies and foundations.

Patients throughout the country can access GPS@WUSTL through their personal physician, says John Pfeifer, MD, PhD, vice chairman for clinical affairs in pathology and immunology. After we receive a patient's tumor sample, results will be returned in days to weeks in a report identifying the mutations detected. We will also provide the names of specific drugs that target the mutations' effects as identified in peer-reviewed medical literature.

GPS@WUSTL administrators chose the 28 genes in the first test because all have implications for cancer therapy. The test can easily be adapted to add newly discovered mutations as they are clinically validated.

To describe how multiple genes can affect treatment, GPS@WUSTL Medical Director Shashi Kulkarni, PhD, cites acute myeloid leukemia (AML), a blood cancer.

In AML, patients who have a mutation in a gene called FLT3 can be treated with a drug that suppresses the mutation's effects, improving chances for recovery, Kulkarni says. Mutations in another gene, DNMT3A, suggest a poor prognosis and call for initial treatment with a bone marrow transplant, a riskier therapy normally reserved for patients whose AML recurs after chemotherapy.

As another example, some lung cancers harbor a mutation in a gene called EGFR. These tumors can be killed much more effectively by specific chemotherapy drugs, so knowledge of the EGFR status helps oncologists choose the best treatment regimen.

The sensitivity of the new sequencing techniques used by GPS@WUSTL will be important for cancers, many of which are genetically unstable, notes Jeffrey Milbrandt, MD, PhD, the James S. McDonnell Professor and head of the Department of Genetics. This instability results in tumors that contain cells that are genetically different.

It's possible that an important mutation that makes the tumor harder to kill will be present only in a small percentage of tumor cells, he says. The new sequencing technology we're using substantially increases our chances of detecting such critical mutations.

GPS@WUSTL faculty and technicians will work in laboratories designed and maintained to meet rigorous clinical testing standards.

All of our labs will meet the requirements of both the College of American Pathologists (CAP) accreditation and Clinical Laboratory Improvement Act (CLIA) certification, says Herbert W. Virgin IV, MD, PhD, the Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology. Those are the gold standards of laboratory testing, and GPS@WUSTL will be among a group of relatively uncommon genetic testing services in the nation to have both of them.

Washington University's new Genome Technology Access Center (GTAC) provides the genetic data interpreted by GPS@WUSTL. Bioinformatics experts in GPS@WUSTL have built a clinical genomicist workstation that can automatically insert references to medical literature that can help doctors assess the treatment options.

Having the system automatically start the interpretive work will help loosen a major bottleneck that has made it difficult to provide physicians with results of genomic tests in a timely fashion, says GPS@WUSTL Bioinformatics Director Rakesh Nagarajan, MD, PhD.

Cancer vaccine impact limited unless drug industry focuses on difficult-to-treat tumors

Mon, 21 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Drug companies currently developing therapeutic cancer vaccines may be determining the cancers they target based on the number of annual cases, not the number of deaths they cause.

This approach may limit the patient benefits of such drugs, according to a new University of Michigan report.

Therapeutic vaccines, an alternative form of cancer treatment that may be more effective than traditional cancer therapies, are currently being tested in clinical trials around the world.

Early studies on these vaccines, which trigger patients' immune systems to attack cancer cells, have shown they may offer new hope for those suffering from difficult-to-treat cancers.

In 2011, there were about 230 clinical trials for therapeutic vaccines targeting 13 different types of cancer, says Matthew Davis, M.D., M.A.P.P., associate professor of pediatrics, internal medicine, and public policy at the University of Michigan Health System and Gerald R. Ford School of Public Policy.

If a cancer is more commonly diagnosed in the United States, it is significantly more likely to have therapeutic vaccines in clinical trials, Davis adds. Focusing on annual incidence is a very common approach by drug companies in developing new therapies.

Therapeutic vaccine development should focus on cancers with higher mortality rates, creating more potential to improve patient outcomes, Davis suggests.

The lack of a connection between therapeutic cancer vaccine development and cancer deaths means that vaccine development in this arena today may not best serve the needs of cancer patients tomorrow, Davis says. As a primary care doctor, I would like to see innovations with therapeutic vaccines that target cancers where our current therapies are less effective than average.

Davis and co-author Elias Dayoub, a second-year medical student, emphasize that lung cancer and pancreatic cancer are two tumor types where the five-year survival is lower than average and the number of patients newly diagnosed each year is higher than average.

Fortunately for patients, there are already some late-stage clinical trials in progress for patients with cancers of the lung and pancreas, Davis says. Based on the typical time course for trials and licensure, if these vaccines are safe and effective, we may able to use them to help patients as early as 2020 and perhaps earlier.

The cancers with the highest number of active clinical trials worldwide in 2011 are melanoma (40), breast (34), lung (30), prostate (22), and brain (20).

The five cancers with the highest five-year mortality (estimated by the authors, based on current U.S. data) are lung (186,000), pancreas (40,000), colon (35,000), breast (21,000) and liver and bile duct (21,000), for a total of 303,000 deaths. There are currently 90 therapeutic vaccines in development against these 5 types of cancer.

In contrast, the five cancers with the most active development (146 vaccines in aggregate) target cancers with a lower five-year mortality of approximately 226,000. This mismatch is unfortunate for patients, says Davis. Cancers with higher mortality currently have fewer vaccines in development. For therapeutic vaccines to make the biggest difference in cancer care, development must focus more on high-mortality tumors.

George Mason University research gives hope to women with deadliest breast cancer

Mon, 14 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Women with the deadliest and rarest form of breast cancer now have a chance of treatment where once their options were severely limited, thanks to a new discovery by George Mason University researchers.

This aggressive cancer, called inflammatory breast cancer, kills about half the women who have it within five years; patients live on average a mere 18 months after diagnosis. About 10,000 women are diagnosed each year with inflammatory breast cancer, according to U.S. government statistics.

In a recent study, Mason scientists pinpointed a key driver in the cancer that is leading to new ways to treat it. This study is not only a success for cancer patients but for a pioneering research method that discovered the finding as well, says Emanuel Chip Petricoin, co-director of Mason's Center for Applied Proteomics and Molecular Medicine (CAPMM) along with Lance Liotta.

This summer, doctors at Philadelphia's Fox Chase Cancer Center under the direction of Massimo Cristofanilli, the center's chair of medical oncology, began treating inflammatory breast cancer patients with a drug originally developed for non-small cell lung cancer because Mason research revealed a commonality between the two cancers. Prior to the research, these breast cancer patients had limited treatment options, Petricoin says.

Discovering how the cancer works using proteomics, an approach that looks at the proteins on the genes, was essential to the finding. If researchers had stuck with traditional genome analysis, they would have missed the protein that can be targeted to treat this particularly dangerous form of breast cancer, Petricoin says. The proteins on the genes are the key for successful treatment.

It is the proteins that the drug targets, not the genes, he says.

Petricoin and Liotta invented a technology called the reverse phase protein array a decade ago, which Mason exclusively licensed to Theranostics Health, Inc, a company the two co-founded over 5 years ago. It's a way of physically arranging proteins to reveal how they work on individual cells, such as cancer cells.

DNA is the information archive, but it is the proteins that do the work, Petricoin explains. Proteins are the software of the cell. They basically direct the cell to die, grow, divide and metastasize. While many think of cancer as a genomic disease, it's actually a proteomic disease. What is actually deranged in the cancer cells are protein pathways. These protein pathways form a linked network of interaction, talking to each other.

And not everyone has the same network of activated proteins. If a patient's cancer doesn't have a particular protein turned on that the drug targets, then the drug fails.

Now we know that's why the one-size-fits-all approach doesn't work, Petricoin says.

When Petricoin, and CAPMM researchers Julie Wulfkuhle and Rita Circo began to study the cells from inflammatory breast cancer patients, they were surprised. They used the array platform and found that a protein called anaplastic lymphoma kinase (ALK), which was previously unconnected to breast cancer, is highly activated in nearly all the samples they looked at.

When we looked at these breast cancer samples, we saw ALK and the entire ALK pathway lit up like a string of lights, Petricoin says.

The best news is that there's already a drug on the market for treating patients with activated ALK, and it can be used for inflammatory breast cancer, too, Petricoin says. If the results of their work are validated in further patients, more people stand to benefit because ALK activation appears much more often in inflammatory breast cancer patients than in lung cancer patients.

Petricoin and his team worked with Fredika M. Robertson, a professor in the department of experimental therapeutics at the University of Texas MD Anderson Cancer Center, who led the study.

More research is on the way. Working with Robertson, the Mason team plans to find better drugs or a new combination of drugs to treat the cancer as patients build resistance to existing treatments. They're also searching for new ways to use current drugs that are already in the pipeline or have been cleared by FDA.

The technology has graduated to the point where we can do this at the bedside, and we hope that through Theranostics Health it can benefit many patients in the future Petricoin says.

The Mason team also is applying its know-how to breast cancer in general, colorectal cancer, multiple myeloma and cancers of the prostate, brain, lung and ovaries.

While Petricoin doesn't expect a complete shift from genomic research, the study boosts the role of proteomics.

It really highlights that you can't put all your eggs in one basket, he says. You can't just invest in genomic analysis. At the very least, proteomic analysis should be done simultaneously with the genomic analysis. This finding basically validates the philosophical approach we're taking and the power that the array platform provides

Risk of contracting diabetes to increase in world of 7 billion people

Mon, 14 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) World citizen number 7 billion is less likely to die from infectious diseases like measles or even AIDS, and more likely to contract diabetes or other non-communicable diseases (NCDs), as they are now the leading causes of deaths globally.

14th of November is official World Diabetes Day. In a world of 7 billion people with changing disease patterns, this day is more relevant than ever, according to external lecturer Siri Tellier from the Copenhagen School of Global Health at the University of Copenhagen.

Our new world citizen number 7 billion is more likely to grow up in an urban setting, which increases his or her risk of getting diabetes, as well as chronic obstructive pulmonary disease (COPD), cancer and heart disease, says Siri Tellier, who teaches demography and health in emergencies, while she also lectures on international perspectives on demographic challenges to Chinese university students in Beijing.

World citizen number 7 billion, who was estimated to be born on 31 October, will face very different diseases than that of children born only a few decades ago. As the population of urban areas keeps growing, it rapidly changes the global health challenges.

Until 2008, the majority of the world population lived in rural areas, but since then the majority has become urban, and most future population growth will happen in urban areas of developing countries. And one third of them, a little more than one billion, live in urban slums, says Siri Tellier.

A high proportion of people who move to cities are young adults, and this has several implications for health. Among them are the consequences of leaving their parents behind in rural areas.

Aging parents can no longer depend on their adult children for care. They will often 'live with' chronic NCDs such as diabetes, and will need daily assistance. It's not just a question of the children sending them money from their new home in a big city - who will care for the old people on a daily basis? The household size is shrinking. In rural areas it may be five, in urban areas only two. So in order to meet that challenge, new patterns of caring for older people will be needed, says Siri Tellier.

In the cities of the world, the health challenge is twofold: Firstly, living conditions in slum areas are poor, both with respect to water and sanitation, and access to health care almost non existent. In addition, life in urban areas often entails a shift toward 'modern' life styles, with inadequate nutrition, especially more fatty, salty foods, smoking, alcohol and lack of exercise - all primers for NCDs.

Secondly, when the young newcomers become parents, their own poor health will have influenced the unborn child's predisposition for NCDs.

Increasing numbers of studies show, that healthy ageing begins in the womb, Siri Tellier continues, and explains that if - for example - children are born with low birth weight, they are more likely to develop diabetes later in life

Our new world citizen nr. 7 billion will probably grow up in an urban setting, and will face factors that increase his or her risk of diabetes, as well as COPD, cancer and heart disease.

There is also an increasing awareness of the need to help even healthy, young people gain the habits which will predispose them for health in later life. Parents may have a hard time ensuring that their teenagers develops healthy habits, which will follow him or her throughout life, especially if a lack og these habits do not cause ill health immediately, Siri Tellier points out.

Of course, the good news is that the child is less likely to die from measles, or even AIDS or diarrhoeal diseases. We have reduced the number of child deaths from around 12 million in 1990 to less than 8 million today, and most of the saved lives are through prevention measures such as vaccinations against infectious diseases. That is not only good news, that is fantastic news. Siri Tellier explains.

Flemming Konradsen, Director of the Copenhagen School of Global Health at the University of Copenhagen, shares this optimistic view, and stresses that we must now deal with the non-communicable diseases as seriously as infectious diseases:

Global disease patterns are changing. As many countries around the world have reduced the great killers such as malaria, we must turn the same effort and resources towards NCD's, as they must be prevented now rather than treated later.

In addition to the personal consequences for the patient, NCDs burden developing health care systems with such high expenses, that can halt their development if we do not intervene, says Professor Flemming Konradsen.

Scientists identify genes that may signal long life in naked mole-rats

Thu, 03 Nov 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists at the University of Liverpool have identified high levels of a number of genes in the naked mole-rat that may suggest why they live longer than other rodents and demonstrate resistance to age-related diseases.

The Liverpool team has recently generated the first whole-genome sequencing data of the naked mole-rat - a rodent that lives for more than 30 years and is resistant to cancer - to understand its longevity and resistance to disease. Scientists, in collaboration with Harvard University, have now compared the levels of its genes with genes in wild mice to investigate what makes naked mole-rats different to other rodents.

They found that genes associated with mitochondria, that provide energy to cells, and genes that affect respiration and the decisions cells make, are expressed at unusually high levels in the naked mole-rat compared to the same genes in wild mice. In animals and humans these genes are thought to play a role in influencing and adapting to cell damage, which is thought to be one of the significant causes of ageing.

Naked mole-rats, however, also have increased levels of oxidative stress, which is an imbalance in reactive molecules containing oxygen. This can lead to mutations in the cells and the growth of cancerous tumours. To date, cancer has not been detected in the naked mole-rat, but these new findings suggest that the rodent has mechanisms of regulating gene responses to limit the potential negative impact of oxidative stress on cells. The research will help scientists focus on particular areas of the genome to further understanding into how the body ages.

Dr Joao Pedro Magalhaes, from the University's Institute of Integrative Biology, said: The naked mole-rat is native to the deserts of East Africa and has unique physical traits that allow it to survive in harsh environments for many years. It has a lack of pain sensation in its skin and has a low metabolic rate that allows it to live underground with limited oxygen supply.

It has been of interest to scientists for some time and we hope that by studying its genome it will help us understand the mechanisms of ageing and how the body protects itself from disease.

These findings add further evidence to research that suggests genes responsible for mitochondria and oxireduction are associated with the ageing processes. It also provides some clues as to how naked mole-rats protect themselves against high levels of oxidative stress. The high levels of genes connected to energy production and cell decision-making systems may help in creating an intracellular environment that prevents cancer and other age-related diseases.

This work provides candidate genes for specifying resistance to ageing and cancer that we can build on in future studies. The next stage of the research will be to observe what happens to the cells if gene levels change from high to low and vice-versa.

The research is published in the journal,

Scientists prove regular aspirin intake halves cancer risk

Fri, 28 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists including those from Queen's University have discovered that taking regular aspirin halves the risk of developing hereditary cancers.

Hereditary cancers are those which develop as a result of a gene fault inherited from a parent. Bowel and womb cancers are the most common forms of hereditary cancers. Fifty thousand people in the UK are diagnosed with bowel and womb cancers every year; 10 per cent of these cancers are thought to be hereditary.

The decade-long study, which involved scientists and clinicians from 43 centres in 16 countries and was funded by Cancer Research UK, followed nearly 1,000 patients, in some cases for over 10 years. The study found that those who had been taking a regular dose of aspirin had 50 per cent fewer incidences of hereditary cancer compared with those who were not taking aspirin.

The research focused on people with Lynch syndrome which is an inherited genetic disorder that causes cancer by affecting genes responsible for detecting and repairing damage in the DNA. Around 50 per cent of those with Lynch syndrome develop cancer, mainly in the bowel and womb. The study looked at all cancers related to the syndrome, and found that almost 30 per cent of the patients not taking aspirin had developed a cancer compared to around 15 per cent of those taking the aspirin.

Those who had taken aspirin still developed the same number of polyps, which are thought to be precursors of cancer, as those who did not take aspirin but they did not go on to develop cancer. It suggests that aspirin could possibly be causing these cells to destruct before they turn cancerous.

Over 1,000 people were diagnosed with bowel cancer in Northern Ireland last year; 400 of these died from the disease. Ten per cent of bowel cancer cases are hereditary and by taking aspirin regularly the number of those dying from the hereditary form of the disease could be halved.

Professor Patrick Morrison from Queen's University in Belfast, who led the Northern Ireland part of the study, said: The results of this study, which has been ongoing for over a decade, proves that the regular intake of aspirin over a prolonged period halves the risk of developing hereditary cancers. The effects of aspirin in the first five years of the study were not clear but in those who took aspirin for between five and ten years the results were very clear.

This is a huge breakthrough in terms of cancer prevention. For those who have a history of hereditary cancers in their family, like bowel and womb cancers, this will be welcome news. Not only does it show we can reduce cancer rates and ultimately deaths, it opens up other avenues for further cancer prevention research. We aim now to go forward with another trial to assess the most effective dosage of aspirin for hereditary cancer prevention and to look at the use of aspirin in the general population as a way of reducing the risk of bowel cancer.

For anyone considering taking aspirin I would recommend discussing this with your GP first as aspirin is known to bring with it a risk of stomach complaints, including ulcers.The research is due to be published in the

Controlling gene expression to halt cancer growth

Fri, 28 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) NUT midline carcinoma (NMC) is a cancer without a cure, and one that affects all age groups. NMC is a rapid-growth disease with an average survival time of four and a half months after diagnosis, making the development of clinical trials for potential therapies or cures for this cancer difficult, to say the least.

But difficult doesn't mean impossible, and Olaf Wiest, professor of chemistry and biochemistry at the University of Notre Dame, is one of a group of collaborators studying the effects of a specific molecule (JQ1) on the trigger that controls the growth of this form of cancer.

Most people are familiar with genetics and the role they play in our height, hair color, and even predisposition to various diseases. But there is this whole other world called epigenetics that controls which genes are expressed and which aren't, says Wiest.

This epigenetic world is made up of three classes of proteins: writers, erasers and readers, collectively the instruction manual that tells a gene when to activate and when to cease activation. Writers will create the instruction for the gene while erasers will remove instructions. Readers control the group and issue the start and stop commands for genes to use their instructions.

The reason NMC is so aggressive is because these cancer cells divide very fast, says Wiest. This rapid-growth is caused by the protein BRD4, an epigenetic reader that interacts with another protein called a histone. Their interaction changes the instructions for the gene and keeps the growth trigger permanently activated.

The solution is that you have to block that protein, Wiest says. Which is something that is traditionally very difficult in protein-to-protein interactions because the binding between them is not very strong. Normally when you're talking to somebody in chemistry and say you're going to target a protein to protein interaction, they say 'you're nuts.'

Of course the way to prove them wrong is to go on and do it, he concludes.

There is already a vast amount of information on writers and a lot of interest in erasers in the research community because there are two FDA approved drugs that control erasers. Research into epigenetic readers, however, is relatively new.

Wiest says it wasn't such a big step for him and his 21 colleagues to move from erasers to readers in their studies. Their recent focus has been on a small molecule called JQ1 that tricks the NUT midline carcinoma cancer cells by disrupting the protein-to-protein interaction. It not only halts the constant growth command but it also makes the cancer cells forget their instructions and begin to resemble normal cells.

Wiest's research showed that the protein is less flexible in the presence of JQ1, allowing it overcome the weak bindings. Animal studies produced very encouraging results. Laboratory mice transplanted with NMC cells from patients and given JQ1 lived, those that were not given JQ1 died.

Wiest's hope is that through continued studies on the effectiveness of JQ1, an effective and non-invasive therapy can be found for NMC and other aggressive cancers.

NYU College of Nursing receives 450 thousand dollar NIH grant to research post-breast cancer lymphedema

Thu, 27 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) New York University College of Nursing (NYUCN) received a two-year, $452,218.00 grant from the national Institutes of Health (NIH) to research Proinflammatory Biomarkers and Post-Breast Cancer Lymphedema. Post-breast cancer lymphedema (LE), a syndrome of abnormal swelling and multiple distressing symptoms, is caused by injuries to the lymphatic system from cancer treatment. As advances in cancer treatment lengthen survival, LE has emerged as a high-impact long-term morbidity that profoundly impairs survivors' quality of life.

According to Fu, the purpose of this exploratory project is to prospectively examine levels and patterns of proinflammatory biomarkers and genetic variations in relation to limb volume change measured with the infra-red perometer-350S over a 12-month period in breast cancer survivors who are at risk for lymphedema.

Among the 2.5 million breast cancer survivors in the U.S. more than 40% of them have developed lymphedema, said NYUCN Assistant Professor Mei Fu, PhD, RN, APRN-BC. All women undergoing breast cancer treatment are at lifetime risk for lymphedema.

While removal of lymph nodes, surgery, and radiation are the major causal factors for lymphedema, cancer treatment is necessary for life-saving. Recent research has revealed that inflammation-infection and higher body mass index (BMI) are the main predictors of lymphedema besides treatment-related risk.

Unfortunately, these studies did not evaluate biomarkers known for inflammation, and thus the role of inflammation-infection in limb volume change and lymphedema development could not be ascertained.

Elevated levels of proinflammatory biomarkers have been speculated to be associated with inflammation in patients with lymphedema. Moreover, genetic variations may be one of the important factors that influence breast cancer survivors' responses to inflammatory processes and vulnerability to lymphedema, including survivors' responses to treatment-related trauma (such as surgery and radiation) and triggering factors (such as infection, burns, minor injuries, and higher BMI or obesity).

The project will employ a prospective, descriptive, and repeated-measure design. A sample of 120 women who are newly diagnosed and treated for invasive breast cancer will be recruited. Data will be collected to evaluate levels and patterns of proinflammatory biomarkers and genotypes known for inflammation in relation to limb volume change.

This project is an important first step toward gaining necessary knowledge and insights into breast cancer survivors' susceptibility, which may help to identify survivors at higher risk based on individual survivors' biomarker patterns and genetic factors, said Fu. Findings of the project are fundamental in developing and testing more intense and personalized interventions to prevent and treat LE among the breast cancer survivors.

CK1 protein in cancer cells identified as possible future therapeutic target

Mon, 24 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have identified a cell cycle-regulated mechanism behind the transformation of normal cells into cancerous cells. The study shows the significant role that protein networks can play in a cell leading to the development of cancer. The study results, published in the October 21 issue of the journal Molecular Cell, suggest that inhibition of the CK1 enzyme may be a new therapeutic target for the treatment of cancer cells formed as a result of a malfunction in the cell's mTOR signaling pathway.

In the study, NYU Cancer Institute researchers examined certain multi-protein complexes and protein regulators in cancer cells. Researchers identified a major role for the multi-protein complex called SCFβTrCP . It assists in the removal from cancer cells the recently discovered protein DEPTOR, an inhibitor of the mTOR pathway. SCF (Skp1, Cullin1, F-box protein) ubiquitin ligase complexes are responsible for the removal of unnecessary proteins from a cell. This degradation of proteins by the cell's ubiquitin system controls cell growth and prevents malignant cell transformation. Researchers show that inhibiting the ability of SCFβTrCP to degrade DEPTOR in cells can result in blocking the proliferation of cancer cells. In addition, researchers discovered that the activity of CK1 (Casein Kinase 1), a protein that regulates signaling pathways in most cells, is needed for SCFβTrCP to successfully promote the degradation of DEPTOR.

"Low levels of DEPTOR and high levels of mTOR activity are found in many cancers, including cancers of the breast, prostate, and lung," said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. "It is critical for researchers to better understand how the protein DEPTOR is regulated. Our study shows it would be advantageous to increase the levels of DEPTOR in many types of cancer cells to inhibit mTOR and prevent cell proliferation."

The mTOR pathway (mammalian Target Of Rapamycin) regulates the growth, proliferation, and survival of a cell, and its proper regulation is essential to prevent the formation of cancer cells. DEPTOR interrupts the mTOR pathway by binding to mTOR protein complexes and blocking their enzymatic activities, restraining cell growth. This helps support the proliferation and survival of cancer cells.

Study experiments showed that a reduction of SCFβTrCP and CK1 proteins in cells resulted in accumulation of DEPTOR. Also, DEPTOR was destroyed in cells only when SCFβTrCP and CK1 were both present. Thus, inhibition of SCFβTrCP or CK1 represents a novel and promising way to inhibit the mTOR pathway. A pharmacologic inhibitor of CK1 was tested by researchers and shown to successfully stabilize DEPTOR in cells, while other pharmacological agents had no effect.

"Our study findings demonstrate that DEPTOR is regulated by the protein complex in cells reentering the cell cycle, and deregulation of this event could contribute to the aberrant activation of the mTOR pathway in cancer," said lead author Shanshan Duan, PhD, a post-doctoral fellow in the Department of Pathology at NYU School of Medicine in Dr. Pagano's Laboratory. "This study suggests a novel approach to stop the deregulation of the mTOR pathway in cancer cells with promising small molecule inhibitors of CK1.This study is another step forward in the translation of laboratory findings into more effective approaches to cancer prevention and treatment."

Association of quantity of alcohol and frequency of consumption with cancer mortality

Thu, 20 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A paper from the National Institutes of Health in the United States has evaluated the separate and combined effects of the frequency of alcohol consumption and the average quantity of alcohol drunk per occasion and how that relates to mortality risk from individual cancers as well as all cancers. The analysis is based on repeated administrations of the National Health Interview Survey in the US, assessing more than 300,000 subjects who suffered over 8,000 deaths from cancer. The research reports on total cancer deaths and deaths from lung, colorectal, prostate, and breast cancers.

The overall message of this analysis is that light to moderate alcohol intake does not appear to increase the risk of all-site cancer (and light drinking was shown in this study to be associated with a significant decrease in risk). Similarly, light to moderate consumption was not associated with site-specific cancers of the lung, colorectum, breast, or prostate.

As quantity consumed increased from 1 drink on drinking days to 3 or more drinks on drinking days (US drinks are 14g), risk of all-site cancer mortality increased by 22% among all participants. For total alcohol consumption (frequency x quantity), the data indicate a significant reduction in the risk of all-site cancers (RR=0.87, CI 0.80-0.94). Moderate drinking consistently shows no effect in the analysis, and only heavier drinking was associated with an increase in all-site cancer risk. For site-specific cancers, an increase in risk of lung cancer was seen for heavier drinkers, with a tendency for less cancer among light drinkers. There was no evidence of an effect of total alcohol consumption on colorectal, prostate, or breast cancer.

The authors excluded non-drinkers in a second analysis in which they used categories of usual daily quantity and of frequency of consumption in an attempt to investigate their separate effects. For all-site cancer and for lung cancer, these results again show an increase in risk only for drinkers reporting greater amounts of alcohol. The data also show an increase in cancer risk from more frequent drinking among women but not among men. For colorectal, prostate, and breast cancer, there is no clear pattern of an increase in risk from quantity of alcohol consumed. For frequency of drinking, again there is a suggestion of an increase in mortality risk with more frequent drinking, although the trends are not statistically significant.

Heavier drinking (three drinks or more per occasion) is known to be associated with a large number of adverse health effects, including certain cancers, as was shown in this study. When considering cancer, alcohol consumption should not be considered in isolation, but in conjunction with, other lifestyle behaviours (especially smoking when considering lung cancer). We agree with the authors that both quantity and frequency of consumption need to be considered when evaluating the relation of alcohol to cancer; further, beverage-specific effects need to be further evaluated.

ASE-EAE to issue guidelines for the echocardiographic evaluation of cancer patients

Thu, 20 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Considering that the early detection of cardio toxicity is a critical issue for patients undergoing chemotherapy, the ASE and the EAE have come together to write guidelines which will highlight the technical advantages of echocardiography in identifying cardio toxicity early, explained Prof Juan Carlos Plana, Co-Director of the Cardio-oncology Center, Cleveland Clinic, from the ASE. This would help select patients who would benefit from cardio protective regimens, so that heart failure does not become an obstacle to the oncologist during therapy, and to the patient during his/her survival.

In the last decade cancer therapy has had an enormous progress leading to an important reduction of morbidity and mortality of several types of cancer. The therapeutic management of patients with cancer includes a combination of drugs, radiation therapy, and surgery. Several of these therapies, mainly anthracyclines, produce potential adverse cardiac reactions which can negatively impact the quality of life as well as the prognosis of oncologic patients. The new generation of targeted therapies (i.e. trastuzumab in breast cancer) has also been associated with unexpected unfavorable side effects on myocardial function. Currently, 17% of patients have to stop cancer therapy due to heart involvement.

Detecting cardio toxicity is a critical issue in the clinical setting, in order to appropriately modulate and, hopefully, not interrupt cancer therapy. The traditional screening of patients with cancer includes a cardiac examination, and both an electrocardiogram (EKG) and a 2D echocardiogram with Doppler at baseline. The monitoring of cardiovascular toxicity might be more accurate using endomyocardial biopsy. However, the test is highly invasive and not free from complications, stated Dr Maurizio Galderisi, from the Federico II University in Naples, Italy and chairperson of the EAE task force.

Echocardiography has emerged as the modality of choice for noninvasive evaluation of cardiac disease in the cancer patient. This tool is essential for the evaluation of left ventricular systolic and diastolic dysfunction, pericardial and valvular heart disease. However, echocardiograms are only routinely performed at the beginning of cancer therapy, in order to document a normal left ventricular systolic function. Further echocardiographic follow up during cancer therapy is performed only as a consequence of the onset of cardiac symptoms and/or signs, in particular following the administration of recognized cardiotoxic drugs or radiation therapy.

Dr Rosa Sicari, FESC, from the CNR Institute of Clinical Physiology, Pisa, Italy and chairperson of the EAE Scientific Committee adds that the assessment of cardiac toxicity remains a critical issue in oncology. Ejection fraction, the time honored parameter of function is not useful for the detection of early and subtle forms of cardiac dysfunction. New tools are needed and the evidence should be built in the near future with appropriately designed studies and with the common efforts of oncologists, cardiologists and pharmacologists. This document is not meant to fill the gap of knowledge but to provide the state of the art of ultrasound in this field and indicate new research pathways.

On these premises, the upcoming joint recommendations of the American Society of Echocardiography and European Association of Echocardiography will present the need and clinical usefulness of serial echocardiographic evaluations, and the potential impact of more advanced ultrasound technologies in patients undergoing cancer therapy.

Terry Fox Research Institute aims to change diagnosis and management of ovarian cancer worldwide

Thu, 13 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) MONTREAL, QUE. -- Women throughout the world will benefit from a new, pan-Canadian Terry Fox Research Institute (TFRI) initiative that aims to change the way in which ovarian cancer is diagnosed and managed. TFRI and the Canadian Partnership Against Cancer are providing a total of $5-million in funding for a five-year, multi-site Ovarian Cancer Pan-Canadian Program called COEUR. The program will identify new biomarkers to predict and treat this relatively rare but deadly form of cancer, which will result in the use and application of current and new drugs more effectively for patients.

Ovarian cancer is the fifth-leading cause of cancer-related deaths in the Western world. One in every four women diagnosed with this form of cancer is resistant to standard first-line chemotherapy. Through TFRI, leading ovarian cancer researchers and clinicians across Canada have joined forces to develop a made-in-Canada solution to this global clinical problem facing cancer doctors.

The team's work will result in a new stratification system for ovarian carcinoma subtypes and will help clinicians better determine what treatment will work best for each patient. Patients who do not respond to standard therapy can be directed to clinical trials where new therapies are being validated.

This project will change the way in which pathologists, physicians and clinicians think about ovarian cancer. It will help us to classify and sub-divide ovarian cancer into different diseases through molecular profiling. A better understanding of the disease will enable the development and delivery of more personalized care for the patient, which is both better and more efficacious, says TFRI President and Scientific Director Dr. Victor Ling.

The program brings together expertise and resources from across the country to improve the lives of women in Canada and beyond who are diagnosed with ovarian cancer, says Dr. Stuart Edmonds, Director of the Research Portfolio at the Canadian Partnership Against Cancer, a national organization funded by Health Canada to lead the implementation of a co-ordinated cancer strategy. This is one of several projects the Partnership is supporting with the practical goal of identifying emerging technologies that can improve the early detection and treatment of cancer and lead to better outcomes.

Momentum to form the consortium of 35 investigators came from within the ovarian cancer community. The project is headed up by three Canadian researchers at two prominent cancer care and research centres. At the University of Montreal Hospital Research Centre (CRCHUM*), molecular oncologist Dr. Anne-Marie Mes-Masson and gynecologist oncologist Dr. Diane Provencher are the principal investigators. Dr. David Huntsman, a genetic pathologist with the Ovarian Cancer Research Program at BC Cancer Agency and Vancouver Coastal Health, will co-lead the study from Vancouver.

Ovarian cancer is a relatively rare disease that is also very complex. Today we know that it consists of several different subtypes; these are not yet well understood and we have significantly more work ahead to determine what treatment will work for patients and their specific tumour subtype, says Dr. Huntsman. This program includes an important knowledge transfer component that will enable the results to be rapidly deployed within the Canadian pathology community and readily translated into practice.

The women who are participating in this initiative by providing tissue samples for collection and analysis are hoping this research will accelerate the pace of discovery and validation of new biomarkers for ovarian cancer, says Dr. Provencher. We hope to redirect women to new clinical trials and, in particular, those women who don't respond to first-line therapy.

The team is building a unique, central scientific platform that will create a rich clinical resource for researchers to validate new biomarkers and treatments for ovarian cancer. By linking together laboratory scientists with the oncologists, surgeons and pathologists who work with the patients on the front lines, our work will be much more relevant and bear fruit that will reach patients much more quickly, says Dr. Mes-Masson. A strength of the program is the ability to link research results across multiple studies underway across the country.

$9.55 million NCI grant targets the resistance of advanced prostate cancer

Tue, 11 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) When caught in its early stages, prostate cancer is treatable in most cases. But once it reaches a critical threshold, the disease becomes largely resistant to current treatments. The National Cancer Institute (NCI) recently awarded a team of cancer biologists $9.55 million over five years to define the molecular changes that occur as prostate cancer progresses to the therapy-resistant state.

The Program Project Grant (P01), Signaling and Progression in Prostate Cancer, brings together a multi-disciplinary team of basic scientists and physician scientists at the University of Colorado Cancer Center and the University of Virginia.

We are excited for the opportunity to bring together some of the world's top researchers in prostate cancer to explore the changes that turn a largely treatable disease into one with a 28 percent five-year survival rate, says Dan Theodorescu, MD, PhD, director of the University of Colorado's Cancer Center and Paul Bunn professor of Surgery and Pharmacology at the CU School of Medicine, co-principal investigator on this study.

These changes include alterations in how the cancer cells respond to signals and what genes are expressed, says Bryce M. Paschal, PhD, professor of biochemistry and molecular genetics and member of the Center for Cell Signaling at the University of Virginia School of Medicine. Understanding these changes are expected to reveal new drug targets and provide a knowledge base for improving prostate cancer therapies.

Specifically, Theodorescu and Paschal and collaborators will explore how cell growth, adaptation to limited nutrients, and cell motility contribute to the disease's progression to its therapy-resistant form.

We're essentially trying to determine which pathways are altered with disease progression, Paschal says.

To discover these altered pathways, the Program Project Grant will utilize a number of cutting-edge technologies, including molecular imaging, ultra-high throughput DNA sequencing, and the development of new transgenic animal models designed to mimic the changes that occur in human prostate cancer.

The biology of prostate cancer is heterogenous and so we hope to combat it with a team whose specialties are equally so, Theodorescu says.

The three projects in the P01 program include determining how hypoxic signals alter gene expression (Theodorescu), creating new transgenic mouse models to determine how kinases cooperate to drive tumorigenesis (Paschal), and examining how micro RNAs regulate cell proliferation and prostate cancer progression (Dutta).

Members at the University of Colorado Cancer Center also include Scott Lucia, MD, professor of pathology, and Jeffry Kieft, PhD, associate professor of biochemistry and molecular genetics.

University of Virginia team members also include Anindya Dutta, MD, PhD, professor and chair of the Department of Biochemistry and Molecular Genetics; Henry Frierson, MD, professor of pathology; Mark Conway, PhD, professor of biostatistics; David Wotton, PhD, associate professor of biochemistry and molecular genetics; and Dan Gioeli, PhD, assistant professor of microbiology, immunology, and cancer biology.

Case Western Reserve receives prestigious $5.4 million grant to study esophageal cancer

Mon, 10 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center are proud to announce the receipt of a highly competitive $5.4 million grant to study genetic determinants of Barrett's esophagus and esophageal adenocarcinoma. This five-year award from the National Cancer Institute will support the Barrett's Esophagus Translational Research Network (BETRNet), which consists of multiple centers collaborating to develop an understanding of the basis of Barrett's esophagus and its conversion to esophageal carcinoma. Researchers will also work to determine the role genetics and environmental factors play in the development and progression of these diseases, with the ultimate goal of reducing the mortality associated with this deadly cancer.

The BETRNet will be led by Amitabh Chak, MD, professor of medicine at the School of Medicine and a gastroenterologist at University Hospitals (UH) Case Medical Center, a leading figure nationally in translational clinical gastrointestinal cancer research.

Dr. Chak has assembled a world-class group of investigators, bringing this group to the forefront of teams in the country to address an exceptionally important public health issue, says Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the Case Comprehensive Cancer Center, and director of the Seidman Cancer Center at UH Case Medical Center.

The awarding of this grant by the NCI now is truly a recognition that the best cancer research is performed most effectively by a team of expert investigators, says Dr. Chak.

The BETRNet will be co-directed by other leaders in cancer research: co-principal investigators Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics at Case Western Reserve and oncologist at the Seidman Cancer Center at UH Case Medical Center; Nathan A. Berger, MD, Hanna-Payne Professor of Experimental Medicine at Case Western Reserve and oncologist at the Seidman Cancer Center at UH Case Medical Center; and Robert Elston, PhD, Amasa B. Ford, MD Professor of Geriatric Medicine and chair of the Department of Epidemiology and Biostatistics; and consortium co-principal investigators Dr. William Grady, Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center and Dr. Nicholas Shaheen, Professor of Medicine at the University of North Carolina at Chapel Hill.

The group of investigators assembled by Dr. Chak is world-class, says Dr. Grady. I am honored to be a part of this group, and I am looking forward to the progress we will make in understanding and treating Barrett's esophagus.

Dr. Chak first developed an interest in esophageal cancer in the 1990s when he lost a patient to metastatic esophageal cancer, a fairly uncommon disease at its time. I began to think that there has to be a genetic reason for why this cancer affected someone so young, remembers Dr. Chak. He credits early collaborative efforts with researchers in both in Cleveland and nationally for helping to expand research on Familial Barrett's esophagus to what it is today. The Familial Barrett's Esophagus Consortium (FBEC), developed by Dr. Chak, is now active in seven major institutions nationally, including Fred Hutchinson Cancer Research Center, University of North Carolina at Chapel Hill, Johns Hopkins University, Washington University in St. Louis, University of Pennsylvania, and the Mayo Clinic.

Collaborations such as these between basic and translational scientists and clinical researchers will be essential to unravel the complex interplay between environmental and genetic influences on cancer development, says Dr. Shaheen.

Although the rate of many common cancers has declined in recent years, the rate of esophageal cancer has increased greater than six-fold over the past three decades. The prognosis for this cancer remains poor, accounting for more than one in 50 adult male cancer-related deaths. Though Barrett's esophagus, a precursor of esophageal cancer, can be easily recognized at endoscopy, current medical strategies of performing endoscopy based on the close association of Barrett's with chronic heartburn in adults are very inadequate. Nearly 40 percent of patients who develop esophageal cancer have no preceding symptoms of heartburn, and most people with heartburn never have endoscopy. Less than 5 percent of cancers are diagnosed at an early stage in patients whose Barrett's was recognized prior to cancer diagnosis.

The BETRNet will build upon Dr. Chak's work that has contributed to novel discoveries in the management of Barrett's esophagus and esophageal adenocarcinoma, such as defining the role of endoscopic ultrasound in the management of esophageal adenocarcinoma, developing unsedated transnasal endoscopy as a method for Barrett's screening, defining the clinical syndrome of familial Barrett's esophagus and demonstrating that it has a genetic basis, and recently discovering a role for insulin and insulin-like growth factors as mediators of obesity-associated cancers.

The BETRNet projects include discovery of genes that cause familial Barrett's esophagus, those which become targets of DNA methylation in Barrett's and in esophageal cancers, and those that are either turned on or turned off in Barrett's esophagus and in esophageal cancers. The overall aims of the network are to develop new methods of identifying individuals at risk for Barrett's esophagus, early detection of Barrett's and esophageal cancers, and monitoring Barrett's esophagus to recognize when it is likely to progress to cancer.

Almost half of cancer survivors have ill health in later years

Mon, 10 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Forty-five per cent of cancer survivors in Northern Ireland suffer from physical and mental health problems years after their treatment has finished, according to new research from Macmillan Cancer Support and Queen's University Belfast.

The report, the first of its kind in Northern Ireland, also found cancer survivors and their carers are more likely to access health services than the general population.

The research highlighted that so-called late effects of cancer and its treatment can include nerve damage, lymphoedema, extreme tiredness, memory problems and severe depression.

The report also found that 40 per cent of cancer survivors say they have unmet health care and social care needs. Caregivers were also just as likely to report poor physical and mental health as cancer survivors.

The study found people who have had a cancer diagnosis reported more visits to their GP, more visits to the hospital, and more illnesses than the general population, often years following treatment.

With the number of people being diagnosed with cancer set to double by 2030, Macmillan says the report provides further evidence that action must now be taken to transform how health care is delivered.

Macmillan's General Manager in Northern Ireland, Heather Monteverde, said: Patients are living longer following their cancer diagnosis due to earlier detection, screening and better treatment.

However, this report clearly shows that many cancer survivors continue to have poorer health often many years after completion of treatment. The fact that 40 per cent say they have unmet needs has significant implications for the future design and provision of cancer services across Northern Ireland.

Of particular concern are issues around the health of carers who have also reported very similar levels of poor physical and mental health. The number of people living with cancer is growing every year so it is essential changes are made now to avoid serious problems in the future.

Dr Olinda Santin, from Queen's University Belfast, said: While the majority of cancer survivors make a good recovery from their cancer, there are number of patients and their carers who may require additional support.

There is a need for further research and service development to identify and support those groups of cancer survivors and caregivers who are affected by poorer health and well-being and who have unmet needs or experience late effects of their treatment.

The report found cancer survivors reported lower health and wellbeing scores than those who hadn't had cancer. They scored lower in areas including physical function, physical limitations, mental health and social functioning.

A quarter of cancer survivors said they believed there was a need for better co-ordinated care, while just over a fifth (21 per cent) said they needed more support to manage their anxiety about their cancer returning.

The report also found that 25 per cent of carers spend more than 22 hours per week providing care, often many years after treatment has finished.

Building on similar research elsewhere in the UK by Macmillan, the report shows people often experience serious health problems years after the end of their cancer treatment.

New research shows PET imaging effective in predicting lung cancer outcomes

Wed, 05 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Advanced imaging with Positron Emission Tomography (PET) scans shows great promise in predicting which patients with inoperable lung cancer have more aggressive tumors and need additional treatment following standard chemotherapy/radiation therapy, according to new research.

Mitch Machtay, MD, of the Seidman Cancer Center at University Hospitals (UH) Case Medical Center and principle investigator for the study, presented the significant data today at 2 pm at the annual meeting of the American Society for Radiation Oncology (ASTRO) in Miami Beach, Fla. The National Cancer Institute-funded trial, led by the American College of Radiology Imaging Network (ACRIN) in collaboration with Radiation Therapy Oncology Group (RTOG), enrolled 251 patients at 60 cancer centers around the country.

Lung cancer remains the number one cancer killer in the United States. These findings have the potential to give cancer physicians a new tool to more effectively tailor treatments for patients with locally advanced lung cancer, says Dr. Machtay, Chairman of Radiation Oncology at UH Case Medical Center and Case Western Reserve University School of Medicine. This cooperative group study determined that the PET scan can show us which patients have the most aggressive tumors, potentially enabling us to intensify their treatment.

A PET scan is a unique type of imaging test that reveals physiologic processes in organs such as the lung. Unlike other types of medical imaging that display the body's structure, PET shows changes in metabolic and chemical activity caused by actively growing cancer cells. The scan visualizes areas of greater intensity, called hot spots, and lights them up to help physicians pinpoint the disease.

In this study, stage III lung cancer patients had PET scans before and after a combined treatment regimen of chemotherapy and radiation therapy. They measured how rapidly tumors absorb a radioactive sugar molecule (known as FDG). Since most cancer cells take up sugar at a higher rate than normal cells, areas of tumor typically light up brightly on PET scans.

The researchers found that the post-treatment scan was predictive for patients' prognosis by identifying that patients with high levels of FDG uptake following treatment had more aggressive tumors that were more likely to recur. The researchers found that the higher the standard uptake value (SUV) for FDG in the primary tumor, the greater the recurrence rate and the lower the survival rate of patients.

The results also showed that there was a strong correlation between the radiation dose intensity and local control of the cancer, indicating that further research needs to be conducted in radiation technology for lung cancer

This is one of the largest studies-of-its kind to show that PET scans have great potential in predicting the prognosis for patients with inoperable lung cancer, says Dr. Machtay. It supports the theory that PET scans add an important new dimension to a physician's ability to determine which patients need additional cancer therapies to best manage their disease.

Survey reveals reasons doctors avoid online error-reporting tools

Tue, 04 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Too busy, and too complicated. These are the typical excuses one might expect when medical professionals are asked why they fail to use online error-reporting systems designed to improve patient safety and the quality of care. But, Johns Hopkins investigators found instead that the most common reason among radiation oncologists was fear of getting into trouble and embarrassment.

Investigators e-mailed an anonymous survey to physicians, nurses, radiation physicists and other radiation specialists at Johns Hopkins, North Shore- Long Island Jewish Health System in New York, Washington University in St. Louis, Missouri, and the University of Miami, with questions about their reporting near-misses and errors in delivering radiotherapy. Each of the four centers tracks near-misses and errors through online, intradepartmental systems. Some 274 providers returned completed surveys.

According to the survey, few nurses and physicians reported routinely submitting online reports, in contrast to physicists, dosimetrists and radiation therapists who reported the most use of error and near-miss reporting systems. Nearly all respondents agreed that error reporting is their responsibility. Getting colleagues into trouble, liability and embarrassment in front of colleagues were reported most often by physicians and residents.

More than 90 percent of respondents had observed near-misses or errors in their clinical practice. The vast majority of these were reported as near-misses as opposed to errors, and, as a result, no providers reported patient harm. Hospitals have specific systems for reporting errors, but few have systems to accommodate the complex data associated with radiotherapy.

It is important to understand the specific reasons why fewer physicians participate in these reporting systems so that hospitals can work to close this gap. Reporting is not an end in itself. It helps identify potential hazards, and each member of the health care team brings a perspective that can help make patients safer, says Johns Hopkins radiation oncology resident Kendra Harris, M.D., who presented an abstract of the data on October 2, 2011, at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

The good news, Harris says, is that few respondents reported being too busy to report or that the online tool was too complicated. Respondents recognized that error events should be reported and that they should claim responsibility for them. The barriers we identified are not insurmountable, she added.

Harris says that online reporting systems should be simple and promoted as quality improvement tools, not instruments for placing blame and meting out sanctions. These systems should not be viewed as punitive; rather, they're a critical way to improve therapy, says Harris. You can't manage what you can't measure.

Most of the respondents said they would participate in a national reporting system for radiotherapy near-misses and errors.

A national system that collects pooled data about near-misses and errors, which are thankfully rare, may help us identify common trends and implement safety interventions to improve care, adds Harris.

Liver cancer incidence lower in patients with nonalcoholic fatty liver disease than hepatitis C

Tue, 27 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Patients with non-alcoholic fatty liver disease (NAFLD) with advanced fibrosis or cirrhosis have a lower incidence of liver-related complications and hepatocellular carcinoma (HCC) than patients infected with hepatitis C virus (HCV), according to the prospective study published in the October issue of Hepatology, a journal of the American Association for the Study of Liver Diseases. Patients with both NAFLD and HCV had similar mortality rates.

NAFLD has become the most prevalent cause of chronic liver disease worldwide, with studies reporting up to 30% of the general population and 75% of obese individuals having the disease. A minority of cases develop fibrosis or cirrhosis of the liver, and NAFLD with advanced fibrosis or cirrhosis can lead to hepatic-related complications, HCC, liver failure or death. While the incidence of NAFLD has increased, studies of the natural history of the disease in conjunction with advanced fibrosis or cirrhosis and later outcomes have been limited.

Our study reports on the long-term morbidity and mortality of NAFLD patients with advanced fibrosis or cirrhosis by prospectively following up cases from four international collaborating hepatology centers, explains lead author Dr. Neeraj Bhala from the University of Oxford in the UK. Understanding the long term prognosis of NAFLD patients compared with patients affected by other liver diseases such as chronic HCV was an important aspect of our study. Medical evidence suggests that while HCV is currently the leading indication for liver transplantation, affecting more than 5 million individuals in the U.S, HCV incidence has plateaued, while that for NAFLD is on the rise.

In the largest prospective study of participants with advanced fibrosis or cirrhosis to date, the team recruited 247 patients with NAFLD and 264 patients with HCV infection who were not previously treated or were unresponsive to therapy from centers in Australia, Italy, the UK and the USA. Patients in both groups were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at the onset of the study. Follow-up in the NAFLD and HCV groups was a mean of 86 and 75 months, respectively.

Of those patients in the NAFLD group, 19% had liver-related complications and 13% died (or received transplants). Liver-related complications and deaths (or transplants) in the HCV cohort were lower at 17% and 9%, respectively. However, after adjusting for age and gender, the incidence of liver-related complications, including liver cancer, was lower in the NAFLD group compared to the HCV cohort. Researchers found that cardiovascular complications and overall mortality were comparable between the groups, although moderate differences cannot be excluded, highlighting the need for even larger collaborative prospective studies.

In a related editorial published this month in Hepatology, Dr. Mary Rinella with Northwestern University Medical School in Chicago, Illinois said, The study by Bhala and colleagues expands our knowledge of the natural history of NAFLD and NASH. While HCC was not surprisingly higher in untreated patients with HCV compared to NAFLD, this study highlights the potential of HCC development in non-cirrhotic patients with HCV and NASH. If patients with NAFLD or HCV are likely to develop HCC before the development of cirrhosis, this has tremendous implications for how and when liver cancer screening should begin in patients with liver disease.

Newly identified DNA repair defect linked to increased risk of leukemia relapse

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A newly identified defect in a DNA repair system might leave some young leukemia patients less likely to benefit from a key chemotherapy drug, possibly putting them at greater risk of relapse. The problem was identified in a study led by St. Jude Children's Research Hospital scientists.

The study's findings offer a potential new marker to help identify acute lymphoblastic leukemia (ALL) patients who are at higher risk of having their cancer return and thus are candidates for more tailored therapies. The research was published in the September 25 online edition of the scientific journal Nature Medicine.

The work focused on a protein named MSH2, which is involved in DNA repair. DNA is the molecule that carries instructions for building and sustaining life. Cell division requires DNA synthesis. The DNA repair system helps correct errors in DNA production. The DNA repair proteins are also involved in how some chemotherapy agents kill leukemia cells.

In this study, investigators discovered a new mechanism responsible for low MSH2 levels in about 11 percent of pediatric ALL and in several adult cancers. Researchers also found low MSH2 levels were associated with leukemia resistance to the thiopurine medications, including mercaptopurine, a drug all children with ALL receive.

If confirmed, this work suggests a patient's MSH2 status might someday be used to guide treatment, said Barthelemy Diouf, Ph.D., the first author. He is a postdoctoral fellow in the laboratory of William Evans, Pharm.D., the paper's senior author. Evans is chief executive officer and director of St. Jude.

In the U.S., ALL is diagnosed in about 3,000 children annually, making it the nation's most common childhood cancer. It is also one of modern medicine's success stories. At St. Jude, 90 percent of young ALL patients are now cured. This study reflects ongoing efforts to understand why treatment sometimes fails.

The research built on earlier work from the laboratory of Evans and others that linked a deficit of MSH2 with an increased risk of certain cancers and resistance to mercaptopurine, a drug that is the backbone of leukemia treatment.

In this study, scientists found that 11 percent of 90 newly diagnosed pediatric ALL patients had low or undetectable levels of the MSH2 protein.

Ten years after an ALL diagnosis, children with low MSH2 protein levels were less likely to be alive and four times more likely to have suffered relapses. The comparison included 97 patients treated in a St. Jude study called Total XV, which ended in 2007. Sixteen patients had leukemia with low MSH2 levels. The analysis took other factors into account, including a patient's age and early treatment response, which are associated with high-risk ALL. The results suggest MSH2 protein levels might help identify a new group of high-risk patients.

Further work revealed no evidence of problems in the MSH2 gene itself, so scientists expanded their search for why some patients had low MSH2 levels in their leukemia cells. Researchers looked for changes in the makeup of eight genes known or suspected of playing a role in the breakdown of MSH2. To do that, they screened DNA from 69 of the 90 newly diagnosed ALL patients at nearly 1 million spots in the genome.

The research showed each patient was missing at least one of the four genes that regulate MSH2 degradation. MSH2 was still made, but the system to protect it from destruction had been impaired or eliminated, leading to more rapid breakdown of MSH2 and a crippled system for fixing DNA, Evans said. The missing genes were FRAP1, HERC1, PRKCZ and PIK3C2B.

A check of leukemia cells from another group of St. Jude ALL patients found that about 12 percent, or 21 of the 170 children, were missing at least one of the same genes. A search of public databases found one or more of the same genes deleted in 13.5 percent of sporadic colorectal cancer patients and 16 percent of adults with ALL.

Evans noted that low MSH2 levels did not increase resistance to other drugs used to treat ALL. In the future, we may want to intensify use of other therapies, he said.

IMRT has less harmful rectal side effects than 3D-CRT for prostate cancer patients

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Men with localized prostate cancer treated with a newer technology, intensity modulated radiation therapy (IMRT), have more than a quarter (26 percent) fewer late bowel and rectal side effects and a statistically improved lower dose of radiation to the bladder and rectum, compared to those who undergo 3D-CRT, according to a randomized study presented at the plenary session October 3, 2011, at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Findings also show there is a significant increase (15 percent) in rectal side effects associated with white men, compared to other races, regardless of the radiation treatment.

The racial differences were definitely surprising and we are still unsure as to why this exists, Jeff Michalski, MD, a radiation oncologist at Washington University Medical Center in St. Louis, said. While it could be a real difference in the tolerance to treatment, it could also represent cultural differences in reporting side effects and physician interpretation of patient descriptions. This will be the topic of further investigation.

Three-dimensional conformal radiation therapy, or 3D-CRT, is a type of external beam radiation therapy that uses computers and special imaging techniques to precisely tailor the radiation beams so that nearby normal tissue receives less radiation and is able to heal more quickly. Intensity modulated radiation therapy, or IMRT, is a newer, specialized form of 3D-CRT that allows radiation to be more exactly shaped to fit the tumor and further limits the amount of radiation received by healthy tissue near the tumor. This may also safely allow a higher dose of radiation to be delivered to the tumor, potentially increasing the chance of a cure.

This study is a preliminary analysis of acute and late toxicity in men receiving high dose radiation therapy on a phase III Radiation Therapy Oncology Group (RTOG) dose-escalation trial. Researchers sought to compare the toxicity rates of high dose radiation therapy to standard dose radiation treatment, using IMRT and 3D-CRT. The toxicities were scored from the grade of zero (no toxicity) to four (severe toxicity). The study also examined what patient characteristics might be associated with toxicity.

The study involved 748 men who were randomized to the high dose arm of the trial. Of this group, 491 were treated with 3D-CRT and 257 with IMRT. Findings show that IMRT is associated with a statistically significant decrease in acute Grade 2+ rectal/bowel and urinary toxicity. There was also a trend for a 26 percent reduction in Grade 2+ late rectal and bowel side effects. This study supports the continued use of IMRT in the management of prostate cancer. It is a safe and very well-tolerated therapy with fewer complications than 3D-CRT, Michalski said.

Shorter radiation course for prostate cancer is effective in long-term follow-up

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A shorter course of radiation treatment that delivers higher doses of radiation per day in fewer days (hypofractionation) is as effective in decreasing intermediate to high-risk prostate cancer from returning as conventional radiation therapy at five years after treatment, according to a randomized trial presented at the plenary session, October 3, 2011, at the 53rdAnnual Meeting of the American Society for Radiation Oncology (ASTRO).

This long-term study confirms that hypofractionated radiation that shortens treatment by about two and a half weeks is a practical approach to effectively controlling prostate cancer, as compared to the more standard treatment for men with intermediate to high-risk prostate cancer, Alan Pollack, MD, chairman of radiation oncology at the University of Miami Miller School of Medicine in Miami, said.

The strategy to compress treatment schedules using hypofractionation is based on years of studies indicating that there could be a radiobiologic advantage to this approach. Prior research has indicated that tumor cells would be killed to a greater degree with hypofractionation than the potentially damaging effects on the surrounding normal tissues, namely the rectum, penile structures affecting erections and bladder. Another newer approach to hypofractionation incorporated into this trial is the use of intensity modulated radiotherapy (IMRT), which further limits dose to the normal tissues. IMRT has proven value in limiting side effects in the treatment of prostate cancer with external beam radiotherapy.

The study involved 303 men with intermediate to high-risk prostate cancer who were randomized to receive either hypofractionated IMRT or conventionally fractionated IMRT between 2002 and 2006. The high risk patients also received a form of hormone therapy for two years. The patients were followed for over five years to find out if their cancer returned by monitoring prostate specific antigen (PSA), a blood test and established indicator of prostate cancer recurrence when increasing levels are seen.

Dr. Pollack said, we are still learning how best to apply hypofractionation and the results in this trial show that the technique is very effective.

The hypofractionation approach used was given in a shorter period of time with higher doses per day and was expected to be equivalent to four extra treatments using conventional fractionation. While the hypofractionation treatment was hypothesized to be superior, the same tumor control rates were observed. The conventionally fractionated patients had better outcomes than expected. The benefit of the hypofractionation method used was that comparable results were achieved in two and a half fewer weeks of treatment.

In terms of side effects, the rates were relatively low for both methods. There were identical long-term rates of bowel/rectal reactions and the frequency of unsatisfactory erections. There was, however, significantly higher bladder control in the conventionally fractionated patients.

Chemo plus radiation before surgery increases tumor response for rectal cancer

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Rectal cancer patients who use a new combination of the chemotherapy, Capecitabine, together with five weeks of radiation (50 Gy) before surgery have an 88 percent chance of surviving the cancer three years after treatment, according to randomized trial presented at the plenary session, October 3, 2011, at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

The results of the trial allow us to recommend a new pre-operative treatment, the 'CAP 50' regimen, in locally advanced rectal cancer. It's safe and reduces the risk of the cancer coming back to less than 5 percent, Jean Pierre Gerard, MD, a radiation oncologist at Centre Antoine-Lacassagne in Nice, France, said.

The primary treatment for cancer of the rectum (found in the lower 15 centimeters of the bowel) is surgery. However, there is a risk of cancer re-growth within the bowel and surrounding tissues. Not only is this recurrence incurable in the majority of patients, but it can cause negative side effects. Depending on the location and stage of the cancer, doctors usually recommend radiation therapy and chemotherapy before surgery. The optimal regimen is still in discussion.

The ACCORD 12 trial involved 598 patients with locally advanced rectal cancer (tumors that have spread to the perirectal fat, but not travelled to distant parts of the body) who were diagnosed and treated in 50 hospitals in France between 2005 and 2008.

Researchers wanted to find the most effective and safe preoperative treatment for rectal cancer by comparing a combination of two different chemotherapies and two different radiation doses. Patients were randomized to receive either Cap45 (chemotherapy, Capecitabine, and radiation treatment at 45 Gy) or Capox50 (chemotherapies, Capecitabine and Oxaliplatin, along with radiation at 50 Gy). At three years after treatment, the Capox50 regimen did not significantly increase the chance of the cancer returning or surviving the disease, compared to the Cap45 treatment. Oxaliplatin, given as part of the Capox50 treatment, was shown to immediately increase side effects, with some cases of severe diarrhea, and was not effective in increasing the chance of local tumor sterilization.

However, the increase of radiation dose from 45 to 50 Gy in five weeks was effective, well tolerated and did not extend the duration of treatment.

The results of this trial, when analyzed together with the Italian STAR01 and the American NSABP R04 randomized trials, bring solid scientific evidence that a 'CAP50 regimen' should be the standard treatment for locally advanced rectal cancer. Using Capecitabine avoids the intravenous injection of fluorouracil, while a radiation dose of 50 Gy in 25 fractions over five weeks increases the chance of tumor sterilization and limits the risk of local recurrence to 5 percent or less, Dr. Gerard said.

High blood pressure is linked to increased risk of developing or dying from cancer

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: Raised blood pressure is linked to a higher risk of developing cancer or dying from the disease according to the findings of the largest study to date to investigate the association between the two conditions.

Dr Mieke Van Hemelrijck will tell the 2011 European Multidisciplinary Cancer Congress [1] in Stockholm today (Tuesday) that there had been contradictory results from previous, smaller studies investigating the link between cancer and blood pressure. However, her study, which included 289,454 men and 288,345 women, showed that higher than normal blood pressure was statistically significantly associated with a 10-20% higher risk of developing cancer in men, and a higher risk of dying from the disease in both men and women.

Dr Van Hemelrijck, a research associate in the Cancer Epidemiology Group at King's College London (London, UK), and her colleagues analysed data on blood pressure and cancer incidence and death in a prospective study that included seven groups of participants in Norway, Austria and Sweden.

They used figures on mid-blood pressure for their calculations. Mid-blood pressure is defined as systolic blood pressure plus diastolic blood pressure, divided by two. The average mid-blood pressure in this study was 107 mmHg for men and 102 mmHG for women [2]. The results were divided into five groups (or quintiles), so that people with the lowest mid-blood pressure were in the first, and those with the highest mid-blood pressure were in the fifth quintile.

After an average of 12 years of follow-up and excluding the first year, 22,184 men and 14,744 women had been diagnosed with cancer, and 8,724 men and 4,525 women died from the disease. The overall risk of developing any cancer increased by 29% between men in the lowest quintile and those in the highest. The researchers also found that, as blood pressure rose, the risk of oral, colorectal, lung, bladder, and kidney cancers, melanoma and non-melanoma skin cancers rose in men. In women, increased blood pressure was not statistically significantly associated with the overall risk of developing any cancer, but was associated with an increased risk of cancers of the liver, pancreas, cervix and endometrium and melanoma.

In both men and women, there was an increased risk of dying from cancer; men in the fifth quintile had a 49% increased risk of dying compared to those in the first quintile, and women in the fifth quintile had a 24% increased risk compared to those in the first.

Dr Van Hemelrijck explained: This means that we found that men with mid-blood pressure in the highest fifth had an absolute risk of developing cancer of 16% compared to an absolute risk of 13% for those with mid-blood pressure in the lowest fifth. Men in the highest fifth had an absolute risk of dying from cancer of eight percent, compared to an absolute risk of five percent for those in the lowest; and for women, those in the highest fifth had an absolute risk of dying of five percent compared to an absolute risk of four percent in the lowest fifth.

Our study shows that blood pressure is a risk factor for incident cancer in men and fatal cancer in men and women. Although the relative and absolute risk estimates were rather modest, these results are important from a public health perspective since a large proportion of the population in many western countries suffers from hypertension. [3]

The researchers adjusted their results to take account of age, sex, body mass index, smoking and random errors in the exposure classification of blood pressure (errors that occur due to inaccuracy in blood pressure measurements or due to an individual patient's variations in blood pressure, which can be corrected by using data from several examinations).

Dr Van Hemelrijck warned that, as the study was observational, it could not show that blood pressure was the cause of the increased cancer risk. We cannot claim that there is a causal link between high blood pressure and cancer risk, nor can we say that the cause of cancer is a factor related with high blood pressure, she said. However a healthy lifestyle, including sufficient physical activity and a normal weight, has been shown to reduce the risk of several chronic diseases. For instance, high blood pressure is a known risk factor for cardiovascular disease, and our study now indicates that high blood pressure may also be a risk factor for cancer.

The researchers are unsure why men with high blood pressure appeared to have a higher cancer risk than women. Our study, which to our knowledge is the largest and the first to take into account random error, showed that the association between hypertension and incident or fatal cancer is stronger for men than for women. In contrast, the second largest study previously found a higher cancer risk for women than for men. The differences in findings might be explained due to our larger sample size, slightly older population, adjustment for random error, or lack of information on anti-hypertensive treatment, she said.

Researchers uncover gene associated with blood cancers

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A genomic study of chronic blood cancer - a precursor to leukaemia - has discovered gene mutations that could enable diagnosis using only a blood test, avoiding the need for an invasive and painful bone marrow biopsy.

Researchers at the Wellcome Trust Sanger Institute identified the SF3B1 gene as being frequently mutated in myelodysplasia, one of the most common forms of blood cancer. Myelodysplasia is particularly prevalent among people over the age of 60, and often the only symptom is anaemia, which makes it a challenge to give a positive diagnosis. Patients with mutations in the SF3B1 gene frequently had a specific abnormality of red blood cells in their bone marrow, called ring sideroblasts.

The findings have significant potential for clinical benefit, as the disease is often under-diagnosed. It is hoped that patients will soon be able to be screened for mutations in the SF3B1 gene through a single blood test.

This discovery illustrates the promise of genome sequencing in cancer, says Dr Elli Papaemmanuil, lead author from the Sanger Institute. We believe that by identifying SF3B1, and working to characterize the underlying biology of this disease, we will be able to build improved diagnosis and treatment protocols.

Significantly, our analysis showed that patients with the SF3B1 mutation had a better overall chance of survival compared to those without the mutation. This suggests that the SF3B1 mutations drive a more benign form of myelodysplasia.

In order to piece together the genomic architecture of myelodysplasia, the team sequenced all genes in the genome of nine patients with the disease. To their surprise, six had mutations in the SF3B1 gene. To expand their analysis, the researchers sequenced the SF3B1 gene in 2,087 samples across many common cancers.

In myelodysplasia, SF3B1 mutations were found in 20.3 per cent of all patients, and in 65 per cent of those patients with ring sideroblasts, making it one of the most frequently mutated genes so far discovered in this disease. Researchers found mutations of the same gene in up to 5 per cent of a range of other common cancers, such as other leukaemias, breast cancer and kidney cancer.

Anaemia affects 1 in 10 people over the age of 65, and we cannot easily find a cause for the anaemia in a third of cases, says Peter Campbell, senior author, from the Sanger Institute and a practicing Haematologist at Addenbrooke's Hospital, Cambridge. To diagnose myelodysplasia, we often have to resort to an invasive and painful bone marrow biopsy, but we hope this and future genetic insights will provide more straightforward diagnosis for patients through a simple blood test.

Ever since I first saw these unusual and damaging blood cells - ring sideroblasts - down the microscope while training to become a haematologist, I have been fascinated by them and determined to find a cause. To discover a major genetic clue to their origins is very exciting, and I look forward to piecing together how the mutations cause these curious cells to develop and lead to this disease.

The SF3B1 gene encodes a core component of RNA splicing, an important editing mechanism that controls how the genome's message is delivered to the cell. The team discovered a strong association between the gene and the presence of ring sideroblasts, making it the first gene to be strongly associated with a specific feature of the disease. Ring sideroblasts are abnormal precursors to mature red blood cells with a partial or complete ring of iron-laden mitochondria (energy generators) surrounding the nucleus of the cell. Their presence is frequently associated with anaemia.

Chemotherapy during pregnancy does not seem to cause developmental problems in children

Mon, 26 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: Children born after their mothers were treated with chemotherapy during pregnancy appear to be unaffected by the experience in terms of the development of their mental processes and the normal functioning of their hearts, according to new research presented at the 2011 European Multidisciplinary Cancer Congress [1].

Professor Frederic Amant will tell the congress: To the best of our knowledge this is the first time that children of 18 months and older have been examined after chemotherapy during pregnancy, and the news is reassuring in respect of the effects of chemotherapy on cognitive and cardiac outcomes.

However, he will say that a significant number (47) of the 70 children born from 68 pregnancies were delivered preterm and the researchers found that prematurity, but not chemotherapy, did affect these children's cognitive development significantly.

Prof Amant, a gynaecological oncologist at the University Hospitals Leuven (Leuven, Belgium), and colleagues in two other European countries (The Netherlands and the Czech Republic) started to recruit children to the study in 2005. They included children who had been born before that time (between 1991-2004) as well as those born between 2005-2010, so that they ranged in age from 18 months to 18 years. The children were examined at birth and at the ages of 18 months, 5-6, 8-9, 11-12, 15-16 and 18 years. The children's health was monitored for an average of nearly two years, with some of them being followed for as long as 18 years.

While the 68 mothers were pregnant, they were being treated with chemotherapy, either on its own or in combination with radiotherapy or surgery or both, for a range of different cancers. The most common cancer was breast (35 women), followed by haematological cancers such as leukaemias and lymphomas (18), ovarian cancer (6), cervical cancer (4); other cancers included brain, skin, colorectal, nasopharyngeal, and Ewing's Sarcoma.

The researchers collected data on the mothers' treatment and medical history, and then assessed the children's general health, school performance, any sporting activity and the family's social situation by means of questionnaire completed by the parents at each assessment visit. They looked at the development of the children's mental processes by evaluating intelligence, verbal and non-verbal memory, attention, working memory and executive functions (the ability to control and regulate other abilities and behaviours). Parents also completed a questionnaire on behavioural and emotional problems. Cardiac function was assessed by electrocardiography (ECG) and echocardiography.

The average gestational age at which the children were born was 35.7 weeks; seven children were born very early (28-32 weeks), nine were born early (32-34 weeks), 31 were born preterm (34-37 weeks) and 23 were born at term (37 weeks or more). There were two twin pregnancies.

Prof Amant and his colleagues found that the incidence and type of congenital malformations were similar to the general population, as was growth, general health and development; no heart abnormalities were detected. Cognitive development was in the normal range for the majority of the children, but those that fell below the normal IQ range were mainly those that had been born early. One set of twins, who were born at 32.5 weeks, had significant neurodevelopmental delay, and for these twins the researchers said they could not rule out prenatal exposure to chemotherapy as being the possible causal factor.

Prof Amant says: Our results so far suggest that children who were prenatally exposed to chemotherapy seem to do as well as children in the general population, and, that the treatment does not influence the development of mental processes or the functioning of the heart in the children we have followed for an average of 22 months. Therefore, although the role played by chemotherapy in the poor outcome of one of the twin pregnancies cannot be excluded, we believe these results do allow us to make a recommendation about chemotherapy in pregnancy: pregnant women with cancer do not need to delay their cancer treatment or terminate their pregnancy. The benefits of chemotherapy to the mothers outweigh any potential long-term harm to the children.

However, it is important to prevent preterm birth if possible and continue pregnancy until at least 37 weeks, as the data suggest the children suffer more from prematurity than from prenatal chemotherapy. Pregnant women who are receiving chemotherapy often have delivery induced from the moment the foetus is viable although not mature. Our results suggest this should be avoided.

He says that that it is not clear whether chemotherapy itself could be a possible cause for premature delivery, but that in many cases preterm delivery is induced and is itself the cause of the cognitive developmental problems seen in this group of children.

Prof Amant will conclude: At this stage we do not know the full, long-term consequences of prenatal chemotherapy, including its effect on the children's fertility and likelihood of developing cancers when they are older. For this reason, we are continuing this international collaboration to follow-up more children for longer periods of time.

Bone-strengthening drug gives pain relief in prostate cancer bone metastases

Sun, 25 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: Many prostate cancer patients develop bone metastases, and controlling the pain these cause can be difficult. Now the first large randomised Phase III trial of a bisphosphonate drug in these patients has shown that a single dose of the drug is as good for pain relief as single dose radiotherapy, the standard treatment for bone metastases. Results of the trial were presented today (Sunday) at the 2011 European Multidisciplinary Cancer Congress [1].

Professor Peter Hoskin, consultant clinical oncologist at the Mount Vernon Cancer Centre, Northwood, UK, and Professor of Clinical Oncology at University College, London, and colleagues, randomised 470 patients with primary prostate cancer and painful bone metastases to receive either a single dose of radiation or a single intravenous infusion of the bisphosphonate ibandronate (IB). Patients reported their primary site of pain at entry into the trial, and then at four, eight, twelve, 26 and 52 weeks after treatment.

Those who had not responded to the first treatment at four weeks crossed over to the alternative therapy and received their second treatment no later than week eight. Pain levels were measured at four and twelve weeks by examining analgesic use, using a combination of scoring via the WHO pain ladder [2] and the Mercadante method, which defines analgesic use in morphine equivalents.

We found that using IB was as good as single dose radiotherapy in controlling pain, said Prof Hoskin. Although there were more patients in the IB group with worse Mercadante scores at four weeks who needed re-treatment, at six and twelve months there was no long-term difference in pain relief between the two groups.

Side effects were few; short-lived nausea and stomach upsets if radiotherapy passes through the abdomen and flu-like symptoms with IB. The patients in the trial were well balanced as to age, site of pain, prior treatment and performance status. The median survival of the four groups was 11.8 months (radiotherapy only), 11.4 months (IB only), 12.7 months (radiotherapy then IB), and 16.8 months (IB then radiotherapy).

We hope to analyse these survival differences further in the hope that it can give us further pointers as to how and whether we should use a combination of treatments, Prof Hoskin said. Currently we are unsure about the optimal timing and scheduling of treatment for these patients.

The constant turnover of bone is kept in balance by the interaction of osteoblasts, which form bone, and osteoclasts, which beak it down. Bisphosphonates work by sticking to calcium and binding to it, thus preventing bone loss through inhibiting the activity of osteoclasts.

Bone metastases are common in many primary cancers. They are a serious problem for many men with prostate cancer, and can cause intense pain as well as fractures and spinal cord compression, Prof Hoskin said. But there are also patients who have bone metastases and only mild or moderate pain, which can be readily controlled by analgesics. Others have multiple metastatic sites, but only one causes significant pain. There are many questions still to be answered in this field.

Zoledronic acid reduces the recurrence of breast cancer in post-menopausal women

Sun, 25 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: A trial investigating the use of zoledronic acid to aid chemotherapy for breast cancer has found a significant benefit for post-menopausal women, according to results presented at the 2011 European Multidisciplinary Cancer Congress [1] today (Sunday). Researchers think it could be the key for a greater understanding of the mechanisms of breast cancer recurrence as well as offering new options for patient care.

Zoledronic acid is one of the bisphosphonates, a group of drugs mainly used to treat osteoporosis. However they are also given to cancer patients to protect against the effects of secondary bone cancer, such as pain and weakness in the bones. Laboratory studies have suggested that zoledronic acid might also have direct anti-tumour effects and enhance other chemotherapy treatments, so the multi-centre AZURE trial was set up to investigate further.

Led by Professor Robert Coleman at the Weston Park Hospital in Sheffield, UK, the trial recruited 3,360 patients with stage II/III breast cancer from 174 centres. They were randomised to receive chemotherapy and/or endocrine therapy, with or without zoledronic acid. An interim analysis of the trial's progress indicated that patients were seeing no clinical benefit from the treatment, so the data were released for more detailed scrutiny.

This confirmed the drug's lack of impact, apart from in a sub-set of women who had undergone menopause five or more years previously. Here, the overall survival rate was 85% compared to 79% for women who did not receive zoledronic acid. The effect was independent of the characteristics of the disease as shown by the stage of the tumour, oestrogen receptor status, and lymph node involvement.

This is a small but significant increase, Prof Coleman explains. The finding is not sufficient to be taken up on its own but in the context of other studies and additional data anticipated later in the year, it is likely to change practice.

The results shed new light on the role that the bones may play in the progress of the disease. The effects on metastasis and recurrence outside bone suggests that the bone marrow is an important sanctuary for tumour cells which can be activated after, sometimes, many years of dormancy, Prof. Coleman says. With help from bone marrow stem cells, they may then spread via the blood stream to set up metastases at other sites.

Even if this is the case, it is still not clear why zoledronic acid is having a beneficial effect. Prof Coleman speculates that it may alter the balance of substances such as cytokines and growth factors that control the bone marrow micro-environment. In this altered state the ability of cancer cells to leave the bone marrow and move to other parts of the body may become dependent on the presence of reproductive hormones. Presumably, these changes are only clinically relevant in the context of low levels of female reproductive hormones that we see after menopause, he says.

Further work will be required to establish whether or not this is the case. We plan to use new, more clinically relevant, animal models of metastasis to assess the early events in the spread of cancer and effects of treatments like zoledronic acid, Prof Coleman says.

Dr Coleman's presentation to the congress coincides with the simultaneous publication of a paper about the research in the

Aromatase inhibitor letrozole guards against breast cancer relapse for up to 8 years

Sun, 25 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: Results from the longest-running trial comparing tamoxifen with the aromatase inhibitor letrozole show unequivocally that letrozole has withstood the test of time and continues to prevent breast cancer recurrences and reduce the risk of death in post-menopausal women with hormone receptor-positive early breast cancer.

Professor Richard Gelber told delegates at the 2011 European Multidisciplinary Cancer Congress [1], in Stockholm today (Monday 26 September) that a 12-year update of results from the Breast International Group (BIG) 1-98 [2] trial showed that if women with early breast cancer (cancer that has not spread from the breast) were given letrozole after surgery for at least five years, they continued to do better and have fewer recurrences of the disease than those who were given tamoxifen.

Over a median of eight years of follow-up, women who were assigned to receive five years of letrozole after surgery had an 18% reduced risk of relapse and a 21% reduced risk of death compared with those assigned to receive tamoxifen, said Prof Gelber, Director of the International Breast Cancer Study Group (IBCSG) Statistical and Data Management Center at the Dana-Farber Cancer Institute, Boston, MA, USA.

The current 12-year update is the longest follow-up to date and includes much more information than we had after ten years. For instance, there have been 32% more relapses and 39% more deaths since the ten-year update, which increases substantially the reliability of the results and provides reassurance regarding the long-term value of letrozole. This additional follow-up and accumulation of information on relapses and deaths show that the overall survival advantage for adjuvant letrozole compared to tamoxifen continues to be statistically significant.

Adjuvant therapy (treatment that is given after surgery), using drugs that target hormones such as oestrogen, is given to patients with early breast cancer who have hormone receptor-positive tumours. These tumours occur in approximately 75% of breast cancer cases. Tamoxifen has been the gold standard hormone treatment for women with early, oestrogen-receptor-positive breast cancer and works by blocking the growth-promoting action of oestrogen on the cancer cells. Aromatase inhibitors, such as letrozole, are newer and alter the function of aromatase, an enzyme involved in oestrogen production. They can be used in sequence with, or as an alternative to tamoxifen for post-menopausal women.

In the BIG 1-98 trial, researchers enrolled 8,010 patients to receive letrozole and tamoxifen either alone or in sequence, with a total of 4,922 patients included in the monotherapy arms of the study.

Efficacy analyses comparing the treatment groups were conducted every two years following the initial report of results, because the patients had a long-term risk of recurrence. This 12-year update shows that, among all 8,010 patients, there were 2,074 relapses and 1,284 deaths, compared with 1,569 relapses and 923 deaths at the ten-year update.

The data also show that the sequential use of letrozole and tamoxifen (two years of one agent followed by three years of the other) provided similar outcomes compared with five years of letrozole alone for patients who are not at high risk for recurrence, said Prof Gelber.

The optimal regimen remains an open question in many areas of the world, and this large trial presents definitive results for the treatment of the largest group diagnosed with breast cancer: post-menopausal women with hormone-responsive early breast cancer.

He added: Letrozole and tamoxifen have different side effects, and clinicians should consider the individual patient's medical history when prescribing treatment. Both agents are considered to be safe, especially in view of the substantial reduction in the risk of recurrence and the improved survival provided by these two endocrine therapies. While long-term safety data are available for tamoxifen, follow-up of patients who have received letrozole or other aromatase inhibitors is still relatively short. Thus, assessment of the long-term safety of letrozole is a critical objective for the BIG 1-98 follow-up study.

The IBCSG recently launched a long-term observational study that will extend patient follow-up for an additional five years in order to provide further information on efficacy and side effects of five years of adjuvant hormone therapy. The follow-up study includes collection of yearly updates of survival, disease status and long-term adverse events. We plan to continue to update results every two years. This study is critically important as more than 74% of the patients enrolled in BIG 1-98 were still alive without a relapse at their most recent study visit. Assessment especially of long-term side effects for these patients is critically important, he said.

BIG 1-98 and other large randomised clinical trials have firmly established the benefits of adjuvant treatment programmes including aromatase inhibitors, such as letrozole. Improved disease control and extended survival will reduce burdens on healthcare systems by reducing the number of patients requiring treatment for metastatic breast cancer. Furthermore, the cost of aromatase inhibitor treatment will decrease in the near future as generic products become available, Prof Gelber added.

Professor Michael Baumann, president of ECCO said: This 12-year update of the study sheds more light on the advantages of aromatase inhibitors over tamoxifen in the adjuvant treatment of early breast cancer. It also clearly demonstrates how important it is to perform long-term follow-up and analysis of clinical studies especially for breast cancer. Long-term analysis is essential for reliably ensuring the efficacy of treatments but also to detect potential long-term side-effects which may affect quality of life. Although it is very difficult and costly to perform such long-term trials, the return for optimising treatments for cancer patients cannot be overemphasised.

Commenting on the study, which he was not involved with, ESMO member Professor Christoph Zielinski from the Medical University of Vienna, Vienna, Austria, said: The BIG 1-98 trial demonstrates the clinical benefits of the aromatase inhibitor, letrozole and also provides further insight into the biology of the disease and how to improve outcomes with the upfront use of letrozole, compared to tamoxifen. This is important for daily clinical practice.

Infusing chemotherapy into the liver gives extra months of disease-free life in melanoma patients

Fri, 23 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stockholm, Sweden: Melanoma of the eye (ocular or uveal melanoma) frequently spreads to the liver and, once this has happened, there is no effective treatment and patients die within an average of two to four months. Only about one in ten patients live for a year. Now, final results from a phase III study have demonstrated that a new treatment significantly extends the time patients can live without the disease progressing.

James Pingpank, associate professor of surgery at the University of Pittsburgh Cancer Institute (Pittsburgh, USA), will tell the 2011 European Multidisciplinary Cancer Congress [1] on Saturday that, by April 2011, the length of time that patients survived without the metastases spreading further in the liver (disease progression) was an average of 8.1 months for those receiving the new treatment compared to 1.6 months in the group of patients that had been randomised to receive the best alternative care.

The new treatment is called percutaneous hepatic perfusion (PHP) and is designed to saturate the liver with high doses of chemotherapy without affecting the rest of the body. The chemotherapy drug melphalan is infused directly into the liver via an intra-arterial catheter over a period of 30 minutes. Blood in the veins leading out of the liver is then captured and filtered through a specially designed, double-balloon catheter to extract the drug before the cleaned blood is returned to the body. This enables the drug to be delivered directly to the liver to target the melanoma metastases there, but in a minimally invasive manner. The patient is monitored in intensive care before being allowed home. Once the liver has recovered from the toxicity of the treatment, the procedure is repeated every four to eight weeks.

In a phase III, randomised trial that took place in nine US clinics, 93 patients were randomised to receive PHP or best alternative care between February 2006 and July 2009. Best alternative care (BAC) was decided by the patient's treatment team and could involve interleukin 2, ipilimumab, transcatheter arterial chemoembolisation (TACE), systemic chemotherapy or inclusion in a clinical trial.

As the study was not designed to show an overall survival benefit, and most of the patients had no other treatment options available to them, patients were allowed to cross over from the BAC arm of the study to the PHP arm once the benefits of PHP became apparent.

PHP patients had an overall progression-free survival time of 6.1 months versus 1.6 months in the BAC group. Overall survival at one year was 29% on PHP versus 26% on BAC. Due to the fact that 51% of patients crossed over from the BAC arm to the PHP arm, overall survival was not significantly different between the two groups: 11.4 months on PHP versus 9.9 months on BAC. However, those patients who did cross over seemed to do well despite being amongst the sickest, surviving for 9.2 months without the disease progressing in the liver, and 6.5 months without any overall progression of the disease.

Prof Pingpank will say: This is the first phase III study of PHP in patients with liver-dominant metastatic melanoma and shows that PHP with melphalan significantly improves overall response rates and progression-free survival, providing a new treatment option for the disease. This report includes all data on patients who are more than one year on from inclusion in the trial and we now have all the final response rates. The only thing that may change over time is the examination of the possible long-term benefits, as all but one of the surviving patients were treated with PHP or crossed over to receive it.

For a disease that currently has few treatment options and no chance of a cure, Prof Pingpank says PHP offers patients extra months of, usually, good quality life. Although the adverse effects of PHP were more severe than BAC, they were short-lived. Side effects were predominantly neutropenia [low white blood cell count] and thrombocytopenia [low platelet count]. The majority of patients were able to undergo multiple treatments in the PHP arm, as toxicity resolved, whereas the major toxicity in the control arm was liver failure and/or death on treatment from disease progression, he will say.

This is the first treatment to show a clinical benefit in patients with liver metastases from ocular melanoma. Most patients retain 80% or more of their daily functional status, and return to full performance once therapy is completed. If subsequent recurrence is noted in the liver, retreatment is possible and effective. At this point, it appears that there are groups of patients surviving substantially longer than those control arm of the study, with good quality of liver and preservation of liver function.

PHP potentially could be used for other cancers that have spread to the liver. We have demonstrated efficacy in a phase II setting for patients with metastatic neuroendocrine tumours [2], so the application of this technology is likely to expand to other tumour types, says Prof Pingpank. In addition, we have previously demonstrated efficacy of high dose regional melphalan for patients with metastatic colorectal cancer, albeit through a different circuit.

The device that delivers and filters the melphalan has been approved in Europe for use in all malignant liver tumours, while approval is pending in the USA for melanoma only.

Prof Pingpank will conclude: Certainly, with 50 percent of melanoma patients with metastatic liver disease dying of liver failure, we see this as a frontline therapy for patients with this disease. There is always controversy surrounding the application of regional therapy to patients with metastatic disease, especially when there is a high risk for metastases elsewhere in the body. However, at present, the dearth of options for patients with metastatic melanoma renders this a moot point, and this therapy will be an early choice for patients with liver-only disease.

Virus kills breast cancer cells in laboratory

Thu, 22 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A nondisease-causing virus kills human breast cancer cells in the laboratory, creating opportunities for potential new cancer therapies, according to Penn State College of Medicine researchers who tested the virus on three different breast cancer types that represent the multiple stages of breast cancer development.

Adeno-associated virus type 2 (AAV2) is a virus that regularly infects humans but causes no disease. Past studies by the same researchers show that it promotes tumor cell death in cervical cancer cells infected with human papillomavirus. Researchers used an unaltered, naturally occurring version of AAV2 on human breast cancer cells.

Breast cancer is the most prevalent cancer in the world and is the leading cause of cancer-related death in women, said Samina Alam, Ph.D., research associate in microbiology and immunology. It is also complex to treat.

Craig Meyers, Ph.D., professor of microbiology and immunology, said breast cancer is problematic to treat because of its multiple stages.

Because it has multiple stages, you can't treat all the women the same. Currently, treatment of breast cancer is dependent on multiple factors such as hormone-dependency, invasiveness and metastases, drug resistance and potential toxicities. Our study shows that AAV2, as a single entity, targets all different grades of breast cancer.

Cells have multiple ways of dying. If damage occurs in a healthy cell, the cell turns on production and activation of specific proteins that allow the cell to commit suicide. However, in cancer cells these death pathways are often turned off, while the proteins that allow the cell to divide and multiply are stuck in the on position.

One way to fight cancer is to find ways to turn on these death pathways, which is what researchers believe is happening with the AAV2 virus. In tissue culture dishes in the laboratory, 100 percent of the cancer cells are destroyed by the virus within seven days, with the majority of the cell death proteins activated on the fifth day. In another study, a fourth breast cancer derived cell line, which is the most aggressive, required three weeks to undergo cell death

We can see the virus is killing the cancer cells, but how is it doing it? Alam said. If we can determine which viral genes are being used, we may be able to introduce those genes into a therapeutic. If we can determine which pathways the virus is triggering, we can then screen new drugs that target those pathways. Or we may simply be able to use the virus itself.

Research needs to be completed to learn how AAV2 is killing cancer cells and which of its proteins are activating the death pathways.

According to Meyers, the cellular myc gene seems to be involved. While usually associated with cell proliferation, myc is a protein also known to promote cell death. The scientists have observed increased expression of myc close to the time of death of the breast cancer cells in the study. They report their results in a recent issue of

New technique to visualise tumour cells during surgery

Mon, 19 Sep 2011 17:22:40 PST

( from http://www.rxpgnews.com ) Ovarian cancer is one of the most frequent forms of cancer that affect women. As tumors can initially grow unchecked in the abdomen without causing any major symptoms, patients are usually diagnosed at an advanced stage and have to undergo surgery plus chemotherapy. During the operation, surgeons attempt to remove all tumor deposits as this leads to improved patient prognosis. To do this, however, they primarily have to rely on visual inspection and palpation - an enormous challenge especially in the case of small tumor nests or remaining tumor borders after the primary tumor excision.

Yet surgeons could now be getting support from a new multispectral fluorescence imaging system developed by a team of researchers in Munich, headed by Vasilis Ntziachristos, Professor of Biological Imaging. A study carried out on nine patients with ovarian cancer has shown that the new system can be used to localize cancer cells during surgery. Before the operation, the patients were injected with folic acid chemically coupled to a green fluorescent dye. Most ovarian tumors have a protein molecule on their surface that bonds with folic acid and transports it inside the cell. This protein is known as the folate receptor alpha. During abdominal surgery, the surgeon can then shine a special laser light onto the patient's ovaries, causing the green-labeled folic acid inside the cancer cells to emit light. Healthy tissue remains dark.

The fluorescent cancer cells, however, cannot be detected by the naked eye. Three cameras, mounted on a pivoting support arm over the operating table, detect optical and fluorescent signals at multiple spectral bands and then correct for light variations due to illumination and tissue discolorations in order to provide truly accurate fluorescence images that can be simultaneously displayed with corresponding color images on monitors in the operating room. The surgeon can thus check whether all the cancer cells have been removed by inspecting for remnant fluorescence light. In eight of the nine patients, doctors were able to remove small clusters of tumor cells that might otherwise have gone undetected. The multispectral fluorescence imaging system has thus passed its first OR test. However, it will have to prove its value to improve clinical outcome in further operations before it can be deployed for routine surgical procedures.

The researchers in Munich and Groningen also want to further develop the camera system so it can be used to detect other forms of tumors during operations. Of significant importance in future developments is the ability to offer accurate fluorescence imaging so that data collected reflect true presence of disease. "The use of advanced, real-time optical technology will allow us to standardize data collection and accuracy so that studies performed at multiple clinical centers can be accurately compared and analyzed" explains Prof. Vasilis Ntziachristos. This is important for the clinical acceptance of the technology and its approval by regulatory agencies. In the future patient selection through personalized medicine approaches, for example by obtaining a molecular profile of the tumor of each patient, would further enable custom-tailored surgical treatment of improved accuracy. The team is also planning to build a version for minimally invasive operations.

SuviCa Inc. of Boulder to commercialize CU-Boulder cancer screening technology

Mon, 19 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) SuviCa Inc. of Boulder and the University of Colorado recently completed an exclusive license agreement for a CU drug screening technology to identify novel therapies for cancer.

The patented drug discovery tool, developed by CU-Boulder Associate Professor Tin Tin Su of the molecular, cellular and developmental biology department, uses a genetically modified Drosophila fruit fly model to screen for compounds effective against various types of cancer, either alone or in combination with existing therapies.

The screening technique will be used to identify new clinical candidates using a methodology that is both time efficient and cost-effective. Because it uses a whole-animal screening model, the technique can more easily eliminate drug candidates with undesired toxicity.

SuviCa looks forward to advancing Dr. Su's technology in order to find better ways to treat cancer patients and to build a world-class business in the Front Range region, said Judy Hemberger, SuviCa's chairman and CEO.

We are excited about the commercial possibilities for the drug screening technology developed by Dr. Su, which has already been used at CU to identify promising therapeutic candidates, said Tom Smerdon, director of licensing and new business development at the CU Technology Transfer Office, or TTO.

SuviCa recently received funding from Colorado's Bioscience Discovery Evaluation Grant Program, an initiative launched in 2007 by the state of Colorado's Office of Economic Development and International Trade to provide early-stage, matching seed grants to enable the development and commercial validation of promising technologies that are licensed from Colorado research institutions.

SuviCa also has received a grant from the Internal Revenue Service through the Qualifying Therapeutic Discovery Project Program aimed at small businesses. Current and future efforts will focus on identifying and optimizing additional lead compounds to enter into formal clinical testing.

SuviCa Inc. is an early-stage cancer drug discovery and development company co-founded by Su, who now serves as its chief science officer. Judith Hemberger, a former co-founder and COO of Boulder-based Pharmion, has joined the senior management team as chairman and CEO.

Working in close collaboration with scientists at CU-Boulder, the University of Colorado Anschutz Medical Campus and Colorado State University, SuviCa is pursuing a promising discovery process based on several small molecules initially identified using its proprietary screening technology and targeted to a distinct cellular process. SuviCa researchers hope to discover and develop novel drugs used as standalone therapies or to prevent tumor recurrence following treatment with a variety of approved anti-cancer therapies.

CU's TTO pursues, protects, packages and licenses to business the intellectual property generated from research at CU. The office provides assistance to faculty, staff and students, as well as to businesses looking to license or invest in CU technology.

Plant compound reduces breast cancer mortality

Tue, 13 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Phytoestrogens are plant compounds which, in the human body, can attach to the receptors for the female sexual hormone estrogen and which are taken in with our daily diet. A number of findings have attributed a cancer protective effect to these plant hormones. At DKFZ, a team headed by Prof. Dr. Jenny Chang-Claude summarized the results of several studies in a meta-analysis last year and showed that a diet rich in phytoestrogens lowers the risk of developing breast cancer after menopause. Now the Heidelberg researchers wanted to find out whether phytoestrogens also have an influence on the course of breast cancer. Prior investigations on this topic had provided contradictory results.

The most important type of phytoestrogens in our Western diet are lignans, which are contained in seeds, particularly flaxseeds, as well as in wheat and vegetables. In the bowel, these substances are turned into enterolactone, which is absorbed by the mucous tissue and which was determined by the Heidelberg researchers as a biomarker in the patients' blood.

From 2002 to 2005, the DKFZ researchers used the MARIE study to take blood samples of 1,140 women who had been diagnosed with postmenopausal breast cancer. After a mean observation time of six years, they related enterolactone levels to clinical disease progression.

The result: Compared to the study subjects with the lowest enterolactone levels, the women with the highest blood levels of this biomarker had an approximately 40 percent lower mortality risk. When the scientists additionally took account of the incidence of metastasis and secondary tumors, they obtained a similar result: Women with the highest enterolactone levels also had a lower risk for such an unfavorable disease progression.

We now have first clear evidence showing that lignans lower not only the risk of developing postmenopausal breast cancer, but also the mortality risk, says Jenny Chang-Claude. There had been prior studies to determine the lignan intake by means of dietary surveys. But the results of such surveys are often unreliable and, in addition, there are big differences in the way individuals actually process the plant substances into effective metabolic products. Therefore, the Heidelberg team chose the more reliable measurement of biomarkers.

However, Chang-Claude narrowed down the result: The result was significant only for the group of tumors that have no receptor for the estrogen hormone (ER-negative tumors). This gives reason to suspect that enterolactone protects from cancer not only by its hormone-like effect. Indeed, studies of cells and animals had already provided evidence suggesting that the substance also has an influence on cancer growth irrespective of estrogen. Thus, it promotes cell death and inhibits sprouting of new blood vessels.

In order to find out whether enterolactone also inhibits the aggressiveness of estrogen receptors in estrogen-positive tumors, we would need to expand this study to include much larger groups of women, said Jenny Chang-Claude. Moreover, the scientist firmly emphasized: By eating a diet that is rich in wholemeal products, seeds and vegetables, which is considered to be health-promoting anyway, everybody can take in enough lignans. At the present time, we can only discourage people from taking any food supplements.

Phytoestrogens have been the subject of intense scientific debates in past years. On the one hand, the results of several studies of cells as well as epidemiological findings suggest that they have a cancer protective effect. Another observation that may be interpreted in this direction is that Asian women are less frequently affected by breast cancer. Their soy-rich diet contains large amounts of another type of phytoestrogens, isoflavones. On the other hand, scientists fear that isoflavones might imitate the growth-promoting properties of real hormones and, thus, accelerate hormone-dependent tumors such as breast cancer and prostate cancer. It has not yet been finally determined whether lignans in the body imitate the hormone effect or, on the contrary, counteract it, says Jenny Chang-Claude. Our studies will help achieve more clarity in this important question, which also concerns our daily diet.

The American Society for Microbiology honors John G. Bartlett

Tue, 13 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) John G. Bartlett, M.D., Johns Hopkins University School of Medicine, Baltimore, MD, has been honored with the prestigious Cubist-ICAAC Award from the American Society for Microbiology. Supported by Cubist Pharmaceuticals, the award rewards outstanding accomplishment in antimicrobial chemotherapy, development of new agents, investigation of antimicrobial action or resistance to antimicrobial agents, and/or the pharmacology, toxicology or clinical use of those agents.

Dr. Bartlett served as Chief of the Infectious Disease Division at the School for 26 years, stepping down in July of 2006. Thomas O'Brien, Academy Fellow from Harvard Medical School, says that Dr. Bartlett has contributed more to our understanding of numerous kinds of infecting microbes and their interactions with antimicrobial agents than anyone else I can think of. Dr. Bartlett's career is distinguished by the breadth of his contributions to ID; the depth of his knowledge across the field; and his enormous productivity. He is a true visionary, able to predict the importance of emerging problems and innovations before most people have taken notice, adds a supporter of the nomination, Joel E. Gallant of Johns Hopkins University School of Medicine.

Dr. Bartlett received his undergraduate degree at Dartmouth College, Hanover, NH, and his medical degree at Upstate Medical Center, Syracuse, NY. He trained in internal medicine at the Peter Bent Brigham Hospital, Boston, MA, and the University of Alabama, Birmingham, and he completed his fellowship training in infectious diseases at the University of California, Los Angeles (UCLA). Before accepting his current position at The Johns Hopkins University, Dr. Bartlett served as a faculty member at UCLA and Tufts University School of Medicine in Boston, MA, and was associate chief of staff for research at the Boston VA Hospital.

Dr. Bartlett has worked in several areas of research, all related to his specialty in infectious diseases. His major research interests have included anaerobic infections, pathogenic mechanisms of Bacteroides fragilis, anaerobic pulmonary infections, and Clostridium difficile-associated colitis. Since moving to Johns Hopkins in 1980, his major interests have been building the Infectious Disease Division, development of the Hopkins HIV Care Program, bioterrorism, antibiotic resistance, C. difficile and AIDS. At a time when HIV was anathema to many ID specialists and hospitals, Dr. Bartlett recognized its scientific importance and the moral imperative of caring for those affected, explains Dr. Gallant. Dr. Bartlett is credited with creating one of the world's first AIDS services, which is arguably the most respected and academically productive of its kind, says Gallant.

Dr. Bartlett is a member of the Institute of Medicine, a master of the American College of Physicians, past president of the Infectious Diseases Society of America (IDSA), and a recipient of the Kass Award from the IDSA. In 2005, Dr. Bartlett was awarded the Alexander Fleming Award by the IDSA and the Finland Award from the National Foundation for Infectious Diseases (NFID). He has been appointed to co-chair the federal guidelines on antiretroviral agents, and spearheaded efforts to control use of antimicrobial agents and encourage pharmaceutical companies to produce new anti-infectives for combating the rising tide of resistance. In addition, Dr. Bartlett has authored over 500 articles and reviews, more than 280 book chapters, and over 60 editions of 18 books. He also participates as an editorial board member for numerous journals.

Sherwood L. Gorbach, Tufts University School of Medicine, was the second supporter on Dr. Bartlett's nomination. He summarizes, it is not an overstatement to say that John Bartlett is one of the giants of contemporary infectious diseases and microbiology... Not only has he moved the field of antimicrobial chemotherapy forward, he has been a mentor and inspiration to many colleagues, fellows and students at UCLA, Tufts, and now at Johns Hopkins.

A chaperone for the 'guardian of the genome'

Wed, 07 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Every cell has thousands of proteins whose activity and lifetime must be regulated to control the cellular life cycle from cell division to cell death. The heat shock protein Hsp90 plays a key role in this process. It is a so-called chaperone, a quality controller, as it were. It monitors and controls the quality and activity of many important signal proteins and helps them take on the right form. When the cell is exposed to high stress levels from heat or a lack of oxygen, Hsp90 is produced in larger quantities to shield its partner proteins from damage.

One of the most important partner proteins of Hsp90 is the tumor suppressor protein p53. It prevents the development of cancer at a number of points in the cell and is thus aptly referred to as the guardian of the genome. When a cell's DNA becomes damaged, p53 ensures that the cell no longer divides and activates repair mechanisms. When too much genetic damage accumulates, the protein initiates a controlled cellular suicide. When p53 is inactive, the cell continues to divide in spite of the damage and a tumor develops. In over half of all tumors the p53 protein is damaged or inactivated, meaning the control function cannot be carried out.

Hsp90, on the other had, binds to p53 and keeps it in a functional state until it can fulfill its actual purpose: Binding to specific DNA elements. However, exactly how and where the binding of p53 to Hsp90 takes place was hitherto neither clear nor had it been structurally characterized.

At the Department of Chemistry of the TU Muenchen, a team of biochemists headed by Professor Horst Kessler, in collaboration with the group of Professor Johannes Bucher, Chair of the Department of Biotechnology, has now succeeded in working out the details of how p53 binds to Hsp90. Horst Kessler was Chair of the Department of Organic Chemistry and Biochemistry at the TU Muenchen from 1989 to 2008 and has been Carl von Linde Professor at the Institute for Advanced Study at the TU Muenchen (TUM-IAS) since October 2008.

Using nuclear magnetic resonance (NMR) spectroscopy, the scientists at the Bavarian NMR Center in Garching were able for the first time to characterize the interaction surfaces between Hsp90 and p53 and show that p53 binds to Hsp90 in an already structured form. p53 is thus kept in a functional state until this interaction is terminated by its actual intended binding partner, DNA. To keep p53 in the desired state, a number of interaction surfaces at different sites of the Hsp90 protein must interact in a closely coordinated manner.

In nuclear magnetic resonance spectroscopy, a sample of dissolved proteins is placed in an extremely strong, homogenous magnetic field and exposed to a complex sequence of radio frequency impulses. The atomic nuclei of the protein react to these impulses with a characteristic response frequency that depends on the environment of the respective nucleus. The scientists can measure this response. Every single stimulated nucleus responds at its own frequency, explains Kessler. In this way we can determine the connections between individual nuclei and thus deduce the structure of the protein. When p53 binds to Hsp90, the response frequencies at specific sites of the protein change. Based on these changes, the scientists can infer the sites at which p53 binds to Hsp90.

Role of alcohol intake and smoking on upper aerodigestive cancers

Tue, 06 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) This paper provides an extensive analysis of the proportion of the risk of upper aero-digestive tract (UADT) cancers in the population (the population attributable risk) that may be due to alcohol consumption and/or smoking. The analyse provides strong evidence that smoking is the most important factor in the risk of these cancers, and the risk is enhanced among those who smoke and also consume 2 or more drinks per day. Alcohol alone (i.e., among non-smokers) has little effect on the risk (less than 1%).

The authors state that their observations are consistent with the hypothesis that alcohol acts as a carcinogen primarily because of its promoting effect on tobacco smoke. In terms of the population-attributable risk, the authors conclude that Our findings confirm that tobacco and alcohol together explain 73% of total UADT cancer burden in Europe. Overall, tobacco use alone explained 28.7%, the combination of smoking and drinking 43.9%, and alcohol use alone only 0.4% of the population attributable risk. However, among women, the risk of these cancers was higher among smokers than among those who both smoked and consumed alcohol.

Comments on the present paper: This was a case-control analysis, which is usual for uncommon types of cancer. Controls were matched on age, gender, and area of residence, but some of the analyses also adjusted for educational level. Forum members thought it unusual that the investigators considered as ever drinkers only subjects reporting 2 or more drinks per day; in most countries, the majority of light-to-moderate drinkers would be classified as never drinkers by this definition. The data presented do not permit an evaluation of effects for lower levels of alcohol intake. However, given that even at 2 or more drinks per day the effects of alcohol alone on population attributable risk were very small, it could be assumed that lighter drinking may have even less of a direct effect on the risk of these cancers.

No information was available on diet (e.g., fruit and vegetable intake) or other lifestyle habits that may affect cancer risk. Thus, it is not possible to judge whether subjects who were both smokers and drinkers may have had other unhealthy lifestyle habits as well. Smoking and drinking might be just two visible markers of subjects with many unhealthy lifestyle habits.

Forum reviewers thought that this was a very good paper, but hoped that in the future we would have more studies that evaluated the effects on risk of varying levels of alcohol consumption, differential effects of various beverages, and even differential effects according to subjects' genetically determined differences in alcohol metabolizing enzymes.

MRI predicts survival in locally advanced rectal cancer

Mon, 29 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A new study has shown that magnetic resonance imaging (MRI) used to evaluate responses to pre-surgery (neo-adjuvant) chemotherapy or radiation may predict survival among patients with advanced rectal cancer. The findings suggest that MRI-assessed tumor responses to neoadjuvant therapy can help physicians to better plan their patients' subsequent treatments.

MRI prior to surgery could help in the management of patients in a number of ways, including offering more intense therapy or alternative chemotherapy to those patients who appear initially resistant to chemotherapy, or changing the surgical plan.

This is the first time that MRI has been shown to predict outcome for patients with rectal cancer who have completed initial chemoradiation therapy, said lead author Gina Brown, MBBS, MD, consultant radiologist and honorary senior lecturer in the Department of Radiology at the Royal Marsden Hospital NHS Trust in Sutton, UK. MRI staging and reassessment of rectal cancers before and after chemoradiotherapy are not routinely done for all patients. We've shown that using MRI this way can help change the course of patient care, perhaps enabling physicians to choose a more effective chemotherapy drug or even in some cases ultimately avoid surgery.

In the study - called MERCURY - researchers used MRI to measure tumor shrinkage in 111 patients who had previously undergone preoperative radiotherapy or both chemotherapy and radiation (chemoradiation) for locally advanced rectal cancer. The group - part of a larger study of MRI use in improving rectal cancer staging begun in 2002 - was followed for five years. The researchers measured tumor response in terms of tumor regression grade (TRG), which measures the degree of tumor shrinkage after therapy, and the involvement of circumferential resection margin (CRM), which refers to the remaining cancer at the tumor edges after treatment, or predicted to remain after surgery. Patients were broadly designated either a good or poor responder to chemoradiation, according to MRI, and researchers compared survival of the two groups.

Investigators found that 72 percent of good responders to chemotherapy/radiation were alive after five years compared to 27 percent of those who were poor responders. The disease-free survival for those with good responses was 64 percent versus 31 percent for the poor responders. In addition, local recurrence rates at five years for those patients for whom there was MRI-predicted CRM involvement was 28 percent compared to 12 percent for patients with predicted cancer-free tumor margins.

Rectal cancer is commonly found in advanced stages, and as a result, neoadjuvant chemoradiation is frequently given to try to shrink tumors and make them easier to remove. While surgeons attempt to completely remove the cancer in order to minimize the chances of cancer returning, advanced tumors are more difficult to completely remove and more likely to have unseen cancer remaining at the edges of tissue at the surgery site. A positive surgical margin (tumor that remains at the borders of the surgical resection) is considered a strong predictor of local recurrence.

Of the 111 patients in the study, 73 percent (81 patients) were expected to have cancer left in the surgical margins prior to initial treatment. After neoadjuvant therapy, only 42 percent (47 patients) were predicted to have disease left in the surgery margins, meaning this group was still at risk for recurrence prior to surgery.

The next step is to take these tumor response grades and decide what the best treatment approach could be based on the degree of responses, Brown said.

She noted that future trials investigating neoadjuvant chemotherapy followed by chemoradiotherapy may be able to identify a subgroup of patients that has a good response and for whom chemotherapy alone might be enough, while also identifying those who needed further therapy prior to surgery. In some cases, the preoperative treatment removed all evidence of the tumor, leading some physicians to question the need for surgery. The investigators have begun a trial to study what happens to those individuals who appear to not have any remaining cancer with chemoradiation alone and have deferred surgery. In some cases, this has resulted in long-term deferral with anal sphincter preservation. Other trials may also be designed to use MRI results in regard to treatment efficacy.

A question of gene silencing

Wed, 24 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) When investigating cancer cells, researchers discovered numerous peculiarities: Particular RNA molecules are present in large numbers, particular genes are overactive. Do these characteristics have a relation to cancer? Do they promote cell growth? Do they inactivate growth brakes or are they just a whim of nature? To find clues for answering these questions scientists perform what are called loss-of-function analyses. They knock out (silence) the gene of interest in living cells or whole organisms and subsequently look for any changes in the cells' metabolism, physiology or behavior in order to find out whether specific cellular functions are lost.

However, what was still missing was a method for selectively silencing those genes that do not code for proteins, said Dr. Sven Diederichs, who is head of a Junior Research Group at DKFZ and at the Institute of Pathology of Heidelberg University. With his team, the molecular biologist has now developed a new method for selectively silencing such non-protein-coding genes and, thus, determining their function. In many cancers we find that specific non- coding genes are particularly active. Therefore, we want to understand what the RNA molecules transcribed from these genes bring about in the tumor cells.

Diederichs and his team have based their method on the use of zinc finger nucleases. These are engineered protein molecules that cut DNA at precisely defined sites and thus facilitate specific targeting and cutting of genes. Although the cell's repair machinery will re-connect the two ends after the cutting process, silencing works well for protein-coding genes. The repair enzymes usually do not repair the site precisely and insert small defects. This destroys the protein information so that the proteins can no longer be formed.

For non-protein-coding genes, however, such small defects are not relevant. Therefore, mere cutting does not bring the desired result. The repair process simply results in another functioning gene that is transcribed into RNA molecules. The Heidelberg researchers therefore used a trick: The repair proteins are also able to integrate small DNA segments when mending the two ends. Therefore, the molecular biologists integrated a signaling sequence at the site where the gene was cut. This sequence causes the RNA transcript of this gene to be broken down at once so that it is not available for any cellular functions. The resulting changes in cellular biology can then be analyzed comprehensively.

We are now able, for the first time, to completely silence the non-protein-coding genes and thus study their molecular and cellular functions, said Sven Diederichs when explaining the goal of his research approach. It is very likely that these genes play an important role in cancer development. We are sure it is not by chance that they are so very active particularly in tumor cells.

Clinical trial shows benefit to adding avastin to neoadjuvant chemotherapy in breast cancer patients

Tue, 23 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Amid the controversy surrounding the Food and Drug Administration's ruling that Avastin should no longer be used to treat metastatic breast cancer, a new multinational Phase III clinical trial shows that Avastin significantly increased tumor response rates in breast cancer patients when given before surgery.

At the annual meeting for the American Society of Clinical Oncology, the nation's premier association of clinical oncologists, Harry D. Bear, M.D., Ph.D., Chair, Division of Surgical Oncology at Virginia Commonwealth University Massey Cancer Center, presented the Avastin findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-40 clinical trial. Bear, who served as the trial's protocol chair, explained that Avastin, when added to preoperative chemotherapy regimens, increased toxicity but also increased pathologic complete response rates by more than 6 percent (34.5 percent versus 28.4 percent) and clinical complete response rates by approximately 8 percent (64.3 percent versus 55.8 percent). Pathologic complete response was defined in the study as no remaining invasive cancer left in the breast, and clinical complete response was defined as a complete disappearance of cancer with no evidence of disease progression. Patients with hormone receptor positive breast cancers appeared to benefit most from the treatment.

While encouraging, the results of this study will probably not affect standard neoadjuvant or adjuvant chemotherapy practices in the near term, says Bear. There are many different types of breast cancer, and we need more definitive biological predictors of response in order to more accurately identify the patients who will benefit most from Avastin.

Though hormone receptor positive patients benefited most from the addition of Avastin in the NSABP Protocol B-40 trial, a second study presented during the same session at the ASCO meeting seemed to contradict the findings. The second study, known as GeparQuinto, was conducted in Germany and found that Avastin benefitted patients with triple negative cancers, but not patients with hormone receptor positive cancers.

The more we understand tumor biology, the more personalized cancer care becomes. By identifying the factors that made Avastin beneficial, we can hopefully test future breast cancer patients to determine whether or not it should be included in their treatment, says Bear.

The NSABP Protocol B-40 trial included 1,206 patients with operable HER2-negative breast cancer and tested different preoperative, or neoadjuvant, chemotherapy regimens. The trial had two objectives. The first was to determine whether adding the chemotherapy agents capecitabine or gemcitabine to the standard neoadjuvant chemotherapy regimen of docetaxel followed by a combination of doxorubicin and cyclophosphamide increased the pathologic complete response rate. The second objective was to test whether adding Avastin to chemotherapy before surgery increased the pathologic complete response rate. While the addition of Avastin did improve the pathologic complete response rate, the addition of the chemotherapy agents capecitabine and gemcitabine did not.

We need more research focusing on patient biology and tumor differences to understand why Avastin works for some but not others. We hope to gain insight by analyzing tumor biopsies and blood samples from patients in the B-40 trial and other recent Avastin studies, says Bear. In addition, since the patients who received Avastin preoperatively also received it after surgery, it is possible the drug may improve long-term outcomes. We will follow these patients for many years to come to determine whether Avastin increased cure rates.

Small molecules shed light on cancer therapies

Mon, 22 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Patients suffering from an aggressive brain cancer will benefit from the results of a University of Illinois study that could advance the development of targeted gene therapies and improve prognosis.

We have advanced the understanding of the role of microRNAs on glioblastoma multiforme, a deadly brain cancer, by studying the networks between the microRNAs and their target genes associated with different stages of cancer development and progression, said Kristin Delfino, a U of I doctoral candidate in animal science with a focus in genetics and bioinformatics.

What exactly are microRNAs? microRNAs are small, non-coding RNA molecules that regulate the expression of genes such as oncogenes or tumor suppressor genes. U of I researchers used a novel approach to identify the simultaneous association between tens of thousands of microRNAs, target genes, and glioblastoma progression and survival.

Delfino integrated clinical information such as race, gender, therapy, survival, and cancer stage from 253 patients together with genome-wide microRNA and gene expression data.

We looked at the big picture and how microRNAs work together, Delfino said. When you look at a single microRNA alone, it can seem significant. But when you evaluate it in the context of all other microRNAs, some turn out to be more significant and others may not be as significant as they appear on their own. The systems biology approach that we implemented is critical for understanding the gene pathways influencing cancer.

The study evaluated 534 microRNAs together, unlike the typical method of studying one at a time. They confirmed 25 microRNAs previously associated with glioblastoma survival and identified 20 other microRNAs associated with initiation or growth of other cancer types such as breast cancer, ovarian cancer and gastric adenocarcinoma.

These findings suggest common pathways that can be targeted with similar drugs already developed and tested for other cancers, said Sandra Rodriguez Zas, co-researcher and U of I professor of animal science and bioinformatics.

In addition, researchers found that some of the microRNA biomarkers of survival are personalized, Rodriguez Zas said. This means that they are particularly useful for patients of a specific race, gender or therapy. Other microRNAs are equally effective regardless of the clinical conditions of the patient.

These biomarkers can serve as the basis to dig deeper into cancer studies, Delfino said. Cancer affects us all in one way or another. Unfortunately, we still don't know how it's caused, what takes place when it is caused and how to cure it. But these biomarkers give us guidance into developing specific gene therapies to target glioblastoma.

Today patients can easily and cheaply be screened for microRNA and target gene levels, Rodriguez Zas said.

Based on our research, that information can be used to select the most effective therapy and develop prognosis strategies, Rodriguez-Zas said.

Targeting a cure: Research looks at developing a bull's-eye therapy to combat lung cancer

Mon, 22 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) MANHATTAN, KAN. -- A Kansas State University professor is trying to create a patient-friendly treatment to help the more than 220,000 people who are diagnosed with lung cancer each year.

Masaaki Tamura, associate professor of anatomy and physiology, and his research team are working on several projects that use nanoparticles to treat and directly target the bull's-eye: cancer cells.

It's estimated that nearly 156,940 people will die from lung-related cancer this year, according to the American Cancer Society. Lung cancer-related deaths are higher than the next three common cancer-related deaths combined: colon, breast and pancreatic cancers.

Given lung cancer's high mortality rate, Tamura has focused his research on peptide nanoparticle-based gene therapy, which is the process of treating diseases by introducing therapeutic genes. His research team is collaborating with University of Kansas researchers to develop a way to treat cancer other than current chemotherapy practices.

We want to generate a safe patient-friendly therapy, Tamura said.

Cancer develops from our own bodies, Tamura said, which makes it very difficult for traditional chemotherapy to distinguish cancer cells from healthy cells. As a result, chemotherapy often kills both cancer cells and healthy cells, which is why patients often experience whole body reactions to treatment, such as hair loss, diarrhea and vomiting. If the chemotherapy treatment damages intestines, it often has fatal consequences for patients.

Tamura has found the potential for safer therapy in cationic peptide nanoparticles. This small peptide helps transfer an important gene called angiotensin II type 2 receptor, which helps to maintain cardiovascular tissue. By attaching this receptor gene to peptide nanoparticles, Tamura hopes to create a form of treatment that can directly target cancer cells without damaging healthy cells.

The peptide itself is a very safe material and it has no harmful effects, said Tamura, who is one of the first researchers to use the peptide for cancer treatment. The gene is actually already expressed in our body -- everybody has this gene.

Here is how the cancer treatment works: The receptor gene containing the nanoparticles spreads to only cancer tissue since the blood vessels in cancer tissues are flimsy. The nanoparticles help the receptor gene kill the cancer cells. The immune system is then stimulated to prevent the cancer from growing back.

This is very exciting because our own immune system can prevent cancer growth, Tamura said.

While the receptor gene works well for tumors that are easier to reach in the body, cancers that are deep within the body, such as gastric or pancreatic cancers, are more difficult to treat. Sometimes the gene needs help targeting and reaching the cancerous cells. That's where the peptide comes in. It can guide the receptor gene directly to the cancer cells so treatment can begin.

Working with lungs also provides a special advantage. If the researchers can develop some sort of spray that contains the peptide, it can help the peptide go straight into the lungs. It's noninvasive to go through the lungs and makes it easier for the peptide to enter the circulatory system and travel to other cancerous tissue.

The cationic peptide was developed by a KU research team led by Cory Berkland, an associate professor of pharmaceutical chemistry. After developing the peptide, they turned to Tamura and his team for help evaluating, testing and developing the peptide nanoparticle therapy. The two schools have been working together on the project for three years. Researchers hope to develop their targeted peptide procedure into a treatment that humans can use.

It has really been nice for the two schools to work together on this project because Kansas is such a hotbed for the biomedical industry right now, Tamura said.

Tamura is also involved in Kansas State University research of the cancer therapeutic possibilities of umbilical cord matrix stem cells. He is on a team of university researchers who have received a patent addressing procedures used to gather stem cells from umbilical cords -- a less controversial source of stem cells that are effective at treating cancer. These stem cells do not generate any additional tumors and can travel deep inside the inflammatory tissue where cancer is located.

Researchers on the trail of a treatment for cancer of the immune system

Fri, 19 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Infection with Epstein Barr means that the B cells, which are the primary memory cells of the immune system, are hi-jacked.

When the virus has penetrated, researchers observe an excess of a special bio-antenna, a receptor known as EB12, suddenly sprouting from the surface of the B cells. But why they do so remains a mystery.

The receptors are a vital component of the way cells communicate with their surroundings via hormones and other bio-molecules, for example, but in a body consisting of millions of cells and transmitters it can be hard to determine the part each molecule plays.

It is possible that the large numbers of EB12 receptors could actually be the B cells response to the virus and an attempt to combat the infection. Another possibility is that the EB virus reprogrammes the cell for this explosive growth in the number of EB12 receptors. What we know for certain is that more EB12 receptors assist the B cell infected by the EB virus to multiply more rapidly thus spreading the infection faster, says postdoc Tau Benned-Jensen from the Faculty of Health Sciences, University of Copenhagen.

No fewer than 95 per cent of us carry the Epstein Barr Herpes virus.

We often encounter it as kids and it is normally harmless. Are we infected later in life EB virus may cause mononucleosis, and it seems to play a part in some forms of cancer, just as HPV affects the risk of cervical cancer. But we have no drugs to combat the Epstein Barr virus, and no vaccines for it.

Under normal circumstances our immune systems can keep the EB virus infection in a latent state and a truce or stand-off may arise between the immune system and the virus, explains Mette Rosenkilde, professor of pharmacology at the Department of Neuroscience and Pharmacology, University of Copenhagen.

We cannot dispense with the infection and we carry it all life long, but to most of us it is harmless. For people whose immune systems do not function due to disease or because they are suppressed by drugs in conjunction with organ transplants it is a very different matter. Now the Epstein Barr virus is suddenly free to reproduce so uninhibitedly and dramatically that it may lead to cancer, says Mette Rosenkilde.

While researchers know that the B cell EB12 receptors play a part when the cell visits the lymph glands, the immune system's Central Station, we have not yet explained the exact role of the receptor.

So the Danish researchers started by mapping the bio-antenna molecule by molecule and then, as the first in the world, they made a blueprint of a tiny molecule they thought could bind to the B cell EB12 receptor.

When we know what receptors react to, it tells us more about the part they play, Mette Rosenkilde explains, and our tiny molecule, a ligand, blocks the EB12 receptor, preventing it from doing its job.

In time this block may be able to help transplant patients. If we can restrain EB virus reproduction when the immune system is being medically suppressed, we may well be able to avoid cancer, Tau Benned-Jensen says.

On the other hand the EP virus also appears to play a part in other immune diseases such as autoimmune disease, where the ability to adjust the immune system would be beneficial, says Mette Rosenkilde.

And shortly after the Danish researchers published their article on their ligand, the first articles appeared about natural substances in the body, which activate the EB12 receptor and direct the B cell to specific areas in the lymph glands.

Our molecule can inhibit the activation of the new substances, and the next step in our research will be experiments to identify even more biochemical dials to twiddle and to help us develop new drugs, Tau-Benned says.

The discovery has just been published in the

New prostate cancer screening test shows promise for diagnosis

Mon, 15 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) CLEVELAND - A new prostate screening test developed by AnalizaDx, Inc., a Cleveland-based biotech company, and studied by researchers at the Seidman Cancer Center at University Hospitals (UH) Case Medical Center along with colleagues at the Cleveland Clinic, the Veterans Administration Boston Healthcare and the National Cancer Institute, may prove to be a promising new tool in the diagnosis of prostate cancer. The study which will be published in the September issue of Urology found that this new screening test, the PSA/SIA assay, may be more sensitive in detecting prostate cancer than traditional screening methods.

This has the potential to be a major advance in the development of more accurate tests for prostate cancer diagnosis, says Mark Stovsky, MD, Principal Investigator and lead author of the study, urologist at UH Case Medical Center and Associate Professor of Urology at Case Western Reserve University School of Medicine. Prostate cancer is the most common cancer in men but traditional screening is not very accurate. This test provides a new way to look at prostate cancer diagnosis utilizing a novel biological assay which differentiates PSA molecular structures arising from cancer versus non-cancerous glands.

The accuracy of traditional prostate cancer screening (serum prostate-specific antigen or PSA) is limited by both relatively high false positive and false negative rates. Current diagnostic strategies that use total PSA to determine the need for biopsy demonstrate false positive rates of approximately 55-75 percent. This finding can therefore lead to unneeded prostate biopsies and unnecessary worry in patients. Additionally, the serum PSA test carries, in some studies, false negative rates of up to 15 percent, meaning that some men with 'normal' PSA values actually have cancer. What is needed is a test that can more accurately predict the presence of prostate cancer on biopsy.

Working with AnalizaDx, Inc., Dr. Stovsky and colleagues studied a urine-based test that works differently than most prostate screening methods by using a novel assay to separate PSA protein structures as being linked to either a 'cancer' or 'non-cancer' pathologic diagnosis based on ultrasound guided biopsy. Instead of attempting to find a single genetic biomarker which predicts the presence of cancer, the PSA/SIA assay is based on the assumption that there may be myriad different ultra-structural changes in the PSA protein which define the cancer phenotype. The authors theorize that the extremely high sensitivity of the test is the result of the ability of the PSA/SIA biological filter to categorize the myriad ultra-structural changes in the PSA protein as being made by either cancer versus non-cancer glands. The PSA/SIA assay was also found to have relatively high specificity (low false positive) results compared to the traditional serum PSA test.

The initial study, which followed 222 men, found that the new screening method had 100% sensitivity (no false negative results) and 80.3% specificity (low false positive results). The study data was collected at three clinical sites - UH Case Medical Center, VA Boston and Cleveland Clinic, and was analyzed at the National Cancer Institute.

This new assay is a complete departure from how the scientific community has looked at biomarkers for cancer, says Arnon Chait, CEO of AnalizaDx, Inc. Instead of just measuring levels of proteins, we are exploring changes in structure which are associated with cancer. This new method of diagnosing cancer truly has significant potential for other types of cancer as well.

The technology will be tested in further clinical research studies to determine its accuracy in serum as well as its ability to predict cancer grade/aggressiveness and the response to curative intent therapies. Study coauthors include Lee Ponsky, Srinivas Vourganti, Peter Stuhldreher, Mike Siroky, Victor Kipnis, Olga Fedotoff, Larissa Mikheeva, Boris Zaslavsky, Arnon Chait and J. Stephen Jones. The study is dedicated to the late Martin Resnick, MD, who served as the original Principal Investigator of this work and was Chairman of the Department of Urology at UH Case Medical Center and Case Western Reserve University School of Medicine.

New approach to thyroid surgery eliminates neck scar

Tue, 09 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO- As the rate of thyroid cancer continues to climb, doctors are urging patients to be more cautious about thyroid nodules, a common disorder that is responsible for a small but growing number of thyroid cancer cases. Thyroid nodules affect nearly 13 million Americans and are a result of abnormal cell growth on the gland. Until recently, the only way to remove nodules and rule out cancer was through surgery that required a five centimeter incision across the front of the neck. The procedure, and the large scar that resulted, was a deterrent for many patients who feared altering their appearance for something that may not be life threatening. Today however, a new option exists that allows surgeons to access the neck through the armpit, allowing for a biopsy of tissue with no visible scar.

We now have a minimally invasive way of determining if a thyroid nodule is cancerous, said Jose Dutra, MD, head and neck surgical oncologist and director of the Thyroid Surgical Clinic at Northwestern Memorial Hospital. It's an approach that more patients are comfortable pursuing. If we can identify cancerous cells earlier we increase the chance of removing the cancer before it spreads.

The procedure, transaxillary robotic thyroid surgery, utilizes 3D cameras and specially designed robotic arms to create a small incision within the armpit, the mechanical arms work just like hands allowing the specialized surgeon to operate remotely with precise control and movements to remove suspicious nodules.

The underarm area has fewer nerve endings than the anterior neck area, so there's less pain, no scarring on the neck, and with good care, the incision will heal faster, said Dutra who is also an associate professor at the department of otolaryngology/head and neck surgery at Northwestern University Feinberg School of Medicine.

This summer, Socorro Delaluz became one of the first patients at Northwestern Memorial to undergo transaxillary thyroid robotic surgery. The mother of two was impressed to have the option that left no visible scar and the quick recovery associated with the technique.

I didn't want to be reminded constantly, every morning when I get dressed that I had a scar across my neck. I would have to explain to everyone what happened all the time, expressed Delaluz.

Another benefit of the minimally invasive approach is that the precision of the robot allows physicians to remove all of the potentially cancerous tissue while sparing more of the structure surrounding the gland.

The thyroid gland controls how the body uses energy. Changes to the gland can cause a myriad of health issues, explained Dutra, member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Thyroid nodules are six-times more common in women than men and can be difficult to diagnose because they often do not present signs or symptoms. Most nodules are small and are often found incidentally during a routine physical or imaging for an unrelated condition. Conditions that can cause one or more nodules to develop in the thyroid gland range from overgrowth of normal thyroid tissue, tumors, a cyst, inflammation and goiters. Individuals should routinely check their neck and should talk with their doctor if they notice any lumps or experience symptoms such as swelling, trouble swallowing, and pain in the throat or hoarseness of the voice.

Robotic surgery is currently widely used for minimally invasive heart and lower abdominal procedures, only recently have the robotic arms been applied to the confined space involved in neck and head surgery. The benefits for robotic thyroid surgery include shorter recovery period, less pain in neck following surgery and better preservation of the laryngeal nerves and the parathyroid glands.

Jennifer Panaro recently had a large nodule removed from her thyroid gland by way of transaxillary thyroid robotic surgery and was back on the tennis court just six weeks after her surgery. The 28 year old was impressed with the speedy recovery and was pleased her voice was protected. I was thrilled to not experience any changes in my voice or to have deal with a large scar on my neck. As an accountant, I talk to clients all day and I would be self conscious about having a foreign mark across my throat, said Panaro, patient at Northwestern Memorial.

While the new technology has great advantages, Dutra stresses this option is not the best for all patients and not all tumors can be removed with this approach.

The effects of smoking and alcohol use on risk of upper aero-digestive cancers

Tue, 02 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Upper aero-digestive tract cancers (UADT), especially those of the oral cavity, pharynx, and larynx, are often referred to as alcohol-related cancers as it has been shown repeatedly that heavy drinkers, in particular, are at increased risk. The combination of heavy alcohol use and cigarette smoking is the key factor in increasing the risk of these cancers.

A distinguished group of scientists from the International Agency for Research on Cancer (IRAC).evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. While this paper only supports much previous research, it is from a part of the world from which little information on the topic is available and it focuses on groups of people where the occurrence of such cancers is high.

The case-control analysis showed that both alcohol consumption and smoking tended to increase the risk of such cancers. However, the predominant cause of these cancers was the combination of smoking and alcohol consumption, with much higher risk than either exposure alone. The effects on risk were greater for smoking than for alcohol: for non-smokers, there was little effect of alcohol alone on risk. For non-drinkers, the risk of cancer associated with smoking was still increased, but was lower than it was for current drinkers.

Interaction of drinking and smoking: Overall, this study confirms that there is a tendency for an increase in risk for these cancers for both alcohol consumption and for tobacco use. More striking, however, was the strong interaction between these two exposures: heavy smokers and heavy drinkers were by far at the highest risk. For never-smokers, there was little effect of alcohol on the risk of these cancers, and none of the associations between alcohol and cancer among such subjects was statistically significant. As for the type of alcoholic beverage consumed, the risk for cancer was always highest among subjects stating that they consumed only aperitifs or spirits, with little apparent effect of the consumption of beer or wine.

An especially important finding in this study was that, among ex-drinkers and former smokers, the increased risks associated with alcohol and tobacco use decreased steadily as the time since quitting increased. As stated by the authors, most of these cancers could be prevented by quitting the use of either of these two agents.

Collaboration of major biomedical centers has shown convergence on a cellular process for head and neck cancers

Sat, 30 Jul 2011 20:30:27 PST

( from http://www.rxpgnews.com ) Powerful new technologies that zoom in on the connections between human genes and diseases have illuminated the landscape of cancer, singling out changes in tumor DNA that drive the development of certain types of malignancies such as melanoma or ovarian cancer.

Now several major biomedical centers have collaborated to shine a light on head and neck squamous cell cancer. Their large-scale analysis has revealed a surprising new set of mutations involved in this understudied disease.

In back-to-back papers published online July 28 in Science, researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center have confirmed genetic abnormalities previously suspected in head and neck cancer, including defects in the tumor suppressor gene known as p53. But the two teams also found mutations in the NOTCH family of genes, suggesting their role as regulators of an important stage in cell development may be impaired.

"This adds a new dimension to head and neck cancer biology that was not on anyone's radar screen before," said Levi A. Garraway, a senior associate member of the Broad Institute, an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and a senior author of one of the Science papers. "Head and neck cancer is complex and there are many mutations, but we can infer there is a convergence on a cellular process for which we previously did not have genetic evidence. It shows that if you do a genome sequencing project of this size you can gain major new biological insights."

"The mutational analysis of NOTCH clearly indicated the power of genetic changes determining the function of these genes," said Kenneth W. Kinzler, professor of oncology and a molecular geneticist at Johns Hopkins, co-director of the Ludwig Center at Johns Hopkins, and an author of one of the Science papers. "It gives us an important clue to start studying their function."

Head and neck cancer is the sixth most common non-skin cancer in the world, with more than half a million new cases each year. Smokers, drinkers, and people infected with the human papillomavirus (HPV) have the highest risk of developing head and neck cancer, which is the collective name for tumors found in the oral cavity, including the mouth, larynx, and pharynx.

Patients often seek medical care only once they are in the later stages of the disease, when they may be offered surgery, radiation, chemotherapy, or a combination. Treatments can be disfiguring and debilitating, leaving patients unable to speak or swallow. The five-year survival rate of 50 percent has improved little over the past 40 years.

Jennifer R. Grandis, a professor of otolaryngology and pharmacology and chemical biology at the University of Pittsburgh School of Medicine and a senior author of one of the Science papers, bemoaned the dearth of genetic information about head and neck cancer several years ago at a conference where Garraway had given a talk about the genomic landscape of melanoma.

"There was a really big gap in knowledge that was an obstacle to doing the right kind of research" about head and neck cancer, she said. "If we didn't know the spectrum of the mutations that were in our patients' tumors, we couldn't begin to develop more appropriate therapies because we were sort of playing in the dark."

Grandis and Garraway decided to study a University of Pittsburgh collection of 74 pairs of tumor and normal tissue samples using the Broad's capacity to perform whole-exome sequencing. The exome represents the tiny fraction of the genome that encodes proteins. Focusing on just these protein-producing genes allows scientists to zero in on mutations that alter key proteins involved in cancer growth. Another collaboration was unfolding among the cancer geneticists, sequencing experts, clinical researchers, and surgical oncologists at Johns Hopkins, MD Anderson, and Baylor College of Medicine to study 32 pairs of head and neck tumor and normal tissue samples by whole-exome sequencing and validate the findings in an additional 88 samples.

Both teams found mutations in the p53 gene in a little more than half of the tumors they studied. The next most common mutation occurred in NOTCH1, which showed up in about 15 percent of tumors.

Normally, NOTCH1 controls how cells differentiate into other kinds of cells, mature, stop dividing, and ultimately die. In head and neck cancer, the scientists saw mutations that turn NOTCH1 off, blocking differentiation and trapping cells in a proliferative, pro-cancer state. Their maturation is arrested, leaving them stuck in an earlier stage, where other damage from smoking or alcohol or even p53 mutations can destabilize the genome.

NOTCH1's inactivation in head and neck cancer was surprising because in other cancers, such as leukemia, too much NOTCH signaling leads to cancer.

"Our study suggests that a gene's role can depend on the tumor type. In some cases, a gene can act as a growth promoter in cancer, and in other cases, such as head and neck cancer, the same gene behaves as a growth suppressor," said Kinzler.

Efforts to combat the mutated p53 tumor suppressor gene with targeted drugs, for example, have so far been unsuccessful.

The next step based on these novel head and neck cancer discoveries, the scientists agree, is to tease out how the genes function in normal cells, whether they form the lining of the larynx, pharynx, or another anatomical site affected by head and neck cancer.

"Both of our studies reveal few clues to the significance of NOTCH mutations. Further studies will be necessary to define its role in prognosis, diagnosis, and/or treatment," said Nishant Agrawal, a head and neck surgical oncologist at Johns Hopkins and a lead author of one of the Science papers. "The idea is to use these genetic alterations to predict a patient's prognosis and define personalized treatment strategies tailored to their cancer's genome."

Both teams confirmed the role of HPV infection in head and neck cancer, particularly oropharyngeal cancer. Thought to be transmitted by oral sex, the infection has become more prominent. The studies reveal that HPV-positive tumors carried fewer mutations than HPV-negative tumors. Patients with HPV-positive head and neck cancers tend to fare better than patients whose cancers are not caused by the virus.

Translating these discoveries into therapies for patients will take more studies and more time, the scientists all said, but the revelations set a course for the future.

Jeffrey N. Myers, professor of head and neck surgery at M. D. Anderson, said both groups' work highlights the complexity of the disease and its multiple gene abnormalities.

"It has told us new things that will give us both clinical and scientific opportunities to study in the near and long term," Myers said. "I think that we're also in a position to design very specific clinical studies to further understand the significance of these mutations, as well as to begin to think about potentially targeting some of the abnormalities."

Those studies could include looking at patients with different mutations in addition to p53 and the NOTCH family to see how well they fare.

"The race will be on to figure out the function and particularly the therapeutically relevant function of these mutations," Grandis said.

Agrawal said the collaborative effort is necessary.

"I think it's great we are advancing head and neck cancer research this way," he said. "Unfortunately, the cancer has been beating us. Now it's time for us to take a permanent lead."

WU studies obesity, cancer link with $9.2 million grant

Thu, 28 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at Washington University School of Medicine in St. Louis have been awarded a $9.2 million grant from the National Cancer Institute (NCI) to study the relationship between obesity and cancer.

The five-year grant will fund the Transdisciplinary Research on Energetics and Cancer (TREC) Center. The Center's researchers will study the effect of diet, weight, physical activity and the environment on cancer and cancer survivorship.

The emphasis is to bring together people from many disciplines, from both the Danforth Campus and the School of Medicine, to investigate the link between obesity and cancer, says epidemiologist Graham A. Colditz, MD, PhD, the Niess-Gain Professor at the School of Medicine and associate director of prevention and control at the Alvin J. Siteman Cancer Center at Washington University and Barnes-Jewish Hospital. Our projects span from looking at cancer risk in animal models to studies of how workplace policies can influence sedentary behavior and cancer risk.

Over the long term, Colditz and his colleagues hope to reduce cancer related to obesity, poor diet and low levels of physical activity and to foster relationships between researchers in different disciplines.

We want to link basic scientists with clinicians helping patients, says Sarah J. Gehlert, PhD, the E. Desmond Lee Professor of Racial and Ethnic Diversity at the Brown School of Social Work and the School of Medicine and a co-principal investigator at the TREC Center. If we can sit down in the same room, we can shape research projects that are more likely to result in a meaningful outcome, such as better treatments based on what we know from the basic science.

Studies funded by the grant will:

Examine the effects of nutrition, such as a mother's high fat diet, on cancer predisposition in multiple generations of mice. Study the influence of physical activity and obesity on urinary and sexual function in men following surgery to remove prostate cancer. Develop models of obesity across a lifespan to investigate how worksite policies and neighborhoods influence obesity and cancer risk. Investigate how policies relating to nutrition and a person's social environment might link obesity and cancer.

Washington University is one of only four TREC Centers funded by the NCI to investigate obesity and cancer, along with Harvard University; the University of California, San Diego and the University of Pennsylvania. A fifth coordinating center, the Fred Hutchinson Cancer Research Center in Seattle, will help investigators at the four research institutions share data and collaborate on various projects. Funding for all five centers totals $45 million.

Agilent Technologies and A*STAR launch all-in-one drug screening platform

Thu, 21 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Agilent Technologies Inc. (NYSE: A) and A*STAR's Experimental Therapeutics Centre (ETC) today announced the launch of a drug screening platform within ETC's new Singapore Screening Centre. This partnership will provide a full spectrum of state-of-the-art automation technologies to biomedical researchers, enabling highly efficient drug screening in one location.

The Singapore Screening Centre conducts high-throughput screening to identify potential drug candidates against disease, using a library of over 300,000 chemical compounds. It now employs Agilent's dual BioCel 1200 integrated system, which automates and coordinates the various processes of high-throughput screening, including compound management, assay plate preparation and experiment replication, to ensure high-quality data while saving time and reducing the possibility of human error.

The location of Agilent's technology platform within ETC's newly set up Singapore Screening Centre will not only enhance our ability to produce proprietary drugs for Singapore, but also enable us to engage a diversity of biomedical research players from across the world, said Dr. Alex Matter, CEO of ETC. We expect collaborations with top private sector partners such as Agilent will go a long way to accelerate the development of medical solutions.

The centerpiece of Agilent's BioCel System is a Direct Drive Robot (DDR) that provides significant advantages in speed and ease of use with its one-touch teaching and innovative design. The BioCel system is also customised specifically to ETC's requirements, linking the instruments to ETC's laboratory information management system so that the BioCel database and sample inventory are synchronised and up to date.

The new platform will boost ongoing drug discovery projects at the Singapore Screening Center, including a collaboration with Duke University and the National University of Singapore Graduate Medical School to screen for novel gastric cancer medicines; and another with DSO National Laboratories and A*STAR's Genome Institute of Singapore to discover anti-bacterial drugs using a novel whole animal-screening platform.

ETC is a leading research institution in Singapore and we look forward to working closely with them to collectively drive drug discovery research, said Yvonne Linney, vice president and general manager, Agilent Automation Solutions Group. We continue to see growth and opportunities for automated solutions in both Asia and the pharmaceutical markets as a whole.

Singapore has built up strong scientific foundations and capabilities in translational and clinical research to support industry efforts to accelerate the drug discovery process with next-generation technologies. Today, leading pharmaceutical, biotechnology and medical technology companies have invested in more than 50 commercial-scale facilities in Singapore. In 2009, Agilent opened a life sciences manufacturing facility in its Yishun, Singapore campus. The facility expanded Agilent's presence in the region and brought it closer to its Asia Pacific customer base.

ACR, SBI support updated ACOG recommendations that women begin annual mammograms at age 40

Wed, 20 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The American College of Radiology (ACR) and Society of Breast Imaging applaud and support updated American College of Obstetricians and Gynecologists' (ACOG) recommendations that women begin getting annual mammograms at age 40. The updated ACOG recommendations now correspond with those of the American Cancer Society, ACR, Society of Breast Imaging (SBI), American Society of Breast Disease (ASBD) and many other major medical associations with demonstrated expertise in breast cancer care.

Three decades of research shows that mammography saves lives. Recently, Tabar et al, an update to a landmark study that involved 130,000 women followed over 29 years, re-confirmed that regular mammography screening reduced the breast cancer death rate by 30 percent. This follows the report of the largest breast cancer screening trial ever performed (Hellquist et al), involving a million women over 16 years, which proved that mammography screening reduced breast cancer deaths in women 40-49 by 29 percent. Both fit with National Cancer Institute data that shows that since mammography screening became widespread in 1990, the U.S. breast cancer death rate, previously unchanged for 50 years, has dropped 37 percent.

The updated ACOG recommendations, now in-step with those of breast cancer experts, differ from the guidelines of the United States Preventive Services Task Force (USPSTF).

ACOG, like ACR, SBI, and others, placed greater importance on saving lives while the USPSTF was primarily concerned with reducing false positive studies, most of which are resolved by a few additional mammographic views or ultrasound. The USPSTF relied largely on computer modeling to argue that, in women 40-49, only those with a family history of breast cancer or other high-risk factors should be screened and that women 50-74 be screened biennially. However, there is no scientific data to support the age of 50 as a biological threshold for screening. It has been artificially marked by inappropriate grouping of data.

Moreover, 75 percent of women who develop breast cancer are not considered at high-risk for the disease. Screening only high risk women would miss three-quarters of breast cancers. The USPSTF conceded that biennial screening of those 50-74 would miss up to a third of cancers present. A report by Hendrick and Helvie, showed that if USPSTF breast cancer screening guidelines were followed, as many as 100,000 women, now ages 30-39, and preparing to enter screening age, would ultimately die unnecessarily from breast cancer.

Mammography is not perfect. It does not identify all breast cancers. However, at present there is nothing to replace mammography as a primary screening tool. By not getting annual mammograms, women increase their risk of dying from breast cancer. In addition, mammography can find cancers at an earlier stage when treatment options are greater.

Women ages 40 and older are strongly encouraged to seek annual mammograms. Those with a family history of breast cancer or other factors that place them at elevated risk for the disease should speak with their doctor about being screened even earlier.

NYU researchers develop compound to block signaling of cancer-causing protein

Sun, 17 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at New York University's Department of Chemistry and NYU Langone Medical Center have developed a compound that blocks signaling from a protein implicated in many types of cancer. The compound is described in the latest issue of the journal Nature Chemical Biology.

The researchers examined signaling by receptor tyrosine kinase (RTK). Abnormal RTK signaling is a major underlying cause of various developmental disorders and diseases, including many forms of cancer. RTK signaling pathway employs interactions between proteins Sos and Ras, and accounts for a broad range of molecular changes that underlie various cancers and other diseases. Disrupting the Sos-Ras interaction, then, is crucial to stemming the production of cancer cells.

However, interactions between large protein molecules such as Ras and Sos have been difficult to modulate with artificial means. Through a series of experimental and computational analyses, the scientists hypothesized that by mimicking a key portion of Sos, they might disrupt its interactions with Ras. Specifically, they observed that Sos activates Ras through a helix—a critical portion of Sos that makes contact with Ras. Creation of this Sos mimetic required a method for locking correct helical shapes in synthetic strings of amino acids – a method previously developed at NYU School of Medicine.

7 in 1 blow: Scientists discover DNA regions influencing prostate cancer risk

Tue, 12 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Doctors have known for a long time that prostate cancer runs in the family. Men with relatives who have been diagnosed with prostate cancer have an elevated risk of also developing this type of cancer. It was only last year that DKFZ scientists calculated that this risk rises with the number of affected direct family members and also depends on the relatives' age at outbreak of the disease (DKFZ Press Release 18/2010).

The exact DNA variants that contribute to prostate cancer risk have now been published by an international research consortium with participation of scientists from the German Cancer Research Center. In a multi-stage study, the collaborators systematically searched the whole genome of cancer patients and healthy controls for specific gene variants. Then they calculated whether specific variants are found more often in patients than in healthy people.

Professor Dr. Hermann Brenner, one of the DKFZ researchers participating in the consortium, explains: Each of these gene variants taken on its own is associated with only a slight increase in prostate cancer risk by a few percent. However, by taking account of the different variants at the same time it becomes possible to identify groups of persons who have a significantly elevated risk. Examining the genetic material for such risk variants might therefore improve medical consultation on the prevention and early detection of prostate cancer in the future.

Such DNA variants are scientifically called single nucleotide polymorphisms (SNPs). They are defined as a single variation of a nucleotide which occurs with varying frequency in the whole population. If a relationship in numbers is found between a particular SNP and cancer incidence, researchers conclude that a gene within the affected DNA region plays a role in cancer.

The first two study stages conducted by the consortium had already identified 16 SNPs in 16 different DNA regions to be associated with an elevated prostate cancer risk. Together with the results of prior association studies, about 30 risk genes for prostate cancer were known then. In the third and last round the research consortium searched in 4,574 cancer patients and 4,164 controls for another 1,536 SNPs. The emerging associations with cancer risk were then verified once more using 51,311 DNA samples of cancer patients and healthy men.

Alongside a number of already identified variants, the investigators found seven SNPs that emerged for the first time in association with an elevation in prostate cancer risk. The variants are all located in DNA regions that also contain genes for which the scientists consider it plausible that they play a role in carcinogenesis. However, an association with the malignancy of cancer could not be established for any of these variants. With the seven newly discovered DNA regions, scientists are now able to explain about 25 percent of familial cancer risk.

Canada's Cancer Risk Management model is an important new health tool for policymakers

Wed, 06 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) If Canada's smoking rates were cut by half to an average national rate of 11% within five years, it would result in 35,900 fewer cases of lung cancer by 2030 and save $656 million in treatment costs, according to analysis using a new web-enabled platform developed for the Canadian Partnership Against Cancer and presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC).

The Cancer Risk Management simulation model developed for the Canadian Partnership Against Cancer simulates the demographic characteristics of the Canadian population and projects cancer occurrences, said the abstract's author, Dr. Bill Evans, M.D., president of the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ontario, Canada. For lung cancer, it can be used to explore the impact of smoking cessation on such things as downstream treatment costs, life-years gained and the impacts on tax revenue. It can also project the impact of introducing a population-based screening program or increasing the uptake of adjuvant chemotherapy for surgically resected lung cancer. The cost impacts of new systemic treatments, such as molecular targeted therapies, can be estimated for specific populations, such as stage IV non-small cell lung cancer, with the budget impact for individual provinces. These simulations can help to inform decision-makers as to the relative costs and benefits of proposed new cancer control strategies.

The Cancer Risk Management (CRM) model uses dynamic, longitudinal microsimulation techniques to simulate and project realistic, representative Canadian populations, offering the potential to study changes in screening, prevention, and treatment.

The impact of decreasing smoking rates is provided as an example. For this simulation, smoking rates were decreased over a 5-year time frame from a 22% national average in 2010 to 11%. Over 20 years, this would save 587,000 person-years of life, or an average of 0.09 years per smoker. By 2030, the lung cancer incidence rate would drop from 87 to 72 per 100,000 people, resulting in cumulative savings in direct lung cancer treatment costs of $656 million and a decrease in tax revenue from cigarettes of $81.1 billion. Compared with the 5-year smoking cessation timeframe, achieving a 50% reduction in smoking rates in 3 or 10 years would add 59,800 life-years or reduce them by 117,900, respectively.

Lung, colorectal and cervical cancer modules have been built that incorporate Canadian demographic characteristics (births, mortality, immigration, emigration), educational status, risk factors (e.g. smoking, radon exposure for lung cancer) and economic factors (earnings, taxes, government transfers). CRM uses the latest data on the incidence, disease management and cancer case fatality in Canada, the impact of cancer treatments on population health and the cost to the health care system. Data sources include large national surveys, cancer registries and census data, as well as medical literature and expert opinion.

Lack of clarity about HPV vaccine and the need for cervical cancer screening

Wed, 06 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The research will be presented today [Thursday 7 July] at the Annual Scientific Meeting of the Society of Academic Primary Care, hosted this year by the Academic Unit of Primary Health Care, University of Bristol.

The HPV vaccination programme, introduced in the UK in 2008, uses HPV vaccine that is effective against the two most common high risk HPV types (16 and 18), and offers 70 per cent protection against cervical cancer. However, vaccinated girls will still need to attend cervical screening in the future to ensure protection against cervical cancer caused by high risk HPV types not included in the vaccine.

Dr Alison Clements and colleagues interviewed parents and vaccination-aged girls about their understanding of the HPV vaccination in relation to vaccine acceptance, and potential future cervical cancer screening behaviour.

They found a lack of clarity amongst both parents and girls about the link between the HPV vaccine and the need for future cervical screening. In some cases parental consent for their daughters to receive the vaccine was based on the false belief that cervical screening would not be necessary. There was also a profound lack of awareness about cervical screening amongst girls of vaccination age.

Dr Clements said: For informed decisions about HPV vaccination to be made, the provision of information about the ongoing need to attend cervical screening is imperative. Our findings have the potential to improve information and educational materials for parents, eligible girls and health professionals. To ensure the uptake of cervical screening is not adversely affected, future invitations for screening will need to stress the importance of attendance regardless of whether the individual has had the HPV vaccination or not.

Hazel Nunn, Cancer Research UK's senior health information manager, said: This is a helpful reminder that renewed efforts are needed to inform girls and their families about the importance of cervical screening in those who have had the HPV vaccination. While the vaccine is very effective at protecting against the two strains of virus which cause most cases of cervical cancer, and one of the biggest steps forward in public health in recent years, it does not protect against all the other strains so the disease can still develop.

Cervical screening can prevent around 34 per cent of cervical cancers in women in their 30s, rising to 75 per cent in women in their 50s and 60s. Women should be reminded of the crucial role of screening in the fight against cervical cancer.

Lung tumors in never-smokers show greater genomic instability than those in smokers

Tue, 05 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Lung adenocarcinomas in people who have never smoked show greater genome instability than those in smokers, supporting the theory that lung cancer in never smokers arises through different pathways, according to research presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC).

We identified several genomic regions that were differentially altered in the lung tumor genomes of smokers and never smokers, said principal investigator Kelsie Thu, a researcher at the BC Cancer Agency Research Centre in Vancouver, Canada. We also found that a greater fraction of lung tumor DNA harbored genetic alterations in never smokers compared to smokers. The discovery that there are different patterns of genetic alterations in smokers and never smokers suggests that lung cancers in these cohorts are likely distinct diseases driven by different molecular mechanisms, and thus, may require different treatments.

Up to 25% of lung cancer cases worldwide occur in people who have never smoked, and never smokers with lung cancer typically exhibit traits different from those of smokers. They are more often women, Asian, have a higher incidence of epidermal growth factor receptor (EGFR) mutations, better responses to EGFR-targeting drugs and are more commonly diagnosed with adenocarcinoma.

There are a few known differences between lung cancers in smokers and never smokers. However, the differences discovered thus far are clinical features or genetic alterations at only a few specific genes, Thu said. For our study, we wanted to use an unbiased, whole-genome approach that would allow us to investigate all of the genes in the genome simultaneously. This enables us to identify genome-wide patterns of genetic alterations in lung tumors from smokers and never smokers. Our study was a comparative study, meaning that we compared the lung tumor genomes from smokers to those from never smokers to identify genetic (DNA level) alterations specific to one group or the other. The genetic alterations specific to the never smoker group may have important roles in driving the development of lung cancer in never smokers.

In the study, researchers extracted DNA from lung adenocarcinomas and matched non-malignant tissues for 30 never smokers, 14 former smokers and 39 current smokers. The DNA was assessed for EGFR and KRAS mutations. Copy number profiles were generated for each tumor using matched non-malignant lung tissue as a baseline for the identification of somatic copy number alterations. Two independent, publicly available datasets composed of lung adenocarcinomas from never smokers and smokers were used as validation datasets.

On average, never smokers' lung tumors showed higher frequencies of copy number alterations and greater proportions of altered genomes compared with those of smokers. This difference was more pronounced when former smokers were excluded and never smokers were compared with current smokers only.

Increased production of a microRNA resulted in better response to chemotherapy

Thu, 30 Jun 2011 17:27:41 PST

( from http://www.rxpgnews.com ) Researchers at the UC Davis Cancer Center have discovered a way of sensitizing muscle-invasive bladder cancer cells so that they succumb to the toxic effects of chemotherapy. The finding adds to mounting evidence that tiny strands of RNA — called microRNA — play key roles in some of the deadliest types of cancer.

In the current study, published online June 28 in International Journal of Cancer, researchers boosted the production of a microRNA found in bladder cancer cell lines — encoded for by the gene miR-34a — and found that this resulted in more of the cells being killed by cisplatin, a chemotherapy drug used to treat many types of cancer.

"When we took the bladder cancer cell lines and activated miR-34a, they were more responsive to chemotherapy," said Ralph deVere White, UC Davis Cancer Center director and professor of urology.

The study establishes, for the first time, a link between sensitivity of bladder cancer cells to chemotherapy and the expression of miR-34a. It suggests that miR-34a may be used as a predictor of response to chemotherapy, as well as a target for new drugs.

Currently, about 50 percent of patients with advanced bladder cancer will survive five years after diagnosis. Although clinical trials have demonstrated that chemotherapy before surgery can improve survival rates, it is rarely used because fewer than 50 percent of patients will respond favorably. Without knowing which patients will improve as a result of chemotherapy, physicians are generally reluctant to use a treatment that can cause their patients to suffer significant side effects.

"So, now we have to prove that it works to predict chemotherapy response in patients," deVere White said. To that end, UC Davis has entered into a partnership with Israel-based Rosetta Genomics to develop a microRNA profile for muscle-invasive bladder cancer that may be used to predict response to chemotherapy.

As part of the current study, deVere White and his colleagues studied 27 patients and found that many who expressed lower levels of miR-34a subsequently did not respond to the combined chemotherapy-surgery treatment. Because the finding was not statistically significant, however, further work in this area is needed.

The team also studied tumor samples taken from eight of the patients who did not respond to chemotherapy. They compared the expression of miR-34a before and after chemotherapy.

"We wanted to see, if you looked at the patient's tissue before chemotherapy, were there differentially expressed microRNAs in the patients who responded to the drugs versus those that didn't respond," deVere White explained.

The team found that expression of miR-34a increased after treatment in only two of the eight cases, suggesting that gene expression levels remained low during treatment and confirming the link between low gene expression and failure to respond to treatment.

"The combined data indicate that the elevation of miR-34a expression levels prior to chemotherapy would be of benefit to muscle-invasive bladder cancer patients, particularly in a setting of low mi-R-34a expression," the authors write.

Since their discovery in 1993, microRNAs have been found to be involved in a number of types of cancer, heart disease and diseases of the nervous system. In 2007, deVere White was part of a team that identified miR-125b, a gene that encodes for a microRNA that jump starts prostate cancer cell growth midway through the disease process, eventually causing it to become fatal.

The microRNA studied here was also recently found to play a role in medulloblastoma, an aggressive type of brain cancer. MicroRNAs, which are usually 22 to 33 nucleotides in length, are known as post-transcriptional regulators. That means they work by turning genes on or off during the part of the protein synthesis process that involves making a strand of RNA from a DNA template. The human genome encodes for an estimated 1,000 microRNAs.

According to the authors, future studies involving miR-34a will focus on testing its ability to increase sensitivity to chemotherapy and analysis of miR-34a expression in patients with muscle-invasive bladder cancer. With the currently low chemotherapy success rate and poor five-year survival rate for patients with this disease, "such studies are clearly warranted," the authors write.

"If we can prove what is causing chemotherapy resistance in patients with muscle-invasive bladder cancer, American ingenuity will come up with ways to overcome it," predicted deVere White.

Scripps Translational Science Institute joins Jackson Laboratory tumor consortium

Tue, 28 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The Scripps Translational Science Institute (STSI) of San Diego, Calif., has joined a national consortium of research institutions headed by The Jackson Laboratory (JAX) that is building a library of primary human tumors with the goal of developing highly targeted cancer therapies.

In its role as a consortium member, STSI will provide solid human tumor samples to JAX, which will graft them into mouse models for scientific study. STSI scientists will then have access to the models to conduct research on how to better understand and treat cancer, including the potential for tumor-specific therapies.

JAX will perform the initial genomic characterization of the tumors and will share this data with all participating institutions. STSI is a major research collaboration involving the nonprofit Scripps Health system and The Scripps Research Institute, both of San Diego.

JAX launched the Primary Human Tumor Consortium in 2009. Other participating institutions outside San Diego include the University of Florida, the Swedish Neuroscience Institute in Seattle and UC Davis Cancer Center.

Mouse models that can accept newly resected human tumors offer a highly productive way to develop and test cancer treatments. Mouse models of virtually any kind of cancer can be developed, providing a more individualized approach to finding new treatments.

This approach stands in stark contrast to the standard way of discovering new therapies for cancer, which relies on the use of tumor cell lines. The tumor cell-line approach can be problematic, since genetic mutations naturally occur as those cells divide and reproduce. Consequently, the cells may drift into a different genetic profile and any treatments designed to target the original tumor won't work. Also, the cell-line approach provides insights into which therapies are ineffective, but doesn't predictably prove which ones are effective.

By joining this consortium, Scripps will contribute to and share in a tumor library that will vastly exceed what any institution could build on its own, said Nicholas J. Schork, Ph.D., director of bioinformatics and biostatistics at STSI. This shared resource ultimately will greatly expand research capacity for all consortium members, with the goal of accelerating drug development for individualized approaches to each type of tumor.

Located at The Jackson Laboratory's JAX--West facility in Sacramento, Calif., the Primary Human Tumor Consortium seeks additional health care and research partners to speed the development of this tumor library resource. To date, the consortium has engrafted 172 tumors, with tumor sites including prostate, pancreas, lung, kidney, colon, breast, brain and bladder.

The biomedical research community needs a common, readily accessible resource to support this vital effort, said JAX Executive Vice President and Chief Operating Officer Chuck Hewett, Ph.D. No single cancer center has a sufficiently broad patient population to meet this need, so we must work together.

New research provides breakthrough in understanding common cancer

Wed, 08 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from the University of Sheffield have discovered valuable insight into how people develop B-cell lymphoma, one of the most common cancers in the UK.

The team, from the University's Institute for Cancer Studies and funded by Leukaemia and Lymphoma Research, Biotechnology and Biological Sciences Research Council (BBSRC) and Yorkshire Cancer Research, found that a mechanism different to that previously thought to be the cause of lymphoma may be responsible for the development of the disease.

Lymphoma is a type of cancer that affects the blood, originating in the lymph glands. B-cells are the immune cells in the human body that are responsible for producing antibodies to fight infections and provide long-term immunity. B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin's lymphomas.

Prior to this research, the main theory to explain the origins of lymphoma was the malfunction of a mechanism (somatic hypermutation) used by B-cells to modify the genes coding for antibodies. This mechanism is required to produce highly specific antibodies, but it also accidentally alters other genes, leading to lymphoma.

However, the team from the University knew that this theory only accounted for affecting a handful of genes, and the model could only explain certain types of lymphoma.

Led by Dr Thierry Nouspikel, the researchers discovered another mechanism, which potentially affects many more genes and can account for a wider palette of lymphomas. The research found that B-cells actually do not repair the bulk of their DNA and only take care of the few genes they are using. When the B-cells are inert in the blood flow, this is not a problem. However, when they receive a stimulation (e.g. an infection) they start to proliferate and then produce antibodies.

To proliferate they must replicate their DNA, and replication of damaged DNA results in the introduction of mutations, the accumulation of which can lead to lymphoma. Dr Nouspikel's team have designed a novel method to specifically detect such mutations, and have proved that they do occur in genes that have been implicated in lymphoma.

The researchers demonstrated that B-cells are deficient in one of the main DNA repair pathways, known as Nucleotide Excision Repair. This pathway repairs a lot of different DNA lesions, including UV-induced damage and chemical adducts (e.g. from air pollution and cigarette smoke). Their model therefore explains why strong UV exposure (e.g. unprotected sun bathing) is the number one environmental risk factor for lymphoma and also supports the evidence that exposure to air pollution and smoking are also risk factors.

Dr Nouspikel said: Lymphoma is one of the ten most frequent cancers in adults in the UK, and the third among children. If we want to come up with efficient strategies for prevention and therapy, it is crucial to understand what causes it. The novel mechanism we have discovered potentially accounts for the development of many different types of lymphoma. It may also explain why strong exposure to sunlight is the main environmental risk factor for this cancer.

Silencing 'hedgehog' molecule halts breast cancer

Mon, 06 Jun 2011 10:43:02 PST

( from http://www.rxpgnews.com ) Sydney, June 6 - Breast cancer cells are known to create the conditions for their own survival by communicating their needs to the healthy cells surrounding them.

Now researchers have identified a molecule known as 'hedgehog' that sits at the centre of the switchboard in breast cancer, transmitting biochemical signals between cancer cells and healthy cells.

When this chat is blocked, the hedgehog is 'silenced,' tumours shrink and stop their spread, the journal Cancer Research reports.

While the finding applies to all breast cancers, it is particularly relevant for women with basal breast cancer, - for which there is no current targeted therapy.

The good news is that drugs for silencing hedgehog are already undergoing Phase 2 clinical trials in other cancer types.

Clinical associate professor Sandra O'Toole and Alex Swarbrick, from Sydney's Garvan Institute of Medical Research, analysed breast tumour samples from a cohort of 279 women with advanced breast cancer revealing that the higher the level of hedgehog, the more aggressive the cancer.

Having discovered high levels of hedgehog in some breast cancer patients, they went on to over-produce the protein in mouse models of basal breast cancer, said a Garvan statement.

Mice developed tumours that grew and spread through the body rapidly. When hedgehog was blocked, the tumour growth and spread were significantly slowed.

'We are hopeful that our findings will drive the progress of clinical trials for anti-hedgehog drugs in breast cancer,' said Swarbrick.

Hormone test predicts ovarian function after chemotherapy for breast cancer

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A test that shows how many eggs a woman has in her ovaries may help young women with breast cancer know what their reproductive function will be after chemotherapy, a new study finds. The results will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Called the anti-Mullerian hormone (AMH) test, this blood test measures levels of an ovarian hormone that reflects the size of the ovarian reserve, or remaining egg supply. Currently, doctors use it to quantify a woman's ovarian reserve before in vitro fertilization treatments. Now researchers from Scotland have found that measurement of AMH indicates how likely it will be for a woman to still have eggs in her ovaries after chemotherapy, which can often damage a woman's eggs and cause infertility.

Future reproductive function is a concern for many young women with cancer, said lead investigator Richard Anderson, MD, PhD, professor of clinical reproductive science at the University of Edinburgh. This test will be of benefit to women with newly diagnosed cancer to help decide whether they need to take steps to preserve their fertility.

In the U.S. alone, breast cancer is diagnosed in more than 25,000 women younger than 45 each year, according to the American Cancer Society.

For this study, Anderson and his colleagues recruited 50 premenopausal women, ages 29 to 51, who had just received a diagnosis of early breast cancer. All women had normal menstrual cycles and were asked to keep a daily record of their menstrual cycle, as an index of ovarian activity, during the two years of the study. Before the women started chemotherapy, they gave blood samples for AMH testing. They again had AMH tests one and two years after starting treatment.

Before chemotherapy the median AMH level was 0.4 nanograms per milliliter (ng/mL). After cancer treatment the AMH level fell rapidly, becoming undetectable (below 0.16 ng/mL) in 68 percent of the women after one cycle of chemotherapy, the authors reported. By one-year follow-up, 11 women withdrew from the study, mostly because of cancer recurrence, Anderson said. Menstrual records were available for 39 women at one year and for 29 women at two years.

A low AMH measurement before treatment correlated well with amenorrhea, or absence of menstruation, after treatment. Women whose AMH before treatment was low (below 0.4 ng/mL) were 16 times likelier to have stopped menstruating after chemotherapy than women with a high pretreatment AMH value, Anderson said. The odds of losing ovarian function remained higher even after statistical analysis controlled for increasing age, which tends to lower AMH levels. Women whose AMH before chemotherapy exceeded 0.92 ng/mL were reportedly almost five times more likely to continue menstruating after treatment.

Our data suggest that the AMH test, taken before cancer treatment, can help individualize a woman's infertility risk after chemotherapy for breast cancer, Anderson said.

He added that results of this study, which was funded by the U.K. Medical Research Council, are likely to apply to other types of cancer as well.

Targeted cancer therapy kills prostate tumor cells

Sun, 05 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds. The results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer, said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones. This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

These patients are left with very few treatment options and usually succumb quickly to the disease, she said.

Ho's team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer. They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1. They also gave G-1 to noncastrated, or intact, male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration, Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitized prostate tumors to the cell growth-inhibiting effects of G-1.

These results mean G-1 won't work without androgen deprivation therapy, she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy. She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer. The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any side effects of estrogen, she said.

Virus associated with prostate cancer tumors and chronic fatigue syndrome unlikely to be the cause

Sat, 04 Jun 2011 17:56:09 PST

( from http://www.rxpgnews.com ) A study that includes authors at UC Davis has found that a retrovirus associated with prostate cancer tumors and chronic fatigue syndrome that evolved in laboratory mice less than two decades ago is unlikely to be widespread in humans and the cause of either disease.

The study of the retrovirus, xenotropic murine leukemia virus-related virus, or XMRV, appears online in the journal Science.

The study traces the lineage of the XMRV virus back through several generations of laboratory-cultured prostate cancer cells. The researchers found the virus to be virtually undetectable in the earliest tumors propagated in laboratory mice, but teeming in abundance after many such mouse passages. In the process, they establish that XMRV derives from two parent retroviruses present in the mice.

“For a retrovirus to cause cancer, almost every cancer cell should harbor the virus. When we found the virus was not in the early passages of the tumor cells, but plentiful in the later ones, it made us suspicious that XMRV was not the cause of the original tumor,” said study coauthor Hsing-Jien Kung, professor and deputy director of the UC Davis Cancer Center. Kung is an expert on retroviruses and the biology of prostate cancer cells.

The study is one of two that refute connections between XMRV and human disease that appear in the journal Science. The second study does not find XMRV in chronic fatigue syndrome patients, including many individuals found to be infected in an earlier survey.

In 2006, scientists reported finding XMRV in 27 percent of human prostate cancer tumors, and in 2009, in the blood of 67 percent of chronic fatigue syndrome patients. Because retroviruses are known to cause a number of human diseases, including AIDS and adult T-cell leukemia, these results made XMRV a potential source of both disorders. However, other studies failed to find a correlation between these diseases and the virus.

“We became interested in finding out whether this virus was really a factor in these diseases and how that came about,” said study coauthor Clifford Tepper, associate research biochemist in the Department of Biochemistry and Molecular Medicine.

Kung had worked with some of the first prostate cancer tumors to be transplanted into and propagated in laboratory mice, as well as with subsequent generations of these tumors, which had been made into cell lines. Such mouse passages are a common method of studying cancer treatments considered too experimental for human use. Kung and Tepper had many of these cells and tumors in their freezers, and kept meticulous records that allowed them to recreate the timeline for when various cell lines and tumor cultures were made.

For the study, the scientists compared viral loads in both early and later generations of these cells. They found that the first seven generations of passaged cells had one to three copies of XMRV-like sequence per 100 cells, while later passages had roughly 60 to 70 copies. More extreme, passaged cells that had been transformed into cell culture lines had on the order of 2,000 to 3,000 copies of viral genomes.

At the same time, two previously undescribed viruses in the mouse lines used to passage the prostate cancer tumors were identified. Both microbes were sequenced, and the two genomes placed side by side.

“When we put them next to each other, they fit together like a puzzle. We knew immediately that they had generated XMRV. It was one of those eureka moments that comes along only a few times in a career,” said study coauthor Vinay Pathak, head of the viral mutation section of the National Cancer Institute, who is a UC Davis alumnus.

The two viruses had shuffled their genetic data in a process called recombination to generate XMRV. A recombination event can be envisioned as a train traveling along parallel railroad tracks, switching back and forth at will between the two. The scientists calculated that six track shifts would have been necessary to generate the XMRV sequence.

The XMRV sequences found in the cell lines are virtually identical. This indicates they all developed recently from a single recombination event.

“If the virus were to be generated again in other instances, its genetic sequence should diverge. It’s unlikely to happen again and again with perfect sequence fidelity. The fact that the virus sequences are so similar is the main reason we suspect that what’s been reported has been due to contamination of laboratory equipment or reagents,” Kung said.

The researchers calculate that the odds of generating an identical XMRV sequence a second time are roughly 1.3 x 10-16 — vanishingly low.

Based on the dates that the cell passages occurred, “we knew it could only have been generated between 1993 and 1996. This virus is so new it could not possibly be in such a broad segment of the human population,” Kung said.

By discounting one potential source of prostate cancer and chronic fatigue syndrome, the study will help scientists focus their efforts on more viable origins for these diseases. “If you’re going to invest research dollars in studying a virus as a cause of a disease, you want to make sure it’s really there,” Tepper said.

“If you’re going to invest research dollars in a virus, you want to make sure it’s really there,” Tepper said.

The finding also speaks to the importance of avoiding laboratory contamination, the most likely cause of the associations between XMRV, prostate cancer and chronic fatigue syndrome.

“Contamination in the lab is a serious issue. Hopefully, when people look for evidence of new viruses in diseases of unknown origin they will take note of this work and rule out contamination before establishing an association between a virus and any human disease,” Pathak said.

Breast cancer surgery patients benefit from adding radiation therapy

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) (Hamilton, ON) June 4, 2011 - Additional radiation treatment improves disease free survival lessening the chance of cancer recurring in women with early breast cancer who have had breast conserving surgery (lumpectomy), interim results of a new study found. The results will be presented Monday, June 6 at the annual meeting of the American Society of Clinical Oncology.

These results are potentially practice-changing, said Dr. Timothy J. Whelan, professor of oncology at McMaster University's Michael G. DeGroote School of Medicine and lead study investigator for the NCIC Clinical Trials Group, which is funded by the Canadian Cancer Society.

In the study of more than 1,800 women with breast conserving surgery, participants received whole breast radiation (WBI) alone or WBI plus radiation to the surrounding lymph nodes called regional lymph node irradiation (RNI). Most of the women had one to three positive lymph nodes while 10 per cent had high-risk, node-negative breast cancer. All had been treated with breast-conserving surgery and adjuvant chemotherapy or endocrine therapy.

After a five-year follow-up, interim analysis of the data showed a greater than 30 per cent improvement in disease-free survival for those receiving RNI. This resulted from a 41 per cent lower rate of recurrences in the breast and lymph nodes and a 36 per cent lower rate of cancer recurrence in other parts of the body.

There was a low, but statistically significant, increased risk of moderate pneumonitis (lung inflammation) and lymphedema (excess lymphatic fluid) in the arm on the radiated side.

Whelan, division head of radiation oncology at McMaster and the Juravinski Cancer Centre and a Canada Research Chair, expects the results will encourage physicians to offer all women with node-positive disease the option of receiving regional nodal irradiation.

Adding regional nodal irradiation improved disease-free survival, lowered the risk of recurrences, and there was a positive trend toward improved overall survival, while not greatly increasing toxicities, he said.

For women with node positive breast cancer who are at high risk of recurrence of their breast cancer, these findings provide an important new treatment option, says Dr. Christine Williams, Director of Research, Canadian Cancer Society. Ultimately, this finding will help more women survive and thrive after treatment.

Treatment for women with node-positive breast cancer has been breast-conserving surgery plus axillary lymph node dissection, followed by radiation to the breast (WBI). If a woman's cancer is considered high-risk, such as a tumour larger than 5 cm or more than three positive axillary nodes, she often receives RNI. However, until now, the benefit of adding RNI for women with one to three positive nodes has been unclear.

Hormone deprivation therapy for prostate cancer may raise diabetes risk

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Men with prostate cancer are at higher risk of developing diabetes or diabetes risk factors if they receive androgen deprivation therapy (ADT) to block the production or action of male hormones that can fuel the growth of this cancer. The results of this new study on the second-most common cancer in men are being presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

These patients may benefit from counseling, screening and closer monitoring for the development of these complications, said the study's lead author, Maria Luisa Cecilia Rivera-Arkoncel, MD, a fellow at the Philippine General Hospital in Manila.

This study adds to the scientific evidence that ADT may increase the chance of diabetes. Sometimes called medical or surgical castration, ADT is a common treatment when prostate cancer has spread outside the prostate. It can be permanent by surgically removing both testicles (bilateral orchiectomy), or, more often, temporary by using medications, such as gonadotropin-releasing hormone (GnRH) agonists, to prevent the testes from making testosterone.

In their study, Rivera-Arkoncel and her colleagues compared 38 men with prostate cancer who received ADT and 36 men with less advanced prostate cancer who did not receive hormonal therapy. Men in the ADT group either underwent bilateral orchiectomy at least six months earlier or received six or more months of treatment with injections of GnRH agonists. Both groups received treatment at the Philippine General Hospital from 2004 to 2010. Although the average age of the two groups was not the same at the beginning of the study, the groups were similar in terms of other diabetes risk factors, Rivera-Arkoncel said.

Based on a review of medical records, the researchers identified patients with Type 2 diabetes or the metabolic syndrome. This syndrome is a cluster of metabolic risk factors that increase the chance of developing diabetes, heart disease and stroke. The criteria used for diagnosis include a large waistline plus two of the following: low HDL (good) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood sugar.

Men in the ADT group had a twofold increased probability of having diabetes after ADT, compared with the non-ADT group, Rivera-Arkoncel reported. According to the data, the prevalence of diabetes was 42 percent in the ADT group and 19 percent in the other group. In addition, the group receiving ADT had a higher prevalence of the metabolic syndrome than the non-ADT group did: 37 percent versus 28 percent, respectively.

An increased risk of diabetes with ADT has not previously been demonstrated in the Filipino population, which already has a high prevalence of diabetes, she said.

She cautioned, however, that their cross sectional analytical study suggests, but cannot prove, that ADT is the cause of the increased prevalence of diabetes in men who received this hormonal therapy.

Antifungal drug delays need for chemo in advanced prostate cancer

Thu, 02 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) The oral antifungal drug itraconazole, most commonly used to treat nail fungus, may keep prostate cancer from worsening and delay the need for chemotherapy in men with advanced disease. Details of the finding, from a clinical trial led by Johns Hopkins experts, are scheduled for presentation on Saturday, June 4 at the 2011 American Society of Clinical Oncology (ASCO) annual meeting (abstract #4532).

Currently, the drug is approved to treat fungal infections in nails and other organs. Serious side effects can include heart failure, and Johns Hopkins experts caution that itraconazole needs further study before it can be considered for prostate cancer treatment.

Identified as a potential anticancer drug after Hopkins scientists scoured a database of more than 3,000 FDA-approved drugs, itraconazole appears to block tumor blood vessel growth -- the only drug in its class to do so -- much like the anticancer drug bevacizumab (Avastin). The antifungal also disrupts a key cancer-initiating biological pathway called Hedgehog. Laboratory testing by Johns Hopkins scientist Jun Liu, Ph.D., has shown that human prostate tumors implanted in mice shrink when treated with itraconazole.

The most effective therapy we have right now for metastatic prostate cancer is hormone therapy, and when it doesn't work, the next step is usually chemotherapy, says Emmanuel Antonarakis, M.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. In a search for compounds that could put off chemotherapy, the Johns Hopkins team turned to itraconazole.

For the study, patients with prostate cancer that had spread to other organs and did not respond to hormone therapy were randomly assigned to receive low or high doses of itraconazole.

Over 24 weeks of daily treatment with oral itraconazole, the investigators tracked the length of time for each patient's prostate cancer to worsen (called progression-free survival). Evidence of worsening disease was measured by a 25 percent increase in their blood level of prostate specific antigen (PSA), a marker for prostate cancer.

Early in the trial, preliminary analysis of 17 men receiving low doses of itraconazole showed that only two of them (11.8 percent) had stable or declining PSA. Because of the limited response, no further men were given low doses of the drug.

However, 11 of 24 (48.4 percent) men taking high doses of itraconazole had stable or declining PSA levels lasting at least 24 weeks. In addition, nearly a third of men taking the high dose had PSA reductions of 30 percent or more. Metastatic prostate cancer patients receiving no treatment typically would worsen in eight to 12 weeks, according to Antonarakis.

The investigators also found that 12 of 14 men taking high doses of itraconazole had lower levels of circulating tumor cells present in their blood after therapy, compared with their baseline levels.

Seven patients experienced side effects, including low potassium, hypertension and fluid retention, but the problems were resolved with potassium replacement pills, anti-hypertension drugs, and diuretics.

We also tested whether itraconazole acted as hormone therapy by tracking levels of testosterone and DHEA (a testosterone derivative) in the blood, and we found no reductions of either testosterone or DHEA, says Antonarakis. This finding shows that itraconazole is not just another hormone therapy, and has a unique mechanism of action.

Antonarakis and colleagues next plan to examine blood and skin samples taken from study participants specifically to look for levels of proteins linked to tumor blood vessel formation and the Hedgehog pathway.

With these results, we believe that high-dose itraconazole is worth studying in a larger group of men with advanced prostate cancer, adds Antonarakis.

UBC researchers to lead $4.7-million study on early-stage oral cancer

Fri, 27 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from the University of British Columbia's Faculties of Medicine, Science and Dentistry are leading a $4.7-million pan-Canadian clinical trial aimed at improving outcomes for patients undergoing surgery for oral squamous cell cancers.

Funded by the Terry Fox Research Institute, the Canadian Optically Guided Approach for Oral Lesions Surgical Trial, or COOLS Study, involves universities and hospitals in nine Canadian cities. Findings from the study could revolutionize clinical practice here and around the world.

According to the Canadian Cancer Society, an estimated 3,400 Canadians are diagnosed with oral cancer every year. In 2010, the estimated number of deaths due to oral cancer was 1,150. Currently, about 30 per cent of patients who receive oral surgery have their cancer recur. The COOLS Study will investigate the effectiveness of a fluorescence visualization, or blue light, to distinguish between healthy tissues from tumours or pre-cancerous cells in the mouth. Under the blue light, normal tissue generates a fluorescence which is absent in tumour or pre-cancerous tissue.

In work we've conducted to date in Vancouver, there has been almost no recurrence where surgery followed the contour of the lesion shown by using FV-guided surgery. Working together with surgeons, pathologists, research staff and scientists, this TFRI-funded study will enable us to test the approach on a broader cohort of patients at sites across the country and obtain the evidence required to change current practice. says principal investigator Dr. Catherine Poh, a senior scientist with BC Cancer Agency, an associate professor at the UBC Faculty of Dentistry and a consulting dentist at Vancouver General Hospital.

Our surgical community has expressed great interest in participating in this trial which provides an unique and important opportunity to assess a surgical intervention in a controlled prospective manner across many sites, says principal investigator Dr. Scott Durham, head of the division of otolaryngology at Vancouver General Hospital and a clinical professor at UBC's Faculty of Medicine. The study aims to build a network of clinicians, pathologists and research staff across the country to fight oral cancer.

This study will have an immediate impact on practice if the study turns out the way we hope, says principal Investigator Dr. Miriam Rosin, a senior scientist with the BC Cancer Agency who holds joint appointments at UBC and Simon Fraser University. If the study is successful, it will help to reduce the number of deaths from oral cancer as well as to improve the quality of life for people living with this disease. Working with scientists, we will have this new approach ready to disseminate to the surgical community at large and even globally.

The study's lead investigators also include Calum Macaulay, a clinical associate professor at the UBC Faculty of Medicine and an associate member in Medical Physics in the UBC Faculty of Science; and Stuart Peacock, an associate professor at UBC's School of Population and Public Health in the Faculty of Medicine.

Investigational drug, RI-BPI, in combination with the drug Gleevec, effective against acute lymphoblastic leukemia

Tue, 24 May 2011 17:25:05 PST

( from http://www.rxpgnews.com ) In a significant breakthrough, investigators at Weill Cornell Medical College and the University of California, San Francisco, have been able to overcome resistance of a form of leukemia to targeted therapy, demonstrating complete eradication of the cancer in cell and animal studies.

Their study, published in the May 19 issue of Nature, shows that an investigational drug, RI-BPI, developed at Weill Cornell, in combination with the drug Gleevec shut down stem cells responsible for about one-third of acute lymphoblastic leukemia (ALL), a cancer of white blood cells that affects young children as well as older adults.

This form of ALL has the so-called Philadelphia chromosome, which is also found in chronic myelogenous leukemia (CML). But while Gleevec has greatly improved survival in CML, it has had a less dramatic effect in ALL, and most patients still die within a relatively short timeframe.

That desperate prognosis may radically change given these results, says co-senior investigator Dr. Ari Melnick, associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College, and a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"I am surprised, and extremely glad, to see that RI-BPI has such strong activity in a leukemia. This opens up the possibility that the agent will have similar beneficial effects in other tumor types," says Dr. Melnick.

Dr. Melnick and his colleagues developed RI-BPI and they have shown its potent effects in non-Hodgkin's lymphoma (NHL) with no toxicity to normal cells. The drug targets the transcription factor BCL6, a master regulator of hundreds of genes that provides strong growth signals to NHL cells.

The new study demonstrated that BCL6 is also active in ALL driven by the Philadelphia chromosome (Ph+ ALL), and that a combination of RI-BPI and Gleevec virtually shuts the cancer down, says Dr. Melnick. After a long search for the source of Gleevec resistance in this form of ALL by the team at the University of California, San Francisco (UCSF), it appears that BCL6 is the fundamental mediator of that resistance, he explains. "This gives us an opportunity to target Gleevec resistance, something that has the potential to substantially improve outcomes for patients with this disease."

The UCSF research team discovered that production of BCL6 is turned on after administration of Gleevec in Ph+ ALL. UCSF investigators then initiated collaborative research with Dr. Melnick, who provided RI-BPI and conducted experiments on how BCL6 regulates genes in leukemia cells.

The UCSF team also conducted animal tests and discovered that BCL6 hits the stem cells that give rise to ALL. "These stem cells continually repopulate disease cells by making copies of themselves," Dr. Melnick says. "We believe RI-BPI counteracts the BCL6 gene regulatory program that these stem cells need to survive.

"BCL6 turns off the brakes that normally limit cancer growth, which is why Gleevec does not work in this cancer, but RI-BPI puts those brakes back on," he says.

The study also suggests that transcription factors like BCL6 may be less impervious than once thought to targeted treatment, Dr. Melnick says. BCL6 is a protein, and it "mediates its cancer-causing actions by attaching to other proteins. Traditionally, however, protein-protein interactions have been viewed as being too difficult to block with small-molecule drugs."

Although it has yet to be tested in refractory CML -- CML that has become resistant to Gleevec, which occurs in most patients over time -- it makes sense that RI-BPI could restore Gleevec sensitivity, Dr. Melnick adds.

"From this study and from the others in my lab, I have become very impressed with how reliant tumor cells are on certain proteins for their survival," he says. "If we can hit several of these brittle and dependent processes, we have the chance to eradicate cancer."

Based on this study, a clinical trial is being developed to treat children with Ph+ ALL with a combination of RI-BPI.

Ensuring the safety of radiation therapy

Thu, 19 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) NEW HYDE PARK, NY -- Radiation oncologists took a blow in a series of front-page newspaper stories published last year on injuries that occurred nationwide in the delivery of radiation treatment. Radiation oncologists at North Shore-LIJ Health System responded to the public charge with a series of steps that will ensure that patients are protected at all points in the treatment process.

Louis Potters, MD, North Shore-LIJ's chairman of radiation medicine, and his colleagues designed a new program that seeks to improve the quality of complex processes by identifying and removing the causes of errors, and reducing variables that increase the risk of mistakes. North Shore-LIJ has literally adjusted for complex technical challenges in the hardware and software that delivers the radiation by ensuring that nothing is rushed.

Patients do not get on the table until every step is accounted for. We want to ensure that our patients are safe, said Dr. Potters, who presented the pilot program recently at the American Radium Society Annual Meeting.

Just imagine all the tasks that must be in place before a patient enters the surgical suite, which is a one-time event. Planning for radiation therapy that is delivered daily for weeks requires the efforts of many caregivers, with coordinated handoffs of complex information. It is important that this happens in an aligned and controlled way, and not rushed. The safety program is specifically designed to decrease the risk of errors due to last-minute, and hurried work.

Understanding the risk for error, Dr. Potters identified all the applications that go into delivering the therapy and then set out to use the clinic as a laboratory to understand the processes. He and his colleagues basically mapped the process every step of the way. The research was necessary to identify the appropriate processes of care, break it down into the eight key components of care and make sure every step is in place before the patient arrives for treatment, Dr. Potters explained. He calls it the no-fly policy, because there will be no treatment unless every step is signed off on and ready to go. If everything is not completed on time, the appointment is pushed back.

The classic culture is not to make patients wait, Dr. Potters said. But it is more important to have all the stress points in the system running smoothly to ensure minimal risk for the patient.

Dr. Potters and his team looked at the treatment process for 520 cases in the last eight months and measured the time points to see whether the time-to-treat improved over the course of the study. And it did. We have created this program to help mitigate risk, said Dr. Potters. On average, 10 percent of patient appointments were pushed back. The department went from a culture of 'just in time' to that of 'proactive' recognition of a need to reschedule. And the number of stops, the times that an appointment had to be re-scheduled because a step in the process was not completed, also went down. During the first month of the study, they had 80 events stopped compared to 20 in the most recent month of the study.

With complex technologies, resource-compromised staff and pressures to hasten treatment, the use of this process seems to reduce patient safety risks, said Dr. Potters. And the patients are educated about the no-fly policy and are more confident that any changes made to the schedule are ultimately done to protect them.

North Shore-LIJ Radiation Medicine Department is the first in the nation to implement such a program for patient safety. We hope that by spreading the word of how to incorporate better safety processes that other radiation oncology departments will develop similar approaches to enhance cancer care, said Dr. Potters.

New treatment regimen shows clinical benefit in advanced colon cancer

Wed, 18 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Washington, D.C. -- A new treatment regimen for patients with metastatic colon cancer appears to offer clinical benefit even when used after multiple other treatments have failed, say research physicians at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center.

The research team found that combining a PARP inhibitor with chemotherapy (temozolomide) offers significant benefit in patients who had no further treatment options. However, the study is small, and does not include a comparison arm, so further investigation is needed, they add. The study will be presented in an oral session on Saturday, June 4th, at the 2011 annual meeting of the American Society of Clinical Oncology in Chicago.

PARP, short for poly (ADP-ribose) polymerase is a key part of a cell's DNA repair apparatus, and is important for protecting our normal cells against DNA damage. However, cancer cells become resistant to chemotherapy in part by increasing PARP expression and thus rapidly repairing DNA damage intentionally caused by chemotherapy. PARP inhibitors are designed to overcome a cancer cell's ability to repair the damaged DNA. (They are showing promise in both breast and ovarian cancers, and are being studied in a variety of other cancer types).

In this clinical study, doctors administered a potent DNA-damaging chemotherapy, temozolomide, with a PARP inhibitor called ABT-888. The theory is that ABT-888 will diminish the ability of these cancer cells to fix the damage that was just inflicted by the temozolomide, pushing the cancer into a death spiral.

This is a classic one-two punch: the chemotherapy damages the cancer cells and the PARP inhibitor prevents it from fixing itself, leaving the cell to die, says lead author, Michael Pishvaian, M.D., Ph.D., an assistant professor at Georgetown Lombardi.

This single-arm, phase II study enrolled 49 patients with metastatic disease who were not eligible for surgery and had exhausted all of the standard therapies currently used. Despite having advanced cancer, all study participants were still active at work or home. Researchers found the drug combination controlled cancer growth for nearly six months in 23 percent of the patients, with two patients having a significant reduction in their tumor burden (partial response).

Pishvaian explains, The treatment was extremely well tolerated, so to have a period of six months with no tumor growth, but also no significant side effects was really meaningful for the patients.

In addition, researchers were able to collect samples of the patients' tumors for further molecular analysis. By testing tissue samples and identifying their molecular fingerprints, perhaps we can identify which patient subgroups are most likely to respond to this new therapeutic combination, concludes Pishvaian.

UCLA cancer researcher wins prestigious Gold Medal from the American College of Radiology

Wed, 11 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Dr. Lawrence W. Bassett, a nationally renowned expert with more than 35 years experience in breast imaging, has been chosen to receive the Gold Medal by the American College of Radiology (ACR), the organization's highest honor given for distinguished and extraordinary service in the field of radiology.

The award will be presented to Bassett May 15 at the annual national ACR conference in Washington, D.C.

I'm very proud to be recognized by my peers for my contributions to breast imaging and radiology, Bassett said. Receiving this award is an incredible honor for a radiologist.

Bassett is the Iris Cantor Professor of Breast Imaging in the Department of Radiological Sciences and a long-time Jonsson Cancer Center scientist. He serves as director for breast imaging at UCLA, a position he has held since 1976. He also served as director of the Radiology Residency Training Program at UCLA from 1978 to 1983 and from 1985 to 1990, and has been assistant dean for Student Affairs in the David Geffen School of Medicine at UCLA since 1985. Bassett has been vice chair for Academic Affairs in the radiology department since 2006.

Judith C. Gasson, director of the Jonsson Cancer Center and a professor of medicine and biological chemistry, congratulated Bassett for his achievement.

It's a real honor to receive this award as it's recognition for a life's work in radiology, Gasson said. We at the cancer center are proud to have Dr. Bassett among our members.

Bassett focuses his research on breast cancer screening and improving the quality of mammography and other breast imaging technologies on the national level. With collaborators, Bassett is working to address the national shortage of breast imaging specialists by training breast imaging fellows using a year-to-year grant from the Avon Foundation. To date, his team has trained 78 breast imaging fellows across the country in a fellowship program that has been recognized as the first in the United States.

In the ACR Bulletin announcing his award, Bassett was lauded for dedicating his life's work to breast imaging, as advances in that field are among radiology's most significant achievements. When the ACR's Committee on Breast Imaging was formed in 1983, Bassett was among the founding members and later served as chairman. Since then, he has served as chair of numerous national committees addressing the problems and issues concerning breast cancer detection and appropriate management of patients with breast symptoms and abnormal screening mammograms.Dr. Carl J. D'Orsi, director of breast imaging research at the Emory University School of Medicine in Atlanta, characterized Bassett's work to train breast imaging fellows as a legacy for breast imaging and radiology in his letter nominating him for the award.

Bassett earned his bachelor's degree in 1964 from the University of Southern California, where he attended on a four-year scholarship. He received his medical degree from the University of California, Irvine, did his internship at Northwestern University and his radiology residency at UCLA. From 1969 to 1970, Bassett served as a captain and battalion surgeon for the 1st Division of the United States Marines in An Hoa, Viet Nam. From 1970 to 1971, Bassett was a lieutenant and chief medical officer for the United States Navy in Oakland, Calif.

New test could give SLE patients a more tolerable life

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) At present, it can take up to a year before a patient is diagnosed with SLE. This is because the symptoms are diffuse and are often mistaken for other diseases. However, with this blood-based test, it is possible to determine quickly whether someone has the disease or not, says Christer Wingren, associate professor in Immunotechnology at CREATE Health, Lund University.

The test can also determine how far the disease has progressed. There are three different variants of SLE, and all require different treatment. With current methods, it is often difficult to find out which variant a patient has, which makes it difficult for doctors to prescribe the right medication. A third advantage of the new technique is that it also makes it possible to predict when the disease will become active.

Characteristic of SLE is that the disease goes in waves, or flares. Without warning, the disease can flare up and put the patient out of action for a long time. With our test, we hope to be able to predict when an episode is about to happen and in this way prevent it using the right medication, explains Christer Wingren.

If all goes well, hospitals could start using the technique in two to three years.

The test itself comprises a small chip, smaller than a little fingernail, on which the researchers create a grid pattern, known as an array, using specially selected antibodies. The antibodies serve as 'capture molecules'; by placing a drop of blood on the chip, the antibodies bind the proteins, or biomarkers, in the body. In this way, a unique 'fingerprint' is produced for each patient, which reflects the disease.

In our article, we show which pattern of biomarkers (the 'fingerprint') to look for. From a technical point of view, we get a large number of data signals that say whether the marker is present and in what quantity. These measurements are then entered into a computer, which can present them to the doctors in a way that is easy to understand. It is this fingerprint which doctors could use in the future in clinical practice, explains Christer Wingren, who has spent most of the past decade developing the technique, and the past two years adapting it for SLE in particular.

According to Christer Wingren, a number of researchers around the world have attempted to develop something similar, but without success. The Lund researchers' success in the task is partly due to them having found a way to make the antibodies stable and thus more functional. The method has also become highly sensitive.

In order for the research to benefit patients, a number of key biomarker signatures, which form the basis for the test, have been patented. The findings have also been transferred to a newly started company, Immunovia, which was founded by Christer Wingren and three of his colleagues at the Department of Immunotechnology.

The research has its origins in the cancer research that Christer Wingren and a number of other researchers at the translational cancer centre CREATE Health work on. Together with Carl Borrebaeck, Dr Wingren uses an equivalent technological platform that can detect and diagnose different types of cancer. They have very promising data for predicting breast cancer recurrence and diagnosing pancreatic cancer.

Mayo Clinic finds robotic surgery effective for removing hard-to-reach throat cancer

Fri, 29 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- Robotic surgery has become a mainstream tool for removing an ever-increasing variety of head and neck tumors. Now, a team of head and neck surgeons from Mayo Clinic has found robotic surgery can treat cancer in the narrow, hard-to-reach area beyond the tongue at the top of the voice box. Some patients were able to avoid further treatment with chemotherapy or radiation, and most could resume normal eating and speaking.

We've known it's useful for tongue base and tonsil cancers, but we wanted to assess its effectiveness in the larynx, says Kerry Olsen, M.D., Mayo Clinic otolaryngologist and senior author of the study that was presented April 29 at the Combined Otolaryngological Spring Meetings in Chicago.

The investigation of transoral robotic surgery (TORS) followed nine patients for up to three years following removal of supraglottic squamous cell carcinoma, which affects the area of the larynx above the vocal cords. Most of the patients had advanced-stage disease. The results showed TORS effectively removed cancer, with clean, disease-free margins, and was easier to perform than the approach of transoral laser microsurgery via a laryngoscope. The patients also underwent the surgical removal of their adjacent neck nodes at the same operation.

We were pleased with the cancer outcomes, Dr. Olsen says. We also found patients had minimal trouble after surgery, in most cases resuming normal eating, swallowing and speaking.

With TORS, the robotic arms that enter the mouth include a thin camera, an arm with a cautery or laser, and an arm with a gripping tool to retract and grasp tissue. The surgeon sits at a console, controlling the instruments and viewing the three-dimensional surgical field on a screen. The camera improves visibility, Dr. Olsen says. We also gain the ability to maneuver and see around corners and into tight spaces, and we believe we'll now be able to take out more throat tumors than with traditional approaches of the past.

The new application of TORS comes at the right time, Dr. Olsen notes. Cancers of the tongue and throat are on the rise. Not all patients will be candidates for robotic surgery; its use will depend on the architecture of a patient's throat and neck, along with the type and extent of the tumor. What we know from this study is that for larynx cancer, we have another effective surgical tool available to us, he says. We can further tailor the cancer treatment for each patient and provide individualized care.

Health-care alliance for tobacco dependence treatment launches training in the Middle East

Tue, 26 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- Global Bridges, a healthcare alliance for tobacco dependence treatment based at Mayo Clinic, and its regional partner, King Hussein Cancer Center (KHCC) in Amman, Jordan, announced today that they will start training health care providers in the Eastern Mediterranean Region (EMRO) on how to successfully treat tobacco users.

The first training, scheduled for April 27-28 at KHCC, will engage 15 health care professionals from Jordan. Feras Hawari, M.D., director of the Cancer Control Office at KHCC and regional director for Global Bridges, will conduct this workshop. In addition, KHCC will collaborate with other regional and international organizations to hold a four-day regional workshop in June.

Prevalence of tobacco use is high in most of the Eastern Mediterranean countries, and only a few countries have structured tobacco dependence services. By offering training, we are making a step towards addressing this epidemic, says Dr. Hawari, who is also chief of pulmonary and critical care service at KHCC.

Global Bridges -- a collaboration among Mayo Clinic's School for Continuous Professional Development and Mayo Clinic's Nicotine Dependence Center, the American Cancer Society and the University of Arizona -- was established in 2010 as a worldwide, science-based initiative to help health care providers unite to treat tobacco use and dependence while advocating for effective tobacco control policies. During its first year, Global Bridges has positively impacted 400,000 patients around the world through training over 5,400 health care providers in Mayo Clinic-led sessions on how to deliver culturally appropriate tobacco dependence treatment.

Global Bridges adapts to regional needs and enhances access to proven treatment methods throughout each of the World Health Organization's (WHO) six regions, says Richard Hurt, M.D., founder and director of the Mayo Clinic Nicotine Dependence Center and principal investigator of Global Bridges. The training that Dr. Hawari will lead is the first in a series of activities we are planning for WHO's Eastern Mediterranean region with our regional partner, King Hussein Cancer Center.

As a Global Bridges regional director, Dr. Hawari and his team will lead activities to grow the network and advance tobacco dependence treatment and tobacco control policies across the WHO Eastern Mediterranean Region that covers 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates and Yemen.

King Hussein Cancer Center is a dedicated medical center that focuses on providing state-of-the-art comprehensive cancer care in Jordan and the Middle East. KHCC is disease-specific accredited by the Joint Commission, making it the first in the region and the sixth worldwide.

KHCC has been a strong advocate for tobacco control in Jordan. KHCC is the first hospital in Jordan to declare its campus 100 percent smoke-free. The tobacco dependence treatment program was established in 2008 under the leadership of Dr. Hawari, and was then incorporated under the umbrella of the Cancer Control Office (CCO) established in 2010.

Prevalence of tobacco use is high in most EMRO countries. The Tobacco Atlas shows rates for men ranging from 82 percent in Afghanistan to 13.4 percent in Oman. For women, rates range from 57.1 percent in Lebanon to less than 1 percent in Oman. Among youngsters, WHO reports that between 1 in 3 and 1 in 4 boys smoke in EMRO countries. In Jordan, prevalence is at 28 percent among adults but is as high as 48 percent among adult males. Thirty-five percent of boys between 13 and 15 years are smokers, and prevalence among girls is on the rise.

Acupuncture helps with side effects of prostate cancer treatment

Fri, 22 Apr 2011 05:21:58 PST

( from http://www.rxpgnews.com ) Acupuncture provides long-lasting relief to hot flashes, heart palpitations and anxiety due to side effects of the hormone given to counteract testosterone, the hormone that induces prostate cancer, according to a study published in the April issue of the International Journal of Radiation Oncology•Biology•Physics, an official journal of the American Society for Radiation Oncology (ASTRO).

The main treatments for men with metastatic prostate cancer are either surgery or hormone therapy to significantly reduce the level of testosterone in the body. Eliminating testosterone has been proven to keep the cancer in check by starving the cancer of hormones it needs to grow and spread. However, about half of the time, this therapy also causes very uncomfortable hot flashes similar to those women experience during menopause. The main way to combat hot flashes is to take antidepressants, but these drugs can cause side effects of their own, including nausea, dry mouth, sleeplessness, altered appetite and sexual changes.

In a prospective study conducted in the department of radiation oncology and the acupuncture section of New York Methodist Hospital and Weill Cornell Medical College of Cornell University, both in New York, researchers evaluated 14 men who were experiencing hot flashes due to hormone therapy for prostate cancer. Upon enrolling in the study, the men were given a hot flash score (HFS) to evaluate their discomfort from daily hot flashes. The mean initial HFS was 28.3.

Participants then received acupuncture twice a week for 30 minutes at a time for four weeks. Two weeks after receiving acupuncture, their HFS was measured again and had dropped more than half to 10.3. At six weeks post-treatment, their HFS was 7.5. After eight months, the men were evaluated again and their mean HFS was 7. "Our study shows that physicians and patients have an additional treatment for something that affects many men undergoing prostate cancer treatment and actually has long-term benefits, as opposed to more side effects," Hani Ashamalla, M.D., lead author of the study and a radiation oncologist at New York Methodist Hospital, said. "We are now designing a randomized clinical trial to further evaluate acupuncture after prostate cancer treatment. I encourage men suffering this symptom to talk to their doctors about enrolling."

Cancer typifies unmoored instability: Pulitzer winner

Tue, 19 Apr 2011 19:33:02 PST

( from http://www.rxpgnews.com ) Cancer is often described as a 'modern' illness because its metaphors are so modern. It is a disease of overproduction, of fulminant growth tipped into the abyss of no control, says Pulitzer Prize winning writer and oncologist Siddhartha Mukherjee in his book, 'The Emperor of Maladies: A Biography of Cancer'.

'The notion of cancer as an affliction that belongs paradigmatically to the 20th century is reminiscent, as Susan Sontag argued so powerfully in her book, 'Illness as Metaphor', of another disease once considered emblematic of another era: Tuberculosis in the 19th century,' Mukherjee compares.

'Both drain vitality, both stretch out the encounter with death, in both cases 'dying', even more than death, defines the illness,' Mukherjee says.

According to the specialist, 'cancer is an expansionist disease'.

It invades the tissue; 'sets up colonies in hostile landscapes, seeking sanctuary in one organ and then migrating to another.

'It lives dangerously, inventively, fiercely, territorially, cannily, and defensively - at times as if teaching us how to survive. To confront cancer is to confront another species, one perhaps more adapted to survive then even we are,' Mukherjee says.

In writing this book, he started off by imagining the project as a 'history' of cancer.

'But it felt inescapably as if I were not writing about something but about someone. My subject daily morphed into something that resembled an individual - an enigmatic, if somewhat deranged, image in a mirror. This was not so much a medical history of an illness, but something more personal, more visceral in biography,' he writes.

To begin with, every biographer must confront the birth of his subject, the writer says. 'Where was cancer born?' 'How old is cancer?'

In 1862, Edwin Smith, part scholar and part huckster, antique forger and Egyptologist, bought - a 15-foot-long papyrus from an antique seller in Luxor in Egypt.

'The papyrus was in dreadful condition, still crumbling, yellow pages filled with cursive Egyptian writing. It is now thought to have been written in the 17th century BC, a transcription of a manuscript dating back to 2500 BC,' Mukherjee says.

Translated in 1930, the papyrus was thought to contain the collected teachings of Imhotep, a great Egyptian physician who lived around 2625 BC. The physician listed 48 cases of illnesses found during his time.

'Describing case forty-three, Imhotep advises, 'if you examine having bulging masses on breast; if you place your hand upon breast and find them to be cool, there being no fever, they have no granulations, contain no fluid, yet they feel protuberant to your touch, you should say -: This is a case of bulging masses I have to contend with',' Mukherjee says in his book.

Imhotep was referring to breast tumours.

And under the section therapy, he offered only a single sentence: 'There is none.'

Mukherjee says: 'In 500 BC, Persian Queen Atossa self-prescribes the most primitive form of mastectomy - which was performed by her Greek slave.'

Atossa's disease and her war against it serves as the cornerstone for cancer research over the centuries - evolving with time.

The book is divided into seven chapters.

In the summer of 2003, after having completed his residency in medicine and graduate work in cancer immunology, Mukherjee began an advanced training in cancer medicine at the Dana Faber Institute and Massachusetts General Hospital in Boston.

'I had initially envisioned writing a journal of that year - a view from the trenches of cancer treatment. But the quest soon grew into a large exploratory journey that carried me into the depths not only of science and medicine, but of culture, history, literature and politics - into cancer's past and its future,' the writer says.

The book, published in India by Harper-Collins, is priced at Rs.499.

Loss of cell adhesion protein drives esophageal and oral cancers in mice

Tue, 12 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) PHILADELPHIA - Squamous cell cancers of the oral cavity and esophagus are common throughout the world, with over 650,000 cases of oral cancer each year and esophageal cancer representing the sixth most common cause of cancer death in men. Research by University of Pennsylvania School of Medicine investigators has shown that a protein that helps cells stick together is frequently absent or out of place in these cancers, but it's unclear if its loss causes the tumors.

The investigators report that mice engineered to lack this protein, called p120-catenin (p120ctn), in the oral-upper digestive tract develop squamous cell cancers. The data, reported Cancer Cell, settle a 20-year debate and prove that p120ctn is a tumor-suppressor protein. What's more, the tumors that form in this mouse model closely resemble human disease and may point the way to novel therapies and early detection strategies.

As the mice aged, what we saw was a dramatic evolution of precancer to cancer, says senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and Genetics and chief of Gastroenterology. Both the precancerous growth, called dysplasia, and the cancer look exactly like what we see in humans. This is really exciting because it supports efforts for prevention and early detection, especially in people who drink alcohol and smoke cigarettes excessively and are at high risk for the disease in many regions of the world.

In healthy tissues, p120ctn is part of a protein complex that holds epithelial cells in tightly packed sheets. When p120ctn (or another of these cell adhesion proteins) is lost, a wide variety of cancers including those in prostate, breast, pancreas, colon, skin, bladder, and the endometrium, can result.

The cells lose their tight cell-cell contacts and can migrate more easily, which likely favors cancer spread and invasion of new cells. However, earlier attempts to test the effects of p120ctn loss on cancer formation were derailed because the animals cannot survive throughout embryonic development or immediately after birth without the protein.

To get around that problem, Rustgi and colleagues used a system called Cre-Lox that allows them to remove a particular gene in only a subset of tissues. In this case, the team deleted p120ctn from the oral cavity, esophagus and forestomach. The mutant animals survived through early development and birth, but by 4 to 6 months, most of the mutant animals had developed precancerous lesions and by 9 to 12 months, 70 percent of the mutant animals had full blown tumors. By contrast, none of the control littermates developed cancer.

The investigators noted that as the lesions developed, the tumor cells secreted inflammatory signals that acted like homing signals for immune cells called immature myeloid cells. These cells, in turn, helped to create a microenvironment that supported tumor growth. In fact, when the researchers blocked recruitment of the immune cells, they saw a dramatic reduction in tumor invasion.

Based on these observations, Rustgi thinks that targeting the immature myeloid cells may reverse or slow tumor grown in humans, although more work needs to be done in animal models before the approach is tested in the clinic.

Rustgi says that the mouse model will help test innovative therapies and early detection tests. He says that although he was born and raised in the United States, he was influenced by five years he spent as a child in India, where oral cancer is common due to the proportion of the population that chews betel nuts. I remember, even as a little kid, I would see people with oral lesions, he says. I didn't know what they were then, but it has always motivated me at a personal level. Esophageal cancer biology has also been a long-standing interest of mine because it affects so many underserved people in the inner cities in the United States.

Possible new approach to treating deadly leukemia in babies

Tue, 12 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) MAYWOOD, Ill. -- A Loyola University Health System study points to a promising new approach to treating an aggressive and usually fatal leukemia in babies.

The study involved a type of leukemia called mixed lineage leukemia, or MLL. Only 25 to 50 percent of babies diagnosed with MLL leukemia survive the disease.

The study demonstrated how it may be possible to kill cancerous MLL cells by targeting a protein called DOT1. Researchers showed that, without the DOT1 protein, cancerous MLL cells died, said Charles Hemenway, MD, PhD, senior author of the study.

We are focusing on the unique biology of MLL leukemia, Hemenway said.

The study was presented at the 2011 meeting of the American Association for Cancer Research.

Between 5 and 10 percent of all leukemias are MLL positive. In children older than 1 who have MLL leukemia, the survival rate is about 75 percent. By comparison, the survival rate for most other childhood leukemias is about 90 percent. Adults who have MLL leukemia also have lower survival rates than adults with other types of leukemia.

MLL is a subtype of leukemia caused by a mutation in a gene called MLL. The mutated gene codes for an abnormal MLL protein, which turns a blood cell into a cancer cell. For reasons researchers don't understand, MLL leukemia is more resistant to chemotherapy than other forms of leukemia.

In previous studies, Loyola researchers developed a small molecule, called PFWT, that binds to the MLL protein. This binding effectively disables the MLL protein, leading to the death of the cancer cell. Later this year, Hemenway plans to begin testing PFWT molecules on mice that have MLL leukemia.

The new study points to a second possible way to attack MLL cells, by targeting the DOT1 protein. DOT1 works in conjunction with the MLL protein. The study demonstrated that DOT1 is critical for keeping cancer MLL cancer cells alive.

Researchers cultured MLL cells from mice. From these cells, researchers removed the gene that codes for the DOT1 protein. Without the gene, the cell no longer produced the DOT1 protein, and without the DOT1 protein, the cancerous cells died.

Loyola researchers are collaborating with researchers from Nemours/Alfred I. duPont Hospital for Children to identify molecules that could disable DOT1.

Hemenway said a double-barrel approach -- targeting both the DOT1 and MLL proteins --potentially could be a more effective treatment than current chemotherapy, with fewer side effects. But it will take years of additional research and testing before such a treatment would be available for patients.

Hemenway said several other Loyola researchers are studying MLL leukemia. There are a lot of opportunities for collaboration, he said.

Thalidomide may help as adjuvant therapy for hepatocellular carcinoma

Sat, 02 Apr 2011 17:57:25 PST

( from http://www.rxpgnews.com ) Thalidomide has shown potential to be used as the first adjuvant therapy for hepatocellular carcinoma (HCC), according to data presented at the International Liver Congress 2011.

A new study found thalidomide gave HCC patients who had undergone grossly curative resection surgical removal of the cancerous part of the liver double the two-year disease free survival rate (65%) compared to placebo (33%).

However, the study did find that the two-year overall survival rate was comparable between patients treated with thalidomide and patients given placebo – 84.2% and 85.7% respectively.

Daniele Prati, EASL's Scientific Committee Member and Press Committee Chairman, commented: "Current options for adjuvant therapy in HCC are very limited and clinical trial results have been disappointing. Thalidomide has already been proven to work well in a number of other areas and this study shows it could potentially benefit HCC patients who are particularly difficult to treat. Overall, it is important to continue research in evaluating adjuvant therapy in HCC."

Surgery is the main form of treatment for HCC, but is only possible for a small proportion of those afflicted. Even after curative resection, recurrence is common and is the main cause of death. Adjuvant therapy that is, chemotherapy after surgery – is thus attempted to try to improve outcomes.

The study is promising because there is currently no adjuvant therapy for HCC patients following curative resection.

Indeed, the most up-to-date Cochrane Review of adjuvant therapies for HCC (conducted prior to this thalidomide study) found insufficient evidence to show that previously investigated adjuvant therapies increased survival for HCC, and only limited evidence to suggest that adjuvant therapy was useful in disease-free survival.

In the double-blind, placebo controlled, randomized, comparative phase-II study, 42 patients were given 200mg per day oral dose of thalidomide (Arm A, 21 patients) or 200mg per day oral dose of placebo (Arm B, 21 patients). Patients started treatment within 6 weeks of complete tumor resection and carried on treatment for 12 months, or until they encountered disease recurrence, intolerably toxicity, or withdrew consent. Overall, thalidomide showed a good tolerability profile.

Thalidomide is currently approved by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) in the US for the treatment of multiple myeloma (a cancer of the bone marrow).

Attacking bowel cancer on 2 fronts

Wed, 30 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Stem cells in the intestine, which when they mutate can lead to bowel cancers, might also be grown into transplant tissues to combat the effects of those same cancers, the UK National Stem Cell Network (UKNSCN) annual science meeting will hear today.

Professor Nick Barker of the Institute of Medical Biology in Singapore will explain how he and his team identified that the stem cells which are crucial to maintaining a healthy intestine are also the site at which bowel cancers first begin, and how he also hopes to use healthy stem cells to regenerate tissues to help patients with Crohn's disease and some cancers.

Having discovered a gene that is only turned on in these particular stem cells Professor Barker and his team have been able to isolate the cells in mice and grow small pieces of intestine in the lab. The researchers hope that if they are able to grow larger pieces, they will be able to produce transplant tissues to replace damaged intestines.

Professor Barker explains: Processing our dinner every day is a tough job so the lining of our intestines quickly get worn out. To keep the intestine working stem cells in little pockets along the surface replace the lining, cell by cell, about once a week.

We already knew these stem cells existed for a while we didn't know much about them because it was difficult to distinguish them from all of the other types of cells in our intestines. Our team was able to single them out and study them because we discovered a gene that is only turned on in these particular stem cells.

Once the researchers had found this gene they were able to track where the stem cells occur throughout the body finding that, as well as the intestine, the stomach lining and in hair follicles, the cells were also present in bowel tumours.

Professor Barker continues: We hope that studying these stem cells will be doubly useful: One day we hope to grow large enough pieces in the lab to form replacement tissues for transplant; and by studying the cells we will be able to find new ways to prevent them from mutating and hence leading to cancer.

Bowel cancer is the third most common type of cancer in England and an estimated 38,000 new cases are diagnosed each year. We know these stem cells are both implicated in causing the cancer but that they also could be useful for treating disease so we hope that studying them will help us to understand how to attack the disease on two fronts.

UAB research targets way to stop brain tumor cell invasion

Tue, 29 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala., - Gliomas are brain invaders. A kind of malignant tumor cell, gliomas branch out like tendrils from a central tumor source, spreading cancer throughout the brain. Traditional therapies, such as cutting out the tumor surgically, can be ineffective if the cells have already spread. Researchers at the University of Alabama at Birmingham may have come upon a way to stop a glioma invasion in its tracks, using a drug already approved for use in Europe.

Much like early explorers of the Old West followed rivers and streams, depending on them to provide drinking water and food, gliomas spread through the brain by following the path of blood vessels, tapping into those vessels for the nutrients they need to survive. Cut that glioma off from the blood supply, and it starves.

An explorer lost in the wilderness without food and water soon succumbs and dies, said Harald Sontheimer, Ph.D., director of the UAB Center for Glial Biology in Medicine and senior author on the paper. A glioma that can't find and tap into a blood vessel will also die.

In a paper published March 30, 2011 in the Journal of Neuroscience, Sontheimer and co-author Vedrana Montana, Ph.D., discovered that bradykinin, a peptide that increases the size of blood vessels, is the mechanism glioma cells use to find blood vessels. Glioma cells carry a receptor for bradykinin, called the B2R receptor. Using that receptor to attract bradykinin gives the cell a navigator to lead it to blood vessels. Block the receptor from interacting with bradykinin and the cell will end up lost in the wilderness.

The researchers introduced a B2R inhibitor known as HOE 140, a laboratory version of a drug approved for use in Europe for hereditary angioedema called Icatibant. HOE 140 bound to the B2R receptor on glioma cells, interfering with the receptor's opportunity to bind to bradykinin. The results were impressive.

We found that 77 percent of glioma cells with bradykinin were able to locate a blood vessel and tap into its nutrients, said Montana. However, when we blocked the B2R receptors from interacting with bradykinin, only 19 percent of glioma cells were able to find a blood vessel.

The researchers used human glioma cells transplanted into a mouse model and, using time-lapse techniques on a laser-scanning microscope, tracked the ability of the cells to navigate to blood vessels by means of fluorescent markers attached to the cells.

Targeting the B2R receptors is an elegant and so far unexplored approach to treat gliomas, one of the most devastating types of brain tumor, said Sontheimer. Icatibant, which is already in use in Europe, and its ability to block B2R receptors may prove to be very promising target for further investigation.