RxPG News : Cancer

SDSC joins other UC San Diego departments, LLNL in oncology collaboration

Sun, 31 Jan 2010 04:59:12 PST

( from http://www.rxpgnews.com ) Researchers from the San Diego Supercomputer Center (SDSC) at UC San Diego have joined forces with the Department of Radiation Oncology in the university's School of Medicine, its Department of Mathematics, and the Lawrence Livermore National Laboratory (LLNL) in a three-year, $1.5 million project to pursue novel applications of high-performance computing (HPC) in radiotherapy.

Under the project, called SCORE for SuperComputing Online Re-planning Environment,SDSC researchers are collaborating with oncology researchers to redesign treatment plans leveraging HPC resources and expertise. The project was awarded from a University of California Office of the President grant based on the Lab Fees Research Program in 2009.

The ultimate goal of the proposed HPC-based radiation therapy, specifically referred to as 'Adaptive Radiation Therapy (ART) Based on High-Performance Computing,' is to deliver a prescribed radiation dose to targets containing tumors and cancerous regions, while sparing surrounding functional organs and normal tissues. Currently, these regions are treated using a so-called optimal treatment plan that is based on patient geometry acquired via imaging prior to commencement of a sequence of 25 to 40 daily treatments administered during a time span of five and eight weeks.

This current treatment paradigm therefore implicitly assumes that the patient is static and ignores the fact that tumor and nearby organs are mobile and distensible, so that their position and shape may vary substantially from day to day, and that there is significant dynamic change in tumor geometry in response to the radiotherapy, said Steve Jiang, associate professor and executive director for the Center for Advanced Radiotherapy Technologies (CART), the research arm of the Department of Radiation and Oncology at UC San Diego's School of Medicine, and director of the SCORE project. As a result, the quality of the current treatment plans may deteriorate during their course.

The biggest challenge for the proposed HPC-based radiation therapy is the real-time requirement of performing three computationally intensive tasks: patient modeling based on deformable image registration, radiation transport simulation and dose calculation using Monte Carlo methods, and treatment optimization as a large scale optimization problem.

Traditional HPC platforms, due to the difficulty in availability to general clinical users and real-time accessibility, are not suitable for real-time re-planning treatment while the patient is lying under the treatment machine waiting for radiation treatment, said Amit Majumdar, head of the Scientific Computing Applications Group at SDSC, and a newly named associate professor in the Department of Radiation Oncology at UC San Diego's School of Medicine.

In the first phase of the project, the research group is exploring the use of graphics processing units (GPUs) as the parallel computing framework for real-time re-planning. Many of the algorithms and codes have been modified and implemented efficiently on GPUs. To date, this work has resulted in three peer-reviewed journal papers for CART, and additional submissions are under review.

The team's work is already receiving attention from the field of cancer therapy. We now can perform a re-planning procedure within 10 seconds, while the current state of the art takes dozens of minutes, said Jiang. Our work shows that online adaptive radiotherapy is possible, and that it has much promise as the next generation of technology for cancer radiotherapy, with great potential to improve local tumor control and reduce toxicities by adapting the treatment to the varying patient anatomy.

The research group is also focusing on developing a comprehensive prototype hardware and software environment integrating GPUs, radiotherapy codes, and clinically efficient graphical user interfaces (GUI) that medical professionals can use in a real clinical environment for patient treatment. Initially, this will be used for patient treatment in a research environment with potential for full clinical implementation in the near future.

Case Western Reserve receives $2.8 million to further breast cancer research

Wed, 27 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Case Western Reserve University School of Medicine has been awarded six Department of Defense (DOD) Congressionally Directed Medical Research Programs (CDMRP) grants for innovative medical research. The grants, totaling nearly $2.8 million, will advance research in the field of breast cancer.

Case Western Reserve School of Medicine investigators received three postdoctoral awards and three Idea Awards. The three postdoctoral awards were granted to Steven Sizemore, Ph.D., to further his research of FoxC1 in basal-type breast cancer; to Melissa Shelton, Ph.D., and her study of LM04 and estrogen responsiveness; and to Nirmala Krishnamurthy, Ph.D., for her research on the role of estrogen receptor beta and hPMC2 in breast cancer.

The School of Medicine faculty members receiving Idea Awards include Mark Jackson, Ph.D., for his analysis of FAM83D, a novel oncogene in breast cancer; M. Edward Medof, M.D., Ph.D., for his study of the augmentation of antitumor T-Cell responses by increasing APC T-Cell C5a/C3a-C5aR interactions; and to Ruth Keri, Ph.D., for her study of p120ctn and breast cancer metastasis.

Through the efforts of these six investigators, Case Western Reserve University School of Medicine is now developing a body of high-level scientists in breast cancer research. The Idea Awards are highly competitive and these dollars represent one of the biggest investments Case Western Reserve has made in breast cancer research, says Stanton L. Gerson, M.D., Professor of Medicine and Director of the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine. Dr. Gerson is a practicing oncologist and Director of the Ireland Cancer Center at University Hospitals.

Since its inception in 1992, Congress has allocated nearly $5 billion through Fiscal Year 2009 across all research programs, including breast cancer. The CDMRP programs consist of awards given to extramural investigators that are selected through a two-tier external peer-review process that includes scientists, clinicians, and consumer advocates. The U.S. Army, on behalf of the DOD, administers a set of biomedical research programs that support basic, translational, and clinical research projects; research training; and research infrastructure for specific diseases identified by Congress.

In 1992, a highly visible lobbying campaign by grassroots advocacy organizations increased awareness among policymakers of the need to expand funding for breast cancer research. These consumer groups emphasized the need to fund research in ways that were different from those employed by traditional medical research organizations such as the National Institutes of Health. In response, the United States Congress allocated specific funds for breast cancer research in the DOD appropriations budget. The DOD was chosen because of its long history in performing medical research studies and because its administrative structure was designed for flexible and quick responses to changing needs and priorities. The success of this effort has resulted in an increase in the number of disease research programs for which Congress has mandated funding through the DOD.

Texas invests $4.5 million in cancer research at UT Health Science Center at Houston

Tue, 26 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Texas plans to invest $3 billion in cancer research over the next 10 years and six scientists at The University of Texas Health Science Center at Houston are among the first to receive grants.

The researchers, whose grants total $4.5 million, are working to protect girls from cervical cancer, to interrupt tumor growth at the molecular level and to develop a new approach for the treatment of colon cancer, among other cutting-edge projects.

Texas voters approved a constitutional amendment in 2007 establishing the Cancer Prevention and Research Institute of Texas (CPRIT) and authorizing the state to issue $3 billion in bonds to fund groundbreaking cancer research and prevention programs and services in Texas. Cancer is the second leading cause of death in Texas and claimed an estimated 37,000 lives in 2009, the Texas Cancer Registry reports.

UT Health Science Center at Houston researchers, along with their colleagues at other University of Texas System institutions, received more than half of the $61 million awarded during the initial round of funding through CPRIT.

We are delighted that our Health Science Center investigators have participated with their colleagues from around the state in this new program to address the prevention and cure of cancer in Texas, said Peter Davies, M.D., Ph.D., executive vice president for research and interim executive vice president for academic affairs at the Health Science Center.

We are particularly pleased with the success of several of these investigators in obtaining substantial research awards from CPRIT. We look forward to having these awards serve as a foundation for additional Heath Science Center research programs that will expand our research in the area of cancer cure and cancer prevention, Davies said.

Sixty-six research projects were selected from nearly 900 research proposals submitted to the institute. Proposals were reviewed by a team of more than 100 scientific experts. CPRIT-funded research will be conducted in state by Texas-based scientists.

John Hancock, Ph.D., chairman of the Department of Integrative Biology and Pharmacology at The University of Texas Medical School at Houston, received a $1,401,529 award for his research into how the growth signals received by cells are scrambled in cancer cells leading to uncontrolled growth. Hancock is a holder of the Fondren Chair in Cellular Signaling at the UT Medical School at Houston.

One major cause of this problem relates to a protein called Ras, which normally functions as a reversible switch that is toggled on and off. In many cancers, including colon, pancreas and lung, the Ras switch becomes stuck in the on position, which drives the cancer cell to replicate itself indefinitely, Hancock said. His CPRIT project is focused on developing drugs that will address this.

Novel personalized medicine trial launched for metastatic colorectal cancer

Fri, 15 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) FAIRFAX, Va. -- Imagine if treatments for disease could be based not on a patient's diagnosis but instead on the characteristics of their tissue. By identifying and decoding the cryptic messages hidden deep inside the human proteome, scientists and physicians who study personalized medicine are seeking more effective treatments and disease management for patients.

Lance Liotta, MD, and Emanuel Petricoin, III, professors of life sciences and co-directors of George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM), are pioneers in the field of patient-tailored research and personalized medicine. The two are studying biomarkers (or indicators of disease in tissue and bodily fluids) related to cancer, heart disease, liver disease and obesity.

They recently launched a unique clinical trial in partnership with oncologists and co-principal investigators Kirstin Edmiston, MD, medical director of cancer services at Inova Health System, and Alexander I. Spira, MD, director of Fairfax Northern Virginia Hematology Oncology Research Program, to treat patients with late-stage colorectal cancer, a fatal cancer that starts in either the colon or the rectum.

The three-year trial will accommodate up to 50 men and women who have late-stage colorectal cancer that has spread to the liver. Striking more than 150,000 men and women each year in the United States, colorectal cancer is the nation's third most commonly diagnosed cancer and third leading cause of cancer death according to the American Cancer Society.

Traditionally, all colon cancers have been lumped together and given similar treatments. The novelty about this is that we can, in a very minimally invasive way, start to treat the metastatic tumor based on its unique protein makeup. If we're going to be successful in treating the metastatic disease, which is what kills people, then we need to focus on using therapies targeted towards the individuality of a patient's disease state. This clinical trial is the first step toward doing that, says Edmiston.

Trial participants will be treated with standard metastatic colon cancer therapy and will test the addition of Gleevec, a medicine that is typically prescribed for certain forms of leukemia and gastrointestinal tumors. Gleevec targets disease pathways in tumor cells that previous CAPMM research revealed were among those found in typically fatal liver metastasis in colorectal cancer patients.

Because the primary tumors in the colon are removed in most colorectal cancer patients as soon as they are diagnosed, this study will focus on treating the often fatal secondary tumors or metastatic lesions that appear when the disease spreads to the liver, causing death through destruction of that organ.

Using a new drug target mapping technology called reverse phase protein microarray that was developed by CAPMM's scientists, the researchers will sample these lesions and create a unique molecular profile or fingerprint that shows which protein pathways or drug targets are activated in the lesion. This process will allow the researchers to determine whether specific drugs such as Gleevec might be an effective treatment for this particular patient before it is even administered.

By monitoring the drug target activity in trial participants' tumors and basing their treatment on those characteristics, the researchers are hopeful that this clinical trial will lead to more effective and individualized treatment for patients who suffer from this devastating disease.

The exciting aspect of this trial is that an established drug is being considered for a new indication, and that's one of the promises of personalized therapy--that a patient's molecular portrait would be considered as the rationale for choice of therapy rather than based on the site or the kind of cancer alone, says Petricoin. Until now, the most cutting edge clinical trials utilize genomic profiling of the tumor to select patients. This is the first trial that uses a direct proteomic approach that maps the drug target activation networks that are in use in each patient's tumor--just technologically being able to do this in a real clinical trial is a first.

Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer

Tue, 05 Jan 2010 13:56:42 PST

( from http://www.rxpgnews.com ) 'Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature' is the title of an article by P-A. Abrahamsson in the January issue of European Urology, the official journal of the European Association of Urology. The author evaluates available evidence regarding the efficacy and tolerability of intermittent androgen deprivation (IAD) and assess its value in the treatment of prostate cancer (PCa).

Prostate cancer (PCa) is the second most common male cancer worldwide and the most frequently occurring in Europe (20.3% of the total in 2006). Androgen-deprivation therapy (ADT) has progressed since 1941 when surgical castration was shown to improve PCa outcomes. The well-known side effect profile of ADT has significant quality-of-life implications such as sexual dysfunction, hot flushes, fatigue etc. Furthermore, it appears that androgen suppression causes a change in stem cells from an androgen-dependent to an androgen-independent phenotype. Because this progression to androgen independence is thought to begin early after treatment initiation, stopping androgen deprivation prior to this change occurring should restore apoptotic potential and help tumour cells remain sensitive to re-initiating treatment.

The strategy behind IAD, therefore, is to alternate androgen blockade with treatment cessation, allowing hormonal recovery between treatment periods, thus potentially improving tolerability and quality of life.

The author wishes to evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of PCa. Key phase 2/3 clinical trials of IAD in PCa published within the last 10 years were identified on Medline using different search terms.

The conclusions were that IAD seems to be as effective as continuous androgen deprivation while showing tolerability and quality of life advantages, especially recovery of sexual potency. IAD has been a treatment option for >20 years and the EAU considers that its status should no longer be regarded as investigational.

However, QoL data are surprisingly limited given that this, rather than survival, is the key driver for IAD and considering the length of time this approach has been under evaluation.

Based on available evidence and general clinical opinion, IAD is a valid treatment option in nonmetastatic PCa cases, i.e. patients with locally advanced disease with or without lymph node involvement and those experiencing relapse following curative treatment. These patients have a higher chance of survival than those with more advanced disease, making QoL a key consideration. Full results from phase 3 trials, which include both locally advanced and metastatic patients, will further clarify target populations.

IAD has come of age, and many clinicians believe it has earned its place in the management of PCa; however, there are still insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.

Acupuncture has added benefits in breast cancer patients

Wed, 30 Dec 2009 13:36:51 PST

( from http://www.rxpgnews.com ) Not only is acupuncture as effective as drug therapy at reducing hot flushes in breast cancer patients, it has the added benefit of potentially increasing a woman's sex drive and improving her sense of well-being, according to a Henry Ford Hospital study.

Study results show that acupuncture, when compared to drug therapy, has a longer-lasting effect on the reduction of hot flushes and night sweats for women receiving hormone therapy for breast cancer treatment. Women also report that acupuncture improves their energy and clarity of thought.

The study, published online this week in the Journal of Oncology, is the first randomly controlled trial to compare acupuncture and drug therapy in this way.

"Acupuncture offers patients a safe, effective and durable treatment option for hot flushes, something that affects the majority of breast cancer survivors. Compared to drug therapy, acupuncture actually has benefits, as opposed to more side effects," says study lead author Eleanor Walker, M.D., division director of breast services in the Department of Radiation Oncology at Henry Ford Hospital.

According to the National Cancer Institute, one in eight women will develop breast cancer in her lifetime. For these women, conventional medical treatment involves chemotherapy and five years of hormone therapy. With such a long course of treatment, side effects of hormone therapy such as vasomotor symptoms – hot flushes and night sweats – can become a major cause of decreased quality of life, and even discontinuation of treatment.

Venlafaxine (Effexor) has been the drug therapy of choice to manage these common and debilitating side effects associated with breast cancer treatment. Venlafixine, however, comes with its own set of side-effects: dry mouth, decreased appetite, nausea and constipation.

Since acupuncture has been shown to effectively reduce hot flushes in menopausal women, Dr. Walker and her research team decided to test the use of acupuncture to combat vasomotor symptoms in breast cancer patients as an alternative to drug therapy.

To compare the two options, 50 patients were recruited from oncology clinics at Henry Ford. Patients were randomly assigned to receive either acupuncture or venlafaxine treatment for 12 weeks. The drug therapy group took venlafaxine orally each night, 37.5mg the first week and then 75mg for the remaining 11 weeks. The other group received acupuncture treatments twice per week for the first four weeks, and then once a week for the remaining eight weeks.

At the end of 12 weeks, all patients stopped their therapy and were followed for one year. Patients kept a diary to record the number and severity of hot flushes, and took surveys to measure their overall health and mental health.

The study found that both groups initially experienced a 50 percent decline in hot flushes and depressive symptoms, indicating that acupuncture is as effective as drug therapy.

Differences, however, between the two groups began to emerge two weeks post-treatment: The acupuncture group continued to experience minimal hot flushes, while the drug therapy group had a significant increase in hot flashes. The acupuncture group did not experience an increase in the frequency of their hot flushes until three months post-treatment.

Inhibition of TNF-receptor associated protein-1possible treatment for prostatic cancer

Wed, 30 Dec 2009 13:28:05 PST

( from http://www.rxpgnews.com ) Current research suggests that TNF-receptor associated protein-1 (TRAP-1) may prevent cancer cell death. The related report by Leav et al, "Cytoprotective Mitochondrial Chaperone TRAP-1 as a Novel Molecular Target in Localized and Metastatic Prostate Cancer," appears in the January 2010 issue of the American Journal of Pathology.

Prostate cancer is the most common type of cancer and is the second leading cause of cancer deaths among men in the United States, following lung cancer. Prostate cancer most commonly develops in men over the age of 50 and is slow-growing; however, it may metastasize to other organs, particular to the bones and lymph nodes. Metastatic phase prostate cancer claims over 30,000 deaths per year in the United States alone.

Prostate cancer cells are often resistant to cell death. Researchers led by Dr. Dario C. Altieri of the University of Massachusetts Medical School, therefore, explored the role of TRAP-1, a protein thought to regulate cell death, in prostate cancer survival. TRAP-1 was highly expressed in both high-grade human prostate cancer lesions and mouse models of prostate cancer, but not in benign or normal prostate tissue. In addition, TRAP-1 overexpression in non-cancer prostate cells inhibited cell death, whereas TRAP-1-deficient prostate cancer cells had enhanced levels of cell death. Moreover, treatment with Gamitrinib, which inhibits TRAP-1, resulted in prostate cancer cell death, but not death of non-cancerous prostate cells. Therefore, targeting TRAP-1 via Gamitrinib treatment may be a viable therapeutic strategy for patients with advanced prostate cancer.

Leav et al suggest that "TRAP-1 [is] a novel marker of localized and metastatic prostate cancer, but not normal glands, required for prostate cancer cell viability, in vivo. Taken together with the preliminary safety of Gamitrinibs in preclinical studies, these data suggest that targeting mitochondrial TRAP-1 may provide a novel therapeutic approach for patients with advanced and metastatic prostate cancer" A similar approach may be also suitable for other types of cancer, as TRAP-1 is broadly expressed in disparate human malignancies. In future studies, Dr. Altieri and colleagues plan to "further dissect the biology of TRAP-1 cytoprotection in cancer cells, and test whether disabling its function may overcome drug resistance, the most common reason of treatment failure and dismal outcome in patients with advanced prostate cancer."

Chlorophyll limits the absorption of the carcinogen aflatoxin

Wed, 30 Dec 2009 12:52:05 PST

( from http://www.rxpgnews.com ) A new study has found that chlorophyll and its derivative chlorophyllin are effective in limiting the absorption of aflatoxin in humans. Aflatoxin is produced by a fungus that is a contaminant of grains including corn, peanuts and soybeans; it is known to cause liver cancer – and can work in concert with other health concerns, such as hepatitis.

Levels of aflatoxin are carefully regulated in the United States, but are often found in the food supplies of developing nations, especially those with poor storage facilities.

OSU scientist George Bailey, a distinguished professor of environmental and molecular toxicology, pioneered studies of aflatoxin in China, where he found that in one region, one out of every 10 adults died from liver cancer.

But what has the science world particularly intrigued with this follow-up study is the methodology used by the researchers – a new "Phase 0" approach that safely tests low levels of carcinogens in human volunteers to measure the total aflatoxin exposure and to determine the effect of dietary chlorophlls on reducing this exposure.

Results of the study were just published in the journal Cancer Prevention Research.

Bailey and several other researchers, including lead author Carole Jubert, were part of the recent study. The journal also included a perspective written by a pair of Johns Hopkins researchers – Thomas Kensler and John Groopman – who praise the methodology and suggest that these Phase 0 "microdosing" studies should be expanded.

They wrote: "…microdosing studies with carcinogens have the potential to provide important insights into chemopreventive interventions and to enhance the overall clinical development and safety evaluation of preventive agents."

The Phase 0 study "…may open the door for all kinds of new research," said Jubert, a former researcher in Bailey's lab at OSU's Linus Pauling Institute. Jubert now works for Life Microsystems, an OSU spinoff company that hopes to continue work with natural products grown in Oregon, including pure chlorophylls.

"The technology is not particularly difficult," she added. "It's just a novel approach to evaluate toxin exposure in humans."

In their study, Jubert and her colleagues gave very low doses of aflatoxin labeled with carbon-14 isotopes as a tracer to four human volunteers. They then gave the volunteers the same doses of aflatoxin along with doses of either chlorophyll or chlorophyllin, which previously had been shown to reduce carcinogen bioavailability in trout and rats. Using an accelerator mass spectrometer, they measured the rate of aflaxtoxin bioavailability. This technique is extremely sensitive, the researchers say, allowing measurement of minute amounts of any labeled compound.

Their research revealed rapid absorption of aflatoxin, which was significantly limited after the chlorophyll and chlorophyllin treatments.

"The beauty of this kind of 'Phase 0' study is the use of ultra-sensitive technology and 'microdoses' of environmental carcinogens to study toxicokinetics within the human body," said John Mata, an OSU pharmacologist and second author on the study. "These measurements can be important because they allow us to better design future studies to understand the effects of dietary constituents on cancer risk.

"In this case, clearly the results merit further study," Mata added. "We showed that aflatoxin is absorbed quite rapidly and that chlorophyll and chlorophyllin have an ameliorating effect, preventing the toxin from getting into the bloodstream. Further studies can more precisely explore the interactions, as well as dosage levels."

Jubert and Mata also have tested the feasibility of using similar technology on human exposure to other toxins, including smokers who ingest carcinogens through cigarette smoke.

Mata, a professor in OSU's College of Veterinary Medicine, is a pharmacologist who previously worked in the drug industry. He said Phase 1 studies are designed to see if a compound is safe; Phase 2 expands the scope of the project, and Phase 3 looks at the compounds' efficacy. Phase 0 represents a new concept – a way to measure the kinetics of a drug by using extremely small doses that pose little risk to the volunteers.

In this case, the amount of radiation given the human volunteers was equal to that you would encounter from a one-hour airplane ride; the level of aflatoxin administered was 1/30th the amount the Food and Drug Administration allows in a peanut butter sandwich.

Chicago Cancer Genome Project studies genetics of 1,000 tumors

Mon, 21 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) No two tumors are alike, but analyzing the genetics of cancers from different parts of the body may reveal surprising details useful for treatment and prevention.

That process is already gaining traction at the University of Chicago's Institute for Genomics and Systems Biology (IGSB), where researchers are one year into a three-year project to collect and analyze the genetic sequence and variations of every gene expressed by 1,000 tumors.

Over the past year, working closely with physicians, the IGSB team collected complete sequence data for genes expressed by 100 tumors--primarily breast cancer, head and neck cancer, and leukemia. Correlating genetic data with patient outcomes, they have begun to identify genetic patterns within tumors that may help them predict how a cancer will behave. Many experts believe such information will increasingly guide treatment.

The long-term goal, said IGSB Director Kevin White, James and Karen Frank Family Professor in human genetics and ecology and evolution, is to translate genomic discoveries into useful diagnostic tools and therapeutic strategies. This should improve patient care.

Not to be confused with the 1,000 Genomes Project--an international effort to sequence all of the DNA from 1,000 individuals selected from hundreds of distinct populations worldwide--the Chicago 1,000-cancer-genomes project is based entirely at the University of Chicago and tightly focused on the genetics of this common disease.

The Chicago Cancer Genome Project is aimed at teaching us how to use the genetic state of the cells as a guidepost for which treatments should be offered to specific patients, White said.

Cancer is a genetic disease. Each tumor's genes provide clues about the severity of the disease. They can sometimes predict whether a cancer will respond to specific treatments, develop resistance to radiation or chemotherapy, relapse after therapy, or spread to a distant site.

Many established cancer treatments grew out of genetic information, beginning at the University of Chicago with Elwood Jensen's discovery of the estrogen receptor in 1958, which led to the development of estrogen blockers such as tamoxifen, and Janet Rowley's descriptions of the first chromosomal translocations in 1972, work that led to the targeted therapy known as Glevec.

But the Chicago Cancer Genome Project is among the first efforts to combine a focus on the genes expressed by multiple cancers with broad scale, systematic implementation. During the pilot phase--sequencing expressed genes from the first 100 tumors--the team established and refined a project framework utilizing the latest in gene-sequencing technology and computational analysis.

We now know how to do this, said White. We have the basic structure in place. In the process, we have identified novel genes associated with clinical outcome in selected cancers.

The next steps are to determine how these altered genes act and expand the project to include more tumor types, including cancers of the bladder, lung, pancreas, prostate, as well as several childhood cancers such as rhabdosarcomas and neuroblastomas.

Analyzing a wide variety of tumors may reveal previously unknown genetic similarities in cancers typically classified as different according to tissue of origin, White said.

The genetics of cancer can be extraordinarily complex, said Michelle LeBeau, PhD, director of the University of Chicago Cancer Research Center. Kevin's team at the IGSB brings all the right tools, she said. They have the ability to collect and manipulate large amounts of genetic data, the capacity to study not just single genes but entire genetic pathways and their interactions, and a close working relationship with multiple teams of cancer specialists.

The Chicago approach differs from several large-scale cancer-genome efforts in progress. A year ago a team from Washington University published the first cancer genome, from a patient with leukemia. Since then, genomes for breast cancer, melanoma and lung cancer have appeared, and the National Cancer Institute is compiling its Cancer Genome Atlas.

Lung cancer and melanoma laid bare

Wed, 16 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Research teams led by the Wellcome Trust Sanger Institute announce the first comprehensive analyses of cancer genomes.

All cancers are caused by mutations in the DNA of cancer cells which are acquired during a person's lifetime. The studies, of a malignant melanoma and a lung cancer, reveal for the first time essentially all the mutations in the genomes of two cancers.

Lung cancer causes around one million deaths worldwide each year: almost all are associated with smoking. The number of mutations found suggest that a typical smoker would acquire one mutation for every 15 cigarettes smoked.

Although malignant melanoma comprises only 3% of skin cancer cases, it is the cause of three out of four skin cancer deaths. The melanoma genome contained more than 30,000 mutations that carried a record of how and when they occurred during the patient's life.

These are the two main cancers in the developed world for which we know the primary exposure, explains Professor Mike Stratton, from the Cancer Genome Project at the Wellcome Trust Sanger Institute. For lung cancer, it is cigarette smoke and for malignant melanoma it is exposure to sunlight. With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent.

We can also see the desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage from ultraviolet radiation. Our cells fight back furiously to repair the damage, but frequently lose that fight.

The studies used powerful new DNA sequencing technologies to decode completely the genome of both tumour tissue and normal tissue from a lung cancer and a malignant melanoma patient. By comparing the genome sequence from the cancer to the genome from healthy tissue they could pick up the changes specific to the cancer. The studies are the first to produce comprehensive genome-wide descriptions of all classes of mutation, producing rich accounts of the genetic changes in the development of the two cancers.

In the melanoma sample, we can see sunlight's signature writ large in the genome, says Dr Andy Futreal, from the Wellcome Trust Sanger Institute. However, with both samples, because we have produced essentially complete catalogues, we can see other, more mysterious processes acting on the DNA. Indeed, somewhere amongst the mutations we have found lurk those that drive the cells to become cancerous. Tracking them down will be our major challenge for the next few years.

The lung cancer genome contained more than 23,000 mutations, the melanoma more than 33,000. Identifying the causative mutations among the large number found poses a challenge, but the complete genome sequences mean, that for the first time, that challenge can be met.

Nearly ten years on, we are still reaping the benefit from the first human genome sequence and we have much still to do to get to grips with these new disrupted landscapes of cancer genomes, explains Dr Peter Campbell from the Wellcome Trust Sanger Institute. But the knowledge we extract over the next few years will have major implications for treatment. By identifying all the cancer genes we will be able to develop new drugs that target the specific mutated genes and work out which patients will benefit from these novel treatments.

A complete genome catalogue for each patient would be expected to help select between treatments and to direct treatment in the most efficient and cost-effective way. The Sanger Institute is already working with researchers at Massachusetts General Hospital on a large scale project to tie genetic changes in cancers to their responses to anticancer treatments.

We want to drive healthcare through better understanding of the biology of disease, says Sir Mark Walport, Director of the Wellcome Trust. Previous outcomes from our Cancer Genome Project are already being fed into clinical trials, and these remarkable new studies further emphasise the extraordinary scientific insights and benefits for patients that accrue from studying the genome of cancer cells.

This is the first glimpse of the future of cancer medicine, not only in the laboratory, but eventually in the clinic. The findings from today will feed into knowledge, methods and practice in patient care.

The human genome is large. Moreover, there are more than one hundred different types of cancer and sequencing genomes is expensive. To ensure that thousands of cancers ultimately are sequenced in the same way as these two, the International Cancer Genome Consortium has been established, on the model of the Human Genome project itself to coordinate cancer genome sequencing across the globe.

These catalogues of mutations across the broad diversity of cancer types will provide powerful insights into the biology of cancer and will be the foundation for understanding cancer causation and improving prevention, detection and treatment.

Nanoprobes hit targets in tumors, could lessen chemo side effects

Mon, 14 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) WEST LAFAYETTE, Ind. - Tiny nanoprobes have shown to be effective in delivering cancer drugs more directly to tumor cells - mitigating the damage to nearby healthy cells - and Purdue University research has shown that the nanoprobes are getting the drugs to right cellular compartments.

Professor Joseph Irudayaraj and graduate student Jiji Chen, both in the Department of Agricultural and Biological Engineering, have found that the nanoprobes, or nanorods, when coated with the breast cancer drug Herceptin, are reaching the endosomes of cells, mimicking the delivery of the drug on its own. Endosomes perform a sorting function to deliver drugs and other substances to the appropriate locations.

We have demonstrated the ability to track these nanoparticles in different cellular compartments of live cells and show where they collect quantitatively, said Irudayaraj, whose results were published early online in the journal ACS Nano. Our methods will allow us to calculate the quantities of a drug needed to treat a cancer cell because now we know how these nanoparticles are being distributed to different parts of the cell.

The nanoprobes, which are about 1,000 times smaller than the diameter of a human hair, are made from gold and magnetic particles. An MRI machine can track the magnetic portions of the nanoprobes while a more sensitive microscopy process can detect the gold.

The nanoprobes were inserted into live human tumor cells during laboratory testing. Using fluorescent markers to differentiate organelles, or sub-units of cells, Irudayaraj's group was able to determine the number of nanoprobes accumulating in the endosomes, lysosomes and membranes of those cells.

Cancer treatments often use high drug concentrations that damage healthy cells near a tumor. While Herceptin is attracted to and attaches to the proteins on the surface of breast cancer cells, healthy surrounding cells absorb some of the chemotherapy drugs through normal fluidic intake.

Irudayaraj said targeting only tumor cells with nanoprobes would require less drugs and mitigate the side effects of cancer chemotherapy drugs.

Each nanoparticle acts like a deliverer of a mail package, or dose, of the drug directly to the appropriate location, Irudayaraj said.

In Irudayaraj's laboratory tests, endosomes received a major portion of the nanorods containing Herceptin. Lysosomes, which act like garbage collection units in cells and hinder a drug's effectiveness, received a lower concentration of nanorods.

Irudayaraj said those percentages are similar to how cells distribute drugs through traditional treatments.

Irudayaraj will next try to attach multiple drugs to a nanoparticle and track their distribution within cells. He also wants to determine the timing of a drug's release from the nanoprobes after attaching to the tumor cells.

Novel detection method unmasks circulating breast cancer cells

Fri, 11 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) SAN ANTONIO - Circulating metastatic breast cancer cells can lose their epithelial receptors, a process that enables them to travel through the bloodstream undetected, according to research from The University of Texas M. D. Anderson Cancer Center.

The findings were presented today at the CTRC-AACR San Antonio Breast Cancer Symposium.

Levels of these circulating tumor cells (CTCs) - which are shed from a primary tumor or its metastases - have been used to monitor and tailor cancer therapy and to predict a patient's prognosis. CTCs that have undergone epithelial-mesenchymal transition (EMT), however, evade current detection methods and lose their traditional prognostic and therapeutic value. Those cancer cells also become more resistant to chemotherapy and radiation therapy. Finding a reliable method to detect these stealth breast cancer cells may reveal additional therapeutic targets that could help eradicate micrometastatic disease in patients with breast cancer or other epithelial tumors.

EMT and the Invasion-Metastasis Cascade

EMT is a process in which cancer cells undergo transdifferentiation (transformation into a different type of cell). The carcinoma cells activate a transdifferentiation program in order to acquire the ability to execute the multiple steps necessary for the invasion-metastasis cascade, said the study's first author Michal Mego, M.D., Ph.D., formerly a fellow at M. D. Anderson. During EMT, epithelial cells acquire a mesenchymal appearance with increased motility and invasiveness.

The researchers hypothesized that these changes render the EMT-CTCs undetectable by current detection assays, such as CellSearch (Veridex). The cells' acquired resistance to chemotherapy and radiotherapy also suggested that EMT-CTCs are tumor-initiating cells and are responsible for tumor dissemination. Moreover, the researchers had found subgroups of high-risk patients with brain metastases, triple receptor-negative disease, or inflammatory breast cancer whose blood tests did not reveal elevated levels of CTCs, further supporting their hypothesis.

Detecting CTCs Through EMT Gene Expression

The researchers then set out to develop a detection method that could identify EMT-CTCs in the peripheral blood of breast cancer patients. They took approximately 5 mL of peripheral blood from 27 patients ranging in age from 34 - 72 years, with a median age of 54. Sixteen of the women had metastatic disease, 19 had inflammatory breast cancer, and 12 had primary, non-inflammatory breast cancer.

Using magnetic beads coated with monoclonal antibodies capable of capturing the majority of hematopoietic cells in peripheral blood, we obtained a fraction of cells enriched for CTCs, said Mego, who is now a scientist at the National Cancer Institute in the Slovak Republic. Next we isolated RNA from these cells to detect genes that are involved in epithelial-mesenchymal transition, using molecular biology technology, such as the polymerase chain reaction.

Five EMT genes were identified: TWIST1, SNAIL1, SLUG, ZEB1, and FOXC2. At least one of these genes was over-expressed in 21 percent of the patients. Over-expression of EMT genes was more common among women with triple receptor-negative breast cancer than among those without this high-risk signature. The researchers found no correlation between EMT gene expression and CTC count as measured by CellSearch or the carcinoma-associated antigen known as Ep-CAM (epithelial cell adhesion molecule).

We found that current CTC detection methods underestimate the most important subpopulation of CTCs involved in tumor dissemination-those with tumor-initiating properties, said James Reuben, Ph.D., professor in M. D. Anderson's Department of Hematopathology, the study's senior author. A novel detection method such as ours that is capable of detecting CTCs after EMT could add important new prognostic information and could be useful for monitoring treatment efficacy in real time.

The M. D. Anderson and the Slovak National Cancer Institute teams have initiated a confirmatory study among patients with metastatic breast cancer, prostate cancer, or colon cancer. They also have initiated studies designed to identify therapeutic targets on EMT-CTCs. In addition to Mego and Reuben, other authors on the M. D. Anderson study include: Massimo Cristofanilli, M.D., Eleni Andreopoulou, M.D., and Summer Jackson, all of the Department of Breast Medical Oncology; Hui Gao, Ph.D. Changping Li, M.D., Sanda Tin, M.D. and Evan Cohen, all of the Department of Hematopathology; and Sendurai Mani, Ph.D., Department of Molecular Pathology.

A new mouse could help understand how some lung cancer cells evade drug treatment

Wed, 09 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Lung cancer is the leading cause of cancer mortality worldwide and lung adenocarcinoma is the most common type. Many cases of lung adenocarcinoma are attributed to a mutation in a gene for the epidermal growth factor receptor (EGFR). Lung cancer with changes in EGFR is initially treatable with a family of chemotherapeutic agents called tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, patients often develop resistance to these drugs through the acquisition of additional changes or secondary mutations that allow cancer cells to evade treatment.

Some secondary mutations to the EGFR gene that allow lung cancer cells to survive in the presence of current chemotherapy are known. These secondary changes are now the focus of targeted efforts to create drugs to specifically interfere with the mutated form of the protein. Unfortunately, in 40% of the cases in which patients become resistant to therapy, the molecular events that confer this resistance are not known. Without knowing the changes that sustain the survival of these cells it remains impossible to specifically and effectively target them with anti-cancer drugs.

Scientists now describe a mouse model of lung cancer that develops resistance to TKI drugs in at least some of the same ways that humans do. Lung cancer occurs in these mice due to a mutation in EGFR that is the same as the mutation that underlies many human lung adenocarcinomas. Some of the defined secondary changes to EGFR, which are known to confer drug resistance in humans, also occur in these mice. But most of these drug resistant mice bear tumors that do not contain known mutations. This important similarity to the human situation suggests that this mouse model might help identify the currently unknown mutations that make lung cancer cells resistant to therapy.

Many techniques are now available to unravel the genetic changes that occur in cancer cells. Since these mice recapitulate many of the known mutations that characterize human lung cancer, the hope is that their cells can be screened to identify the currently unknown mutations that promote drug resistance in lung cancer cells. This provides a model to uncover the molecular events responsible for the 40% of patients that become resistant to TKI therapy due to unknown causes. Once novel mechanisms of resistance are identified, these mice might also become valuable preclinical systems to evaluate the efficacy of therapeutics developed to combat drug-resistant disease.

Controversial kidney transplant technique could provide lifeline for very ill patients

Mon, 07 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Surgeons who successfully performed kidney transplants after removing small cancerous and benign masses from the donated organs, have published their results in the December issue of the urology journal BJUI.

The technique, carried out by US surgeons at the University of Maryland School of Medicine in Baltimore, could offer a vital lifeline to patients with end-stage renal disease as well as increasing the supply of viable organs.

Transplanting a living donor kidney which has been affected by a renal mass is controversial and considered a high risk says co-author Dr Michael W Phelan.However the ongoing shortage of organs from deceased donors, and the high risk of dying while waiting for a transplant, prompted five donors and recipients to push ahead with surgery after the small masses were found in the donor kidneys.

The five renal masses, which were discovered during routine donor evaluation, ranged from 1.0cm to 2.3cm in size. Cancerous cells were found in three of the five masses and the other two were benign.

The kidneys were removed from the donors, put on ice and taken to the recipients' operating rooms. Surgeons carefully removed the renal mass and a portion of the tissue near the mass was rushed through to pathology for confirmation that the tumour had been completed removed. The kidneys were then reconstructed and transplanted into the recipients.

One patient developed acute humoral rejection after surgery and was treated appropriately. There were no long-term problems in the transplanted kidneys and four of the patients were alive at the last follow-up, which ranged from nine to 41 months. The fifth died from an unrelated accident about a year after the transplant. None of the donors or recipients showed any evidence of recurring tumours.

The patients in the study ranged from 47 to 61 years of age, with an average age of 54, and the donors ranged from 38 to 72, with an average age of 38. Two of the five donor pairs were unrelated and three were genetically related. All the patients had end-stage renal disease, together with significant other illnesses, such as severe high blood pressure and complex heart problems.

Prior to the transplant, detailed discussions were carried out with each recipient and donor following the discovery of the renal masses in the donor kidney, so that they were both aware of the risks, including recurrence of the tumour.

The global increase in patients with end-stage renal disease highlights the importance of identifying novel means to increase the donor pool says Dr Phelan.

Although donor transplants using organs from deceased people have risen 16 per cent and living donor transplants have risen by 68 per cent, there continues to be a significant shortage and many patients die each year while waiting for a transplant.

The current study provides evidence to suggest that kidneys from donors with renal masses offer a minor, yet feasible, solution to the current organ shortage. These organs can be transplanted into recipients with limited life-expectancy on haemodialysis after careful removal of the renal mass. However, diligent follow-up of the donor and recipient is imperative in these cases.

Defibrotide improves response rate in patients with severe veno-occlusive disease of the liver

Mon, 07 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Defibrotide, a novel drug which modulates the response of blood vessels to injury, was markedly more effective than standard treatment in post-stem cell transplant patients with hepatic veno-occlusive disease, a life threatening toxicity of transplant caused by blockages in tiny blood vessels of the liver, according to a study led by Dana-Farber Cancer Institute scientists.

A phase III trial being reported at the American Society of Hematology's (ASH) annual meeting on Monday, Dec. 7 (Abstract 654, Ernest N. Morial Convention Center, Room 353-355, 5:45 p.m. CT), showed that 24 percent of patients had complete responses to defibrotide, compared to 9 percent of historical controls, referring to a rigorously analyzed group of patients with this syndrome, previously treated with best supportive care, which is the current standard approach to this often fatal syndrome.

There was a highly significant improvement in the complete response rate using defibrotide, and this translates into an encouraging trend for improved survival, said Dana-Farber's Paul Richardson, MD, first author of the study that involved patients at 35 medical centers across the United States, Canada and Israel. The mortality rate 100 days after transplant was reduced to 62 percent for patients receiving defibrotide, compared with 75 percent in the control patients who did not get the drug.

Veno-occlusive disease (VOD) is an important complication of stem-cell transplants in cancer patients. Obstructions from clots and debris in the very small vessels of the liver cause the organ to swell, leading to an excessive accumulation of bilirubin (a breakdown product of red blood cells), progressive jaundice, fluid retention, kidney failure and respiratory failure (so called multiple organ failure, or MOF), and death.

Defibrotide, derived from porcine tissue, is a polydeoxyribonucleotide that modulates damage to the lining of blood vessels when given orally or by injection. Previous studies showed that defibrotide could reverse VOD and MOF and was effective in preventing these complications in both adults and children undergoing transplant, with minimal toxicity.

The 102 patients treated with defibrotide in the current study had a mean age of 21 years, and the mean duration of treatment with the drug was 21 days. They were already very seriously ill when treatment was started. For comparison, the researchers identified 32 similar historical control patients from a survey of almost 7000 previous transplant patients at participating centers. The study used a novel method for evaluating historical controls compared to prospectively treated patients, in part because the death rate from this complication is so high, making a randomized prospective approach neither feasible or ethical in this setting.

Era of Hope Scholar Award funds unique breast cancer research

Wed, 02 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) HOUSTON - A novel approach to detecting and targeting flaws in first line of defense against cancer has earned an Era of Hope Scholar Award from the U.S. Department of Defense for a scientist at The University of Texas M. D. Anderson Cancer Center.

The award, one of only three given nationally, provides $3.5 million over five years to Shiaw-Yih Lin, Ph.D., associate professor in M. D. Anderson's Department of Systems Biology, to study early defects that lead to breast cancer. The awards support outstanding early-career scientists with high potential for innovation in breast cancer.

Lin's research focuses on the DNA damage response, which detects defects in dividing cells and either repairs them, destroys the cell or deprives it of its ability to divide. The grant funds will be used to explore a crucial component of that process called replication stress response or RSR.

When cells begin to proliferate very rapidly due to activation of cancer-causing genes or the loss of tumor-suppressor genes, the replication stress response detects that change and blocks these cells from replicating, Lin said. Genetic defects or flawed proteins in the replication stress response allow precancerous or cancerous cells to bypass this important blockade.

Defects in the RSR pathway occur very early in a normal cell's transition to a cancerous state. There are no biomarkers for early detection of these defects, Lin said. We believe we can identify biomarkers that will detect premalignant cells, allowing us to target those cells before they become fully malignant and providing an avenue for preventing breast cancer as well as treating existing disease.

Lin and colleagues plan to characterize the genes involved in the RSR pathway, identify the genetic signature and membrane proteins associated with defective RSR, identify drugs that target the defects, and then develop targeted nanoparticles for diagnostic imaging, prevention and treatment of breast cancer.

There are more than 100 genes involved in the replication stress response. Lin says his team will use state-of-the-art technology to narrow the field to the top five candidates.

The concept of targeting the RSR pathway in cancer research, the scope of the project and its ambition to go from biomarkers to potential treatments in five years, made it an ideal fit for an Era of Hope award.

One of the key points in the Era of Hope Scholar Award is to select outstanding scientists who are willing to do high-risk, high-yield studies in addition to the incremental science we do that moves us ahead but moves us ahead slowly, said Gordon Mills, M.D., Ph.D., professor and chair of the department of Systems Biology. These high-risk, high-yield projects are extremely difficult to fund by conventional mechanisms.

This Era of Hope Scholar Award to Dr. Lin will allow him to take the brand new approach that he's developed and begin to understand a new process of DNA repair, DNA stress and potentially how we can target this, Mills said. With Dr. Lin's approach, we might be able to help a whole new set of breast cancer patients who do not benefit from current therapies.

Common pain relief medication may encourage cancer growth

Wed, 18 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports--to be presented November 18, 2009, at Molecular Targets and Cancer Therapeutics, a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer--highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients, said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. It also suggests potential new applications for this novel class of drugs which should be explored.

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

Moss's palliative-care patients were taking methylnaltrexone (MNTX), developed in the 1980s for opiate-induced constipation by the late University of Chicago pharmacologist Leon Goldberg. Goldberg modified an established drug that blocks morphine so that it could no longer cross the protective barrier that surrounds the brain. So MNTX blocks morphine's peripheral side effects but does not interfere with its effect on pain, which is centered in the brain. It won FDA approval in 2008.

These were patients with advanced cancer and a life expectancy of one to two months, Moss recalled, yet several lived for another five or six. It made us wonder whether this was just a consequence of better GI function or could there possibly be an effect on the tumors.

So Singleton, Moss and colleagues, including Joe G.N. Garcia, MD, professor of medicine at the University of Chicago, began a series of studies looking at the many peripheral effects of opiates and the potential benefits of blocking those effects.

In laboratory studies, morphine can directly boost tumor-cell proliferation and inhibit the immune response. The researchers found that opiates also promote angiogenesis, the growth of new blood vessels, and decrease barrier function--effects that may exacerbate diseases involving vascular leakiness including acute lung injury in experimental models. In a surgical setting, decreased barrier function may make it easier for tumors to invade tissue and spread to distant sites. Increased angiogenesis helps cancers thrive in a new site.

In the studies to be presented Nov. 18, Singleton and colleagues focus on the mu opiate receptor as a regulator of tumor growth and metastasis and examine the ability of methylnaltrexone to attenuate these effects.

Using two different models of non-small cell lung cancer, the research teams showed that MNTX inhibited the tumor-promoting effects of opiates. In one study, using bronchioloalveolar carcinoma cells, MNTX blocked oncogenic signaling and prevented tumor-cell proliferation and migration.

In the other study, using Lewis lung carcinoma cells, mice without the mu opiate receptor did not develop the tumors that normal mice did when injected with cancer cells. The researchers further showed that MNTX reduced proliferation of cancer cells by 90 percent in normal mice. It also prevented invasion in cell culture and tumor growth and metastasis in mice.

The opioid receptor promotes Lewis lung cancer tumor growth, angiogenesis and metastasis, the authors conclude in a summary of the second study. Methylnaltrexone attenuates these oncogenic effects.

In conjunction with previous studies on opiate-induced angiogenesis by our laboratory and others, these experimental data suggest a plausible explanation for the epidemiologic observations, notes Moss, professor of anesthesiology and critical care at the University of Chicago. If these laboratory studies are confirmed clinically, the selection of anesthetic technique used during the operative procedure and the possible use of opiate antagonists in the perioperative period may be important.

Faulty immune memory can trigger cold sores

Thu, 12 Nov 2009 12:35:46 PST

( from http://www.rxpgnews.com ) A faulty immune memory can trigger infections that may lead to cold sores and even cancer in some people, say researchers.

The memory circuit, identified by the research team, involves a gene and protein called DOCK8, which helps white blood cells form synapses, tiny points of cell contact, that are responsible for memory in the brain.

An increased understanding of immune memory would not only lead to enhanced vaccines but also improve the treatment of cancer, transplant rejection, auto-immunity and allergies.

'Vaccines that provoke long-lasting immunity are among the greatest advances delivered by health research, but the circuits that determine whether they work or not have been among the most difficult to decipher,' said Chris Goodnow from the John Curtin School of Medical Research in Australia and co-leader of the research team.

Lapses of immunological memory also explain the reactivation of infections responsible for cold sores, shingles, yeast infections, and possibly some forms of cancer.

Katrina Randall, clinical immunologist and co-research team leader said: 'Immunity normally lasts for years after we are immunised or infected because our immune system remembers the shape and 'fingerprints' of an infecting microbe...'

'When immunological memory wanes we become susceptible to infection again. For some vaccines like the tetanus vaccine this occurs after several years, and for many experimental vaccines their memory has so far proved just too short to be useful.'

The findings were published in the latest issue of Nature Immunology.

Study finds higher risk of cancer recurrence in women with dense breasts

Tue, 10 Nov 2009 12:14:32 PST

( from http://www.rxpgnews.com ) Women with heavier busts who have been treated for breast cancer are at higher risk of its recurrence, says a new study.

These findings indicate that such patients may benefit from additional therapies, such as radiation, following surgery.

Researchers suspected that high breast density - may also increase the risk of cancer recurrence after lumpectomy, but this theory has not been thoroughly studied.

Lumpectomy is a surgical procedure that involves removing a suspected malignant - tumour, or lump, and a small portion of the surrounding tissue from a woman's breast.

Researchers led by Steven A. Narod, Women's College Research Institute - in Toronto reviewed the medical records of 335 patients who had undergone lumpectomy for breast cancer.

Researchers found that patients with the highest breast density had a much greater risk of cancer recurrence than did women with the lowest breast density.

Over 10 years, women in the highest breast density category had a 21 percent chance of cancer recurrence, compared to a five percent chance among women in the lowest category, according to a WCRI release.

'The composition of the breast tissue surrounding the breast cancer is important in predicting whether or not a breast cancer will return after surgery,' Narod said.

The study authors say their findings indicate that women with low breast density, who have a low chance of recurrence after surgery, may not need radiation but that women with high breast density could significantly benefit from the additional therapy.

These findings are slated for publication in December issue of Cancer, a journal of the American Cancer Society.

Minimally invasive surgery shown safe and effective treatment for rectal cancer

Tue, 10 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Laparoscopic surgery has been used in the treatment of intestinal disorders for close to 20 years, but its benefits have only recently begun to be extended to people with rectal cancer. In a prospective study of 103 patients who underwent straightforward or hand-assisted laparoscopic surgery for rectal cancer, a team of colon and rectal surgeons at NewYork-Presbyterian Hospital/Weill Cornell Medical Center has shown that the minimally invasive approach can be as effective as traditional open surgery in treating rectal cancers.

The advantages of laparoscopic and other minimally invasive surgical techniques are well known. After laparoscopic surgery, patients experience shorter hospital stays, smaller scars, far less pain and faster recovery, compared with open surgery. NewYork-Presbyterian/Weill Cornell has offered these procedures for many years, and continues to be at the forefront of innovation, applying the minimally invasive approach to diseases and conditions once considered treatable mainly using open surgery techniques. Until recently, rectal cancer was one such disease -- and its treatment via laparoscopic surgery is still seen by some as controversial.

Rectal surgery, according to Dr. Jeffrey Milsom, chief of colon and rectal surgery at NewYork-Presbyterian/Weill Cornell, is inherently more challenging than colon surgery. For one, the pelvic cavity of the body where the rectum lies, is a narrow space, making rectal tumors difficult to access. Surgical success depends not only on the complete removal of the cancerous tumor and repair of the rectum, but also on restoring continence. For these reasons, rectal cancer has been a difficult arena to apply advances in minimally invasive surgery.

Delaying matters further, initial reports on the use of laparoscopic surgery in patients with rectal cancer described a higher incidence of cancer-positive cells at the edges of removed tumors compared with open surgery, says Dr. Milsom. Early data suggested that as a result, more patients could experience a local recurrence of their rectal cancer after laparoscopic surgery than open surgery. But the current study refutes these initial findings.

Between January 1999 and December 2006, three colon and rectal surgeons at NewYork-Presbyterian/Weill Cornell (Dr. Milsom and his colleagues Dr. Toyooki Sonoda and Dr. Sang Lee) treated 103 patients with mid or low rectal cancer using an operation called total mesorectal excision (TME), performed via laparoscopic-assisted (LAP) or hand-assisted laparoscopic surgery (HALS). To gather the relevant data and analyze outcomes, Dr. Milsom and his team relied on inpatient and outpatient medical records, telephone interviews with patients, and standard actuarial survival calculations. Patients received regular follow-up for five years.

More than 90 percent of the patients in our study were able to undergo laparoscopic surgery successfully, says Dr. Sonoda, one of the study's key surgeons. We define 'success' in both the short- and long-term sense: More than 95 percent emerged with an intact and functioning rectum and, as expected after a minimally invasive procedure, recovered rapidly. None had cancer-positive tumor margins, which has been a major concern in the medical literature all along. In fact, after five years, overall survival has remained high at 91 percent, with more than 73 percent of patients completely free from disease.

In terms of cancer cure and recovery, says Dr. Lee, the other key surgeon on the study, these outcomes are at least as good as the best outcomes seen with open surgical techniques. And when you add in all the advantages of laparoscopic surgery, it seems clear that this is an approach that could evolve to become the surgical standard.

Reported earlier this year in the professional journal of the

St. Jude and UF Proton Therapy Institute to begin proton therapy clinical trial

Mon, 09 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) St. Jude Children's Research Hospital and the University of Florida Proton Therapy Institute have formed a collaboration to provide proton therapy for St. Jude patients. The announcement follows the approval of the first clinical study to evaluate the use of proton therapy for rare brain cancers in children younger than 3 years old.

Under the clinical protocol, St. Jude will refer patients to receive proton therapy at the UF Proton Therapy Institute in Jacksonville, Fla. The purpose of the clinical study is to improve response rates and decrease treatment-related side effects.

Proton therapy is being studied as a way to reduce potential damage to healthy tissue that may result from conventional radiation therapy. This is especially important in treating children with brain and spinal tumors to potentially avoid interference with development, growth and cognitive functioning.

St. Jude has the world's largest protocol-based, pediatric brain tumor research and treatment program, which puts it in an excellent position to scientifically document the advantages realized with proton beam radiation therapy.

Proton beam therapy is potentially of great importance to St. Jude and our patients, said Dr. Joseph H. Laver, St. Jude executive vice president and clinical director. Although most proton facilities operating in the U.S. recognize pediatrics as a major area of focus, there is very little meaningful data using this modality in children. Working with UF Proton Therapy Institute, we are well-positioned to answer key questions regarding this therapy for children with cancer.

St. Jude patients accepted for the clinical study will be in Jacksonville for proton therapy treatment for six to eight weeks. It is expected that up to 15 patients will receive treatment during the first year of the study. While in Jacksonville, hospital care for St. Jude patients will be provided by Nemours Children's Clinic Jacksonville and Wolfson Children's Hospital. The Ronald McDonald House in Jacksonville will house St. Jude patients while they are receiving treatment in Florida.

It is central to our mission to realize the full potential of protons in the treatment of children, said Dr. Nancy Mendenhall, medical director at UF Proton Therapy Institute. In cooperation with St. Jude, we will have both clinical and research expertise to provide the best outcomes for patients and to create new knowledge that will guide the development of proton therapy for future patients.

St. Jude leads the field in the application of intensified modulated radiation therapy, known as IMRT. The technique is effective at avoiding damage to adjacent tissues; however, IMRT can still deliver significant radiation doses to underlying tissues resulting in unavoidable side effects for some children. Proton therapy can be focused more precisely and intensely on specific areas of cancerous activity. Protons can also be energized for a desired degree of tumor penetration, thus sparing underlying tissues from radiation exposure.

UF Proton Therapy Institute is one of only six proton therapy centers in the United States. Since opening in August 2006, UF Proton Therapy Institute has treated 100 pediatric patients.

Cancer patients want honesty, compassion from their oncologist

Wed, 04 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) What do patients want from their radiation oncologists? The most significant preference is that more than one-third of female cancer patients (37 percent) prefer to have their hands held by their radiation oncologists during important office visits, compared to 12 percent of men, according to a randomized study presented November 4, 2009, at the 51st Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Another significant finding is that almost three-quarters of the patients (72 percent) preferred to be called by their first name, even among elderly patients. There is a greater preference for this among females than males (76 percent to 66 percent), and white patients compared to blacks (74 percent to 56 percent). The study also shows that while 95 percent of all patients want their oncologist to be honest with them about their chances of cure and expected survival, there is a significantly increased preference for honesty among prostate cancer patients versus lung cancer patients (97 to 91 percent).

In oncology, a strong physician-patient relationship is essential because the patient's interactions with their doctor can help the patient confidently make life or death decisions, such as what cancer treatment is best for them, Ajay Bhatnagar, M.D., lead author of the study, a radiation oncologist at Cancer Treatment Services International in Casa Grande, Ariz., and Adjunct Assistant Professor of Radiation Oncology at the University of Pittsburgh Cancer Institute in Pittsburgh said. Oncologists can use these results to provide greater patient satisfaction for their patients, and therefore significantly improve patient care.

The study sought to find out what cancer patients wanted from their patient-doctor relationship and whether their physicians would be able to change their behaviors to satisfy their patients' preferences if they had knowledge of these preferences. The prospective randomized trial took place between June 2006 and March 2008 and involved 508 patients, who underwent radiation for breast, prostate or lung cancer. Patients answered a survey about their preferences of their radiation oncologist, with a variety of questions focusing on the patient-doctor relationship. The survey was given at three time periods: prior to initial consultation, midpoint of radiation treatment, and at completion of radiation therapy.

The patients were randomized into two groups, based on whether their oncologist reviewed their initial patient preference survey responses (experimental group) or did not (control group). At time of completion, the patient also completed a satisfaction survey.

In addition to other findings, nearly three-quarters of all patients (70 percent) are neutral about their radiation oncologist wearing a white coat or professional clothing. The study also shows that 95 percent of high school graduates show a greater preference for having their radiation treatment described in everyday language by their radiation oncologists, compared to 91 percent of college graduates and 84 percent of post-graduate patients.

Low cholesterol may shrink risk for high-grade prostate cancer

Tue, 03 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Men with lower cholesterol are less likely than those with higher levels to develop high-grade prostate cancer - an aggressive form of the disease with a poorer prognosis, according to results of a Johns Hopkins collaborative study.

In a prospective study of more than 5,000 U.S. men, epidemiologists say they now have evidence that having lower levels of heart-clogging fat may cut a man's risk of this form of cancer by nearly 60 percent.

For many reasons, we know that it's good to have a cholesterol level within the normal range, says Elizabeth Platz, Sc.D., M.P.H., associate professor at the Johns Hopkins Bloomberg School of Public Health and co-director of the cancer prevention and control program at the Johns Hopkins Kimmel Cancer Center. Now, we have more evidence that among the benefits of low cholesterol may be a lower risk for potentially deadly prostate cancers.

Normal range is defined as less than 200 mg/dL (milligrams per deciliter of blood) of total cholesterol.

Platz and her colleagues found similar results in a study first published in 2008, and in 2006, she linked use of cholesterol-lowering statin drugs to lower risk of advanced prostate cancer.

For the current study, Platz, members of the Southwest Oncology Group, and other collaborators analyzed data from 5,586 men aged 55 and older enrolled in the Prostate Cancer Prevention Trial from 1993 to 1996. Some 1,251 men were diagnosed with prostate cancer during the study period.

Men with cholesterol levels lower than 200 mg/dL had a 59 percent lower risk of developing high-grade prostate cancers, which tend to grow and spread rapidly. High-grade cancers are identified by a pathological ranking called the Gleason score. Scores at the highest end of the scale, between eight and 10, indicate cancers considered the most worrisome to pathologists who examine samples of the diseased prostate under the microscope.

In Platz's study, cholesterol levels had no significant effect on the entire spectrum of prostate cancer incidence, only those that were high-grade, she says.

Platz cautions that, while the group took into account factors that could bias the results, such as smoking history, weight, family history of prostate cancer, and dietary cholesterol, other things could have affected their results. One example is whether men in the study were taking cholesterol-lowering drugs at the time of the blood collections, a data point the researchers expect to analyze soon.

Results of the current study are expected to be published online Nov. 3 in the journal

Shorter radiation course stops cancer growth in high-risk prostate cancer patients

Tue, 03 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Hypofractionated radiation treatment, a newer type of radiation treatment that delivers higher doses of radiation in fewer treatments than conventional radiation therapy, is significantly more effective in stopping cancer from growing in high risk patients, compared to receiving standard radiation treatment, according to a study presented November 4, 2009, at the 51st Annual Meeting of the American Society for Radiation Oncology (ASTRO). In addition, findings show there is no increased risk of negative side effects later in patients who undergo hypofractionated radiation.

The study not only shows that hypofractionated radiation improves the control of prostate cancer, but it also cuts the number of treatment visits in half for patients. This is an important benefit for these high-risk patients, who are typically an older, less mobile population, Giorgio Arcangeli, M.D., lead author of the study and a radiation oncologist at the Regina Elena National Cancer Institute in Rome, Italy said. It's also especially helpful for those living at long distance from radiation treatment centers.

All men in the study were treated with three-dimensional conformal radiation therapy, or 3D-CRT. It is a type of external beam radiation therapy that uses computers and special imaging techniques to show the size, shape and location of the tumor as well as surrounding organs to precisely tailor the radiation beams to the size and shape of the tumor. Because the radiation beams are very precisely directed, nearby normal tissue receives less radiation and is able to heal more quickly.

During external beam radiation therapy, a beam of radiation is directed through the skin to the cancer and the immediate surrounding area in order to destroy the main tumor and any nearby cancer cells.

From January 2003 to December 2007, a total of 168 high risk prostate cancer patients were randomized to receive either hypofractionated or conventional schedules of 3D-CRT to the prostate and surrounding area. Patients who received hypofractionated radiation had only 20 sessions of radiation (four weeks of daily radiation therapy treatments), instead of the 40 to 45 (eight to nine weeks of daily treatments) sessions typically required during standard radiation treatment.

Study findings show that the patients treated with hypofractionated radiation had a better chance (87 percent vs. 79 percent) that their cancer would stop growing, compared to patients treated with standard radiation therapy. There was also no difference in the late side effects of genito-urinary and gastro-intestinal function between the two groups of patients.

Studies are in progress to test the benefits of even shorter treatment schedules, Dr. Arcangeli said.

New treatment option emerging for some with early stage lung cancer

Tue, 03 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) San Diego, Calif -- Patients with early stage, non-small cell lung cancer who are not able to undergo surgery, now have a highly effective treatment option. Physicians say that option, radical stereotactic radiosurgery performed with CyberKnife, leads to a 100 percent overall survival after three years in patients with good lung function before treatment. These are the results of a study presented today at the annual CHEST meeting in San Diego. The study is a semifinalist for an Alfred Soffer Research Award, selected for outstanding original scientific research.

For patients with small tumors characterized as early-stage disease, surgical removal of the affected lobe (lobectomy) is the standard of care. However, surgery is sometimes not an option because of other pre-existing medical conditions such as emphysema or heart disease.

Our goal has been to find a reasonable option for patients who don't want or can't tolerate surgery, says the study's lead author, Brian T. Collins, MD, a radiation oncologist with the Lombardi Comprehensive Cancer Center at Georgetown University Hospital. What we discovered is a very promising option that may be relevant for other stage one patients as well. More follow up with these patients is planned to see how they progress five years after treatment.

Twenty-four patients were treated as part of the study. Each patient's forced expiratory volume in 1 second or FEV1was measured.

We use the FEV1 to grade the severity of a patient's COPD, says Eric D. Anderson, MD, a pulmonologist at Georgetown University Hospital and presenting author of the abstract. It measures the ability of a patient to exhale forcefully. COPD stands for Chronic Obstructive Pulmonary Disease and is commonly referred to as emphysema.

At an average follow up of 36 months, the overall survival for all patients was 79 percent with five deaths occurring due to progressive lung dysfunction. For patients with a better FEV1, survival was 100 percent.

Collins says the treatment was well tolerated with mild fatigue only reported by the majority of patients.

What we also learned from this study is that patients with poorer lung functioning don't do nearly as well, Collins explained. The overall survival in this group of patients was only 30 percent.

This information is important for the doctor and patient when making treatment decisions, says Collins. In treating someone with poor lung function, it would seem prudent to modify the treatment dose in order to reduce further damage to the lungs that stereotactic radiosurgery causes.

Lung cancer is the leading cause of cancer deaths with more than 215,020 people diagnosed each year and 161,804 dying of the disease, according to the American Cancer Society. While there is no screening test for lung cancer that would allow doctors to find the disease in its earliest, most curable stage, some tumors are found early because of medical tests being done for other conditions.

These results are important because lung cancer is typically the result of long term smoking which causes significant health problems like emphysema. For these patients traditional lung surgery can be too risky because of their other health issues. This study shows that CyberKnife is a viable and promising option for patients to consider when their lung tumor has not spread to the lymph nodes or to distant parts of the body and surgery is too high-risk, explains Collins.

Short-term hormone therapy added to radiation increases survival for medium-risk, but not low-risk, prostate cancer patients

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Short-term hormone therapy given prior to and during radiation treatment to medium-risk prostate cancer patients increases their chance of living longer, compared to those who receive radiation alone, however there is no significant benefit for low-risk patients, according to the largest randomized study of its kind presented at the plenary session November 2, 2009, at the 51st Annual Meeting of the American Society for Radiation Oncology (ASTRO).

This phase III study is one of the largest clinical trials of prostate cancer therapy ever completed, with 2,000 low- and intermediate-risk patients enrolled in the trial from October 1994 to April 2001. Researchers from the Radiation Therapy Oncology Group (RTOG) followed men with early-stage prostate cancer for a period in most cases of more than nine years. This timeframe was sufficient to show improved survival benefits of short-term hormone therapy added to what was then the standard radiation treatment for prostate cancer, which involved slightly lower doses of radiation than are currently used today with newer techniques, such as intensity modulated radiation therapy (IMRT).

The study provides strong scientific evidence that shows us when to deliver hormone therapy with radiation in patients with localized prostate cancer, Christopher U. Jones, M.D., an author of the study and a radiation oncologist at Radiological Associates of Sacramento in Sacramento, Calif., said. Our findings show that men with low-risk disease, which is the vast majority of prostate cancer patients, have little to gain from adding hormone therapy to radiation. However, men with intermediate-risk disease, which is a significant minority of patients, gain abenefit in overall survival from the addition of only four months of hormone therapy. Prior to this trial, it was unclear whether or not combining hormone therapy with radiation for medium-risk prostate cancer patients improves survival.

Androgen deprivation therapy is hormone therapy used to treat prostate cancer by stopping or lowering the level of male hormones, or androgens, thereby removing the strongest growth factor for prostate cancer cells.

In the study, a total of 1,979 eligible men who had cancer confined to the prostate and a PSA less than or equal to 20 were randomized to receive total androgen deprivation therapy two months prior to and two months during radiation treatment, or radiation alone.

Findings show that short-term hormone therapy given to early-stage prostate cancer patients prior to and during radiation treatment significantly increases their chance of living longer (51 percent), compared to those who receive radiation alone (46 percent). Nearly all of the survival benefit was in the intermediate-risk group. Secondary endpoints of disease-free survial, freedom from biochemical failure, and positive two year re-biopsy rates were also better in the group who received short-term hormone therapy and radiation treatment.

Proton therapy is well-tolerated in prostate cancer patients

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Proton beam therapy can be safely delivered to men with prostate cancer and has minimal urinary and rectal side effects, according to a study presented November 2, 2009, at the American Society for Radiation Oncology's 51st Annual Meeting in Chicago.

Researchers sought to determine if delivering higher doses of radiation with proton therapy would cause early harmful side effects to urinary function within the genitourinary system (GU) function and rectal function within the gastrointestinal (GI) system.

Proton therapy is becoming more popular as a treatment for prostate cancer, but it is unclear at this point whether the long-term outcomes with proton therapy will be better than those achieved with other treatments. These protocols were designed to establish benchmark results with proton therapy given with relatively high daily doses. At this point, we can say that early tolerance of proton therapy has been excellent, with a very low rate of urinary and rectal toxicity, Nancy Mendenhall, M.D., a study author and medical director of the University of Florida Proton Therapy Institute in Jacksonville, Fla., said. This study shows that prostate cancer patients can receive proton therapy with a very low likelihood of compromised urinary or rectal function.

Proton beam therapy is a form of external beam radiation treatment that uses protons rather than photons (X-rays) to treat certain types of cancer and other diseases. The physical characteristics of the proton therapy beam allow the radiation oncologist to deliver more radiation to the tumor with less radiation to nearby healthy tissues.

During external beam radiation therapy, a beam of radiation (X-rays or protons) is directed through the skin to the cancer and the immediate surrounding area in order to destroy the main tumor and any nearby cancer cells.

From August 2006 to October 2007, 212 prostate cancer patients enrolled in one of three prospective trials to receive proton therapy. High-risk patients also received the chemotherapy drug, docetaxol, followed by hormone therapy. Researchers followed the patients for at least a year after treatment and examined the genitourinary and gastrointestinal toxicity scores using both International Prostate Symptom Scores (IPSS) and Common Toxicity Criteria for Adverse Events (CTCAE, v. 3) for each patient.

Findings show that there was minimal early GU and GI toxicity on prospective trials of proton therapy. Less than one percent of patients had severe Grade 3 genitrourinary side effects. There was a significant association between GU side effects after treatment and patients' pretreatment urinary function. Less than one-half percent of patients experienced Grade 3 gastrointestinal toxicities. The most common gastrointestinal side effect was minimal rectal bleeding, which was associated with the percentage of rectal wall receiving a range of radiation doses. The incidence and severity of rectal symptoms were also impacted by post-treatment colonoscopic interventions.

These results are very encouraging. While some toxicities may occur later, we are very pleased with the early toxicity profile in comparison with other treatment options. Further follow-up will be necessary to ensure that these men do not have any side effects that appear years after the treatment, added Dr. Mendenhall.

Obesity significantly increases side effects of stereotactic body radiation therapy in lung cancer patients

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Obesity, not the amount of radiation given, is the greatest factor in whether early-stage lung cancer patients develop chest wall pain after receiving stereotactic body radiation therapy to the chest wall, with obese patients being more than twice as likely to develop chronic pain compared to those who have less body weight, according to a first-of-its-kind study presented Tuesday, November 3, 2009, at the 51st Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Researchers studied other factors associated with obesity, such as diabetes, to find out why obesity in patients increased chest wall pain. Findings show that obese patients who are diabetic are over three times more likely to develop chest wall pain after receiving stereotactic body radiation therapy to the chest wall, compared to patients who do not have diabetes.

The study shows that physiological factors, such as obesity and diabetes, can play a major role in the development of radiation-related toxicity, James Welsh, M.D., lead author of the study and a radiation oncologist at the M.D. Anderson Cancer Center in Houston said. This is a surprising finding, since most side effects of radiation treatment are based on the amount of normal tissue that is treated and the volume of the dose.

The main purpose of the study was to find out what the highest amount of radiation that could be delivered to the chest wall using a specialized type of radiation treatment called stereotactic body radiation therapy (SBRT) without patients developing the late side effects of pain and skin reactions. The study shows that patients who receive a high dose of radiation tocancer close to the chest wall (in the amount of 35 gray (Gy) have an increased chance of having pain and skin reactions, compared to those who have a lower radiation dose.

SBRT is a specialized type of external beam radiation therapy that pinpoints high doses of radiation directly on the cancer in a shorter amount of time than traditional treatments. Cancer centers often call the treatments by the brand names of the manufacturers, including Axesse, CyberKnife, Gamma Knife, Novalis, Primatom, Synergy, X-Knife, TomoTherapy and Trilogy. Treatment is typically delivered in 1 to 2 weeks, instead of a period of 6 to 8 weeks.

SBRT is now being investigated as a replacement to surgery for early-stage lung cancer. If this non-invasive technique is to replace surgery, not only does it need to be effective, but also safe, Dr. Welsh said. Since this study shows that a 35Gy dose of radiation, obesity, and diabetes increase the risk of developing late negative side effects after high dose radiation, then we can take steps to reduce these side effects.

The study involved 265 patients with tumors within less than 2.5 centimeters of the chest wall, who were treated with SBRT between August 2004 and August 2008. Of these patients, 39 percent developed skin toxicity, while six percent developed acute pain and 22 percent developed chronic pain. In patients who are considered obese, diabetes mellitus was found to be a significant contributing factor in the development of chest pain.

Short-term hormone therapy and intermediate dose radiation increases survivial for early stage prostate cancer

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Short-term hormone therapy given prior to and during intermediate dose radiation treatment for men with early stage prostate cancer increases their chance of living longer, compared to those who receive the same radiation alone, according to a Radiation Therapy Oncology Group (RTOG) study, the largest randomized trial of its kind, presented November 2, 2009, at the American Society for Radiation Oncology (ASTRO) annual meeting. The RTOG trial noted that this benefit appeared to be greatest for men currently defined as at medium-risk for disease failure.

The phase III study is one of the largest clinical trials of prostate cancer therapy ever completed, with 2,000 low- and intermediate-risk patients enrolled in the trial from October 1994 to April 2001. This trial was conducted by the RTOG and followed men with early-stage prostate cancer in most cases for more than nine years. This time period is sufficient to show improved survival benefits of short-term hormone therapy added to what was then the standard radiation treatment for prostate cancer, which involved slightly lower doses of radiation than are currently used today with newer techniques, such as intensity modulated radiation therapy (IMRT).

This landmark RTOG study provides strong scientific evidence that shows us when to deliver hormone therapy with radiation in men with localized prostate cancer. Prior to this trial, it was unclear whether or not combining hormone therapy with radiation for medium-risk prostate cancer patients would increase survival, said Christopher U. Jones, M.D., an author of the study and a radiation oncologist at Radiological Associates of Sacramento in Sacramento, Calif. It remains uncertain whether the addition of hormone therapy to the higher radiation dose and new technology treatments being employed today would provide the same or greater benefit to that documented in this study. It is possible that it could.

According to Walter J. Curran, Jr., M.D., the RTOG Group Chair, and the Executive Director of the Emory Winship Cancer Institute and Associate Vice President for Cancer, Woodruff Health Sciences Center, RTOG recently opened a new trial examining the role of hormone therapy combined with modern radiotherapy techniques for men with intermediate stage prostate cancer. When completed, the results of our new trial, RTOG 0815, will provide a complement to the results of our current landmark trial.

Androgen deprivation therapy is hormone therapy used to treat prostate cancer by stopping or lowering the level of male hormones, or androgens, thereby removing the strongest growth factor for prostate cancer cells.

In the study, a total of 1,979 eligible men who had cancer confined to the prostate and a PSA less than or equal to 20 were randomized to receive total androgen deprivation therapy for two months prior to and two months during radiation treatment, or to receive only radiation therapy.

Findings show that short-term hormone therapy given to early-stage prostate cancer patients prior to and during radiation treatment significantly increases their chance of living longer (51 percent), compared to those who receive radiation alone (46 percent). Nearly all of the survival benefit was in the intermediate-risk group. Secondary endpoints of disease-free survival, freedom from biochemical failure, and positive two year re-biopsy rates were also better in the group who received short-term hormone therapy and radiation treatment.

Adding proton therapy 'boost' to X-ray radiation therapy reduces prostate cancer recurrences

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Men who receive a boost of proton therapy after receiving a standard course of X-ray radiation therapy have fewer recurrences of their prostate cancer compared to men who did not receive the extra dose of proton radiation, according to a first-of-its-kind study presented November 2, 2009, at the American Society for Radiation Oncology's 51st Annual Meeting in Chicago. The multi-institutional, randomized trial also shows that the high dose treatment is safe for these patients and causes no severe problems later with urinary or bowel functions.

There is a lot of interest in proton therapy for prostate cancer. This study proves the importance of giving high radiation doses to prostate cancer patients with low- and intermediate-risk disease because it demonstrates that even these 'favorable' patients still benefit from the extra high-dose treatment, Carl J. Rossi Jr., M.D., a study author and a radiation oncologist at the Loma Linda University Medical Center in Loma Linda, Calif., said. It also shows that so long as these higher doses are given with a highly conformal technique, such as proton beam therapy, then they can be delivered safely and with minimal side effects.

Proton beam therapy is a form of external beam radiation treatment that uses protons rather than photon X-rays to treat certain types of cancer and other diseases. The physical characteristics of the proton therapy beam allow the radiation oncologist to more effectively reduce the radiation dose to nearby healthy tissue.

During external beam radiation therapy, a beam of radiation is directed through the skin to the cancer and the immediate surrounding area in order to destroy the main tumor and any nearby cancer cells.

The study involved 391 patients with early prostate cancer (cancer that has not spread out of the prostate) receiving proton treatments at Loma Linda University Medical Center and Massachusetts General Hospital in Boston. Patients were randomized to receive either standard dose or high dose radiation, with proton beams being used to deliver the high-dose radiotherapy to prostate.

Findings show that in patients with a low risk of having the cancer return (recurrence), only six percent of patients who were treated with high dose radiation had the cancer return after 10 years, compared to 29 percent who had conventional radiation doses. Similarly, of the patients with an intermediate risk of cancer recurrence, 37 percent who underwent high dose radiation had cancer come back, versus 45 percent of those who had conventional doses of radiation. There were no significant differences between the two groups in how long they survived and in their urinary and bowel functions.

Discovery offers potential new pancreatic cancer treatment

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Tiny particles that can carry drugs and target cancer cells may offer treatment hope for those suffering with pancreatic cancer. New research to be presented in November at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles reveals that tumor-penetrating microparticles (TPM) have been specifically designed to break through hard-to-infiltrate barriers and deliver drugs more effectively and efficiently than the standard form of chemotherapy such as those injected through a vein.

According to Jessie L.S. Au, Pharm.D., Ph.D., an AAPS fellow and a distinguished university professor at Ohio State University who initiated the study, TPM are designed to treat cancer in the peritoneal cavity. The peritoneal cavity contains organs, including the pancreas, that are home to more than 250,000 new cases of cancer a year in the United States alone (www.cancer.org). Pancreatic cancer cells are surrounded by specialized cells that protect them from chemotherapy, explains Dr. Au. Our goal is to use TPM to pass this barrier and successfully deliver drugs to the tumor cells, which is currently the biggest hurdle a physician faces in pancreatic cancer treatment.

According to the American Cancer Society, pancreatic cancer is the fourth leading cause of cancer in the U.S., with more than 80 percent of the 38,000 patients stricken with the disease dying within one year of diagnosis.

Dr. Au, who is also co-founder of Optimum Therapeutics LLC, the company bringing TPM to clinical trials, goes on to explain that TPM releases what the researchers call a smart bomb of drugs to create holes in the tumor so TPM can reach tumor cells. Once inside a tumor, TPM slowly releases drug levels that are sustained over several weeks, targeting both the rapid- and slow-growing tumors. Because the TPM were designed to move about and reach tumors without being swept away by the lymphatic system, they are able to stay in the peritoneal cavity longer and deliver highly concentrated drug doses to the cancer-affected organ. It is this two-tiered drug attack that is unique in pancreatic cancer treatment.

With just one TPM dose of drugs proving to be equally as effective as multiple injections of chemotherapy, TPM delivers less toxicity to patients, making it a safer option than the standard form of other therapies. Based on the encouraging results in mice carrying implants of human pancreatic cancer, we are cautiously optimistic that TPM may provide benefits to patients with this disease, says Ze Lu, Ph.D., principal scientist and project leader. TPM may prove to be especially helpful to patients with late stages of the disease. According to Dr. Lu, the researchers have been working on TPM for more than 10 years and look forward to receiving FDA approval for testing TPM in patients in 2010.

The researchers are collaborating with physicians at the Medical University of South Carolina who believe a potential use of TPM, in addition to treating patients with peritoneal metastases, is to downstage or downsize the tumors so that they are operable.

UCSF diabetes, brain tumor stem cell grants to drive development of therapies

Thu, 29 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Two teams of UCSF scientists have received grants from the California Institute for Regenerative Medicine to advance their stem cell based strategies for treating diabetes and brain tumors. The intent of the grants is for teams to file new drug applications to the U.S. Food and Drug Administration within four years, driving potential therapies toward clinical trials.

The two grants, awarded to collaborative scientific teams, total $39.2 million.

The diabetes grant is co-led by investigator Jeffrey Bluestone, PhD, director of the UCSF Diabetes Center, in collaboration with Novocell, Inc. Other UCSF members of the team are Michael German, MD, PhD; Matthias Hebrok, PhD; and Qizhi Tang, PhD.

The brain tumor grant is led by Mitchel Berger, MD, chair of the UCSF Department of Neurosurgery, in collaboration with Ludwig Institute for Cancer Research and Burnham Institute for Medical Research. Other UCSF members of the team are C. David James, PhD; Tomoko Ozawa, MD, PhD; Russell Pieper, PhD; Mei-Yin Polley, PhD; Michael Prados, MD; and Elizabeth Read, MD.

The projects are among 14 disease team grants announced today (Oct. 28, 2009) by CIRM. The grants focus on conditions ranging from brain tumors and diabetes to HIV, heart damage and amyotrophic lateral sclerosis, among others. They are the first issued by CIRM with the explicit intent of driving the development of therapies for approval by FDA for testing in clinical trials.

The multidisciplinary collaborations are intended to hasten the clinical trial development process, avoiding mistakes sometimes discovered late in the game and ensuring that clinically relevant issues are considered early.

The diabetes team, lauded as a dream team by the CIRM working group reviewers, received $19,999,937 over four years. The goal is to encapsulate islet progenitor cells generated from human embryonic stem cells in a durable, retrievable device and implant them into patients. The cells, which differentiate into glucose responsive islet beta cells after transplantation in vivo, have proven to be a successful strategy in treating rodents with chemically-induced diabetes.

The critical early proof-of-concept milestones have been completed, says Bluestone. Now we need to perform the manufacturing and laboratory testing required to assure reliable production of a safe and effective product, thereby generating the data needed to seek Food and Drug Administration approval to test the therapy in humans.

This is a very exciting early pre-clinical step, but, as is always the case in science, there are likely to be unexpected hurdles as we move forward, he says.

If successful, a Phase 1 safety trial in Type 1 diabetic patients could begin in three-four years from the initiation of the project.

The brain tumor team, which received $19,162,435, was characterized by the CIRM leaders as pioneers and leaders in their respective fields. The team will refine their strategy of using adult and fetal neural stem cells, as well as mesenchymal stem cells, genetically engineered to contain a tumor-killing gene to home in on glioblastoma multiforme, the most common and aggressive form of brain tumor. The studies in rodents engineered to develop human brain tumors were successful.

The strategy is based on the team's discovery that neural stem cells naturally seek out brain tumor cells and other types of disease cells. If successful, this approach would be an important advance in treating brain tumors of all kinds, says Berger. Current approaches -- surgery, radiation, pharmacological drugs and gene therapies -- are unable to reach widely disseminated tumor cells that become dispersed within normal brain structures.

If the strategy is approved by the FDA, it would be tested first in patients with recurring glioblastoma multiforme.

NIEHS awards Recovery Act funds to address bisphenol A research gaps

Wed, 28 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) For Immediate ReleaseWednesday, October 28, 2009

Contact:Robin Mackar, NIEHS(919) 541-0073

NIEHS Awards Recovery Act Funds to Address Bisph

Researchers studying the health effects of the chemical bisphenol A (BPA) gathered in North Carolina to launch an integrated research initiative to produce data that will allow for a comprehensive assessment of its possible human health effects.

Researchers who just received funds from the American Recovery and Reinvestment Act to study BPA were brought together to meet with scientists from academia and government already working on the compound. The meeting was held Oct. 6, 2009 at the National Institute of Environmental Health Sciences (NIEHS).

The meeting is part of an effort to support human and animal research that will help determine if current exposures to BPA in the general population pose a potential health risk. NIEHS is part of the National Institutes of Health (NIH) and has the lead in supporting research to study the potential effects that chemicals, such as BPA, may have on human health. President Obama allocated $5 billion in Recovery Act funds to the NIH, with about $14 million going to NIEHS for research on BPA.

We know that many people are concerned about bisphenol A and we want to support the best science we can to provide the answers, said Linda Birnbaum, Ph.D., who serves as director of the NIEHS and the National Toxicology Program (NTP), an interagency program for the U.S. Department of Health and Human Services. Bringing the key BPA researchers together at the onset of new funding will maximize the impact of our expanded research effort.

NIEHS will invest approximately $30 million over two years on BPA-related research. This includes existing grants, the newly awarded Recovery Act grants and supplements, in-house research and NTP projects. The NTP effort is part of a larger five-year commitment to collaborate with the U.S. Food and Drug Administration's National Center for Toxicological Research to examine long-term health outcomes resulting from developmental exposures.

BPA is a chemical used primarily in the production of polycarbonate plastics and epoxy resins. People, including children, are exposed to BPA in food and beverages when it leaches from the internal epoxy resin coatings of canned foods and also from consumer products such as polycarbonate tableware, food storage containers, water bottles and baby bottles. In 2008, NTP and NIEHS concluded that there is evidence from animal studies that BPA may be causing adverse effects. But researchers are uncertain about whether the changes seen in the animal studies would result in human health problems. For this reason, NIEHS identified BPA as a priority area.

The innovative two-year grants provided through the Recovery Act will support human and animal studies that address many of the research gaps identified by expert scientific panels, and provide a better understanding of how this chemical may impact human health.

We want the new grantees to be able to hit the ground running, said Jerry Heindel, health scientist administrator at the NIEHS who oversees much of the institute's portfolio on BPA. Having the key players talking to one another as they begin new research efforts will stimulate collaboration, create opportunities to share resources, and encourage researchers to develop reliable and reproducible methods that will allow for a comprehensive assessment of the human health effects of BPA.

In animal studies, there is some evidence linking BPA exposure with infertility, weight gain, behavioral changes, early onset puberty, prostate and mammary gland cancer and diabetes. For the newly funded research, two-year animal and human studies will focus on either developmental exposure or adult chronic exposures to low doses of BPA. Researchers will be looking at a number of health effects including behavior, obesity, diabetes, reproductive disorders, development of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects. The 10 Recovery Act NIH Grand Opportunities grants focusing on BPA research have been awarded to:

Engineering center to probe forces that cause cancer to spread

Mon, 26 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers from the Johns Hopkins Institute for NanoBioTechnology have been awarded $14.8 million from the National Cancer Institute to launch a research center aimed at unraveling the physical underpinnings of the growth and spread of cancer.

The new Johns Hopkins Engineering in Oncology Center at INBT includes 11 Johns Hopkins faculty members affiliated with the INBT and four from partner universities. The project's participants say that they hope this new line of research will lead to never-before-considered approaches to cancer therapy and diagnostics.

The Johns Hopkins center is one of 12 being launched by the National Cancer Institute to bring a new cadre of theoretical physicists, mathematicians, chemists and engineers to the study of cancer. During the five-year initiative, the NCI's Physical Sciences-Oncology Centers will take new, nontraditional approaches to cancer research by studying the physical laws and principles of cancer; evolution and evolutionary theory of cancer; information coding, decoding, transfer and translation in cancer; and ways to deconvolute cancer's complexity.

By bringing a fresh set of eyes to the study of cancer, these new centers have great potential to advance, and sometimes challenge, accepted theories about cancer and its supportive microenvironment, NCI Director John E. Niederhuber said.

The NCI, part of the National Institutes of Health, will allocate the Johns Hopkins-based Engineering in Oncology Center's funding over five years. As the name of the center suggests, the researchers will look at how physical sciences play a role in the way cancer spreads, commonly called metastasis.

Physical scientists think in terms of time, space, pressure, heat and evolution in ways that we hope will lead to new understandings of the multitude of forces that govern cancer, Niederhuber said, and with that understanding, we hope to develop new and innovative methods of arresting tumor growth and metastasis.

Denis Wirtz, a professor of chemical and biomolecular engineering in the Whiting School of Engineering, will direct the center, and Gregg L. Semenza, a leading researcher at the School of Medicine, will serve as associate director.

Metastasis is a highly coordinated, multistep process, Wirtz said. Cancer cells break free from a primary tumor, penetrate into the bloodstream, evade host defenses, stick to the interior walls of blood vessels and travel to other organs, where they set up new cancer cell colonies. During this cascade of events, tumor cells push on and are pushed by mechanical forces within their microenvironment. Cells translate those mechanical forces into biochemical signals that affect cell growth and function. If we can gain a better understanding of this process, we may find new and better ways to treat cancer.

Wirtz, who is principal investigator, also serves as associate director of the university's Institute for NanoBioTechnology, a cross-divisional institute launched in May 2006 with 185 Johns Hopkins faculty members who are using nanoscience to answer questions in medicine, the basic sciences and public health.

The new cancer center will similarly draw on Johns Hopkins researchers with diverse expertise to study the role of physical forces involved in the development and spread of cancer.

Mechanical forces inside the body, such as shear exerted by blood flowing through blood vessels, typically destroy the millions of cancer cells that are constantly shed from tumors, Wirtz said. But the 'fittest' of cancer cells survive these Darwinian-like selective pressures and may become the culprits that spread cancer. Little is known about the effect of mechanical forces on the regulation of cancer cell growth. That is what the Engineering in Oncology Center and the National Cancer Institute want to find out. The results should point us to therapies and diagnostic tools that complement existing genetic or molecular treatments.

2009 Pearl Meister Greengard Prize goes to pioneering geneticist

Mon, 26 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The recipient of the 2009 Pearl Meister Greengard Prize is Australian geneticist Suzanne Cory, professor and former director of the Walter and Eliza Hall Institute of Medical Research. Created to recognize the accomplishments of outstanding female scientists and administered by The Rockefeller University, the prize will be presented at a ceremony in the university's Caspary Auditorium on November 5.

The Pearl Meister Greengard Prize was established by Paul Greengard, Vincent Astor Professor at the university and head of the Laboratory of Molecular and Cellular Neuroscience, and his wife, sculptor Ursula von Rydingsvard. Greengard donated the proceeds of his 2000 Nobel Prize in Physiology or Medicine to Rockefeller University and, in partnership with generous supporters of the university, created the yearly award. Named in memory of Greengard's mother, the prize was founded to honor women who have made extraordinary contributions to biomedical science, a group that historically has not received appropriate recognition and acclaim.

The 2009 prize recognizes Cory, a world-renowned geneticist and pioneering scientific leader. The first woman to serve as director of Australia's prestigious Walter and Eliza Hall Institute, she has been an influential force in shaping science policy in her nation.

Along with her colleague and husband Jerry Adams, Cory was instrumental in introducing gene cloning technology to Australian research by establishing the country's first facility for cloning eukaryotic genes in 1977.

Research by Cory has yielded key insights in immunology and cancer biology. She and her colleagues made important contributions to understanding how immune system cells known as B lymphocytes assemble their antigen receptors by antibody gene recombination. In later work, they helped to elucidate how abnormal chromosome rearrangements can lead to the development of cancer. Cory and associates further broadened the molecular understanding of cancer through studies of mechanisms that promote tumor formation by interfering with the cell death programs that normally protect against cancer.

Cory's current line of research, examining the methods by which bcl-2 and other genes affect the cell death process, carries implications not only for cancer but for certain autoimmune and neurodegenerative diseases as well.

Cory received her Ph.D. in 1968 from the MRC Laboratory of Molecular Biology, then the center of molecular biology research. Following postdoctoral research at the University of Geneva, she returned to Australia in 1971 and established her laboratory at the Walter and Eliza Hall Institute, where from 1988 to 2005, she was joint head, with Adams, of the molecular genetics of cancer division. From 1996 to 2009, Cory served as the institute's first female director, a position from which she exercised a strong influence on Australian science and health policy. From 1992 to 1997 she was an international research scholar with the Howard Hughes Medical Institute. She is a fellow of the Australian Academy of Sciences and of Great Britain's Royal Society, which awarded her its Royal Medal. She is also a foreign associate of the United States National Academy of Sciences and was recently named a knight of the French Legion of Honor.

Depression in older cancer patients can be effectively treated with collaborative approach

Tue, 20 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Depression in older cancer patients can be effectively treated with collaborative approach in primary-care settings

Depression in older cancer patients is very common, and has debilitating effects on their quality of life both during and after treatment. University of Washington (UW) researchers are showing that there are ways to better this situation.

Little is known about the optimal approach to treating depression in this population, and older cancer patients are less likely to be treated for their depression than are younger cancer patients, said Dr. Jesse Fann, University of Washington associate professor of psychiatry and behavioral sciences. Fann is the director of psychiatric services at the Seattle Cancer Care Alliance, and an investigator in the Clinical Research Division at the Fred Hutchinson Cancer Research Center in Seattle.

Fann and his colleagues evaluated the effectiveness in older, depressed cancer patients of an intervention called Improving Mood-Promoting Access to Collaborative Treatment (IMPACT), in comparison to a similar set of patients receiving usual care. All participants had either major depression or a type of chronic depression called dysthymia, or a combination of both.

IMPACT participants worked with a depression care manager in their primary-care clinic for up to a year. Under the supervision of the patient's primary-care provider and a psychiatrist, the care manager offered the patient support in taking anti-depressants if prescribed by the primary-care provider, education about depression, care coordination and structured counseling sessions that helped the patient engage in pleasant activities and that taught problem-solving skills.

The intervention was tested in 18 primary-care clinics in 5 states. The clinics served a variety of different socio-economic, geographic, and ethnic populations.

At the end of six months, 55 percent of the patients in the IMPACT group and 34 percent of the usual care participants showed a 50 percent or greater reduction in their depression symptoms. The IMPACT participants also had higher remission rates from depression, more depression-free days, less fatigue, a better quality of life, less functional impairment and fewer thoughts of death. Many of these benefits persisted during the one-year follow up period after the intervention was completed.

Among the functional impairments older cancer patients can experience with depression are fatigue and thinking problems, such as forgetfulness, feeling mentally slowed down, and having difficulty concentrating or solving problems. Decisions that used to be straightforward or easy for them have become challenging, Fann explained.

Based on their findings, the researchers concluded that the IMPACT collaborative care program is feasible and more effective than standard care in managing depression among older cancer patients in primary-care, and is widely applicable.

The IMPACT intervention can be successfully provided in diverse types of primary-care settings in various locations, and not just at specialized cancer centers. It can literally double the likelihood that the patient's depression will improve over time, said Dr. Jurgen Unutzer, UW professor of psychiatry and behavioral sciences and a co-investigator on the study with Fann and Dr. Ming-Yu Fan, UW research assistant professor of psychiatry and behavioral sciences.

The results were published today, Oct. 20, in a supplement of the

Exercise can aid recovery after brain radiation

Sun, 18 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Exercise is a key factor in improving both memory and mood after whole-brain radiation treatments in rodents, according to data presented by Duke University scientists at the Society for Neuroscience meeting.

This is the first demonstration that exercise can prevent a decline in memory after whole-brain radiation treatment, said lead researcher and graduate student Sarah Wong-Goodrich of the Duke Department of Psychology and Neuroscience. Whole-brain radiation is sometimes used to treat brain cancers in humans.

We found that exercise following radiation prevented a decline in erasable memory in mice and this is analogous to the type of memory problems people have after whole-brain radiation for brain tumors, said senior researcher Christina Williams, Ph.D., professor of psychology and neuroscience. This is the type of short-term memory people use to find their car after they have parked it in a large lot. After radiation, this type of memory becomes impaired in many people.

In the experiment, one group of mice that had brain radiation stayed in their cages under normal conditions, living with other mice, eating and playing as they liked. But a different group of mice that had radiation were given daily access to a cage with a running wheel, which they could use if they wanted to.

The animals were tested for how well they remembered spatial features in their environment for locating a preferred escape hole to exit a well-lit maze and hide. The mice completed tests at the two-week and the three-month mark after their irradiation to get a baseline and then to see how they fared over time.

Mice that had radiation plus access to running did as well at remembering where the hole was as normal mice that didn't exercise. Irradiated mice that had no access to an exercise wheel eventually showed no particular preference for the section of the maze with the escape hole.

It was remarkable that the irradiated, running mice were just like the normal, non-irradiated mice that didn't exercise, said Wong-Goodrich, who conducted the experiments in the Williams' laboratory. We were expecting some memory retention issues with a longer delay and there weren't any.

Exercise appears to actually protect against the loss of memory and the increase in depressive-like behaviors, Wong-Goodrich said.

The mice also were tested for depressive-like behavior, using gentle restraints which they worked to escape from. Two weeks after radiation, the irradiated mice gave up sooner than the normal mice. Three months after radiation, the runners that had brain radiation, however, tried just as hard as the normal mice, while their non-running counterparts gave up more readily.

Researcher Lee W. Jones, Ph.D., research director of the Duke Center for Cancer Survivorship and associate professor in the Duke Department of Radiation Oncology, said the findings show how powerful exercise is and how many benefits it can provide, and even restore, after radiation.

Jones said that he is beginning to look at neurocognitive outcomes for cancer patients at Duke who undergo radiation, in addition to their body health indicators. Once a patient gets a doctor's clearance, I think exercise is a good thing during whole-brain radiation, he said. I think telling patients to take it easy is the worst advice we can give, because we know they will become deconditioned physically, and this study shows exercise potentially could provide cognitive and psychological benefits.

Radiation knocks out the ability of the brain to produce new nerve cells, called neurons. Williams said that they were able to measure increases in certain growth factors in the exercising mice that might be necessary to help cells divide.

Exercise might help by increasing blood flow to the hippocampus area of the brain, which is an important structure for learning, memory, and spatial navigation, Wong-Goodrich said.

Case Western Reserve University receives $20.5 million

Tue, 13 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Case Western Reserve University has received a $20.5 million gift from Donald Goodman, DDS (DEN '45) and Ruth Weber Goodman.

The Donald J. and Ruth Weber Goodman Philanthropic Fund will reside at the University and the Cleveland Foundation. Income will be used to support education and research programs at the schools of medicine and dental medicine. The gift has been used to establish two professorships at the School of Medicine: The Dr. Donald and Ruth Goodman Professorship in Innovative Cancer Therapeutics, which is currently held by Mary J. Laughlin, MD; and The Dr. Donald and Ruth Goodman Professorship in Innovative Cardiovascular Research, which has not yet been appointed.

Don and Ruth Goodman cared deeply about the university, and we are truly thankful to them and their family for their commitment to pre-eminent research and education at our schools of medicine and dental medicine, said Barbara R. Snyder, president of Case Western Reserve University.

Donald Goodman, who died in 2007, was a Cleveland-area dentist who made his fortune through decades of savvy stock market investment. He and his wife, Ruth, who died in 2008, traveled to more than 260 countries and islands, met Mother Theresa and saw the Dalai Lama. Ruth was the daughter of Arthur F. Weber, founder of Cuyahoga Heights, OH-based Triplex Screw Co.. The company was sold to Murray Corp. of America in 1952.

As a couple, Don and Ruth shared the same goal to improve the lives of others. They realized this goal by setting an example with an incredible legacy gift to this community, said Donald Goodman's son, Bruce Goodman.

Donald Goodman's granddaughter Kayleen Goodman-McDowell added, This gift has allowed them to extend their values through a family legacy beyond any of our expectations.

Donald Goodman credited the research at the School of Medicine and Mary Laughlin, MD, of the Ireland Cancer Center with prolonging his life for six years through an experimental treatment for acute myeloid leukemia.

It is always gratifying to see a patient who has directly benefited from the application of cutting-edge medical research and who wishes to recognize the value of this through such a wonderful philanthropic commitment. This gift is truly inspiring, said Pamela B. Davis, dean and vice president for medical affairs at the School of Medicine. In addition to making a substantial investment in our faculty who work at the cutting edge, the endowment income will ensure that the school remains a pace-setter in educating world-class physicians and advancing the cure and treatment of disease.

Donald Goodman was a 1945 graduate of the Case Western Reserve University School of Dental Medicine, which will also benefit from the endowment.

Study finds no relationship between PCR rate and race in women with breast cancer

Fri, 09 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) SAN FRANCISCO - Locally advanced breast cancer patients who received the same class of neoadjuvant chemotherapy were found to have no evidence of disease at the time of their surgery, or achieved pathological complete response, at the same rate regardless of race, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, presented in a poster discussion session at the 2009 Breast Cancer Symposium in San Francisco, is the largest in a homogenous group of breast cancer patients evaluating pathological complete response (pCR) according to race. Only one other study, also conducted at M. D. Anderson but limited to triple negative breast cancer patients (estrogen and progesterone receptor negative, HER2 negative), has analyzed the relationship between the two.

Our findings confirm pathological complete response is a strong prognostic indicator and a surrogate for good survival, despite a patient's race, and that it's vital we continue to strive towards achieving this milestone for all women with breast cancer, said Mariana Chavez Mac Gregor, M.D., a medical oncology fellow at M. D. Anderson. The study also mandates that we continue to research the differences across races in breast cancer.

Racial disparities in breast cancer are known: the American Cancer Society (ACS) estimates that 19,540 blacks and 14,200 Hispanics will be diagnosed with the disease in 2009. While the overall incidence rate is 10 percent lower in blacks than whites, in 2001-2005, they had a 37 percent higher death rate. ACS also reports that overall breast cancer mortality rates are lower in Hispanic women than white women.

Understanding the reasons for such disparities - be it access to care and screening, biological differences in tumors and/or breast cancer subtypes - is the focus of ongoing research efforts across the cancer community, explained Chavez Mac Gregor, the study's first author.

While these disparities are known, we also understand that breast cancer patients who achieve pathological complete response have better outcomes, said Chavez-Mac Gregor. What we didn't understand until now was if pathological complete response rates had any relationship with race. If a specific ethnic group had a better or worse response rate, maybe we could then determine which groups may be in need of additional and /or improved therapies.

Using the M. D. Anderson Breast Medical Oncology database, the retrospective study identified 2,074 patients diagnosed with Stages II and III breast cancer and treated at the institution between 1994 and 2008. Of the patients, 1,334 (64.3 percent) were white, 302 (14.6 percent) black, 316 (15.2 percent) Hispanic, and 122 (5.9 percent) were classified as other race groups. The median age of the women was 50. All received neoadjuvant anthracycline- and taxane-based chemotherapy; receiving similar class of therapy was an important component in the design of the study, said Chavez Mac Gregor.

At the time of surgery, the researchers found no difference of statistical significance in pCR rates among racial groups: 12.3 percent in whites; 12.5 percent in blacks; 14.24 percent in Hispanics; 11.5 percent in other.

Among all patients, at a median follow-up of 30 months, there were 438 recurrences and 327 deaths. The five year unadjusted recurrence-free (RFS) and overall survival (OS) rates were: 71 percent and 79 percent in whites; 60 percent and 57 percent in blacks; 76 percent and 79 percent in Hispanics; and 75 percent and 84 percent in other, respectively. Lack of achieving pCR, HER2-positive and triple-negative subtypes, lymph node involvement were all found to be independent predictors of worse RFS and OS.

In further analysis, the study reconfirmed what had been noted in literature - although not statistically significant, blacks tended to have poorer outcomes, while Hispanics had improved outcomes compared to whites, said Chavez Mac Gregor.

The study is not without limitations, she noted: in design, it was both retrospective and a single-institution study, and race was self-reported. In addition, the research focus was until the time of surgery, with less attention towards patients' experience post-surgery, such as compliance to hormone therapies or other adjuvant treatments, other than RFS and OS.

In the same cohort of patients, Chavez Mac Gregor plans further analysis of patients who did not achieve pCR to better understand why they might not have reached this milestone.

M. D. Anderson team chosen to help navigate Cancer Genome Atlas

Wed, 07 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) HOUSTON -- The Cancer Genome Atlas (TCGA) will fund an effort by scientists at The University of Texas M. D. Anderson Cancer Center to siphon buckets of meaningful information from an ocean of data about the aberrant genetics that drive human cancers.

Analysis and interpretation of genetic data from tumor samples is a major bottleneck to progress in understanding and treating cancer, said the project's lead principal investigator John Weinstein, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Bioinformatics and Computational Biology, as well as professor in the Department of Systems Biology.

The five-year $8.3 million grant from the TCGA will allow Weinstein and colleagues to put new computational tools to work parsing the multiple genetic pathways that fuel more than 20 types of cancer. The team proposes a more flexible and efficient approach to wringing information from overwhelming quantities of data researchers generate about gene expression and variation in tumors.

The bottom line is personalizing cancer medicine. If we can generate molecular portraits of these cancers, we will be better able to choose the right therapy for each patient, Weinstein noted. And it also will improve cancer risk assessment, early diagnosis, prognosis and assessment of the likelihood of recurrence.

The M. D. Anderson group is a new Genome Data Analysis Center of the TCGA, which is a joint enterprise of the National Cancer Institute and the National Human Genome Research Institute, both of the National Institutes of Health. The grant is part of the expansion of TCGA, after a pilot project focused on glioblastoma, lung cancer and ovarian cancer.

Co-leaders of the project are Gordon Mills, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Systems Biology, and W. K. Alfred Yung, M.D., professor and chair of the Department of Neuro-Oncology. They will provide extraordinary expertise in the systems-oriented and clinical aspects of the overall project, Weinstein said.

Rather than focusing on individual or pairs of genetic variations in tumors, the M. D. Anderson analysis center will study multi-gene pathways and combinations of pathways, a systems biology approach that addresses the complexity of cancer growth and survival.

Weinstein's group is developing a bioinformatic pipeline to analyze TCGA data and translate findings to the clinic. We will use several nuggets of innovation to develop applications that will usefully address the questions that biologists and clinicians have at the end of the day, Weinstein said.

A major strength of the project is M. D. Anderson's leading expertise in translational and clinical research, Weinstein said. That expertise will keep bioinformatics development connected to important questions that must be addressed for each tumor type and for different types of molecular information. Additionally, M. D. Anderson is by far the largest contributor of tumor tissue samples to TCGA. That will be particularly important in the study of less common cancers.

The team will tap M. D. Anderson's leadership in the use of Bayesian statistical analysis, an efficient and informative approach to data analysis and clinical trial design, as developed under Donald Berry, Ph.D., Professor and Head of the Division of Quantitative Sciences.

Weinstein and colleagues will apply a number of advanced computational tools and concepts based on pathway analyses, artificial intelligence-based prediction methods, and the clustered heat map representations of genomic data that Weinstein introduced in the early 1990s.

Professor of Bioinformatics and Computational Biology Jonas Almeda, Ph.D., is a leading expert in semantic web, a flexible database infrastructure that's easily expandable to accommodate new types of searches. Searching a standard relational database requires loading the data and then searching it for the desired information, Weinstein explained. A semantic web structure allows searches based on a subject-predicate-object format that can home more directly to the information sought, dramatically speeding up searches. With an appropriate graphics card, more data crunching can be done in the browser of the user's laptop, rather than in a distant server. That also speeds processing time and relieves pressure on the server.

Team member David Kane of SRA International, a longtime collaborator of Weinstein's, is an expert in the Agile software development paradigm. Traditional software development involves extensive planning and consultation with users before any code is written. The central tenet of agile development is that you get something working quickly via close consultation between biologists and software engineers. The biologists then are the initial testers and users, and the software is grown organically. The initial investment is small, so you don't have to be afraid of changing direction if necessary, Weinstein said.

Kane used the agile approach to develop the Miner Suite of bioinformatics software with Weinstein at the National Cancer Institute. Weinstein worked at the NCI for more than 30 years, and directed what has been considered a precursor project to the Cancer Genome Atlas before coming to M. D. Anderson in January 2008. Advances based on the Miner Suite will be used in this project.

The TCGA grant application was Weinstein's first to his former employer.

Findings and tools generated by the project will be open source, available to other TCGA research teams, and in a format compatible with both The Cancer Genome Atlas and the NCI's Cancer Biomedical Informatics Grid (caBIG).

Strategy for mismatched stem cell transplants triggers protection against graft-vs.-host disease

Wed, 07 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) BOSTON--A new technique being tested in stem-cell transplants from imperfectly matched donors has revealed a striking, unforeseen response that can suppress graft-versus-host disease, a common and dangerous complication of mismatched transplants, report scientists from Dana-Farber Cancer Institute.

Analysis of blood samples from a small number of clinical trial patients showed that the novel method -- which inactivates specific immune cells from the donor that would attack the recipient's body -- also unleashes a surge of T-cells that further dampen the immune reaction.

The previously unrecognized specificity of these regulatory T-cells (also called Tregs) helps explain why the patients treated with the new strategy -- known as co-stimulatory blockade -- have shown a gratifyingly low level of graft-vs-host disease, according to the report published online by the new journal Science Translational Medicine.

The findings also suggest that optimizing the activity of Tregs in this manner might prove valuable in transplants of kidneys and other solid organs, as well as in treating autoimmune disease, say the scientists, led by Eva Guinan, MD, senior author, of Dana-Farber and Children's Hospital Boston, and Jeff Davies, MD, PhD, first author, of Dana-Farber. Both are also on the Harvard Medical School faculty.

The innovative method for improving mismatched bone-marrow and stem-cell transplants was first described clinically 10 years ago in the New England Journal of Medicine by Guinan, Lee Nadler, MD, also at Dana-Farber and a co-author on the new publication, and others. They employed a technique called co-stimulatory blockade to prevent certain T-cells in the donor material from recognizing and attacking cells in the patient's body, causing graft-vs-host inflammatory reactions that can affect the gastrointestinal system, skin, and other organs. The need for techniques that can reduce complications in mismatched transplants is great; the odds of a patient having a perfectly matched sibling for a donor are only about 25 percent.

Originally we thought that using this method to specifically block the harmful response by donor T-cells explained the decrease in graft-vs-host disease and the rapid recovery of immune function we have seen in the clinical trials, said Guinan. Now we learn that there is another powerful mechanism that is induced -- the generation and rapid expansion of Treg cells in the three months following the transplant.

Regulatory T-cells are a special population of T-cells that suppress immunity. They have two important functions: Turning off immune reactions following a successful defense against infectious organisms, and preventing immune cells from attacking the body's own tissues, which are identified by distinctive self-antigen markers.

In the past five years or so, scientists have used new tools to study Tregs and consider ways they could be harnessed for therapy in transplantation and autoimmune disease. In 2008, Davies and Guinan reported low levels of graft-vs-host disease in a small number of mismatched transplants using co-stimulatory blockade, which not only neutralized the T-cells that cause the harmful graft-vs-host response but also led to rapid reconstitution of the patients' bone marrow.

The researchers then designed experiments to learn more molecular details about how the blockade strategy had reduced graft-vs-host complications. Based on few reports in the literature, We wondered whether Tregs were playing an additional role, said Davies.

Prostate cancer gives a new outlook on life

Mon, 05 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Men who have prostate cancer often feel quite healthy, but the diagnosis still gives them a whole new outlook on life. Once they have learned to live with their cancer, they choose to focus on valuable relationships and appreciate the little things in life, shows a dissertation thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden.

We need a better understanding of how men with prostate cancer experience their illness and how they choose to adapt their new circumstances, says district nurse Annikki Jonsson, who interviewed 37 men with prostate cancer for her thesis. We can then support them better and tailor their treatment to the phase they are in.

The results show that the men go through different phases of adjustment in succession after getting their diagnosis, and that their everyday lives are affected differently according to which phase they are in.

Those with less serious prostate cancer find themselves in an emotional vacuum immediately after receiving their diagnosis. During this phase, which normally lasts around a week, it is pointless for medical personnel to try to give men information about their illness.

But they do appreciate positive reception without pity during this initial phase. And, of course, if they do choose to get in touch and ask some questions, it's important to answer and tell where you can turn to with diffrent thoughts.

Once these men have negotiated this initial phase, they regain control over their lives and find their driving force for life. They begin actively seek out information about their illness.

Men who learn that they have an aggressive form of prostate cancer find that the disease is allways at present and they feel often a sense of emptiness during the initial period following the diagnosis. For these men, the disease is an existential threat.

They think a lot about how the future will be and how they will die.

The men I interviewed said that they lived life more intense, but that they had their ups and downs, says Jonsson. Sometimes they felt more alive, and in the next minute got a feeling that they risked losing control or being reminded of their changed masculinity.

The men were interviewed again two years after receiving their diagnosis. They told that they had realised that life is fragile, and they were aware that they did not know how long the life will be. They got more faith and trust in life and had discovered that they could preserve their autonomy and integrity despite their illness.

Life changes, and it's important to achieve some kind of balance, says Jonsson. The men focused their energy on the relationships which were valuable for them. They appreciated the little things in life in a different way nowadays and developed an inner strength to be true to themselves.

DNA test could be key to targeting treatments for head and neck cancer

Mon, 05 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) It is estimated that more than 7,000 people are diagnosed with head and neck cancer each year in the UK and approximately 3,500 cases result in death. These cancers include tumours of the mouth, lips, throat and voice-box, and some have been linked to the sexually transmitted infection, HPV-16. Scientists at Liverpool analysed the DNA of more than 90 cancerous tissue samples to look for genes that indicated infection.

The team found that nearly two thirds of tonsil tumour samples showed evidence of the HPV-16 gene. It is thought that chemical alterations in the virus's DNA trigger the production of proteins that can alter the rate at which cells grow and repair. This strongly increases the possibility of subsequent cancer development. Recent studies have found, however, that patients who have the HPV infection when they are diagnosed with cancer, respond better to chemotherapy or radiation therapy than those that do not have the infection. The work will be presented at the National Cancer Research Institute's (NCRI) Cancer Conference in Birmingham today.

Mr Richard Shaw, from the School of Cancer Studies, explains: Recent evidence demonstrates the possible involvement of HPV in the development of tonsil cancer, particularly in non-smokers. Interestingly, the treatment efficiency of chemotherapy and radiation, seems to differ between HPV positive and negative cases. We also need to find out why only a small percentage of people with this common infection develop this cancer. Our study, however, gives us a new lead towards a risk marker.

It is thought that HPV interacts in the cell with genes controlling the chemical modification of DNA, which affects gene expression and tumour behaviour. Our study shows that HPV may be a trigger of tonsil cancer, independent of the known common causes, such as smoking or drinking. The work also suggests that a DNA test to determine the activity of HPV, could be used to identify the most effective treatment for each individual patient.

Liverpool has the largest centralised head and neck oncology practice in the UK and our data show a doubling in the rate of non-drinkers and non-smokers presenting with tonsil cancer. As head and neck cancer is one of the cornerstones of the new CR-UK Cancer Centre in Liverpool, we are pleased to be making real progress in this area of research.

Researchers are now working to develop a clinical trial for a therapeutic HPV vaccine in head and neck cancer.

NIH announces expansion of Rare Diseases Clinical Research Network

Mon, 05 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The National Institutes of Health announced today a second phase of the Rare Diseases Clinical Research Network (RDCRN) including funds for 19 research consortia. The Rare Diseases Clinical Research Consortia and a Data Management Coordinating Center (DMCC) will be awarded a total of just over $117 million over the next five years. The research conducted with the new funding will explore the natural history, epidemiology, diagnosis, and treatment of more than 95 rare diseases.

The progress made by researchers through the network over the past six years is important and impressive, said NIH Director Francis S. Collins, M.D., Ph.D. We have shown that this approach can be a catalyst for progress in meeting the challenge of rare diseases, and we are eager to launch this next phase of the program.

A rare disease is defined as a disease or condition affecting fewer than 200,000 persons in the United States. Approximately 6,500 such disorders have been identified, affecting an estimated 25 million Americans.

Initially created in 2003, the RDCRN is unique in its approach to addressing rare diseases as a group. Previously, the NIH's institutes and centers funded research on individual rare diseases in their respective disease-type or organ domains. The RDCRN is the first program that aims to create a specialized infrastructure to support rare diseases research.

Since its creation, the RDCRN has enrolled over 5,000 patients in 37 clinical studies in rare diseases. Patient recruitment for clinical studies is a fundamental challenge in rare diseases research because there are typically so few affected patients in any one area. The RDCRN was designed to address this problem by fostering collaboration among scientists and shared access to geographically distributed research resources. Network consortia have also established training programs for clinical investigators who are interested in rare diseases research.

Collaboration is a critical element of rare diseases research and the partnerships represented in this program have tremendous potential to make great strides in understanding these diseases, said Stephen C. Groft, Pharm.D., director of NIH's Office of Rare Diseases Research (ORDR). The network emphasizes collaboration not just among investigators from multiple research sites but between investigators and patient advocates as well.

The direct involvement of patient advocacy groups in network operations, activities, and strategy is a major feature of the RDCRN. Each consortium in the network includes relevant patient advocacy groups in the consortium membership and activities. These patient advocacy group representatives serve as research partners within their own consortia. Collectively, the Coalition of Patient Advocacy Groups (CPAG) represents the perspective and interests of all patient advocacy organizations associated with the RDCRN. The CPAG participants meet frequently throughout the year via teleconference and face-to-face meetings. They participate in network-level discussions and meetings. The CPAG chairperson is a voting member of the RDCRN Steering Committee.

Funds and scientific oversight for the RDCRN will be provided by ORDR and seven NIH Institutes, which will also contribute considerable administrative support to the network: the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Heart, Lung and Blood Institute (NHLBI). Several consortia will also receive financial support from their associated patient advocacy groups.

Revolutionary statewide UC collaboration targets breast cancer

Tue, 29 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The University of California is launching an unprecedented statewide collaboration for breast cancer patients with the goal of revolutionizing the course of their care by designing and testing new approaches to research, technology and health care delivery.

Named the ATHENA Breast Health Network, the groundbreaking project will initially involve 150,000 women throughout California who will be screened for breast cancer and followed for decades through the five UC medical centers. ATHENA is a University of California system-wide project supported by a $5.3 million University of California grant and a $4.8 million grant from the Safeway Foundation.

The project is expected to generate a rich collection of data and knowledge that will shape breast cancer care in the way the renowned Framingham heart study changed the care of patients with heart disease.

ATHENA is a model of multi-institutional collaboration and demonstrates the enormous potential in shared systems, said John D. Stobo, MD, UC senior vice president for health sciences and services. This is a great example of the power of our statewide university network of academic medical centers; this initiative will demonstrate that the total of what can be accomplished by UC functioning as an integrated system can far exceed the sum of contributions by the individual campuses. ATHENA represents an unprecedented opportunity to play a leadership role in driving critical changes in health care. The public nature of the UC institutions make them uniquely positioned to study the appropriateness and effectiveness of treatment. It also allows for the applied use of new scientific evidence, much of which has been developed in the UC medical centers, to truly change the delivery of care.

The medical centers involved in the large-scale demonstration project are UC San Francisco as the host campus, UC Davis, UC Los Angeles, UC San Diego, and UC Irvine. Also participating in the collaboration are the UC Berkeley School of Public Health, the Northern California Cancer Center, Quantum Leap Healthcare Collaborative, the National Cancer Institute's BIG Health Consortium, and the Center for Medical Technology Policy.

We are excited to be supporting this innovative collaboration that, to date, has the clearest potential to produce ground breaking research that will bring us closer to a cure, said Larree Renda, Safeway Inc. executive vice president, chief strategist and administrative officer and chair of the Safeway Foundation.

Breast cancer, the most common cancer in women, is a devastating and costly disease, striking more than 200,000 women annually and killing more than 40,000 women each year, according to the American Cancer Society. In the United States, more than $20 billion is spent annually screening and treating the disease.

ATHENA is designed to more efficiently integrate financing, technology, research and clinical care, creating an infrastructure model that could be utilized for many medical conditions.

Our goal is to improve survival and reduce suffering from breast cancer, to accelerate research and compress the time to implement innovations in clinical practice, said ATHENA principal investigator Laura Esserman, MD, MBA, professor of surgery and radiology, director of the UCSF Carol Franc Buck Breast Care Center and co-leader of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center.

By working together as a community, the University of California medical centers, their affiliates, primary care and specialty physicians and patient advocates will work to change the options for patients today and create a better future for all women at risk for developing breast cancer, she added.

The goals of the ATHENA initiative are:

Research needed to learn which DCIS patients may be candidates for less invasive therapy

Thu, 24 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Ductal carcinoma in situ (DCIS), the most common non-invasive lesion of the breast, presents unique challenges for patients and providers largely because the natural course of the untreated disease is not well understood. Because most women diagnosed with DCIS are treated, it is difficult to determine the comparative benefits of different treatment strategies versus active surveillance, meaning systematic followup. An independent panel convened by the NIH urged the scientific community to identify appropriate biomarkers and other prognostic factors to better predict the risk of developing breast cancer.

Instead of treating all women diagnosed with DCIS, we need to determine which individuals are likely to develop invasive breast cancer and which will not, said Dr. Carmen Allegra, panel chair and Chief of Hematology and Oncology at the University of Florida. If we could accurately predict this, we might save some women from undergoing unnecessary invasive treatments while achieving the same positive outcomes.

DCIS is a condition in which a spectrum of abnormal cells are found in the breast duct and have not spread outside the duct to other tissues in the breast. Since the advent of widespread screening mammography in the early to mid 1980's, rates of DCIS have increased sharply. It is estimated that more than one million U.S. women will be living with a prior diagnosis of DCIS by 2020.

Despite the connotations associated with the term carcinoma, DCIS is associated with ten-year survival rates close to 100% when treated with currently available therapies. These include breast-conserving surgery (local excision, with or without radiation), removal of the breast (mastectomy), and/or tamoxifen. It is important to stress that each of these treatment options has physical and emotional impacts to patients and should be weighed accordingly. The panel recognized that there are relatively few reliable data on the comparative effectiveness of both diagnostic and therapeutic options in DCIS.

To improve our understanding of this complex disease, the panel recommended efforts to ensure detailed collection of clinical, pathological, imaging, and molecular data about DCIS using standardized reporting measures, annotated specimen repositories, and multicenter databases.

The panel emphasized the importance of patient preferences and recommended improved communication between patients and providers, and serious consideration of new nomenclature that more closely reflects the excellent survival rates for this condition.

Efforts to improve communication would also include further development of formal decision aids. Such tools would reduce misinformation and improve understanding of a DCIS diagnosis and the risks and benefits of various treatment options. Individuals who have DCIS should have access to the best possible information and guidance to aid them in making care decisions that reflect their unique circumstances, perspectives, and preferences.

The panel's updated draft state-of-the-science statement will be available later today at

Prestigious $4.9 million NIH grant awarded to Case Western Reserve for colon cancer research

Thu, 24 Sep 2009 03:59:12 PST

( from http://www.rxpgnews.com ) A prestigious National Institutes of Health (NIH) Transformative R01 Program grant for $4.9 million has been awarded to Case Western Reserve University School of Medicine. The five-year grant will fund research to identify patients' inborn genetic susceptibility to the development of colon cancer metastasis. Case Western Reserve was one of only 42 recipients of this competitive new grant designed to support exceptionally innovative, high risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms.

The distinction of being selected for this award reflects the leading role played by Case Western Reserve University School of Medicine and the University Hospitals Ireland Cancer Center at the national level, says Sanford Markowitz, M.D., Ph.D., the study's principal investigator and the Markowitz-Ingalls Professor of Cancer Genetics.

Colon cancer is the second leading cause of cancer deaths in the United States. One third of individuals with colon cancer die of a metastatic spread of the disease. The School of Medicine team proposes there is a new paradigm in colon cancer metastasis, which has historically thought to be due to the accumulation of multiple gene mutations in the cancer cell. Dr. Markowitz and team hypothesize that cancer metastasis is not due to new metastasis-causing genetic mutations in the cancers, but rather is crucially dependent on inborn genetic susceptibility factors. This proposal is based on the team's prior research studies showing that no new mutations acquired in a colon cancer metastases are any different from the preceding primary colon cancer tumor. These findings directly challenge the paradigm that has dominated cancer genetics for more than two decades.

Specifically, the team will identify these susceptibility genetic markers using the technique of a whole genome association study to compare the frequency of more than one million genetic variants between individuals whose colon cancers never metastasized, versus those whose colon cancers were metastatic at the time of diagnosis, and versus individuals whose colon cancers relapsed and metastasized following initial complete surgical resections. By identifying genetic markers that track with individuals who have developed cancer metastases, the team will seek to hone in on and identify the underlying metastasis susceptibility genes; identify the causative metastasis susceptibility variants present in these genes among different ethnic groups; determine if these variants or genes also impart susceptibility to metastasis in other common solid tumors; and determine the biologic pathways by which these susceptibility alleles promote cancer metastasis.

Acceptance of this paradigm will result in the identification of entirely new biological pathways that will be key to the management and prognosis of colon cancer, and to developing new and more effective anti-cancer therapies.

ESMO recognizes leading oncologists with prestigious awards

Tue, 22 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The European Society for Medical Oncology (ESMO) has recognized the outstanding achievements of three leading cancer specialists with its three prestigious annual awards: the 2009 ESMO Award, Hamilton Fairley Award and ESMO Lifetime Achievement Award.

Professor T. Andrew Lister, Center Lead for Medical Oncology, Institute of Cancer, Barts and the London School of Medicine, UK, has been awarded the 2009 Hamilton Fairley Award. The award commemorates one of the founding fathers of medical oncology in Europe and is presented to candidates who are internationally recognized for lifetime achievements in science and clinical / laboratory research.

Professor Lister is a physician, clinical academic and teacher who is recognized internationally for his leading role in improving the outcome of hematologic cancer malignancy. He is particularly well known for his pioneering work on the biology and treatment of follicular lymphoma, and the Medical Oncology Unit he leads in the Barts and the London School of Medicine and Dentistry is one of the leading cancer centres in the UK, with a worldwide reputation. Professor Lister was chairman of the Association of Cancer Physicians and of the Royal College of Physicians Committee on Medical Oncology from 1988-1991. The award for Professor Lister is especially significant as he had the privilege of having Gordon Hamilton Fairly as his as his mentor and role model.

I am most flattered and honored to receive the Hamilton Fairley Award in respect of the work that has been carried out in the Unit of which he was the first director, Professor Lister said. I am delighted to accept it on behalf of the CR-UK Medical Oncology Unit at Barts.

Professor Elisabeth de Vries, head of the department of medical oncology at University Medical Center Gronigen in The Netherlands has been named as the recipient of the 2009 ESMO Award. The ESMO Award is conferred on an ESMO member who has made an outstanding contribution to the development of oncology in Europe and who recognizes the importance of promoting oncology as a specialty within the international community.

Professor de Vries is working to develop personalized treatments for cancer patients. She uses interdisciplinary, translational research to improve the diagnosis and treatment of breast cancer and other malignancies, and applies molecular imaging to search for drug targets in cancers of the breast and neuroendocrine tissue. In 1997, she was appointed as the first female Professor in Medical Oncology in the Netherlands and the first female head of a department of medical oncology in a Dutch university medical centre. In addition to her experimental work, Professor de Vries treats patients and teaches medical students. She has also been part of initiatives run by the Netherlands Organisation for Scientific Research and the Royal Netherlands Academy of Arts and Sciences.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research, London, has been awarded the 2009 ESMO Lifetime Achievement Award. The award is open to all international research teams/individuals with demonstrated commitment to cancer research treatment.

In 1995, Professor Ashworth contributed to the discovery of the breast cancer susceptibility gene BRCA2, and ten years later his team uncovered the exquisite sensitivity of cells that carry mutant forms of BRCA1 or BRCA2 to a class of drugs known as PARP inhibitors. The early results from clinical trials of this approach have generated considerable excitement. Professor Ashworth has been director of the Breakthrough Breast Cancer Research Centre since 1999 and the Centre now has more than 120 staff working on diverse aspects of the disease. In 2008 he was elected as a fellow of Britain's Royal Society.

I am delighted and honored to receive this important award which is testament to all the hard work of my colleagues in the Breakthrough Centre over the past 10 years, Professor Ashworth said.

Researcher awarded $1.2 million grant to study centrosomes and cilia

Tue, 22 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) TALLAHASSEE, Fla. -- If you don't know how a human cell is supposed to work, it's hard to offer a good explanation when the cell goes haywire -- as it does in cancer. That's why a Florida State University College of Medicine researcher has been awarded a $1.2 million grant to explore the role of centrosomes and cilia in cell division and development and their connections to human disease.

Tim Megraw, a veteran researcher who joined the College of Medicine as an associate professor in August, received the four-year grant from the National Institutes of Health this month. The grant continues through August 2013.

The focus of Megraw's work is cell division. Cancer occurs when renegade cells start dividing uncontrollably. Anti-cancer drugs such as Taxol, Megraw noted, target the microtubule, a key molecule that regulates cell division. Along with other areas of focus, he's looking into microtubule regulation and its relationship to another component of the cell called the centrosome.

We're studying how microtubules are regulated in cells normally, Megraw said, and the key roles that the centrosomin family of proteins play in this process. Centrosomes are the main centers for organizing microtubules. So we're interested in how centrosomes are assembled and regulated. Both of those goals are outlined in this new grant.

Remarkably, centrosomins regulate not only centrosome assembly and their functions in cytoskeleton assembly, but also the replication of centrosomes in the cell cycle.

This is a continuation of work Megraw and his wife, Ling-Rong Kao, now an assistant in research at the medical school, began in 2003 at the University of Texas Southwestern Medical Center in Dallas. They have explored cells in the brain of the fruit fly and, more recently, the mouse.

Based on their work, researchers better understand the nature of centrosome-based diseases.

Most of the diseases affect these little hair-like structures that stick out of our cells -- cilia, said Megraw, noting that interest in cilia has experienced a renaissance in recent years. It's funny because, if you read a review article from 15 or 20 years ago, people wrote statements like 'These appear to be useless vestiges.' And now they appear to be key signaling centers. I have trouble keeping up with the list of diseases that are now associated with defective cilia.

Among those diseases are polycystic kidney disease, as well as other syndromes that lead to deafness, visual degeneration, obesity and primary microcephaly, a condition in which brain development is impaired.

NIH funds grantees focusing on epigenomics of human health and disease

Wed, 16 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The National Institutes of Health announced today that it will fund 22 grants on genome-wide studies of how epigenetic changes -- chemical modifications to genes that result from diet, aging, stress, or environmental exposures -- define and contribute to specific human diseases and biological processes.

The awards will build on the important work undertaken as part of the NIH Roadmap for Medical Research's Epigenomics Program. Approximately $62 million will be awarded over the next five years to study the epigenome in a number of diseases and conditions, including tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development.

Epigenomics represents the next phase in our understanding of genetic regulation of health and disease, says NIH Director Francis Collins, M.D., Ph.D. These awards will address the extent to which diet and environmental exposures produce long lasting effects through changes in DNA regulation. The initiative was launched through the NIH Director's Office and, as part of the Roadmap, is expected to profoundly alter the way we understand, diagnose, and treat disease.

This is the largest effort to date to apply epigenetics on a genome-wide scale to specific diseases, said James F. Battey, M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, one of the lead NIH institutes for this Roadmap program.

The Roadmap Epigenomics Program was designed to characterize epigenetic modifications and to correlate the presence or absence of specific modifications with disease status. DNA methylation is a fundamental epigenetic modification that regulates gene expression and chromosome stability. This and other epigenetic modifications control gene activity by changing the three-dimensional structure of chromosomes. (See scientific illustration of epigenetic mechanisms at http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp.)

The awards announced today are funded by 11 NIH institutes and the NIH Office of the Director and are part of the NIH Roadmap for Medical Research's Epigenomics Program that began in 2007. The NIH contributors include the National Cancer Institute, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and the Office of Behavioral and Social Sciences Research and the Office of Strategic Coordination in the NIH Office of the Director.

The new grantees being announced will join a larger collaborative research effort that is working together to understand epigenetics and how it affects human health and disease, said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse.

This health and disease-focused component of the NIH Roadmap Epigenomics Program builds on the previous four interrelated initiatives, but is the first to tackle questions related to diseases. The other four initiatives include the establishment of four epigenome mapping centers, the funding of an epigenomics data analysis and coordination center. the development of innovative technology in epigenetics, and the discovery of novel epigenetic changes.

These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases, said Linda S. Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences.

The following awards are being made by NIH:

International event brings world's top cancer doctors to Queen's

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Over 200 of the world's top cancer specialists will be in Belfast this week to share their knowledge at an International Cancer Symposium organised by Queen's University.

The event, being hosted by the Centre for Cell Biology and Cancer Research (CCRCB) on Wednesday and Thursday, will be attended by leading academics from across America, Australia and Europe, including those from Harvard Medical School in Boston and from Oxford and Cambridge universities.

One in three people in Northern Ireland will be diagnosed with cancer at some stage in their life and the conference aims to build on international links to improve cancer treatments for sufferers.

CCRCB is currently carrying out around 50 national and international clinical trials into various cancers with the aim of offering patients new treatment options which will have the best outcomes for them as well as fewer and less severe side effects.

The Centre has three successful spin-out companies - ALMAC Diagnostics, Fusion Antibodies and I-Path - employing nearly 200 people.

Two young researchers will present their studies at the event entitled 'Cancer: Found in Translation'.

Dr Kelly Redmond from Newry and Dr Jenny Quinn from Londonderry will be among the international line-up of speakers sharing their knowledge about the latest developments in cancer research.

Dr Redmond will speak about her research into a molecule called FLIP which blocks chemotherapy from working in non-small cell lung cancer (NSCLC), the leading cause of cancer death in the US and Europe. By decreasing FLIP levels in NSCLC cells they become more sensitive to chemotherapy.

She said: This is an important finding as it suggests that if we can decrease FLIP levels with new types of drugs, the cancer but not the normal lung tissues will be more effectively killed by chemotherapy.

Dr Quinn's research has focused on trying to find the best chemotherapy treatment for both breast and ovarian cancer sufferers.

She has investigated the effects of the drugs on patients with and without the BRCA1 gene, which controls cell growth in normal breast and ovarian cells, preventing tumours forming.

Ovarian cancer patients are generally treated with both platinum and taxane based chemotherapy. However Dr Quinn has found that patients without BRCA1 benefited significantly from platinum only chemotherapy while those with normal BRCA1 levels gained an almost two year improvement in survival if they also received taxane chemotherapy.

Dr Quinn said: We are now planning further studies that may ultimately lead to the development of a test involving BRCA1 for determining the best chemotherapy treatments for patients with ovarian cancer. Such a test may also prove useful in breast, lung and prostate cancer.

The symposium has been organised by Professor Dennis McCance, Director of the Centre for Cancer Research and Cell Biology at Queen's University, who leads a team of around 250 staff.

He said: This event reflects CCRCB's achievements in cancer research and highlights our aspirations to see our knowledge about basic research translated into better and more effective treatments for patients.

Through clinical trials we are working to offer patients new treatment options which will have the best outcomes for them.

We are using novel ways to select treatments and personalise or tailor them to the patient's particular mutations.

The calibre of speakers coming to our conference and the international links that we have formed demonstrate that our work is considered of a world-class standard.

Professor Peter Gregson, Vice-Chancellor of Queen's University, said: Cancer is a disease feared around the world. Its impact is global. It therefore demands a global response, a response where leading researchers work together across academic disciplines and geographical frontiers.

We are pleased to bring together leading academics and researchers from across the world to discuss innovative scientific and medical research that will help those who suffer from cancer.

New reagents for genomic engineering of mouse models to understand human disease

Wed, 19 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The ability to specifically target and modify genes in the mouse allows researchers to use this small rodent to study how certain genes contribute to human disease. A common method used to make genetic changes in mice and cells is called site-specific recombination, where two DNA strands are exchanged. The two strands may contain very different sequences, but are designated at their ends by specific target sequences that are not commonly found elsewhere in the genome. A protein, called a recombinase, cuts the DNA at its target sites and rearranges it. Scientists use this technique to exchange a naturally occurring DNA sequence for an altered or deleted gene to gain insight into the gene's normal function or how it contributes to disease.

Currently there are a few systems available to create genetic mutations in mice, including the recombinases FLP and Cre. These proteins are very efficient genetic modifiers and specifically target their appropriate sequences. They can also be turned on or off at precise times, or within specific tissues, to make carefully reegulated genetic changes. However, the small number of available methods that can be used together to mutate genes limits the complexity of the modifications that can be produced. For example, it would be informative to independently regulate the temporal and tissue-specific expression of genes with overlapping functions to understand their individual and combined effects.

Scientists now report that a new recombinase, Dre, induces controlled genetic changes in mice. Dre works similarly to the currently popular recombinase Cre, with an important exception: Dre recognizes a distinct target sequence and only recombines DNA around its target sequence, even if the target sequence for Cre is present. The ability of the related proteins, Cre and Dre to distinguish their own target sequences indicates that Dre can be used in combination with Cre, and other recombinases, to produce more sophisticated mouse models. This should facilitate the analysis of complex gene interactions and how they function in disease.

This technological advance also highlights the progress that might be made through open reagent sharing within the scientific community. The discovery of Dre recombinase was originally reported by Sauer and McDermott at the Stowers Institute for Medical Research. The Institute holds an intellectual patent for the system that allows it to be shared openly for non-commercial purposes and evaluates requests on a case-by-case basis for its use by for-profit institutions. Thus, the authors of the new DMM report do not have any proprietary claims to the system that they used to create this valuable mouse model. This is the first of a series of Resource Articles that will appear in

Delays in UK child brain tumor diagnosis

Fri, 07 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Significant numbers of children in the UK are suffering from preventable levels of disability, particularly blindness, and premature death because of poor diagnosis of brain tumours.

A new study by scientists at The University of Nottingham's Children's Brain Tumour Research Centre, funded by the Samantha Dickson Brain Tumour Trust, shows that prolonged and slow diagnosis can make long term survivors of childhood brain tumours up to 10 times more likely to suffer disability. 450 children in the UK are diagnosed with a brain tumour every year. The average time between the onset of symptoms and diagnosis in children in the UK is between two and three months, that's up to three times longer than the rest of Europe and the USA.

David Walker, Professor of Paediatric Oncology at the Children's Brain Tumour Research Centre, University of Nottingham, said: Our study showed that the UK health system is the slowest system for making this diagnosis compared to reports from other countries. It takes more than 13 weeks in the UK to make this diagnosis for half of the patients, whilst in the US and Poland this is achieved within 5 weeks. The research also showed that symptoms increased in number and that disability increased in severity as time passed before diagnosis. This indicates that delays in diagnosis are affecting the severity of disability for the children and young people, which can have life-long consequences.

Chief Executive of the Samantha Dickson Brain Tumour Trust, Paul Carbury said: A quarter of all childhood cancers now occur in the brain and more children are dying of brain tumours than any other cancer. We are concerned that children in the UK are being short-changed by delays in diagnosis, which are leading to poor outcomes compared with the rest of Europe and the USA. This is true for teenagers too, with evidence suggesting that many visit their GP numerous times before being referred.

David Kershaw, who lost his two year old son, Jake, to a brain tumour, is angry about the slow diagnosis they suffered. He said: There is still so much ignorance regarding the diagnosis of brain tumours. I had to fight extremely hard to be taken seriously when Jake became unwell. It is very clear to me that more work needs to be done within the medical profession to hasten diagnosis, which will improve the long term outcome for other children.

$7M grant establishes new UIC center to eliminate health disparities

Tue, 04 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The University of Illinois at Chicago has been awarded a $7.2 million federal grant to establish the UIC Center of Excellence in Eliminating Health Disparities.

The new center, funded by a five-year grant from the National Center on Minority Health and Health Disparities of the National Institutes of Health, will focus on health disparities in prostate and colorectal cancer, community-based breast cancer initiatives, and training and educating the next generation of health disparities researchers.

The new center will be a multi-faceted, university-wide resource to integrate health disparities research and activities, said Elizabeth Calhoun, associate professor of health policy and administration at the UIC School of Public Health, and director and principal investigator of the new center. We plan to engage new investigators in health disparities, reaching not only into our undergrad and graduate populations, but even into high school, to build a pipeline of researchers interested in health disparities.

Carol Ferrans, professor and associate dean for research at the UIC College of Nursing, is co-director of the center.

Researchers at the center will build upon prior UIC research to implement a community project to eliminate breast cancer disparities in South Side Chicago communities disproportionately affected by high rates of breast cancer deaths. The project will use culturally sensitive messages to promote mammography screening, address beliefs that contribute to screening reluctance, and address personal and health system barriers to screening.

The center's primary research projects will specifically look at disparities in prostate and colorectal cancer.

Colorectal cancer is the second most common cancer among African-American women and the third most common for African-American men. Late stage diagnosis, method of detection, delays from detection to surgical intervention, and disparities in treatment may all contribute to African Americans having the highest mortality from this disease of any racial or ethnic group, according to researchers.

In one study, led by Garth Rauscher, UIC assistant professor of epidemiology, researchers will enroll 500 African-American patients newly diagnosed with colorectal cancer to obtain information about screening, stage at diagnosis and treatment. The researchers will look at personal barriers such as cultural beliefs about cancer, social support, transportation, housing, literacy, perceived stress, fear, medical trust, as well as access barriers such as insurance status.

A second study, led by Vince Freeman, UIC assistant professor of epidemiology, will compile data on prostate and colorectal cancer cases diagnosed between 1995 and 2008 in Chicago to conduct a population-based analysis of clinical, socioeconomic and health care factors that account for mortality differences between African Americans and Caucasians.

Ultimately, these statistical models will allow researchers to predict hot-spot areas heavily burdened with disease, said Calhoun, and provide effective measures for deploying resources such as targeted cancer screenings.

The center has a research core, a training and education core, and a community engagement core, led by Richard Warnecke, Faye Davis, and Carol Ferrans, respectively, who are researchers at the UIC Institute for Health Research and Policy.

Rauscher and Freeman are researchers at the UIC Institute for Health Research and Policy and the UIC Cancer Center.

The new UIC Center of Excellence in Eliminating Health Disparities will involve faculty from all six of UIC's health sciences colleges, the UIC Institute for Health Research and Policy, the UIC Center for Clinical Translational Science, and the UIC Cancer Center to develop a comprehensive strategy to incorporate research, education, policy changes and community partnerships to reduce health disparities in Chicago and beyond.

Too many ways to say 'it hurts'

Wed, 29 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO --- There are at least 100 ways to say, It hurts! And that is the problem.

David Cella is on mission -- backed by nearly $10 million in National Institutes of Health funds -- to revolutionize the language of pain, as well as fatigue, depression and anxiety. These are some of the important symptoms researchers measure when they try to figure out if a medical treatment improves the quality of life for a patient with a chronic disease.

Are they in too much pain to unload groceries from the car? Are they too tired or depressed to go out to lunch with a friend? The answers are vital for researchers to know if new treatments are useful or useless.

But the glitch is every group of researchers asks patients different questions to measure their symptoms. Thus, one group's measurement of severe pain or fatigue or depression may be different than another's. Because researchers aren't speaking a common language, doctors and other health care providers can't compare the results across studies to decide which is the best approach. Instead, study results remain separate puzzle pieces that never fit together into a whole picture.

Can you imagine if a doctor wanted to check your hemoglobin and there weren't any numbers to measure whether it was normal? asked Cella , professor and chair of the new department of medical social sciences at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. When you say a patient's hemoglobin is 11, everybody knows what it means, but nobody knows what a pain of 36 means or a fatigue of 32 because we don't use common measures.

That's about to change. Cella is leading a far-reaching new national project that establishes a common scientific vocabulary. In August, he and colleagues from six other institutions and the NIH will release a set of free publicly available computerized tests for researchers to measure pain, fatigue, depression, anxiety and physical and social functioning. Now there will be a pain measurement of 75, for example, that will mean the same thing to every doctor and scientist.

The new project is called Patient-Reported Outcome Measurement Information System (PROMIS). More than 1,000 researchers have already registered to try the new tools.

Cella's project addresses President Obama's call for greater accountability in medical treatment. In order to have a system that works that way you need a consistent measure of outcomes that people can understand and relate to, Cella said. That's what we have developed.

The lack of a common vocabulary has hurt research, Cella noted. It's a Tower of Babel, a hodge-podge of language. It's a big problem because you can't migrate the results of one study to a broader understanding, he said. We keep having to learn the same things over and over. We are not building on a foundation of knowledge.

Not only have Cella and his team created a new language and tool for researchers, but the PROMIS project also represents a shift in the way researchers evaluate the benefits of treatments. The goal is not just to help people live longer but also live better.

X-rays, CT scans and lab tests may have minimal relevance to the day-to-day functioning of patients with chronic diseases. We help measure directly if people are living better by asking them, Cella said. Sometimes it's as simple as asking, 'Do you think this treatment has made your life better?' That question is surprisingly absent from many studies.

RI Hospital first in country to enroll patient in new study for recurrent chest wall breast cancer

Mon, 20 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) PROVIDENCE -- Rhode Island Hospital is one of only four sites across the country to participate in a new clinical trial called the DIGNITY Study. The study will investigate the effectiveness of a chemotherapeutic agent, ThermoDox, used in conjunction with mild hyperthermia (a form of heat therapy) for treating recurrent chest wall breast cancer.

Recurrent chest wall (RCW) breast cancer is a return of breast cancer on the chest wall, most commonly presenting in the skin overlying the mastectomy scar, affecting approximately 20,000 to 30,000 women each year in the United States. Following a mastectomy, RCW disease will usually present as a small lump in the mastectomy scar or under the skin of the chest or abdominal area. It may be visible or can be felt under the skin, and often goes undetected for some time as it may be mistaken for a leftover stitch or scar tissue from the mastectomy surgery. A significant number of women who are diagnosed with RCW disease frequently cannot be treated with further surgery, radiation or chemotherapy because their available treatment options have been exhausted. As a result, these women often face a poor prognosis.

Rhode Island Hospital is the only hospital in New England to participate in the DIGNITY study that will test 100 patients nationally with an encapsulated chemotherapeutic agent called ThermoDox combined with hyperthermia treatment. ThermoDox is a heat-activated version of an approved and frequently used oncology drug for the treatment of a wide range of cancers, including breast cancer.

Rhode Island Hospital was the first to enroll and treat a patient. That patient has undergone the first three of a 6-cycle course of treatment. Brigid O'Connor, MD, PhD, a radiation oncologist at Rhode Island Hospital, is the principal investigator for the trial in Rhode Island.

According to O'Connor, We treated our first patient recently and she tolerated the procedure well. I am excited to see her response to this new treatment. She continues, The rapid development of ThermoDox is warranted so we can provide these women who are experiencing recurrent chest wall cancer with a better treatment for this devastating disease. We look forward to the outcomes of this trial in the hope of gaining increased local tumor control and improved quality of life for our patients.

To be eligible for participation in the trial, patients must have a confirmed diagnosis of RCW disease, had prior radiation to their chest wall and received two chemotherapy regimens.

New technique could sustain cancer patients' fertility

Tue, 14 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers funded by the National Institutes of Health have completed a critical first step in the eventual development of a technique to retain fertility in women with cancer who require treatments that might otherwise make them unable to have children.

The researchers have developed a method to advance undeveloped human eggs to near maturity, in laboratory cultures maintained outside the body. The technique focuses on the follicle, a tiny sac within the ovary that contains the immature egg. The researchers were able to grow human follicles in the laboratory for 30 days, until the eggs they contained were nearly mature.

The research seeks to provide women who require a fertility-ending treatment with options for reproduction after their treatment is complete. Men facing such treatments can freeze their sperm for use at a later date. Female cancer patients have fewer options. Unlike sperm, eggs rarely survive freezing and thawing.

The accomplishment represents the successful completion of the first of three steps needed to preserve a woman's fertility after radiation treatments or chemotherapy. For the next step, researchers will need to induce the egg's final division, so that it contains only half the genetic material of its precursors. Finally, the researchers will have to demonstrate that they can freeze and thaw human follicles before growing them in culture.

The new technique could provide an option for women and girls who have cancer and are not yet ready to start families, said Duane Alexander, M.D., director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the research as part of the NIH Roadmap Interdisciplinary Research Consortium program. An additional benefit is that it will allow researchers to more closely follow the process by which immature eggs grow and mature. In turn, these observations may lead to new advances for treating other forms of infertility.

The best option currently for a female cancer patient to preserve fertility is to collect eggs, fertilize them with sperm, and freeze the resulting embryos. But that technique may not be acceptable to all female cancer patients.

Researchers have already identified experimental methods to freeze entire ovaries or strips of ovarian tissue and implant them in a woman's body when she is ready to have children. This is a good option for some patients, but it is possible that some cancer cells may hitch hike on the ovarian tissue and result in a new cancer after treatment is completed.

Developed by Teresa K. Woodruff, Ph.D. and Lonnie D. Shea, Ph.D., of Northwestern University's Feinberg School of Medicine, and their colleagues, the new technique would avoid both concerns.

The findings were published online in

New technique could sustain cancer patients' fertility

Tue, 14 Jul 2009 03:59:36 PST

Predicting the return of prostate cancer: New Johns Hopkins study betters the odds of success

Wed, 01 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Cancer experts at Johns Hopkins say a study tracking 774 prostate cancer patients for a median of eight years has shown that a three-way combination of measurements has the best chance yet of predicting disease metastasis.

The new prediction method comprises the length of time it takes for PSA (prostate-specific antigen) to double, Gleason score (a numeric indicator of prostate cancer aggressiveness as seen under the microscope), and the interval between surgical removal of the prostate and the first detectable PSA level. According to Johns Hopkins investigators, combining these three measurements more accurately estimates risk that the cancer has spread than do other methods and should help determine which patients may benefit from additional therapy when PSA levels rise after surgery to remove the prostate.

Findings from the study presented at the June 2009 annual meeting of the American Society of Clinical Oncology (ASCO) may also help resolve the debate on when and in what form secondary treatments should occur.

There is much debate on whether to prescribe immediate treatment for a man whose PSA begins to rise after he has had prostate cancer surgery, or to delay it, says Emmanuel Antonarakis, M.D., Johns Hopkins Kimmel Cancer Center investigator. Studies suggest that most men live the same length of time overall whether they receive therapy at the first sign of a rising PSA or wait until the cancer has spread to other sites.

After reviewing the records of 774 men whose PSA rose after surgery to remove the prostate, the researchers found that Gleason score and two measurements for PSA were the strongest risk factors for prostate cancer metastasis. Men with Gleason scores in the highest range, between eight and 10, were twice as likely to develop metastatic cancer. In men whose PSA became detectable within three years after surgery, cancer was more than three times more likely to spread to other organs. Finally, men whose PSA doubled the fastest, within three months, were more than 20 times more likely to develop metastatic cancer than men whose PSA look longer than 15 months to double.

For men enrolled in the study, it took a median of 10 years for the disease to reappear on imaging scans. The 10-year average will not apply to every man, so we wanted to know what factors put men at higher risk for their cancer progressing earlier, says Mario Eisenberger, M.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center.

An increase in PSA, or prostate specific antigen, occurs in approximately 20 percent to 30 percent of men after surgery to remove the cancerous prostate, says Antonarakis. In these patients, the newly emerging prostate cancer cells are rarely detectable on imaging scans. When faced with the likelihood that their cancer has spread, many men opt to undergo hormone therapy, which blocks testosterone production, a fuel for prostate cancer. The side effects, which mimic those of menopausal women, include hot flashes, night sweats, osteoporosis, metabolic syndrome and coronary disease, and can be debilitating, says Antonarakis.

Besides immediate hormone therapy, other options for men whose PSA is rising are to use hormone therapy intermittently, enroll in clinical trials testing experimental therapies or combinations of them, or to watch and wait until imaging scans can locate metastatic disease.

Alcohol, cigarettes can cause bowel cancer

Mon, 22 Jun 2009 11:11:40 PST

( from http://www.rxpgnews.com ) Beware of alcohol and cigarettes, they can cause bowel cancer, says a new study.

A new global study has shown that people who consume large quantities of alcohol - have a 60 percent greater risk of developing the cancer, compared to others.

Rachel Huxley, professor at The George Institute, who led the study, said the most startling finding was 'the strong, and largely, unknown association between high intakes of alcoholic beverages with risk of colorectal - cancer.'

'Most people probably know that being overweight and having poor dietary habits are risk factors for the disease, but most are probably unaware that other lifestyle risk factors such as alcohol consumption, cigarette smoking and diabetes are also important culprits,' she added.

Smoking, obesity and diabetes were also associated with a 20 percent greater risk of

developing bowel cancer - the same risk linked with consuming high intake of red and

processed meat.

One million new cases of bowel cancer are diagnosed worldwide every year. The disease claims more than half of them.

According to a George Institute release, Australia's National Health and Medical Research Council recommends individuals shouldn't be drinking more than two standard drinks per day,

On a positive note, researchers also demonstrated that physical activity lowered an individual's risk of the disease but surprisingly, there was little evidence to indicate that high intakes of fruit and vegetables protected from bowel cancer.

Electronic nose potent new weapon against brain cancer

Thu, 18 Jun 2009 13:23:27 PST

( from http://www.rxpgnews.com ) An electronic 'nose' developed by NASA for air quality monitoring on Space Shuttle Endeavour can also act as a potent new weapon against brain cancer.

The 'nose' can detect odour differences in normal and cancerous brain cells, opening up new possibilities for neurosurgeons in the fight against the condition.

Neurosurgeons from the City of Hope Cancer Centre, along with scientists from the Brain Mapping Foundation - in West Hollywood and Jet Propulsion Laboratory -, used NASA's electronic 'nose' to investigate the role of cellular odour in cellular trafficking, brain cancer metastasis and stem cell migration.

The 'electronic nose', which is to be installed on the International Space Station to automatically monitor the station's air, can detect different contaminants, some with concentrations as low as one part per million.

In a series of experiments, the BMF used NASA's electronic nose to sniff brain cancer cells and cells in other organs. These experiments will help pave the way for more sophisticated biochemical analysis and experimentation, said a NASA release.

Babak Kateb, study co-author said: 'This pilot study lays the groundwork for future research that may help us better understand cellular trafficking, contribute to designing better approaches for the detection and differentiation of brain cancer, and understand the pathophysiology of intracranial gliomas.'

The results will be presented at the sixth Annual World Congress for Brain Mapping & Image Guided Therapy at Harvard Medical School, Aug 26-29.

Dual role in breast tissue for a protein involved in leukemia

Fri, 12 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Washington, DC - A protein known to play a role in growth of some types of leukemia appears to have a mixed function in breast cancer development, say researchers from the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC).

The findings, presented at the annual meeting of the Endocrine Society in Washington, DC, indicate that the function of this protein, known as Stat5a, may be different in developing breast cancer cells that are estrogen receptor-positive as compared to estrogen receptor-negative. When estrogen receptor levels were overexpressed, loss of Stat5a reduced development of a lobular type of preneoplasia. However, when estrogen receptor levels were normal, loss of Stat5a not only had no effect on reducing preneoplasia, but increased susceptibility to carcinogen-induced breast cancer. The results illustrate the importance of breast cancer heterogeneity when testing new therapeutic targets.

The researchers say Stat5a could be a target for treatment of leukemia, but add, If Stat5a is to be used as a drug target for leukemia or other cancers, it is important to fully understand how altering its function impacts the breast, especially since it appears it may play different roles in different types of breast cancer, says the study's lead author, Anne Miermont, MS, a doctoral graduate student in tumor biology at Georgetown University Medical Center.

Stat5a is a member of the STAT family of proteins, which are key to regulating cell growth and differentiation. Because they have been found to be over-expressed in leukemia, Miermont and Priscilla Furth, MD, a professor of oncology, sought to see if they were important in breast cancer development. Estrogen receptors are over-expressed in more than half of human breast cancers, so the investigators set up studies to test if the function of Stat5a was the same or different in cells with estrogen receptor overexpression.

They found that Stat5a A is rather two-faced when it comes to its role in breast tissue. Previous studies had shown that mice born without the gene produce breast cells that are a little less differentiated than they should be, meaning that they are not fully developed enough to participate in milk production. Miermont found that when the animals were exposed to a cancer-causing chemical, they were more likely to develop breast cancer than mice with intact Stat5a genes. At the same time, however, Miermont found that when estrogen receptor was over-expressed, Stat5a collaborated with it to promote growth of a type of precancerous lesion of the breast termed a hyperplastic alveolar nodule.

Our studies in in vivo mouse models illustrate a dual role for the Stat5a protein in breast tissue. While it can contribute to the growth of one type of precancerous lesion in the breast, this protein also appears to protects mammary cells from carcinogenic exposure, says Miermont.

These findings need to be validated and expanded, Furth says, but she adds that while Stat5a is obviously a complicated protein that has many functions, the results underscore the need to specifically understand the mechanisms that regulate its different roles in breast cells and how changes in Stat5a activity may affect different types of breast cancer generation.

Common chemotherapy drug triggers fatal allergic reactions

Mon, 08 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO -- A chemotherapy drug that is supposed to help save cancer patients' lives, instead resulted in life-threatening and sometimes fatal allergic reactions.

A new study from the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program at Northwestern University Feinberg School of Medicine identified 287 unique cases of hypersensitivity reactions submitted to the FDA's Adverse Event Report System between 1997 and 2007 with 109 (38 percent) deaths in patients who received Cremophor-based paclitaxel, a solvent-administered taxane chemotherapy.

Adverse event reports generally only represent from 1 to 10 percent of actual incidence, so the number of hypersensitivity reactions and deaths is likely significantly higher. The severe allergic reactions are believed to be caused by Cremophor, the chemical solvent - a derivative of castor oil -- that is used to dissolve some insoluble drugs before they can be injected into the blood stream.

Two patients who died from an allergic reaction had early-stage breast cancer, which had been surgically removed, and were being treated with Cremophor-containing paclitaxel to prevent the cancer from coming back. Both of these patients had received medications before the chemotherapy to reduce the risk of hypersensitivity reactions.

The study was led by Charles Bennett, M.D., RADAR program coordinator and a professor of hematology/oncology at Northwestern's Feinberg School, and Dennis Raisch, a professor of pharmacy at the University of New Mexico.

The deaths of women with early-stage breast cancer are particularly disturbing because without the adverse reaction, they could have likely had 40 years of life ahead of them, Bennett said.

RADAR investigators also found that 22 percent of all fatalities occurred in patients despite patients having received premedication to prevent hypersensitivity reactions, while another 15 percent of such patients experienced life-threatening respiratory arrest.

The report was presented at the 45th Annual Meeting of the American Society of Clinical Oncology held recently in Orlando, Fla.

Cremophor-containing paclitaxel has been associated with hypersensitivity reactions, with responses ranging from mild skin conditions to more severe effects, including anaphylaxis and cardiac collapse. Current U.S. product labeling for Cremophor containing paclitaxel includes a black-box warning alerting physicians and patients of potential toxicity and recommending the use of corticosteroids and other medications before chemotherapy administration to reduce the risk of hypersensitivity reactions.

The results of our review suggest that physicians should be vigilant in monitoring the safety of their patients undergoing chemotherapy treatment, said Bennett, who also is the A.C. Buehler Professor in Economics and Aging at the Feinberg School and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Patients receiving Cremophor-based paclitaxel should be given medications to prevent hypersensitivity reactions, but what is sobering, as the study has shown and as the black-box warning indicates, women suffer anaphylaxis despite receiving steroid premedication, Bennett said. Physicians should be diligent in reporting adverse events to regulatory agencies to better monitor the impact of Cremophor on patient safety. Physicians may also want to consider exploring other alternative chemotherapy options that do not include Cremophor.

In addition to the two women with early-stage breast cancer who died after treatment with the Cremophor-based paclitaxel, four other women with early-stage breast cancer experienced life-threatening anaphylaxis reactions. Each of them had received prior medications to prevent the reactions.

The fatal outcomes observed in patients with early-stage breast cancer were particularly striking as this is a patient population with a good prognosis that is generally treated with curative intent, said Raisch.

For the report, Bennett and Raisch reviewed adverse event reports submitted to regulatory agencies in the U.S., Europe and Japan. The most common cancer diagnosis for these patients with allergic reactions was lung cancer followed by breast cancer and ovarian cancer.

Singapore scientists elected into National Academy of Sciences

Mon, 01 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Renowned Singapore-based cancer geneticists Neal Copeland, Ph.D., and Nancy Jenkins, Ph.D., who are among the top 50 most-cited biomedical scientists in the world today, have been elected into the prestigious National Academy of Sciences (NAS).

Dr. Copeland, Executive Director of the Institute of Molecular and Cell Biology (IMCB) of Singapore's A*STAR (Agency for Science, Technology and Research), was elected to NAS this year. NAS elected Dr. Jenkins, Deputy Director of IMCB's Genetics and Genomics Division, in 2008. Their membership takes effect this year.

Drs. Copeland and Jenkins, who have co-authored over 750 papers and been cited over 30,000 times, have worked together for 30 years since they met as postdoctoral follows in Harvard Medical School.

Prior to joining IMCB in 2006, Drs. Copeland and Jenkins were scientists at the National Cancer Institute (NCI). He headed NCI's molecular genetics of oncogenesis section and was director of the mouse cancer genetics program, while she headed the molecular genetics of development section.

Since joining A*STAR, they have set up and now jointly run IMCB's cancer genetics laboratory and have been working on new ways of analyzing the cancer genome, by characterizing the genetic changes required to promote or sustain tumor formation.

In their research to induce different types of human cancer in mice, their IMCB group has recently discovered ways of manipulating the genetic structure of Sleeping Beauty, a mutagenic transposon, a sequence of DNA that can move around to different positions within the genome of a single cell. In moving around, a transposon can cause mutations and change the amount of DNA in the genome.

In addition, Drs. Copeland and Jenkins' group plans to use another whimsically named transposon, PiggyBac, to model cancer in mice and potentially zebrafish. With these cancer models, as well as recent advancements in cloning and sequencing technologies, they hope to better understand and devise more effective treatment strategies for various forms of cancer.

A*STAR Chairman Lim Chuan Poh said, Neal and Nancy are two of the most outstanding cancer geneticists in the world, and their election to the National Academy of Sciences is a fitting recognition of their excellent and impactful work. I would like to congratulate them on this well-deserved recognition. A*STAR is happy that both Neal and Nancy are committed to inspire and mentor our own crop of young scientists seeking to make their own mark in the world of science and to make a difference to society.

Dr. Copeland said, This is a true honor for us both. Nancy and I function very much as a team, and we owe our success in the laboratory to each other. We are extremely happy to have been elected, and excited to be helping IMCB build up its capabilities and train its future generation of scientists to be at the forefront of science research.

Dr. Jenkins said, Through the years Neal and I have had a rich and very fulfilling journey in science and in life, and we are especially glad to be sharing one of the highest honors that can be accorded a scientist or engineer in the USA. We look forward to making more exciting and impactful discoveries together.

I-SPY trial offers key insights into locally advanced breast cancer

Mon, 01 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Scientists are reporting two findings that could influence the way researchers screen for, treat and assess prognosis for women with locally advanced breast cancer, an aggressive form of the disease. One finding offers a critical message regarding treatment strategy, they say.

Women with locally advanced breast cancer and their clinicians need to be aware that a growing breast mass should not be ignored even if someone has had a recent normal mammogram, says Laura Esserman, MD, UCSF professor of surgery and radiology and director of the UCSF Carol Franc Buck Breast Care Center.

The findings emerged from I-SPY, a multi-center clinical trial designed to evaluate the impact of chemotherapy before surgery on patients with locally advanced breast cancer. Assessments in the trial focus on biological markers as predictors of pathological complete response and survival. Locally advanced breast cancer tumors develop in younger patients, have a worse prognosis and are large (min. 3 cm.).

The results were reported in the scientific session Oral Abstract Session-Breast Cancer -- Local-Regional and Adjuvant Therapy (Esserman) and the Oral Abstract Session- Cancer Prevention,(Lin 4pm) at the American Society of Clinical Oncology annual meeting on Saturday, May 30, 2009.

One study revealed that most locally advanced breast cancers are discovered in the interval between routine mammogram exams, which are conducted every one or two years. Of the women who were receiving regular screening mammograms, 83 percent had developed such so-called interval cancers.

This finding suggests that the growth rate of locally advanced breast cancers precludes early detection by conventional screening, says the senior author of the study, Laura Esserman, MD, UCSF professor of surgery and radiology and director of the UCSF Carol Franc Buck Breast Care Center.

We need to develop a better understanding of the molecular signatures of these tumors. Understanding their biology will be important for developing better strategies for prevention and early detection.

The study, led by Cheryl Lin, MD, postdoctoral research fellow in surgery, contains a critical message, says Esserman. For these faster growing cancers, patients with' interval cancers' should explore the potential of standard chemotherapy and/or clinical studies that add novel agents in addition to standard therapy in advance of surgery (so called neoadjuvant chemotherapy), which is increasingly the standard of care in this set of patients, says Esserman.

In another report of the findings from the I SPY trial, scientists determined that the molecular profiles of locally advanced breast cancer tumors predicted the response of the tumors to chemotherapy drugs given in advance of surgery. The scientists identified one subset of patients who fared well regardless of how they responded to the chemotherapy treatment. The team also determined that in those patients with poor prognosis profiles response to the chemotherapy was a very good predictor of long term outcome.

The study demonstrated that locally advanced breast cancers have aggressive biology, says first author Esserman. Response to therapy and outcome can be predicted by many biomarkers. The I-SPY data set provides a platform to study marker signatures to tailor therapy and demonstrates the power of the neoadjuvant setting.

The response to therapy of the 216 patients examined was measured by serial magnetic resonance imaging, pathologic complete response and residual cancer burden. The study revealed that residual cancer burden was a more refined way to measure pathologic complete response .The study also revealed that magnetic resonance volume is highly predictive of pathologic complete response and residual cancer burden (reported in Sunday Poster Discussion (Local/Regional Breast Cancer).

I-SPY 1, the first phase of a longer term clinical study series, is a collaboration of numerous cancer centers nationwide, and the National Cancer Institute. The second phase, I-SPY 2, now in development, is a collaboration of the NIH Foundation, Food and Drug Administration, NCI, and pharmaceutical and biotechnology companies.

Chemotherapy combination outcomes differ for aged, younger colon cancer patients

Fri, 29 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla.--The combination of chemotherapies 5FU and oxaliplatin compared to 5FU alone after surgery for colon cancer decreases colon cancer recurrence and promotes longer survival for patients under 70 -- but not for those who are older, according to Mayo Clinic and Dana-Farber Cancer Institute scientists who will present their findings at the American Society of Clinical Oncology's (ASCO) annual meeting in Orlando, Fla.

By combining information about many patients from a collection of studies, our analysis determined that the more aggressive combination chemotherapy does not benefit older colon cancer patients as it does for those who are younger, said Nadine Jackson McCleary, MD, PhD, Dana-Farber gastrointestinal oncologist and the lead author on the study. Jackson-McCleary is the recipient of a 2008-2009 ASCO Young Investigator's Award.

The data (abstract 4010) will be presented on Saturday, May 30, 3 p.m. ET (Level 2, West Hall D2).

Adding oxaliplatin to chemotherapy treatment with 5FU reduces the risk of recurrence among patients less than 70 years of age who have had their primary cancer removed, the study determined, a finding that was expected based on the results of previous individual trials. Patients under 70 who were treated with 5FU and oxaliplatin had improved disease-free survival, with the addition of oxaliplatin relatively reducing the risk of recurrence or death by approximately 15 percent. Those patients aged 70 and older who were treated with the combined drug therapy, however, did not have improved outcomes compared to patients who received 5FU alone.

We found that adding chemotherapy agents to the standard 5FU regimen in older patients after surgery did not provide the benefits that younger patients see, Dan Sargent, PhD, Mayo Clinic, a collaborator on the study, agreed. For the older patient, this means that it is appropriate to choose the better tolerated treatment strategy of 5FU alone.

The benefit of post-surgical treatment for both young and older colon cancer patients with 5FU was documented in a 2001 New England Journal of Medicine study by Sargent and colleagues. By 2003, however, oxaliplatin was approved for use in combination with 5FU because the combination boosted the impact of 5FU on extending disease-free survival after colon cancer surgery. While the combined treatment carried additional risk of side effects, physicians prescribed the treatment strategy to patients of all ages. Initially, studies that examined age-related impact of the aggressive chemotherapy combination did not indicate a difference in survival or recurrence related to patient age.

The current study presented at the ASCO annual meeting includes a large enough patient base to powerfully discern differences related to age that are due to treatment regimen.

The younger patients do get an additional boost from both drugs used together, Jackson McCleary noted. Older patients don't benefit from that combination of treatment.

The findings arise from analysis of combined data collected within an expanded database by the Adjuvant Colon Cancer End Points (ACCENT) Group, a consortium of scientists. The ACCENT database includes data from more than 33,500 patients from the United States, Canada, Australia, and Europe. ACCENT is supported by the North Central Cancer Treatment Group (NCCTG); Sargent is chair of ACCENT.

At this point we can only speculate as to why older patients do not benefit from combined chemotherapies, Jeffrey Meyerhardt, MD, MPH, of Dana-Farber and co-investigator on the trial said. We do know that a higher number of older patients have to stop the drug before completing the full six month prescribed course of treatment.

These studies add to the knowledge base that defines how to choose treatment strategies for every individual patient, Sargent said. Age may become as important a consideration as tumor-specific factors when defining individual medical options for colorectal cancer patients.

Approximately half of all colon cancer patients are older than 70. While about half of the colon cancer patients over 70 will live for five years, those with recurrence typically develop additional tumors within three years. The disease is diagnosed in a million people worldwide every year. In the United States, colorectal cancer accounts for 10 percent of new cancer cases, as well as 10 percent of cancer-related deaths every year.

One in ten advanced colon cancer patients worry about prescription drug costs

Fri, 29 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla.--The vast majority of advanced colon cancer patients in a clinical trial were not concerned about the cost of prescription drugs for managing chemotherapy side effects, such as infection, pain and nausea and few adopted strategies to reduce drug cost burdens after joining the clinical trial, according to a study led by researchers at Dana-Farber Cancer Institute in Boston. Although few patients reported substantial worry about drug costs, still fewer reported discussing drug cost issues with their physicians, suggesting there are opportunities for improving how physicians integrate discussions about drug costs into clinical practice.

The study's findings (abstract 9503) will be presented at the American Society of Clinical Oncology's annual meeting in Orlando, Fla. on Friday, May 29, 5:30 pm ET, Level 4, W414A.

We were reassured to learn that few patients enrolled in the clinical trial engaged in coping strategies to minimize the impact of prescription drug costs, but we also recognize that these findings may not generalize to patients treated outside the clinical trial context, said the study's lead author, Deborah Schrag, MD, MPH, of Dana-Farber.

Schrag added that given the current state of the economy, with a growing number of people losing their jobs and possibly some or all of their insurance coverage, we could witness growing anxiety among cancer patients about their ability to pay for medications that may help them adhere to their therapy.

The researchers surveyed 409 patients with metastatic colorectal cancer who were enrolled in a Cancer Leukemia Group B (CALGB) Phase III clinical trial that compared outcomes of patients who received combination chemotherapy in conjunction with bevacizumab and cetuximab together or with cetuximab alone. The participants also received prescriptions for supportive drugs, such as anti-nausea medications, antibiotics and painkillers.

They explored whether financial concerns prompted the patients to take money-saving steps that could negatively impact their care. They found that 10 percent of the patients were very worried about paying for their supportive medications, less than 15 percent adopted a money-saving strategy -- such as not filling a prescription, taking less than the recommended dose -- and 12 percent of the patients reported speaking with their physicians about drug costs.

The cost of cancer care today does force patients to make some hard financial decisions, said Schrag. As oncologists, we need to be mindful that this issue may be a concern for some patients and that communication about this topic both may help alleviate anxiety and identify strategies to minimize the cost burden.

New blood test greatly reduces false-positives in prostate cancer screening

Thu, 28 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla.--A new blood test used in combination with a conventional prostate-specific antigen (PSA) screening sharply increases the accuracy of prostate cancer diagnosis, and could eliminate tens of thousands of unneeded, painful, and costly prostate biopsies annually, according to a study led by researchers at Dana-Farber Cancer Institute.

At the annual meeting of the American Society of Clinical Oncology in Orlando, Fla., William K. Oh, M.D., and Robert W. Ross, M.D., will report that the six-gene molecular diagnostic test, when combined with a PSA test, accurately detected prostate cancer more than 90 percent of the time. Earlier studies suggest that the conventional PSA test is 60-70 percent accurate in detecting cancer.

The findings (abstract #5052) will be discussed at a poster session on Sunday, May 31, 8-11 a.m., Level 2, W230A.

Men who are found to have elevated levels of PSA in routine screening tests are often referred for a biopsy of the gland to check for tumors. Nearly two-thirds of biopsies performed -- a painful procedure with some risk of complications -- do not find any cancerous cells. This high rate of false positive PSA test results underscores the need for a more accurate method for detecting prostate cancer, said Oh, who is the clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber.

The two-year study involved 484 participants. The group comprised 204 men with known prostate cancer, 110 men with benign prostatic hypertrophy (BPH), and 170 healthy men in a control group. (BPH can elevate PSA levels in the blood, which often leads to a biopsy to rule out prostate cancer.) These groups were split into age-matched training and validation sets.

The researchers sought to measure the accuracy of a six-gene whole blood RNA transcript-based diagnostic test developed by Source MDx in Boulder, Colo., both in terms of its sensitivity (the ability to detect prostate cancer) and specificity (the ability to identify people who don't have prostate cancer).

Source MDx researchers developed the test after initially working with a set of 174 candidate genes whose activity was compared in the different study groups. They narrowed the pool down to just six genes that, as a group, were highly sensitive in predicting which patients had prostate cancer and which were normal.

The study found that the six-gene model was more accurate than PSA alone at predicting cancer if you had it and no cancer if you didn't, said Oh. The test's accuracy improved even more when PSA measurements were added. Combined, the two tests achieved a diagnostic accuracy of more than 90 percent in specificity and sensitivity and eliminated most of the false-positives yielded by the PSA test.

Based on these findings, the researchers are planning to conduct a larger, multicenter clinical trial involving approximately 1,000 men to determine if the findings remain valid.

These findings are very encouraging and suggest that this new test could spare tens of thousands of men from undergoing an unnecessary biopsy, Oh said. However, until we can verify our findings, it is important to recognize that the PSA test, despite its limitations, is still the best test available for diagnosing prostate cancer at this time.

Lombardi scientist brings 'dream team' breast cancer research effort to GUMC

Wed, 27 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Washington, DC -- It's called a Dream Team. Lombardi Comprehensive Cancer Center's incoming scientific director V. Craig Jordan, OBE, PhD, DSc, and 12 of the nation's top breast cancer researchers have been awarded a multi-million dollar grant from Stand Up To Cancer (SU2C) to form a scientific Dream Team. This collaboration of the best and brightest scientists will conduct new breast cancer research with the goal of producing tangible research results benefiting patient care within three years.

This is a very innovative approach to funding research, explains Jordan, a pharmacologist who will serve as vice chairman of Lombardi's department of oncology when he joins the cancer center in July. We hear a lot about the need to accelerate cancer research but this is the first effort that could truly speed up the translation made in the laboratory and impact cancer care.

SU2C is a charitable initiative supporting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated timeframe. SU2C represents an unprecedented collaboration uniting the major television networks, entertainment industry executives and celebrities, and prominent leaders in cancer research and patient advocacy. The majority of the $73.7 million awarded in this first round of three-year grants for the five Dream Teams was raised in connection with an SU2C telecast on September 5, 2008 that aired simultaneously on the ABC, CBS and NBC networks.

The grant awarded to Jordan and his scientific collaborators recognizes the pursuit of the most promising research -- accelerating the discovery of new therapies for cancer patients and/or advancing efforts in cancer prevention research. Jordan and his Dream Team colleagues will work toward a greater understanding of hormone receptor positive, HER2 positive and triple negative subtypes of breast cancer.

Breast cancer claims the lives of 40,000 women in the United States each year. While called breast cancer, tumors that develop in the breast can have many different characteristics and require tailored treatment based on these characteristics. Still, many cancers don't respond to treatment, grow resistant to therapy or can recur. Understanding the molecular diversity of human breast cancer has been a driving force in leading to a new and exciting era in cancer treatment. This understanding has already led to more effective and less toxic treatments.

Jordan is an internationally recognized breast cancer scientist whose research focuses on the response of breast cancer cells to preventive and treatment agents. He is recognized by many as the father the anti-cancer drug tamoxifen, a drug that blocks estrogen from fueling some breast cancers. Millions of women around the world continue to be treated with tamoxifen. Jordan's team, led by Dennis Slamon, MD, PhD, University of California, Los Angeles and Joe Gray, PhD, Lawrence Berkley National Laboratory, is focused on understanding the molecular subtypes of breast cancer.

The Teams' goals include: expanding the underlying molecular understanding of each subtype of breast cancer in order to better understand the efficacy of a given therapy; evaluating the mechanisms that lead to therapy resistance within the different subtypes of breast cancer; understanding the role stem cells, or cells known to be the biological foundation of human breast cancer, play in each subtype of breast cancer; developing cell line and laboratory models of each breast cancer subtype; and developing an information distribution center to allow the greater scientific community to benefit from this knowledge.

Jordan's research will be part of Lombardi's Nina Hyde Center for Breast Cancer Research, which is home to a dedicated corps of more than 30 faculty members working exclusively on the prevention and cure of breast cancer. The Nina Hyde Center, founded in honor of the late Washington Post fashion editor, celebrates its 20th anniversary this year. Georgetown University has consistently ranked in the top 10 institutions conducting breast cancer research worldwide as measured by Thomson Reuters Science.

All grants will be administered by the SU2C's scientific partner, the American Association for Cancer Research (AACR), which reviewed Dream Team applications and made recommendations on funding to SU2C's Management Committee.

TSPAN1 expression-a useful tool to evaluate prognosis in colorectal cancer

Sun, 24 May 2009 10:38:06 PST

( from http://www.rxpgnews.com ) The colorectal cancer is thought to be resulted from a combination of environmental factors, diet, lifestyle, chronic inflammation and accumulation of specific genetic alterations. The pathogenesis and development of colorectal cancer involve multi-genes and multi-steps. TSPAN1 (GenBank Accession No. AF065388) is a new member of TM4SF located at chromosome 1 p34.1. It encodes a 241 amino acid protein. TSPAN1 was reported as a tumor-related gene recently.

A research team led by Dr Jian-Wei Zhu from Nantong University, China, investigated the association between TSPAN1 and human colorectal adenocarcinoma. Their study will be published on May 14, 2009 in the World Journal of Gastroenterology

In this study, total RNA was extracted in 20 human adenocarcinoma tissues for TSPAN1 mRNA assay by RT-PCR. Eighty-eight specimens of human colorectal adenocarcinoma were surgically removed. TSPAN1 protein levels in cancer tissues were determined by immunohistochemistry using a polyclonal antibody against self-prepared TSPAN1. The correlation between TSPAN1 expression and the clinicopathological factors and the overall survival rate was analyzed by univariate and multivariate assay.

By RT-PCR assay, it was shown that TSPAN1 mRNA was detected in 90.0% (18/20) of cancerous tissue. The light density of TSPAN1 mRNA expression levels was 0.89 ±0.30 in adenocarcinoma by gel-image system. TSPAN1 protein expression was detected in 78.41 %( 69/88) and weakly expressed in 40% normal colorectal tissues by immunohistochemistry. There were significant differences between colorectal adenocarcinoma and normal control epithelium (P < 0.05). TSPAN1 protein expression in colorectal cancerous tissue was significantly correlated with the histological grade, cell expression PCNA, lymph nodal metastasis and TNM staging of the disease. Patients with TSPAN1 protein over expression had a significantly shorter survival period than that in patients with TSPAN1 protein negative or weak expression, respectively (P<0.05). Furthermore, by multivariate analysis TSPAN1 protein expression demonstrated an independent prognostic factor for human colorectal cancers (P<0.05, relative risk 0.755; 95% confidence interval 0.302-1.208).

The result indicated that testing TSPAN1 expression in tissues would be a useful tool to evaluate the prognosis of patients with colorectal cancer

'Happy hour' gene discovery suggests cancer drugs might treat alcoholism

Thu, 21 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A class of drugs already approved as cancer treatments might also help to beat alcohol addiction. That's the conclusion of a discovery in flies of a gene, dubbed happyhour, that has an important and previously unknown role in controlling the insects' response to alcohol.

Animals with a mutant version of the gene grow increasingly resistant to alcohol's sedative effects, the research shows. The researchers report further evidence that the gene normally does its work by blocking the so-called Epidermal Growth Factor (EGF) pathway. That EGF pathway is best known for its role in cancer, and drugs designed to inhibit the EGF receptor, including erlotinib (trade name Tarceva) and gefitinib (trade name Iressa), are FDA-approved for the treatment of non-small cell lung cancer.

Now, the researchers show that flies and mice treated with erlotinib also grow more sensitive to alcohol. What's more, rats given the cancer-fighting drug spontaneously consumed less alcohol when it was freely available to them. Their taste for another rewarding beverage -- sugar water -- was unaffected.

This is a very powerful example of how simple model organisms -- and the little fruit fly in particular -- can be used to move quickly from an unknown gene to a potential therapy for drug addiction, said Ulrike Heberlein of the University of California, San Francisco, noting that erlotinib and gefitinib, along with other EGFR inhibitors, not only cross the blood-brain barrier in humans, but they are also well-tolerated in general.

Alcohol is one of the most popular and abused drugs in the world, the researchers said. Therefore, a better understanding of the genetic and environmental factors that lead to its addiction would have considerable benefit for those who suffer its consequences and for society at large. Despite the well-known effects of alcohol consumption on behavior and cognition, the underlying basis for those effects on the nervous system are still rather incomplete.

Human studies have pointed to a strong genetic component to alcoholism, but identifying the specific genes responsible has proved difficult. Studies have also indicated that an individual's sensitivity to alcohol intoxication acts as a predictor of future alcoholism, with a link between lower initial response and increased risk of addiction. Therefore, Heberlein's team explained, genes and pathways involved in the acute response to alcohol can yield insight into the genetic factors contributing to the more complex process of addiction.

Earlier studies have shown that fruit flies are a useful tool for unraveling the basis for the effects of alcohol. Several genes previously identified as playing a role in fruit flies' alcohol response hold similar roles in mammals.

In search of more in the new study, the researchers screened mutant flies for those less sensitive to ethanol. That screen led them to happyhour, a gene closely related to mammalian enzymes known as the Ste20-family kinases of the GCK-1 subfamily.

Heberlein said they still don't know exactly how alcohol exerts its influence on the EGFR pathway or how that leads to the telltale changes in behavior that come with alcohol intoxication. Those questions will be the subject of future investigation. Her team is also exploring other new gene candidates that turned up in the fly screens. She says that several of those appear to be tied to the EGFR pathway in different ways.

It's not yet clear how it all fits together, she said. But the fact that we've come, in an unbiased way, to molecules in the same pathway is telling us this is really, really important.

NC State and UNC Lineberger collaborate to combat cancer

Tue, 19 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Chapel Hill, NC - What do a college of veterinary medicine and a cancer treatment and research center have in common? The answer may be as plain as the nose on your dog's face. Researchers from North Carolina State University's College of Veterinary Medicine and the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center are combining their expertise to pinpoint the cause of -- and improve treatments for -- non-Hodgkin lymphoma in human and canine patients.

The dog is an excellent model to study human cancer, particularly lymphoma. The disease is biologically similar in human and canine patients, but is much easier to narrow down problematic areas in a dog's genome because the genetic variation among dogs of the same breed is so much lower than genetic variation in humans. These factors, coupled with the publication of the human and canine genomes, make the dog the perfect candidate for this collaborative research.

Drs. Steven Suter, professor of clinical sciences, and Matthew Breen, professor of genomics, along with statistics professor Dr. Alison Motsinger-Reif and Dr. Dahlia Nielsen, research assistant professor of genetics, lead the NC State component. Researchers at UNC Lineberger are led by Dr. Kristy Richards, geneticist and clinical oncologist. The team is recruiting dogs diagnosed with lymphoma to collect tissue samples for study. A simple and speedy procedure at the NC State Veterinary Teaching Hospital, the collection causes no discomfort to the dog and owners receive $1,000 for their pet's participation.

Labs from both institutions will study tissue samples from human and canine patients, with the hope of creating a genomic profile of non-Hodgkin lymphoma that would give oncologists and veterinarians greater insight into the disease's biology, and improve their ability to diagnose the illness early.

Non-Hodgkin lymphoma ranks fifth in cancer deaths among human patients, and the mortality rate for dogs is even higher, Suter says. By combining the strengths of our programs, we expect to enhance our understanding of the disease and speed improved treatments for people and pets. This is another example of 'One Health,' the concept of comparative medicine that acknowledges human and animal health relies on a common pool of medical and scientific knowledge and is supported by overlapping technologies and discoveries.

Richards adds, Traditionally, lymphoma researchers have used laboratory mouse models of lymphoma, but it would be advantageous to study lymphoma in a large animal model with spontaneously occurring lymphomas that more closely mimic the situation in humans. There are very few places in the country where a top-rate veterinary program is in such proximity to a top-rate medical school with a comprehensive cancer center. We aim to take full advantage of this partnership to discover, develop and test new treatments much faster than could be done in either organism alone.

Quick test for prostate cancer

Mon, 18 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A new 3-minute test could help in diagnosing prostate cancer, the most common cancer in men in the UK, according to scientists.

Researchers have developed the test by using light energy to measure the level of citrate in fluid samples from the prostate gland. The technique could provide the basis of a rapid means of detecting prostate cancer in the future. Almost a quarter of male cancers in the UK are diagnosed as prostate cancer and more than 10,000 men die from the disease each year.

Scientists, led by Prof David Parker from Durham University's Chemistry Department, have worked with experts from the University of Maryland, USA to develop the technique that measures the wavelength of light as it is shone through diluted samples of body fluids.

The research team, funded by the North East Proof of Concept Fund and the EPSRC, believe that the technique which can measure, with speed and accuracy, how citrate levels fall in the prostate gland as cancer develops, could also find use for the diagnosis of other medical conditions, associated with poor kidney function.

Prof Parker said: Citrate provides a significant biomarker for disease that may provide a reliable method for screening and detecting prostate cancer, and for the monitoring of people with the disease. This technique could form the basis of a simple screening procedure for prostate cancer that could be used in outpatient departments at local hospitals.

His team have shone light into over 100 different chemical structures to see how they function and respond to the presence of certain important bioactive species. They have looked particularly closely at how citrate and lactate bind to luminescent structures within fluids. Citrate and lactate are vital for our bodies' metabolism for normal function. Citrate provides energy for cells and the amount found in the prostate varies considerably due to an enzyme called m-aconitase which transforms it. This enzyme is very sensitive to zinc and, in prostate cancer sufferers, zinc levels are depressed and the enzyme switches on again.

Prof Leslie Costello from the University of Maryland said: Citrate is formed in cell metabolism processes which alter as cancers grow. The analysis of the citrate concentration of prostatic fluid can provide an accurate way to screen and diagnose prostate cancer. Since citrate concentrations decrease markedly early in malignancy, this technique makes it possible to analyse what's happening quickly in the early and treatable stage of prostate cancer. It shows much promise as a clinical tool.

The new test requires only a microlitre of fluid and the sample can be easily measured in an optical instrument. Using samples from male volunteers, the researchers have developed a portable instrument that can give results in 3 minutes.

The team's challenge has been how to accurately measure changes in the amount of citrate or lactate in fluid samples using the technique. The early results are promising and the team intends to look at the analysis of other body fluids. A possible way forward is to examine the citrate levels in seminal fluid samples, which are made up of 50% prostate fluid.

The University has launched a spin-out company called FScan Ltd to develop the technique and to seek commercial backing. The team has looked at 20 samples so far and verified the analysis in every case. The next stage is to work with a local hospital and examine samples from 200 volunteers to see whether the first Durham results correlate.

Prof Parker says: It's been a complex process to develop the technique but we're very optimistic about it. Ultimately, this could provide an accurate method of screening for prostate cancer in men that could be carried out in 3-minutes once a biopsy has been obtained from the patient at a hospital outpatient department.

The discovery follows the invention in 2006 by Durham University Professor Douglas Newton of a Urine Flow Meter. The UFlow Meter helps men to assess if they have a restricted rate of urine flow - one of the warning signs of prostate problems.

The establishment of FScan Ltd is part of the University's aim to enhance the exploitation of the Intellectual Property generated by high quality research activities.

Tim Hammond, Head of Technology Transfer at Durham University, said: 'We quickly realised the potential of this research and have worked closely with Professor Parker and his team to secure initial proof of concept funding through NorthStar Equity Investors and the North East Proof of Concept Fund and to establish FScan Limited as the vehicle to validate and commercialise the technology.

Process for testing:

Survival predictors may help customize treatment options for men with metastatic prostate cancer

Thu, 14 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Four risk factors that help predict how long men may survive with metastatic prostate cancer could help doctors choose more effective treatments, according to a study led by researchers in the Duke Comprehensive Cancer Center.

There is a need for identification of accurate and simple-to-use prognostic factors for men with prostate cancer that has spread beyond the prostate, so that patients and their doctors can determine which treatment regimen makes the most sense for their situation, said Andrew Armstrong, M.D., a medical oncologist at Duke and lead investigator on this study. Our study was aimed at developing accurate predictors which may be used to assist in clinical decision-making and also in planning clinical trials for men whose disease has stopped responding to hormone therapy.

The researchers will present their findings on a poster at the 2009 American Society of Clinical Oncology meeting in Orlando, on Sunday, May 31. The study was funded by the Duke Comprehensive Cancer Center.

Researchers examined the records of more than a thousand patients who were part of a study that led to the approval of the chemotherapeutic drug docetaxel for the treatment of metastatic prostate cancer in 2004. The researchers identified four independent risk factors that predicted whether a patient's PSA levels -- which indicate the presence or absence of cancer -- went down in response to treatment, Armstrong said. The factors included the presence of significant cancer-related pain; anemia (low blood counts); the extent of cancer spread to other organs; and progression of cancer in bone.

Using these predictors, we were able to assign patients to risk groups of good -- indicating an average survival of about two years; intermediate -- with survival of about 1.5 years -- and poor, with survival of less than a year, Armstrong said. By knowing a patient's prognosis and expected responses to chemotherapy, we are better able to discuss and determine whether a more or less aggressive treatment plan might be advisable.

Accurately classifying patients' prognoses and their expected responses to therapy may indicate which prostate cancer drugs are promising enough to test in phase III trials, Armstrong said.

These data are very exciting and we're eager to use this information to accurately estimate what to expect with current therapies, and to better direct novel combination treatments to those men in need of aggressive therapies, he said.

In 2008, over 185,000 men were diagnosed with prostate cancer in the United States and more than 28,000 died of the disease, according to the National Cancer Institute.

Worldwide success in treatment of liver tumors

Tue, 12 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Leicester consultant surgeon who has developed a pioneering technique using microwaves to destroy liver tumours has treated more than 100 patients in the UK and other patients are now being treated internationally.

Worldwide, about one million people a year die of primary liver cancer, with another million dying with secondary liver cancer where the cancer has spread from other tumour sites such as cancer of the colon.

The incidence of primary liver cancer is gradually increasing in the Western world, but it is very common in Asia and the Far East where it is associated with endemic hepatitis. Most patients with liver cancer are deemed inoperable but with the development of this microwave equipment, literally thousands of patients worldwide could be offered curative treatment, even if they have established liver cirrhosis.

Mr David M Lloyd, MBBS, MD, FRCS, a consultant surgeon with University Hospitals Leicester NHS Trust, is also acclaimed for his innovative work in keyhole surgery. The University of Leicester has awarded him an Honorary Senior Lectureship, and earlier this month he won the title of Honoured Citizen of the Year for the City of Leicester.

David Lloyd's research, in collaboration with Professor Nigel Cronin and Dr. Peter Clegg at the University of Bath, has led to the development and production of a microwave generator and probe, now being manufactured by Acculis Ltd, UK. The treatment of more than 100 patients with liver cancer has resulted in curing or extending life for many of them, whose life prognosis was less than twelve months. More than one third of the patients treated are still alive after three years and some have been, quite simply, pronounced cured and discharged.

The earliest patient to be discharged is one of David Lloyd's trial patients treated nine years ago. Several more are alive and well five years after receiving treatment.

The importance of this application of microwave technology is immense, as Mr Lloyd explained: The technique will have a significant effect on liver cancers, because we are operating on people who have been declared inoperable. Someone with cirrhosis of the liver can't be operated on in a conventional way to remove a tumour, but we can place a microwave probe in by keyhole or percutaneous (through the skin) methods and can destroy these tumours.

Because of the pioneering research done at the University Hospitals Leicester, the microwave generator is being used as far afield as Hong Kong, Singapore, the USA and Australia. In particular, the microwave technology has been embraced by many of the top cancer hospitals in the US, including the Memorial Sloan-Kettering Cancer Institute in New York, The Johns Hopkins University in Baltimore, and the M D Anderson Cancer Centre in Texas. Mr Lloyd added: We've placed several in France and Switzerland and many of the world's leading liver surgeons have now expressed an interest in using the generator.

Because David Lloyd was the only surgeon with this specialised equipment he was referred patients from all over the world for treatment. He is extremely pleased that more centres are now using the microwave device and, in the UK, there are now generators in major teaching hospitals in Liverpool, Manchester, Leeds, Basingstoke and Edinburgh. David Lloyd calculates that within a couple of years, every major liver centre in the UK will probably have a microwave generator.

The advantage the microwave technique has over other machines designed to destroy tumours, such as laser, ultrasound and radio-frequency (which is similar to an electric current) is that it is quick and produces cancer cell death with very few side effects.

Only tissue in the immediate field of the microwave energy is destroyed, David Lloyd explained, and not in other parts of the body, which is a danger with other methods, such as radio-frequency, where the electric current has to have an exit point from the body, with the risk of burning at that site.

Microwaves don't cause collateral damage elsewhere in the body, he said. They only heat up the tissue at the end of the probe and no energy is sent through the body. We can now treat very large tumours up to 6-8 cms in diameter within 4-6 minutes. This makes it ideal for someone who may have multiple tumours, which by other techniques, might take several hours to treat.

People have come to Leicester from all over the world, he added. It has really put Leicester on the map, within this field. For the last ten years I have been invited to every world and European congress in liver surgery to talk about this development. There has been tremendous interest because of the frustration with other forms of energy which haven't delivered. Our system is safe, fast and reproducible and it does work.

If it's used correctly there are no side effects, but because this is a very powerful device, it has to be used correctly. I tend to work in collaboration with a radiologist so that accurate placement of the microwave probe can be achieved. We have not seen significant side-effects so far.

Alzheimer's, asthma, cancer, malaria and TB focus of new Singapore grants

Tue, 28 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Over 50 research grants totaling $24 million in U.S. dollars have been awarded to Singapore universities, research institutes and hospitals to fund studies related to asthma and other immune system disorders, infectious diseases, aging and cancer.

The extramural grants were awarded by the Biomedical Research Council (BMRC) of A*STAR (Agency for Science, Technology and Research), the government agency driving Singapore's transformation into an international powerhouse in the biomedical and physical sciences.

In addition to extramural research grants, A*STAR sponsors the research institutes at Singapore's Biopolis and Fusionopolis.

The common dust mite, Blomia tropicalis, which can have an immense impact on quality of life and even be life threatening when it causes allergies in patients with chronic diseases such as cancer, is the focus of three grants awarded to Chua Kaw Yan, Ph.D., of the National University of Singapore's Department of Pediatrics.

One of Dr. Chua's studies will examine the mechanisms of an oral vaccine against the predominant allergen, the Blo t 5 protein, in B. tropicalis, which is responsible for 60-70% of allergy cases in Singapore, including asthma, allergic rhinitis and eczema.

Optimizing the potency of a genetic vaccine against the dust mite will be the focus of her second grant, while the third project will be directed at creating a modified or recombinant protein to foster immunity against Blo t 5.

Immunotherapy remains the only truly disease-modifying treatment for asthma and allergic rhinitis, said Dr. Chua. Traditional forms of immunotherapy use natural sources of allergens and have numerous disadvantages, such as the presence of undefined material, huge variability in sample composition, and contamination of allergens from other sources.

We therefore hope to use the major allergen, Blo t 5, to develop a novel and effective therapeutic vaccine for immunotherapy, she added.

Grants also were awarded to support research using genomics, proteomics and bioimaging to investigate the mechanisms of infection in tuberculosis and malaria, which cause deaths as well as serious illness despite widespread efforts to prevent their transmission.

In their studies of Mycobacterium tuberculosis (MTB), which infects an estimated two billion people worldwide, National Cancer Centre of Singapore (NCCS) scientists will sift through a bank of DNA samples extracted from drug-resistant MTB strains to identify novel mutated genes conferring resistance to Isoniazid, the main drug now used to treat tuberculosis.

In Singapore, the incidence rate of tuberculosis has increased for the first time in 10 years, leading to concerns over increased transmission of the MTB bacteria.

Ann Lee, Ph.D., who heads the NCCS research team that will investigate MTB, said: The identification of additional genes associated with Isoniazid resistance is important for the development of comprehensive molecular strategies that are potentially more efficient than current susceptibility testing methods, and could aid in giving more appropriate treatment to patients and decrease the spread of resistant strains. In addition, the discovery of new genes may reveal novel targets suitable for the development of alternative therapeutic options.

At Nanyang Technological University (NTU), a research team led by Peter Preiser, Ph.D., was awarded a grant to conduct basic research on the pathology of malaria, which infects as many as 600 million people worldwide and kills over 1 million yearly.

Survival rates for cancer rise across Ireland

Fri, 24 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Survival rates for cancer are continuing to rise even though the number of cases being diagnosed is increasing, an all-Ireland report launched today reveals.

The report entitled Cancer incidence, mortality, treatment and survival in the North and South of Ireland: 1994-2004, was compiled by the Northern Ireland Cancer Registry (NICR), at Queen's University Belfast, and the National Cancer Registry (NCRI) of Ireland, in Cork.

This is the third joint report between the NICR and the NCRI and reveals that each year over 21,000 people across Ireland are diagnosed with a form of cancer, with the most common being breast, colorectal, prostate and lung cancers.

Between 1994 and 2004 the most common cancers among men were prostate, colorectal and lung cancers and lymphoma, while among women breast, colorectal, lung and ovarian cancers were most often diagnosed.

According to its authors people can take action to prevent certain forms of cancer including stopping smoking, reducing their alcohol intake, following a healthy diet, exercising and taking care in the sun.

Total incidence rates were 10 per cent higher for men and 2.2 per cent higher for women in the Republic of Ireland compared with Northern Ireland. The difference for men was mainly due to differences in prostate cancer diagnosis through increased testing in the Republic.

The report also showed that mortality rates were around 4 per cent lower in Northern Ireland for men and women.

While the overall number of cancers has increased due to population growth and ageing and increased detection for some cancers including prostate and breast cancer, the number of cancer deaths has fallen.

Improvements in survival for breast, colorectal and prostate cancer were recorded over the last decade and survival rates are not falling for any cancer.

Dr Anna Gavin, director of NICR, said: This is the first time we have been able to compare treatment differences in addition to the usual incidence, mortality and survival.

Surprisingly, even though we are dealing with two different healthcare systems there is remarkably little variation in treatment, with improvements over time in both countries. Cancer is a significant burden on health and this comparative analysis will point to areas for further research to improve cancer prevention and standardise care for patients.

Over 94,000 people who were diagnosed with cancer between 1994 and 2004 were still alive at the end of 2004. Many of them have been cured but many others still need care and treatment so support services are extremely important.

Dr David Donnelly, lead author of the report, said some of the major cancers in Ireland were preventable: Lung, oesophageal, stomach, head and neck, kidney, bladder and cervical cancer all have a common risk factor in tobacco use. Most of these cancers especially lung, oesophagus and stomach have very poor survival.

Tobacco use is also a major factor in explaining higher rates of cancer in the urban areas of Belfast, Dublin, Cork and Derry and in the most deprived geographic areas in Ireland compared to the most affluent. Fortunately incidence of several smoking related cancers has fallen among males, although incidence of lung cancer among females in Ireland is increasing.

Poor diet and obesity also increase the risk of several cancers, including breast cancer and colorectal cancer, two of the major cancers in Ireland. Improvements in diet and increased physical exercise would likely result in a reduction in the levels of colorectal cancer, and help reverse the increases in breast cancer seen over the last decade.

Dr Harry Comber, Director of the NCRI, said increased testing for prostate cancer in the Republic of Ireland had made a difference to the figures: Comparing survival between the North and South of Ireland reveals that five-year survival for men was higher in the Republic of Ireland than in Northern Ireland by 5.2 per cent, while there was no difference for women.

The difference for men is a result of greater survival from prostate cancer in the Republic of Ireland, a side effect of increased tests to diagnose it. Excluding this cancer, male survival is the same in each country.

Survival is the real test of countries' programmes of prevention, early detection and treatment.

The report was launched at the Royal College of Physicians of Ireland in Dublin by Irish Minister for Health and Children, Mary Harney.

Speaking at the launch she said: I welcome the fall in cancer mortality and continued improvements in cancer survival in Ireland which have been increasing faster than most other countries'

I acknowledge the role of the National Cancer Control Programme in reducing the burden of cancer and the importance of prevention through smoking cessation and following a healthy lifestyle.

Vitamin K with sorafenib showed anti-tumor effects in pancreas cancer, hepatocellular carcinoma

Wed, 22 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) (PHILADELPHIA) A combination of sorafenib and vitamin K had an effect in vitro on both human pancreas cancer and hepatocellular carcinoma, according to researchers from the Kimmel Cancer Center at Jefferson. Data from the two studies were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #5470 and #5483)

Vitamin K1 or vitamin K2, plus sorafenib (Nexavar) each have shown activity against the growth of human cancer cells by inhibiting the extracellular signal-regulated kinase (ERK) pathway according to Brian Carr, M.D., Ph.D., a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University. ERK plays a major role in cell growth of cancers.

Although sorafenib has demonstrated success at extending survival in patients with hepatocellular carcinoma (HCC, or primary liver cancer), hand-foot syndrome is a common adverse effect that affects approximately 20 percent of patients who receive the drug. It typically manifests as painful sores on the soles of patients' feet that can prevent the patients from walking, Dr. Carr said. Profound tiredness and weight loss is also seen in at least 30 percent of patients.

In the pancreas cancer study, Dr. Carr and his colleagues tested each K vitamin in combination with sorafenib in pancreatic cell lines. Each combination inhibited cell growth, induced cell death and decreased the expression of ERK. They found that when combining vitamin K and sorafenib, the sorafenib dose required for inhibiting cancer cell growth decreased by more than 50 percent. This dose was ineffective when used alone.

So few agents have activity against pancreas cancer, Dr. Carr said. One of the attractions of the combination of sorafenib and vitamin K is that both of these agents are already approved for human use. K vitamins also have no known adult human toxicities, and appear to enhance the effects of sorafenib, thus requiring lower, less-toxic doses.

In the second study, vitamin K1 also enhanced the effects of sorafenib in HCC. Sorafenib is FDA-approved for the treatment of HCC, which typically arises on a cirrhotic liver, which tolerates conventional chemotherapy poorly. The researchers previously had shown that vitamin K alone is a weak inhibitor of HCC growth. In this study, they found that the combination inhibits the growth of HCC, induces cell death and decreases the expression of ERK.

Many patients need to discontinue treatment with sorafenib because of the debilitating side effects, Dr. Carr said. If we could lower the dose, more patients would be able to complete their treatment.

These data also pave the way for potential studies to evaluate the combination of sorafenib and vitamin K as an HCC prevention strategy in patients who are at greater risk for developing the disease. This population includes patients with cirrhosis or patients who have previously had surgery for HCC. According to Dr. Carr, the recurrence rate for HCC after surgery is 40 percent.

Instead of fighting breast cancer, immune cell promotes its spread

Wed, 22 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers at the UC San Diego School of Medicine and the Moores UCSD Cancer Center have new evidence that a type of immune system cell thought to be part of the first line of defense against breast cancer may also help promote its spread. They have found that when these cells, known as lymphocytes, make an inflammatory protein called RANKL (RANK ligand), breast cancer is more likely to spread to the lungs.

They have also shown that blocking a cascade of cellular signals that follow RANKL's docking to its receptor (RANK) on tumor cells can halt cancer progression, or metastasis, and may be a possible target for drug therapy.

The scientists, led by first author Wei Tan, PhD, a postdoctoral fellow in the Department of Pharmacology at the UC San Diego School of Medicine and Michael Karin, PhD, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, say that the findings establish RANKL as a potential marker that can be used to help determine breast cancer prognosis and adds further proof to the potentially important role of inflammation in cancer development and spread. They reported their findings April 22, 2009 at the AACR 100th Annual Meeting 2009 in Denver.

According to Tan, the role of lymphocytes in breast cancer progression has been controversial for the last 20 years. Such cells are supposed to detect and eliminate cancer cells, but paradoxically, the infiltration of lymphocytes such as B cells and T cells into breast cancer is sometimes an indicator of poor prognosis, including cancer recurrence and metastasis. RANKL has been shown in previous studies to be an important inflammatory protein that can lead to bone loss by activating cells that help break down bone. Along with another protein, IKK alpha, it has been implicated both in tumor formation and metastasis.

The researchers created two types of mice that developed breast tumors. One group had lymphocytes in the tumors and expressed RANKL while the other group did not. They found that the group lacking RANKL had significantly fewer lung metastases than those mice with RANKL. They then took tumor cells from both types of mice and injected them into mice with the same genetic background to avoid rejection and monitored the ability of the mice to form tumors and metastases to the lung.

The researchers didn't find any lung tumor metastases in mice without lymphocytes. Yet, when RANKL was injected into the animals, the same potential for the cancer to spread was restored, indicating that the lymphocytes, which make RANKL, are critically important to the process.

Without lymphocytes, there is no metastasis, said Tan. If we treat the mice with RANK ligand, there are metastases, which indicate that RANK ligand can compensate for the function of lymphocytes.

The study establishes the role of RANKL-expressing lymphocytes as a promoting factor in breast cancer metastasis and provides a potentially good marker for breast cancer prognosis, the researchers said.

Tan noted that additional experiments showed that blocking both RANKL and IKK alpha in those breast tumor cells inhibited lung metastases. More importantly, he said, blocking the signaling pathway downstream of RANKL blocks primary metastasis and can potentially be developed as a treatment strategy.

Results such as these are helping to change the thinking about inflammation and cancer. In general, we used to think that inflammation in the immune response is a part of the host defense against the tumor, but now we think that there are different kinds of inflammation, Tan said. For example, T-helper cells can activate an anticancer response, but can also promote a separate tumor promoting response. In this study, if we target the host pro-tumor inflammation and immune response, we can also reduce tumor metastasis and are very likely to develop a therapy that is more effective.

Peregrine's PS-targeting antibodies highlighted in AACR Annual Meeting studies

Tue, 21 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DENVER, Colorado and TUSTIN, Calif., April 21, 2009--Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing monoclonal antibodies for the treatment of cancer and serious virus infections, today reported that two preclinical studies presented during the AACR 100th Annual Meeting 2009 provided further confirmation of the immunomodulatory mechanisms contributing to the anti-tumor activity of its phosphatidylserine (PS) targeting antibodies. One study confirms the anti-tumor effects and immune stimulating ability of a fully human anti-PS antibody and the other demonstrates the ability of a second fully human anti-PS antibody to stimulate development of a critical component of the adaptive immune system.

These human PS-targeting antibodies, which are currently being evaluated for both anti-cancer and anti-viral applications, increase the number of product candidates in Peregrine's anti-PS pipeline. Peregrine's lead anti-PS antibody bavituximab is currently in Phase II clinical trials in advanced breast and lung cancers.

These preclinical studies further elucidate the unique immunomodulatory mechanisms contributing to the observed anti-tumor activity of anti-PS antibodies in preclinical and clinical studies, said Dr. Philip Thorpe, professor of pharmacology at UT Southwestern Medical Center in Dallas, a scientific advisor to Peregrine and co-author of one of the AACR presentations. These presentations provide additional insight into the mechanisms that act to selectively destroy the blood vessels supporting tumor growth and spread and also to reverse the ability of tumors to suppress the body's natural immune response, resulting in the mobilization of important inflammatory and other anti-tumor components of the immune system. Together, the studies provide compelling evidence suggesting that PS-targeting antibodies facilitate an important cytokine shift in the tumor environment that subsequently encourages multiple types of immune system cells to mount anti-tumor responses.

In a presentation1 on Monday, a series of preclinical studies by a team of scientists from Peregrine Pharmaceuticals and Affitech A/S used a fully human anti-PS antibody, PGN635, to confirm previous observations that in vitro, anti-PS antibodies stimulate the tumor microenvironment to recruit monocytes and other immune cells to the tumor with resulting anti-tumor effects, most likely via cell-mediated mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC). Their data further define the role of anti-PS antibodies in mediating tumor cell cytotoxicity and the tumor microenvironment, showing that the anti-PS antibody induced a sequential release of cytokines and beta-chemokines and stimulated enhanced macrophage recruitment to tumors. Furthermore, the researchers showed that in vitro, PGN635 induced antibody-dependent death of endothelial cells, the same cell type found in the tumor vasculature, a key target of anti-PS cancer therapy. The studies also demonstrated the anti-tumor potential of PGN635 in vitro and in a number of animal cancer models.

Data from our experiments has helped to clarify details regarding the mechanisms responsible for the anti-tumor results observed with Peregrine's PS-targeting antibodies, said Dr. Monica Friedrich, a Peregrine research scientist and lead author of the study. In data presented at this conference last year, we demonstrated that our fully human antibody PGN635 localizes to tumors and causes an increase in several inflammatory cytokines while decreasing an important anti-inflammatory cytokine. The new data we present confirms that PGN635 also triggers immune cells to produce other chemokines and cytokines that have the potential to alter the suppressed immune environment commonly found in tumors, attracting additional immune cells and stimulating more aggressive anti-tumor responses. We believe this upregulation of the immune response contributes to the encouraging anti-tumor effects demonstrated by PGN635 and other anti-PS antibodies.

A second study2 presented on Monday by researchers from UT Southwestern Medical Center and Affitech demonstrated the ability of Peregrine's fully human PS-targeting antibody PGN632 to promote the maturation of dendritic cells, important antigen-presenting cells of the immune system. In the in vitro studies, immature dendritic cells cultured in the presence of PGN632 exhibited a significant increase in the production of inflammatory cytokines and chemokines. PGN632 also induced an increase in the expression of cell-surface molecules that are indicative of mature dendritic cells and that assist in antigen presentation functions, as well as in stimulating T-cell proliferation.

Dr. Xianming Huang, assistant professor of pharmacology at UT Southwestern Medical Center and lead author of the study, noted, Dendritic cells are the professional antigen-presenting cells of the immune system and they play a crucial role in initiating adaptive immune responses. Dendritic cells must be mature, or activated, to be effective, yet tumors and other pathogens such as viruses often possess the ability to undermine this maturation, thereby suppressing the immune response. The results presented today suggest that by blocking exposed PS, anti-PS antibodies have the potential to promote dendritic cell maturation in the body and thereby stimulate a more effective immune response.

The fully human PS-targeting antibodies in these studies were developed through Peregrine's collaboration with Affitech A/S. The study by Dr. Huang, et al. was partly supported by the Gillson Longenbaugh and Meredith D. Chesler Foundations.

Peregrine president and CEO Steven King commented, It is noteworthy that these studies were primarily conducted using our new fully human antibodies, which could serve as the basis for the next generation of anti-PS therapies. Our PS-targeting antibody platform now includes several promising antibodies in preclinical evaluation that vary in their binding profile and in their specific immunomodulatory activity. The unique functional characteristics of these different antibodies open the door to new product candidates and extended applications for our anti-PS technology. We are more encouraged than ever that our anti-PS platform has very broad potential, and we look forward to further development of our growing preclinical pipeline of PS-targeting candidates both through internal efforts and collaborations with partners.

High levels of PEA-15 shrink breast cancer tumors

Mon, 20 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DENVER - Overexpression of PEA-15, which binds and drags an oncoprotein out of the cell nucleus where it fuels cancer growth, steeply reduced breast cancer tumors in a preclinical experiment, researchers at The University of Texas M. D. Anderson Cancer Center reported at the 100th annual meeting of the American Association for Cancer Research.

Human breast cancer grafts in mice dropped to nearly undetectable levels after 35 days when treated with an adenoviral PEA-15 vector that overexpressed the protein in tumors.

Treated mice had a dramatic response, while tumors continued to grow in control mice, said first author and presenter Chandra Bartholomeusz, M.D., Ph.D., a post-doctoral fellow in M. D. Anderson's Department of Breast Medical Oncology. Bartholomeusz presented the findings at a minisymposium titled Up and Coming Targeted Biologic Strategies.

This first animal model experiment demonstrates the therapeutic potential of PEA-15, said senior author Naoto Ueno, M.D., Ph.D., associate professor of breast medical oncology. PEA-15 is a different way of modulating growth because it's based on location of the protein in the cell rather than, for example, protein regulation by phosphorylation.

Ueno and colleagues previously showed that PEA-15 stymied ovarian cancer in lab experiments, and that high expression of the protein in tumors is tied to improved overall survival. They had also examined PEA-15 expression in 26 breast cancer specimens and found the protein was more heavily expressed in the 13 low-grade tumors analyzed.

In the breast cancer experiments, the team first tested overexpression in three breast cancer cell line cultures. Lines treated with PEA-15 developed 30 to 60 percent fewer colonies of cancer cells than did control cultures. Further analysis of one cell line showed that adenovirally delivered PEA-15 overexpression inhibited cell growth and reduced DNA synthesis.

They also found that activated ERK - a protein active in growth, differentiation and mobility of cells that can fuel cancer growth when in the nucleus - was sequestered in the cell's cytoplasm. This is consistent with previous research by Ueno's team that showed PEA-15 works by binding and dragging ERK and phosphorylated ERK from the nucleus, inducing cell death.

Cell cycle analysis indicated the onset of apoptosis - programmed cell death - in breast cancer cells treated with PEA-15. In the case of ovarian cancer, the team found evidence of death by autophagy - cellular self-consumption - rather than apoptosis. The varied forms of cellular death may indicate that the protein's mechanisms differ from one form of cancer to another, Ueno said.

PEA-15 is a versatile protein, serving multiple cellular functions, including glucose metabolism and regulating the tumor necrosis factor (TNF) pathway in addition to its role regulating ERK, Ueno said.

We are committed to further developing PEA-15 and making it a druggable target, Ueno said. The team is developing a non-gene therapy treatment because adenovirally delivered gene therapies such as those used to overexpress PEA-15 in the mouse experiments have had less success in humans.

Pregnancy hormone hCG protects against breast cancer even in short-term treatments

Mon, 20 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) One of the most effective ways to prevent breast cancer is through a full-term pregnancy at an early age. Studies out of Fox Chase Cancer Center have linked this protective effect to the presence of human chorionic gonadotropin (hCG), a hormone produced by the placenta to maintain the early stages of pregnancy. Their findings in an animal model of breast cancer showed that rats exposed to hCG over a 21 day period (the length of rat pregnancy), are far less likely to develop breast cancer when exposed to a known carcinogen.

Today, at the 100th Annual Meeting of the American Association for Cancer Research. Johana Vanegas, M.D., a research associate at Fox Chase, presents findings suggesting that even a much shorter exposure to hCG can prevent breast cancer in rats.

Venegas is a member of the laboratory of Jose Russo, M.D. and Irma Russo, M.D., who were the first scientists to propose hCG as an anti-cancer agent. Their studies have shown that hCG offers lasting, protective changes within breast tissue. Clinical trials of hCG in women, based on their work, are currently under way at three locations, nationally, including Fox Chase Cancer Center, and in one European country. The hCG hormone is an FDA-approved agent frequently used for fertility treatments.

The ability to replicate the naturally protective effects of pregnancy against breast cancer will hold a significant public health value, says Vanegas. In order to translate our finding into humans, a clinical trial with hCG as a preventive agent against breast cancer, is already ongoing in pre-menopausal women with no previous pregnancy.

Vanegas and her colleagues studied virgin female rats, which had been divided into four groups: a control group, which did not receive hCG, and three groups that received hCG for five, ten or fifteen consecutive days. Following the treatment, each rat received a single dose of a breast cancer-inducing agent.

According to Vanegas, 90.9 percent of the rats in the control group developed breast tumors, compared to 71.4 percent, 57.1 percent, and 15.4 percent in the five, ten and fifteen day-treated animals, respectively. In addition, the average tumor size was also smaller in all the animals that received any of the three hCG treatments.

The animals that received hCG, but still developed breast cancer did so much later than the control group, which further demonstrates the protective effects of hCG, Vanegas says. While we don't foresee side effects among humans in using hCG, it is helpful to know that even smaller doses confer benefits on breast tissue.

Genetic variants predict recurrence of bladder cancer, patient survival

Mon, 20 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DENVER - Scientists at The University of Texas M. D. Anderson Cancer Center have discovered genetic variations in the inflammation pathway that reduce the likelihood of recurrence and increase survival of patients with non-muscle invasive bladder cancer (NMIBC) who are treated with mainstream therapy.

Patients with risk-reducing genotypes were 84 percent less likely to have their disease recur after treatment with Bacillus Calmette-Guerin (BCG), the prevailing immunotherapy to prevent high-risk NMIBC patients from developing recurrence. The recurrence-free median survival time among these patients was 96.7 months compared with 47 months among those with the more typical genotype, the team reported at the 100th Annual Meeting of the American Association for Cancer Research.

The future purpose of this kind of study is personalized cancer therapy, said senior author Xifeng Wu, M.D., Ph.D., a professor in the Department of Epidemiology at M. D. Anderson. This genetic information is an essential step toward constructing a blueprint that will determine treatment response and follow-up strategy.

Currently, the primary treatment for NMIBC is transurethral resection - surgical removal of the tumor tissues from bladder - combined with chemotherapy or immunotherapy such as BCG injection. Overall, the recurrence rate is around 50 percent over four years.

In this study of 596 patients at M. D. Anderson, 46 percent of those who had a common genotype of the inducible nitric oxide synthase (iNOS) gene experienced a recurrence after receiving maintenance BCG therapy. Only 22 percent of patients with the variant-containing genotypes had a recurrence with the same treatment. The results suggest that BCG may be more effective when administered to individuals with genotypes containing the variant allele of the iNOS gene.

We aimed to determine why some patients respond to BCG and others don't, said lead author Hushan Yang, Ph.D., a postdoctoral fellow in the Department of Epidemiology at M. D. Anderson.

Yang and his colleagues evaluated 59 single nucleotide polymorphisms (SNPs) in 35 major inflammation genes. Using a combined analysis, they stratified patients into multiple risk groups. Those patients in the high-risk group were found to have a median survival time of only 13.5 months, while those in the low-risk group were recurrence free for more than 96.7 months.

Once validated, the next step will be to create a risk prediction model, said Wu. Combining the information we have with other aspects such as clinical, epidemiological and behavioral variables, as well as tumor characteristics, patient characteristics and other genetic information will allow treating physicians to know whether their patient is likely to respond to therapy or experience a recurrence.

Mayo Clinic researchers formulate treatment combination lethal to pancreatic cancer cells

Sun, 19 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DENVER - A combination of two targeted therapies packs a powerful punch to kill pancreatic cancer cells in the laboratory, Mayo Clinic cancer researchers report. With further testing of these drugs that are from classes of pharmaceuticals already used in patients, the Mayo research may lead to new treatment opportunities for patients with pancreatic cancer, which is extremely difficult to treat.

In a study being presented at the annual meeting of the American Association for Cancer Research, Mayo Clinic Cancer Center investigators found that rapamycin and panobinostat (also known as LBH589) act synergistically when used in combination, destroying up to 65 percent of cultured pancreatic tumor cells.

The finding is particularly significant, says the study's first author, Mamta Gupta, Ph.D., because the three cell lines studied were all resistant to the effects of chemotherapy - as are many pancreatic tumors - and because the drugs studied are already available for treatment of patients. Panobinostat is approved as therapy for cutaneous T cell lymphoma (CTCL), and rapamycin is best known as an immunosuppressant to help prevent rejection of transplanted organs.

We need new therapies and strategies for the treatment of pancreatic cancer because these tumors are resistant to almost all known treatments, says Dr. Gupta, a research associate in the Division of Hematology. No targeted treatment has shown much value to date.

Dr. Gupta studied the combination of agents in pancreatic cancer cells because her previous research at Mayo Clinic had shown that this combination worked well in laboratory tests of non-Hodgkin's lymphoma. A phase one clinical trial to test this combination in patients with lymphoma will open soon at Mayo Clinic under the direction of Thomas Witzig, M.D.

While our pancreatic cancer cell line results look very promising, these are laboratory, not clinical, studies, she says. We are preparing to take this combination of drugs to clinical trial to evaluate whether they can be safely given to patients.

While clinical studies will ultimately determine the benefits of panobinostat and rapamycin, Dr. Gupta and her colleagues remain focused on trying to understand the mechanism for how these agents together are so powerful.

Rapamycin and a closely related drug, everolimus (RAD001), have both been tested in pancreatic cancer cells, but by themselves have shown minimal activity, Dr. Gupta says. They belong to a class of agents known as mTOR inhibitors. The mTOR pathway is a major cellular survival mechanism that is persistently activated in pancreatic cancer cells.

In this study, rapamycin killed less than 5 percent of pancreatic cancer cells, and previous tests with RAD001 showed the same minimal effect, Dr. Gupta says. Panobinostat is a histone deacetylase (HDAC) inhibitor. In cancer, HDAC proteins silence tumor suppressor genes, so an HADC inhibitor restores expression of these beneficial genes. The agent is also believed to block angiogenesis - the growth of new blood vessels needed for tumors to grow, Dr. Gupta says.

Panobinostat killed about half of pancreatic cancer cells studied, she says. But both agents combined inhibited growth of pancreatic cancer cell lines and induced apoptosis (cell death) in up to 65 percent of the cells, Dr. Gupta says.

Dr. Gupta noted that panobinostat is effective at extremely low concentrations that are consistent with optimal pharmacological doses. Our aim is always to use as little of a drug as possible in order to reduce potential side effects in patients, she says.

Although the researchers say they don't yet know the synergistic mechanism responsible for the combined drugs' effectiveness, they hypothesize that the agents are primarily interfering with the mTOR pathway, which is involved in growth and angiogenesis.

Overall, these results indicate that rapamycin and panobinostat disrupts essential survival and proliferating pathways in pancreatic cancer cells, and this is a good start toward a novel treatment of this cancer, Dr. Gupta says.

Mayo Clinic-led researchers confirm gene variants associated with the most common adult leukemia

Sun, 19 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DENVER - A national team of researchers led by Mayo Clinic has found that patients with chronic lymphocytic leukemia (CLL) are more likely to have similar DNA changes or variants in up to six genes, compared to people who do not have the cancer.

The findings, being presented at the annual meeting of the American Association for Cancer Research, are an independent validation of an earlier European study that found a link to seven different gene variants. Six were replicated in the Mayo Clinic study.

Together, the two studies demonstrate a genetic basis for the development of CLL, the most common adult leukemia in the United States, says the study's lead investigator, statistical geneticist Susan Slager, Ph.D., an associate professor of biostatistics at Mayo Clinic.

In our study of American patients, we replicated six out of seven gene associations that were linked to this white blood cell cancer in Europeans, and in my field this level of replication is not common, Dr. Slager says. This is a very exciting finding, and our job now is to investigate these genes to understand how they biologically affect the development of the cancer.

These findings could potentially lead to new treatments or even prevention of CLL, but we have a lot more work to do before we can reach that ultimate goal.

Dr. Slager estimates the risk of developing the cancer doubles if a person has any of these gene variants, but overall, that absolute risk is still very small. Four out of every 100,000 people develop CLL, so having the variant genes could increase risk to eight out of every 100,000 people, she says.

Although CLL can be generally controlled, it is considered an incurable cancer, she says. Researchers from across the country collaborated with Dr. Slager and her team to collect genetic information on 399 CLL patients and 632 participants who did not have the cancer. Within the group of CLL patients, 99 were from high-risk CLL families - defined as two or more relatives diagnosed with CLL.

Using blood samples, investigators performed a genome-wide association study. They combined patients into one group and controls into another and then compared the two groups, looking for differences in genetic variants across the chromosomes. The first analysis of this data focused on the seven single nucleotide polymorphisms (SNPs) that European researchers had found. An SNP is a variation that occurs within a single nucleotide - the structural units of DNA - within a gene, and in most studies like this, the genes in which SNP changes occur are largely known. Analyses of the other genetic variants are under way.

They found that for six of the seven variants examined, CLL patients tended to have the variant more often than patients without the disease. Dr. Slager says these variants are associated with risk of developing the disease, not with prognosis - the outcome of a patient once disease has developed. We do know that some patients have lost regions of certain genes due to the cancer and this is associated with a poorer outcome. However, we are looking for changes in the genome that potentially determine who will get the disease in the first place, she says.

Our general theory is that these changes, which a person inherits, combined with environmental risk factors, can predispose a person to developing CLL, she says. The more you understand about these gene variants and how they affect risk, it becomes possible to think about ways to treat or even prevent CLL.

The researchers have identified some candidate genes that correspond to the identified SNPs, while other SNPs seem to be located near genes or in regions with no genes, i.e., what scientists call gene deserts.

Herb-based anti-cancer chemical made in lab

Thu, 16 Apr 2009 13:32:33 PST

( from http://www.rxpgnews.com ) Washington, April 16 - Club moss Lycopodium serratum is a flowerless plant whose potent brew of alkaloids, which could have anti-cancer properties and may combat memory loss, have drawn considerable scientific and medical interest. Now scientists have made one of the alkaloids in a lab, in quantity sufficient for use.

However, the plant makes many of these compounds in extremely low amounts, hindering efforts to test their therapeutic value.

That is no longer a problem for what is arguably the most complex of these alkaloids, a compound called Serratezomine A: an alkaloid that could have anti-cancer properties and may tackle memory loss.

A team of synthetic chemists at Vanderbilt University reported that they have created an efficient way to make this molecule from scratch. It took six years to develop the process because the researchers had to invent some entirely new chemical methods to complete the synthesis.

These methods should make it easier to synthesise other Lycopodium alkaloids as well as other natural compounds with therapeutic potential.

Besides therapeutic possibilities, Vanderbilt chemists were attracted to these compounds because they are among the most intricately structured and functionally dense of all the small molecules produced by living organisms. The compounds consist of carbon and nitrogen atoms assembled in unique ring structures.

'This was a challenging problem,' said Jeffrey Johnston, a chemistry professor who led the research. 'It takes years to develop a new chemical reaction and then apply it to the natural product target. So, once we start, we don't stop.'

In the world of total synthesis chemistry, it is not enough to figure out a way to synthesise a naturally occurring molecule, said a Vanderbilt release.

The process has to produce large enough quantities of the molecule that it can be tested for biological activity. That means that the number of sequential steps in the process - what chemists refer to as the longest linear sequence - should be as small as possible to maximise production.

For example, if a sequence has 30 steps and each step has an 80 percent yield, the overall yield of the sequence is about a tenth of one percent. At the same time, one low-yield step will knock a process out of contention.

These findings was published in the March 18 issue of the Journal of the American Chemical Society.

Leading cancer organizations team up on tumor-promoting protein

Thu, 16 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) An inflammatory protein implicated in a variety of cancers is the target of the first joint symposium between the nation's two premier cancer research organizations.

The presidents of the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) organized the session focused on the COX-2 enzyme and cancer treatment Monday afternoon -- April 20, 2:30-4:30 p.m., in rooms 205-207 of the Colorado Convention Center -- at the AACR's 100th Annual Meeting 2009 in Denver. A similar symposium on new molecular targets will be conducted at ASCO's annual meeting in May 29- June 2 in Orlando.

COX-2 is best known as a target for preventing dangerous polyps that lead to colorectal cancer, but it is also advancing as a target for treatment of many solid tumors.

Our symposium is timely because we are starting to see data from Phase II and Phase III clinical trials about COX-2 inhibition following post-surgical chemotherapy in colon cancer patients, said Raymond DuBois, M.D., Ph.D., president of AACR and provost and executive vice president at The University of Texas M. D. Anderson Cancer Center.

There's been a great deal of preclinical and translational research addressing COX-2 overexpression in tumors and its role in cancer growth and survival. In prevention, inhibiting this enzyme reduces the number of high-risk precancerous polyps by 66 percent, DuBois said. The time is ripe to combine basic science and clinical expertise to advance the therapeutic potential of this approach.

Joint efforts are critical to the development of new approaches against cancer, said ASCO President Richard L. Schilsky, M.D., professor of medicine at the University of Chicago Medical Center.

The development of targeted therapies for cancer prevention and treatment requires the close collaboration and combined resources of basic scientists and clinical investigators, Schilsky said. The success of targeted therapy for cancer depends first and foremost on a comprehensive understanding of the biology of the drug target coupled with a robust assay to assess target inhibition and a drug that hits the target. With these ingredients in place, clinical trials can be designed to assess the impact of treatment in the population most likely to benefit.

The AACR/ASCO Symposium illustrates these core principles and demonstrates that continued progress against cancer requires the partnership of all investigators and practitioners represented by these two great organizations, Schilsky said.

The idea for joint symposia at each organization's annual meeting has been discussed for years and was advanced by immediate past presidents William Hait, M.D., Ph.D., of AACR and Nancy Davidson, M.D., of ASCO.

Novel lung cancer vaccine shows promise in fighting early-stage lung cancer

Mon, 06 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO - An experimental vaccine that triggers the patient's immune system to identify and attack specific tumor cells is showing new promise for the treatment of early lung cancer. Thoracic surgeons at Rush University Medical Center are researching the vaccine called MAGE-A3 Antigen-Specific Cancer Immunotherapeutic, which is designed to kill cancer cells without harming normal cells. Rush is one of only five hospitals in Illinois offering the vaccine.

The MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell LunG Cancer Immunotherapy) study is a randomized, double-blind and placebo controlled trial that will enroll patients with MAGE A-3-positive, non-small-cell lung cancers. The experimental vaccine targets MAGE-A3, a protein expressed in certain cancer cells but not in normal cells. Thirty-five percent of non-small-cell lung cancers have this protein which also is present in some melanomas and head and neck cancers.

The principle is that you can possibly teach a patient's immune system to eliminate cancer cells that express certain proteins such as the MAGE-A3 protein, said Dr. Anthony Kim, thoracic surgeon and principal investigator of the study at Rush. In a trial of early-stage lung cancer patients whose tumors expressed MAGE-A3, preliminary results showed that the vaccination reduced the risk of recurrence and the need for repeat surgery.

The vaccination may be a promising alternative treatment solution for lung cancer patients that may not be ideal candidates for chemotherapy. Many surgically treated lung cancer patients are not able to tolerate the side effects of chemotherapy.

Surgery is the standard treatment for patients with early-stage lung cancer, but approximately 50 percent of patients who have surgery ultimately die of lung cancer.

Adding the tumor vaccine to surgery has the potential to boost the survival rate by 10 percent, which was the figure that was observed in the initial phase of the MAGE-A3 trial, said Kim. This is a potential alternative for patients that otherwise would not undergo chemotherapy treatment either because of their tumor stage or other co-morbidities such as their age or other medical problems.

A total of 182 patients with non-small-cell lung cancers were included in the early phase of the study sponsored by GlaxoSmithKline, which is developing the vaccine therapy. All the patients had cancers expressing MAGE-A3, the tumor-specific antigen. After having surgery to remove the tumors, 122 patients were randomly assigned to treatment with the MAGE-A3-targeting vaccine and 60 patients received placebo vaccines. The preliminary research shows that the treatment was well tolerated by patients and the MAGE-A3-treated patients seemed less likely to have recurrences and die from their disease than the placebo-treated patients. Further studies need to be completed to test the safety and efficacy of the vaccine.

Patients were given five injections every three weeks at the beginning of treatment and then eight injections every three months later for a total of 27 months. Earlier phases of the study indicate the immunotherapy treatment was well tolerated by patients.

Naturally fluorescent molecules may serve as cancer biomarker

Thu, 02 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Excess amounts of a naturally fluorescent molecule found in all living cells could serve as a natural biomarker for cancer, according to bioengineers.

NADH, or nicotinamide adenine dinucleotide, is a key coenzyme -- a non-protein molecule necessary for the functioning of an enzyme -- found mostly in the inner membrane of a cell's power plant, or mitochondria. It fuels a series of biochemical reactions that involve various enzymes to produce ATP, the major energy source in cells. In the event of disease or a metabolic disorder, these enzymes and their related reactions can become disabled, causing a buildup of unused NADH.

Dysfunctional enzymes in the mitochondria are known to be associated with serious health problems such as cancer and neurodegenerative diseases, said Ahmed Heikal, associate professor of bioengineering, Penn State. By detecting the level of NADH and its distribution inside living cells, we should be able to monitor the mitochondrial activity and thus the integrity of any given cell, without adding potentially toxic dyes or actually destroying the cell.

According to Heikal, one of the main challenges in cancer diagnosis is the ability to differentiate cancer cells from normal ones at the early stages of tumor progression.

To tease apart the critical difference between normal and cancerous cells, the researchers used the fluorescence of natural NADH. Using a combination of state-of-the-art spectroscopy and microscopy techniques, the researchers were able to convert such fluorescence into an accurate measure of NADH concentration in live cells. Heikal and Yu, graduate student, bioengineering, have found that the average concentration of NADH in breast cancer cells is about twice that in normal breast cells.

If we are given two live cells, one normal and the other cancerous, we could differentiate between the two with confidence, said Heikal, whose team's findings appear today (April 2) in the Journal of Photochemistry and Photobiology B: Biology. For the first time, we have been able to quantify the concentration of NADH in both live breast cells and breast cancer cells.

The researchers also looked at the amounts of NADH in the cell that is free and how much is bound to other enzymes. These amounts are different in normal and cancer cells.

We realized that the fluorescence intensity not only depends upon the concentration of NADH but also on its structure -- free or enzyme-bound -- as well as its place inside the cell -- in the cytoplasm (non-nucleus part of the cell) or in mitochondria, explained Heikal. Since a free NADH molecule would rotate -- tumble -- faster than enzyme-bound NADH, we were able to develop a technique called rotational diffusion imaging to establish a direct measure of the concentrations of free and enzyme-bound NADH throughout a living cell, whether in the cytosol (cell fluid) or the mitochondria.

To confirm their findings that disruption of chemical reactions that produce ATP can lead to an increase in NADH, Heikal and Yu exposed normal breast cells to potassium cyanide, a known inhibitor of some of these critical mitochondrial enzymes.

The researchers found that the NADH concentration in the normal cells increased when exposed to potassium cyanide. The relative amounts of NADH in the mitochondria also rose significantly.

Other researchers have previously measured the amount of NADH in cells using conventional biochemical techniques that require destroying the cells. However, Heikal believes measurements of dead cells provide no information about NADH distribution in the cells and may not be accurate or relevant for diagnostic or clinical use.

The advantage of our non-destructive approach is that the NADH location in a cell relates to its function in cell survival, explained Heikal. When you destroy the cell, you do not know where the NADH molecules existed inside the cell and what role they might have played in cell survival. For accurate diagnosis, you need to have the cellular context to better understand the problem.

According to the Penn State researcher, the ability to accurately measure NADH levels in a cell without killing it could have potential implications for related research on human health and drug delivery.

Our technique is not limited to detecting cancer. Other neurodegenerative diseases related to mitochondrial anomalies can also be detected with our method, Heikal said. We can also use our approach to quantify the efficiency of a new drug on manipulating the activities of mitochondrial enzymes associated with energy production in cells.

Bionic Nose to Detect Cancers

Tue, 31 Mar 2009 12:12:23 PST

( from http://www.rxpgnews.com ) Washington, March 31 - Both cancer cells and chemicals used in bombs evade detection because they are present in very small quantities. But now a new method being developed can detect them by amplifying near invisible traces of biomarkers in cancer, materials in explosives or pollutants in water.

Pioneered by Doron Shabat, a bio-organic chemist and professor at Tel Aviv University's School of Chemistry, the technology being developed aims to amplify signals millions and billions of times.

'We are developing a molecular system that amplifies certain events,' said Shabat.

'That way we'll be able to respond faster to medical, security and environmental threats. In effect, our device can amplify just about any chemical system that has a certain kind of reactivity.

'It has the potential to help doctors diagnose diseases - those with biomarkers, and enzymatic activities that are compatible with our molecular probe,' Shabat explained.

'The long list includes a few kinds of cancers, including prostate cancer. But it also has applications for testing for impurities in water. It has both biological and non-biological applications,' he was quoted as saying in a Tel Aviv University release.

Shabat's invention is a molecular sensor that acts in a solution. A chemist would add trace amounts of the test material from the field - a spoonful of contaminated drinking water, for example - into the solution and would simply see if the colour of the solution changes. If so, the targeted material - the cancer, explosive or pollutant - is present.

These findings were published in Chemical Communication.

What's in your water?: Disinfectants create toxic by-products

Tue, 31 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Although perhaps the greatest public health achievement of the 20th century was the disinfection of water, a recent study now shows that the chemicals used to purify the water we drink and use in swimming pools react with organic material in the water yielding toxic consequences.

University of Illinois geneticist Michael Plewa said that disinfection by-products (DBPs) in water are the unintended consequence of water purification. The reason that you and I can go to a drinking fountain and not be fearful of getting cholera is because we disinfect water in the United States, he said. But the process of disinfecting water with chlorine and chloramines and other types of disinfectants generates a class of compounds in the water that are called disinfection by-products. The disinfectant reacts with the organic material in the water and generates hundreds of different compounds. Some of these are toxic, some can cause birth defects, some are genotoxic, which damage DNA, and some we know are also carcinogenic.

The 10-year study began with an EPA grant to develop mammalian cell lines that would be used specifically to analyze the ability of these compounds to kill cells, or cytotoxicity, and the ability of these emerging disinfection by-products to cause genomic DNA damage.

Our lab has assembled the largest toxicological data base on these emerging new DBPs. And from them we've made two fundamental discoveries that hopefully will aid the U.S. EPA in their regulatory decisions. The two discoveries are somewhat surprising, Plewa said.

The first discovery involves iodine-containing DBPs. You get iodine primarily from sea water or underground aquifers that perhaps were associated with an ancient sea bed at one time. If there is high bromine and iodine in that water, when you disinfect these waters, you can generate the chemical conditions necessary to produce DBPs that have iodine atoms attached. And these are much more toxic and genotoxic than the regulated DBPs that currently EPA uses, he said.

Plewa said that the second discovery concerns nitrogen-containing DBPs. Disinfectant by-products that have a nitrogen atom incorporated into the structure are far more toxic and genotoxic, and some even carcinogenic, than those DBPs that don't have nitrogen. And there are no nitrogen-containing DBPs that are currently regulated.

In addition to drinking water DBPs, Plewa said that swimming pools and hot tubs are DBP reactors. You've got all of this organic material called 'people' -- and people sweat and use sunscreen and wear cosmetics that come off in the water. People may urinate in a public pool. Hair falls into the water and then this water is chlorinated. But the water is recycled again and again so the levels of DBPs can be ten-fold higher than what you have in drinking water.

Plewa said that studies were showing higher levels of bladder cancer and asthma in people who do a lot of swimming - professional swimmers as well as athletic swimmers. These individuals have greater and longer exposure to toxic chemicals which are absorbed through the skin and inhaled.

The big concern that we have is babies in public pools because young children and especially babies are much more susceptible to DNA damage in agents because their bodies are growing and they're replicating DNA like crazy, he said.

Some public pools have been closed because they have high levels of bacteria. Public pools keep a high level of chlorine in the water to keep bacteria and pathogens down but very little work research is conducted on evaluating levels of generated dangerous disinfection by-products.

The idea is to keep the pools disinfected, keep them in compliance, just as with drinking water but then use engineering techniques that reduce the levels of these toxic by-products. Plewa described another project he is working on as a researcher with a National Science Foundation Center called WaterCAMPWS at the University of Illinois. We're working with engineers and chemists to develop new technologies that will disinfect water, that will desalinate water, that will remove pharmaceuticals from water but in so doing, don't generate by-products that are even more toxic than the things you're trying to remove.

Ironically, the DBPs that are regulated by the EPA tend to be some of the least toxic DBPs in Plewa's study. We've found that the emerging DBPs are much more genotoxic and much more cytotoxic. But I can't fault EPA because these data were not present at the time and in fact the development of the database of over 70 DBPs has been done in concert with our colleagues at the federal EPA.

Plewa said that until new technologies are engineered to safely disinfect the water in public pools, education is needed to encourage people to bathe or shower before entering a public pool. It's the organic material that gets in the pool that is disinfected and then recirculated over and over again. That's why we call swimming pools disinfectant by-product reactors. But by public education, by personal behavior, there should be ways that we can reduce the levels of the dissolved organic material that should reduce the level of DBPs.

Plewa, along with a team of scientists received a United States Environmental Protection Agency Science and Technology award for their paper Occurrence, genotoxicity and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. It was published in the scientific journal

Montana State grad's work helps diagnose skin cancer without a biopsy

Mon, 30 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) BOZEMAN -- A recent Montana State University master's graduate is working with doctors at Vanderbilt Medical Center in Tennessee to build a handheld laser microscope that could someday reduce the number of biopsies needed to diagnose skin cancer.

Suspicious spots on the skin often prompt dermatologists to remove skin samples for analysis. These procedures are currently the best way to diagnose skin cancers, said Chris Arrasmith, who recently earned his master's degree and now works as a researcher in MSU's electrical engineering department.

But biopsies are invasive procedures that are often painful. Millions are conducted each year in the United States, and according to the American Cancer Society, most of those biopsies -- as many as 80 percent for some types of cancers -- come back negative.

The handheld microscope could help doctors get a better idea when biopsies are absolutely necessary. That would cut down on the number of biopsies that have to be performed and streamline the process of diagnosing cancers, Arrasmith said.

Any combination of tools we can provide to enable early detection of any kind of disease is a good thing, said Arrasmith, 25.

Like most microscopes, the MSU-Vanderbilt device uses lenses to look at a patient's skin, but instead of illuminating the skin with normal white light, the device uses laser light.

The laser light is used to form an image of the skin's cellular structure, and it monitors the way a patient's cells change the reflected laser light, Arrasmith said. Those changes to the light can tell scientists the chemical composition of the skin cells -- a process called spectroscopy.

Within the microscope's image, we can select an area of interest, and from that we can take a spectrum and get chemical data, Arrasmith said.

Doctors would then compare that chemical signature to a database containing the chemical signatures of known cancers to see whether the patient's cells are cancerous.

The project, which Arrasmith began working on when he was an undergraduate at MSU, is funded by a five-year grant from the National Institute of Biomedical Imaging and Bioengineering, part of the National Institutes of Health. The NIBIB focuses on researching new biomedical imaging devices and techniques to improve the detection, treatment and prevention of disease.

The $1.79 million grant is administered by Vanderbilt. MSU will receive $500,000 from the grant over all five years. That money covered, among other things, the cost of the microscope itself and Arrasmith's graduate tuition.

David Dickensheets, an associate professor of electrical and computer engineering at MSU and adviser to Arrasmith's work, said other labs have built microscopes that work on the same principles, but they have been desktop instruments that still required skin samples to be taken from patients.

Shrinking the microscope takes advantage of MSU's expertise in a field called micro-electrical-mechanical systems, or MEMS.

The handheld microscope contains a tiny mirror made of silicon that scans the laser beam across the skin, Dickensheets said. This allows the microscope to form an image and lets it look at cells beneath the patient's outer skin layer.

Merging MSU's expertise in microscopy and MEMS with Vanderbilt's spectroscopy research will produce a device that could one day find its way into dermatology clinics around the world, Dickensheets said.

We think that microscopic imaging of cell structure combined with the chemical specificity provided by spectroscopy is the real key to making it a useful tool, Dickensheets said.

For Arrasmith, who has worked on the microscope since 2006, the approaching end of his time at MSU is both satisfying and bittersweet.

It's satisfying, he said, because he's been able to build a prototype microscope that's now being tested at Vanderbilt's medical clinics. It's bittersweet, he said, because he knows he won't be around to see the finished second-generation model, which he hopes will be about the size of a chalkboard eraser.

As a person who likes to see things from start to completion, it's difficult to leave in the middle of a long project like this, he said.

But he said the experience he's gained from having a hand in every aspect of the project -- from theory and design to machining parts -- will give him a leg up in searching for an engineering job after he leaves MSU.

This project has really allowed me to see how things come together from multiple facets of design, he said. What I'm taking away from MSU is a general knowledge base that I can apply to any other situation.

Two NYU Scientists Named Howard Hughes Medical Institute's early career scientists

Thu, 26 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Two researchers from NYU School of Medicine have been named Early Career Scientists by the Howard Hughes Medical Institute (HHMI). The honorees, Iannis Aifantis, Ph.D. associate professor of pathology, co-director of the Cancer Stem Cell Program at the NYU Cancer Institute and Jeremy S. Dasen Ph.D., assistant professor of physiology and neuroscience at NYU School of Medicine are among 50 of the nation's top scientists being honored by HHMI under this new initiative to establish, develop and grow unique research programs.

Dr. Aifantis, a cancer biologist investigating T-cell acute lymphocytic leukemia, a common form of leukemia in children and Dr. Dasen, a neuroscientist investigating the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control, will both receive a six-year appointment to the HHMI and funding to further explore their areas of research. HHMI will provide each NYU researcher with his full salary, benefits, and a research budget of $1.5 million over six-years.

The entire NYU Langone Medical Center community is proud of the groundbreaking work being conducted by Dr. Aifantis and Dr. Dasen and we congratulate them on their selection as HHMI Early Career Scientists, said Robert I. Grossman, M.D., Dean and CEO of NYU Langone Medical Center. These awards are recognition of the immense talent of these two scientists and the importance of the work that they are pursuing.

Dr. Aifantis has made majors strides towards understanding and developing new treatments for T-cell acute lymphocytic leukemia. He recently discovered a molecular door by which T cells, the soldiers of the immune system, slip into spinal fluid and the brain after they become malignant. Blocking this process could save thousands of lives each year. Aifantis is now testing hundreds of potential drugs that might prevent malignant T cells from reaching the nervous system. At the same time, he is learning what goes awry in blood stem cells that transform into leukemic T cells. Such insights may provide even more ways to combat deadly blood cancers.

Dr. Dasen's research focuses on deciphering the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control. Understanding this code, which relies on a large family of genes that produce proteins called Hox factors, may help scientists restore motor neuron function in people whose spinal cords have been damaged by trauma or disease. Dasen, has found that Hox proteins are not just present in motor neurons; they are pervasive throughout the nervous system. He plans to explore whether Hox proteins in interneurons and sensory neurons, which control motor neuron firing patterns and transmit feedback about muscle action, help assemble the complete circuits that control walking and running.

New book chronicles the journeys of women physicians and scientists to fighting cancer

Mon, 23 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) HOUSTON - Just more than one year after it was created, the office of Women Faculty Programs at The University of Texas M. D. Anderson Cancer Center has introduced a collection of essays by leading women faculty aimed at inspiring generations of women scientists to come.

Legends and Legacies: Personal Journeys of Women Physicians and Scientists at M. D. Anderson Cancer Center presents the reflections of 26 current faculty women on their formative years and influences, their hurdles and opportunities as they pursued rewarding careers - and leadership roles - in science and academic medicine.

Anecdotes and insight shared throughout the book reveal personal struggles and bias based on gender, race or social/economic background, as the women sought to balance personal and professional lives, including the often competing demands of motherhood and the tenure track. The women profiled represent diverse ages, backgrounds and cultures and various professional roles, from clinicians and physician scientists to basic scientists and veterinarians. (Please see sidebar.)

In his foreword, John Mendelsohn, M.D., president of M. D. Anderson Cancer Center, noted I was struck by how diverse - and often difficult - their pilgrimages have been, yet all share the common bond of growing up knowing they wanted to make a difference.

Editor Elizabeth Travis, Ph.D., a professor in the departments of Radiation Oncology and Pulmonary Medicine and the first associate vice president for Women Faculty Programs at M. D. Anderson, conceived the book project to recognize the accomplishments of M. D. Anderson's women faculty while spotlighting advocacy efforts intended to improve opportunities for women already in the field, as well as inspire others to choose and then stay in the field.

Legends and Legacies is about seeing dreams through in the face of adversity, says Travis. I hope it serves as a source of inspiration for young women dreaming of careers in science and medicine - and as a reminder to those women and men who are mentoring the next generation.

Mendelsohn also credited the women's innate tenacity to succeed, commending Travis and the faculty women for their efforts to make M. D. Anderson a top destination for women physicians and scientists. We are proud to be the home of so many remarkable women physicians and scientists who continue to be leaders in cancer patient care, research, education and prevention.

Through its Women Faculty Programs, M. D. Anderson promotes workplace initiatives for women physicians and scientists, such as creating a better work-life environment; nominating women faculty for prizes and awards; increasing the number of women leaders; providing career development and mentoring programs; reviewing faculty salaries annually; hosting women physicians and scientists to give scientific and women-in-science talks; promoting institution-wide gender-balanced participation; and reviewing status of women faculty annually.

Offering the book's final note, Raymond N. Dubois, M.D., Ph.D., provost and executive vice president of M. D. Anderson, said, We must discard past gender stereotypes and do everything possible to attract, train and support the best and brightest minds to meet the challenges of conquering such relentless and stubborn problems as cancer. Future generations are counting on all of us.

Legends and Legacies features personal photographs, capturing the women as children and teens, with their families, at work and at play alongside the essays. Legends and Legacies (ISBN: 978-0-9753878-1-8) is available in hardcover for $24.99 and can be purchased securely online at www.Amazon.com. In Houston, the book can be purchased at: Half Price Books (Rice Village, Montrose, and Pearland locations); Majors Books; River Oaks Book Store; Blue Willow Bookshop; Brazos Bookstore; and The University of Texas Health Science Center at Houston (Dental Branch, Medical School, School of Nursing bookstores).

Proceeds from the sale of Legends and Legacies will benefit internships for women interested in careers in cancer medicine or science at M. D. Anderson.

Each woman featured in Legends and Legacies overcame personal struggles and their stories shine a light on obstacles that many may think are long gone. Take these:

New RNA treatment can shrink cancers

Fri, 20 Mar 2009 15:23:31 PST

( from http://www.rxpgnews.com ) Washington, March 20 - A newly-identified type of microRNA could tackle aggressive cancers by helping to kill off their cells.

'MicroRNAs are very small, newly-identified RNA elements of the cell, and we've shown that one in particular - microRNA-7 or miR-7, can play a profound role in reversing cancer cell growth,' said Peter Leedman, a professor who led the research team.

Leedman, deputy director of Western Australian Institute for Medical Research -, added that miR-7 can significantly reduce the growth of some cancer cells, as well as killing off others - particularly in cancers of the brain, lung, breast and prostate.

'What's special about this discovery is that we've shown, on a cellular level, that we can inhibit cancer cell growth and kill-off some cancerous cells very effectively with miR-7.'

Leedman said the research showed miR-7, which is normally found in some healthy cells, especially the brain and pancreas, can be almost undetectable in cancerous cells.

'Without miR-7, some cancer cells have free rein to grow, but when we add miR-7, the cancer cells start to die-off, which has the potential to assist current treatments, especially in rapid-growing, fatal cancers like brain tumours,' he said.

'In many patients, cancers don't respond to treatments well enough or fast enough to totally eradicate the cancer, so what we are continuing to investigate is if miR-7 has the potential to make cancer cells respond better to these treatments - we still have a long way to go, but it's a very exciting discovery,' he said, according to a WAIMR release.

The discovery was published in the Journal of Biological Chemistry.

Lung cancer: Molecular scissors determine therapy effectiveness

Tue, 17 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) In the past few years, a number of anti-cancer drugs have been developed which are directed selectively against specific key molecules of tumor cells. Among these is an antibody called cetuximab, which attaches to a protein molecule that is found in large amounts on the surface of many types of cancer cells. When this surface molecule, called epidermal growth factor receptor, or EGF-R for short, is blocked by cetuximab, the cancer cell receives less signals stimulating cell division.

Clinical studies of non-small cell lung cancer, which is the most frequent type of lung cancer, have shown so far that only part of the patients treated with cetuximab benefit from the treatment. Therefore, doctors are urgently searching for biomarkers which reliably predict responsiveness to the antibody therapy.

Professor Heike Allgayer heads the Department of Experimental Surgery of the Mannheim Medical Faculty of the University of Heidelberg and the Clinical Cooperation Unit Molecular Oncology of Solid Tumors at DKFZ. The scientist suspects that the therapeutic antibody can disarm, in particular, individual cancer cells that have detached from the primary tumor, invade other tissues and grow into secondary tumors there. Therefore, Allgayer and her team focused on lung cancer cells' ability to metastasize. Indeed, the investigators were the first to show in lung cancer cell lines that cetuximab inhibits growth and invasion of cancer cells and reduces the frequency of metastasis.

For invading surrounding healthy tissue, cancer cells needs specific proteins which act like molecular scissors to cut a trail for them. One of these cutting tools is the u-PAR protein which is considered a marker molecule for the invasion ability of cancer cells. Allgayer's team found out that cancer cells produce less u-PAR after treatment with cetuximab: The antibody appears to block the cell's u-PAR production.

Allgayer's team also showed that non-small cell lung cancer is resistant to cetuximab treatment, in particular, when the cancer cells produce large amounts of u-PAR. When the researchers switched off u-PAR production using a genetic trick, the cells responded to cetuximab again.

Our results show, for the first time, that u-PAR might be an indicator of the effectiveness of cetuximab treatment in non-small cell lung cancer, Heike Allgayer says. The more u-PAR the cells produce, the less they are responsive to the drug. This conclusion is in line with first observations made in lung cancer patients. Tumor cells of patients who did not respond to cetuximab usually produced higher amounts of the molecular scissors u-PAR.

It came as a surprise for Allgayer that EGF-R itself, the target molecule of the drug cetuximab, did not correlate with responsiveness. Further investigations are needed to verify these results. We want to find possibilities to prescribe the drug only for those patients who can actually benefit from it, says Allgayer, a doctor and scientist. Finding suitable biomarkers is one of the most urgent tasks when introducing novel, target-specific therapeutics.

Rearrangements of multifunctional genes cause cancer in children and young people

Tue, 10 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A doctoral thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden, shows that three genes that lie behind a number of malignant tumour diseases are normally involved in several fundamental processes in the cell. This may be the reason that the tumours arise early in life and principally affect children and young people.

A family of genes known as the FET genes has been investigated in the work presented in the thesis. This family contains three genes that are found in modified forms in several malignant soft-tissue tumours and several forms of leukaemia. The FET genes are found in these tumours in the form of what are known as fusion genes in which parts of two different genes have merged to form one gene. Fusion genes are translated into abnormal fusion proteins, which can in certain cases transform normal cells to cancer cells.

The human body consists of many different types of specialised cell types such as nerve cells, fat cells and intestinal cells. These are formed when stem cells multiply and mature gradually along different developmental pathways. Cancer may arise if something goes wrong in this process. The study has shown that the activities of the genes in the FET family fall as the cells mature, and scientists therefore believe that these genes play a role during the early stages of cell maturation, when the cells are not far from the stem cell stage. The normal maturation pathway of a cell becomes blocked when fusion genes that contain FET genes arise. The result is a cancer cell with properties similar to those of stem cells, and such a cell can multiply in an uncontrolled manner.

We found that the FET genes are also involved in the response of the cell to external and internal stress, and when cells spread. Alterations of such processes are common in cancer cells, says Mattias Andersson.

It normally requires damage to several different genes before cancer cells develop, and this usually takes a long time. However, since the FET genes are involved in several of the normal cell processes, scientists believe that in their rearranged form they can affect in parallel several of the control systems that prevent a normal cell from becoming a cancer cell. This may give rise to rapid development of cancer, and it may be the reason that tumours with FET fusion genes are often found in children and young people.

Studying normal FET genes has increased our understanding of what may go wrong in cancer cells having rearrangements of these genes. This may in the long term lead to new methods of treatment for tumour diseases that contain FET fusion genes, says Mattias Andersson.

Immune-based drug approved in Europe for pediatric cancer patients

Tue, 10 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) HOUSTON ? The European Commission, which oversees legislation and regulation for the European Union, has approved a therapy for pediatric patients with non-metastatic, resectable osteosarcoma, a type of bone cancer. The approval is based on clinical studies led by researchers at The University of Texas M. D. Anderson Cancer Center and a national co-operative group.

MEPACT (mifamurtide, L-MTP-PE) is an immune-based therapy, that when combined with chemotherapy, resulted in approximately a 30 percent decrease in the risk of death with 78 percent of patients surviving more than six years following treatment. This therapy is the first in more than 20 years to improve the long-term survival of osteosarcoma patients.

Eugenie Kleinerman, M.D., head of the Children's Cancer Hospital at M. D. Anderson Cancer Center, was the first investigator to translate the drug from preclinical testing to a Phase I clinical trial in humans. She also led the Phase II clinical trial for pediatric patients with relapsed osteosarcoma, which was followed by a Children's Oncology Group Phase III trial for newly diagnosed patients.

Kleinerman originally proposed the use of this immune therapy for osteosarcoma after Isaiah J. Fidler, D.V.M., Ph.D., professor in M. D. Anderson's Department of Cancer Biology and director of the Center for Metastasis Research, demonstrated that MEPACT induced the regression of melanoma lung metastases in mice.

When he showed that MEPACT caused the macrophages in the lung to kill tumor cells, I decided that the drug may have therapeutic potential in patients with osteosarcoma, which most often metastasizes to the lungs, says Kleinerman. From my own preclinical research, we were able to show how MEPACT stimulated human immune cells to react against osteosarcoma cells.

MEPACT works by stimulating certain white blood cells, called macrophages, to kill tumor cells. The drug is shaped in a sphere, also known as a vesical, made up of lipids. Inside the vesical is muramyl tripeptide (MTP). The lipids trigger the macrophages to consume MEPACT. Once consumed, the MTP stimulates macrophages, particularly in the liver, spleen and lungs, to find tumor cells and kill them.

Patients undergo pre-operative chemotherapy followed by surgery to resect the bone tumor and then receive post-operative chemotherapy. While receiving post-operative chemotherapy, patients also are given the immune therapy intravenously twice a week for three months and then once a week for six months. The chemotherapy acts like a bomb sent in to destroy the tumor, while MEPACT acts as a special forces unit sent in to clean out any remaining pockets of microscopic disease.

Relapsed osteosarcoma is often resistant to chemotherapy, says Kleinerman. By giving MEPACT to newly diagnosed patients, we hope to prevent relapse by taking care of any remaining tumor cells after chemotherapy.

Currently, only relapsed pediatric patients with osteosarcoma are able to receive treatment with MEPACT through compassionate use in the United States. MEPACT was granted orphan drug status in the United States in 2001 but has not been approved by the Food and Drug Administration for use in newly diagnosed patients. Orphan drug status is given to therapeutic agents that target rare diseases as an incentive for pharmaceutical companies to manufacture these agents.

We have been working with this therapy for more than two decades, so getting approval in Europe is a huge milestone for those of us fighting pediatric cancer, says Kleinerman. This drug has made significant strides for long-term survival of children with osteosarcoma.

New staging technique might save bladders in some bladder cancer patients

Mon, 09 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) MAYWOOD, Ill. -- Pathologists today (March 9, 2009) reported encouraging results from a new technique to increase the accuracy of staging bladder cancer tumors that could reduce the need to remove bladders from some patients.

The technique is performed by pathologists before surgery. It can confirm that in certain cases, tumors are at an early enough stage so that the cancer can be treated without removing the bladder.

In a study of 70 bladder cancer specimens, the technique was 95.2 percent accurate, Dr. Gladell Paner of Loyola University Health System reported at a meeting of the United States and Canadian Academy of Pathology annual meeting in Boston.

The American Cancer Society estimates there were about 69,000 new cases of bladder cancer in the United States last year, and about 14,000 people died of the disease.

There are five stages of bladder cancer, ranging from Stage 0 (earliest) to Stage 4 (most advanced). Stage 0 and Stage 1 cancers generally do not require removal of the bladder. Stage 2 and above typically require removal of part of or the entire bladder.

In Stage 0 and Stage 1, the tumor is confined to the surface of the bladder, or just below the surface. In Stage 2, the tumor has penetrated down to a deep muscle layer. But in some cases, Stage 2 cancer can look like Stage 1. The reason is that a layer of muscle near the surface can look like the deep muscle layer. Such a mistake can result in the bladder being needlessly removed. In as many as 4 percent of biopsies, it is extremely difficult to distinguish between Stage 1 and Stage 2 cancer, Paner said.

In the new technique, developed by Paner, the specimen is exposed to an antibody called smoothelin. Smoothelin reacts strongly with deep muscle, and this reaction shows up as a stain when seen under the microscope. By contrast, smoothelin does not react or leave stains on muscle near the surface.

The goal is to avoid the potential mistake of calling a tumor Stage 2 when it actually is Stage 1, Paner said. Paner is an assistant professor in the Department of Pathology at Loyola University Chicago Stritch School of Medicine.

In Paner's study, the technique correctly identified 97.9 percent of the specimens that had deep muscle and 95.2 percent of the specimens that did not have deep muscle.

These results are very encouraging, Paner said. However, we still need to be cautious. The technique needs to be studied further.

At the USCAP meeting, Paner and other Loyola researchers are lead authors of 16 study abstracts and co-authors of another nine abstracts.

The USCAP meeting is the world's largest gathering of physician-pathologists. Researchers from more than 430 medical schools and universities around the world will present nearly 2,800 study abstracts. Loyola is among the top 20 centers in the number of first-authored abstracts. All abstracts undergo a blind, peer-reviewed process.

Your institution has worked hard to support and generate these important studies which will help advance the specialty of pathology as well as medicine in general, USCAP Executive Vice President Dr. Fred Silva wrote in a letter to Dr. Eva Wojcik, chair of the Department of Pathology, Loyola University Chicago Stritch School of Medicine.

MRI and PET/CT improve cervical cancer patient's chances for optimal treatment

Wed, 04 Mar 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Pretreatment MRI and PET/CT for cervical cancer may direct more women to optimal therapy choices and spare many women potential long-term morbidity and complications of trimodality therapy (surgery followed by chemoradiation), according to a study performed at the Institute for Technology Assessment in Boston, MA.

An interdisciplinary team of investigators developed a decision-analytic model to determine the value of pretreatment imaging with MRI and/or PET/CT in patients with FIGO Stage IB cervical cancer. Stage IB cervical cancer, in the absence of pre-treatment imaging, is treated with surgery. As surgery cannot completely resect the cancer in many of these patients, they receive post-surgical chemoradiation, i.e. trimodality therapy, said Pari Pandharipande, MD, lead author of the study. The goal of pre-treatment imaging is to identify these patients noninvasively, spare them surgery and have them treated with chemoradiation alone, she said. Study results showed that while imaging does not improve survival, PET/CT resulted in the highest percentage of patients receiving correct primary therapy (89%) and use of both MRI and PET/CT spared the most patients of trimodality therapy (95%).

Pretreatment imaging can triage patients to optimal primary treatment choices that minimize the risk of long-term complications and morbidity while preserving chances for survival, said Dr. Pandharipande. Because both over- and underestimation of disease extent can result in adverse patient outcomes, determining the extent of disease accurately up front is critical. For example, when patients are subjected to pelvic surgery, and then are radiated in the same operative field, complication rates can increase by a substantial percentage, as compared to if they were simply treated with surgery alone or chemoradiation alone. Our study shows how pre-treatment imaging may improve chances of correctly receiving surgery or chemoradiation instead of both, said Dr. Pandharipande.

MRI and PET/CT are expensive, but long-term consequences of trimodality therapy can severely affect long-term quality of life and are also expensive. Further study of these long-term consequences is needed to more precisely consider the cost implications of upfront MRI and PET/CT, she said.

Currently there are no specific guidelines that prescribe MRI or PET/CT for determining a plan of action for the treatment of stage IB cervical cancer patients. It remains important for patients to make imaging and treatment decisions with their gynecologic-oncologist on a case-by-case basis, said Dr. Pandharipande.

My goal as a researcher in radiology is to continue to objectively look at what we do and how it impacts patient care. A better understanding of what happens to people after they receive imaging tests both improves patient care directly and focuses further research efforts in areas most influential to patient outcomes, she said.