RxPG News : Carcinogens

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.

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.

New study aims to reduce risk of childhood leukemia

Sun, 25 Jan 2009 04:59:36 PST

( from http://www.rxpgnews.com ) A study led by Dr Marcus Cooke at the University of Leicester and funded by World Cancer Research Fund (WCRF) UK is looking at whether consuming caffeine during pregnancy might affect the unborn baby's risk of developing leukaemia in childhood.

Dr Cooke sees the study as a unique opportunity to determine the sources of chromosomal alterations during pregnancy, with the ultimate aim of reducing the risk of childhood leukaemias.

Leukaemia is a cancer of the bone marrow and white blood cells. It can affect people of all ages and around 7,000 cases are diagnosed each year in the UK. While it is the most common type of childhood cancer, accounting for 35 per cent of cases, it is still rare. Only 1 in 10 of leukaemia patients are children, accounting for 500 child diagnoses a year in the UK.

We want to find out whether consuming caffeine could lead to the sort of DNA changes in the baby that are linked to risk of leukaemia, said Dr Cooke. This is an important area of research because it is vital that mothers are given the best advice possible.

While childhood leukaemia could be initiated by DNA alterations in the unborn child, it is thought that leukaemia would only develop if there was another secondary trigger. There is currently no single proven cause of childhood leukaemia, though exposure to radiation and/or a rare response to a common infection are thought likely to play a part.

Although there are currently no convincing links between caffeine and cancer risks, previous studies have found a link between alterations to DNA, which are sometimes found in newborn babies, to an increased risk of leukaemia. Caffeine has been shown to cause these kinds of changes to DNA.

Scientists know caffeine can pass back and forth across the placenta, meaning the unborn baby will come in contact with caffeine consumed by the mother. Dr Cooke and his team want to find out what impact this can have on the unborn baby.

Their research will involve working with a group of 1,340 pregnant women. After birth, a blood sample is routinely taken from each newborn baby's heel. It is these samples that will then be tested for DNA changes. By comparing any DNA changes to the levels of caffeine the mother consumed, the team will try to find out if the two are linked.

If a link is discovered, further research would be needed to see whether this meant babies with these DNA changes would be more likely to develop leukaemia, and to examine evidence of exposure to other DNA damaging agents. The study will also collect other lifestyle and dietary data to see if there are other factors which might increase the risk.

Dr. Marcus S. Cooke, of the Leicester Department of Cancer Studies, and the Department of Genetics, will be working with Drs. Roger Godschalk and Sahar Barjesteh van Waalwijk van Doorn-Khosrovani from the Department of Health Risk Analysis and Toxicology, Maastricht University.

This study is not the first research into the link between cancer risk and caffeine. In the past, research has suggested a possible link with cancers of the pancreas and kidney, but after examining all the research, the WCRF/AICR Expert Report found that a substantial effect on risk was unlikely.

LSUHSC's Fontham makes history

Thu, 20 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Elizabeth T. H. (Terry) Fontham, MPH, DrPH, Dean of the LSU Health Sciences Center New Orleans School of Public Health, will become the first non-physician elected national President of the American Cancer Society when she is inducted at a special ceremony during the Society's National Assembly Meeting on November 20, 2008 in New York City. She will also be the first epidemiologist and the third female to serve as president in the organization's 96-year history.

The American Cancer Society is the nationwide community-based voluntary health organization dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer through research, education, advocacy, and service. With more than two million volunteers nationwide, the American Cancer Society is one of the oldest and largest voluntary health agencies in the United States.

Dr. Terry Fontham has dedicated a great deal of her life to fighting cancer, and she has made enormous and life-saving contributions, said Dr. Larry Hollier, Chancellor of LSU Health Sciences Center New Orleans. We are very proud that the American Cancer Society has recognized Dr. Fontham's strong leadership ability, something we have had the privilege to know firsthand for many years.

Dr. Fontham is the first Dean of LSU Health Sciences Center New Orleans School of Public Health and is Professor of Epidemiology as well as Professor of Pathology in the LSUHSC School of Medicine. A graduate of Tulane University School of Public Health and Tropical Medicine, Dr. Fontham has been on the faculty in the LSU Health Sciences Center since 1980 and was Chairman of the Department of Public Health and Preventive Medicine prior to the establishment of the School of Public Health. She is Associate Director of the LSUHSC Stanley S. Scott Cancer Center and is Senior Consultant Epidemiologist to the Louisiana Office of Public Health.

Dr. Fontham's major area of research is cancer epidemiology with a focus on the etiology of tobacco- and diet-related cancers. She has made significant contributions in establishing the risk of lung cancer associated with involuntary exposure to tobacco smoke. She was an author of the first U.S. case-control study of lung cancer reporting an increased risk of lung cancer in nonsmokers passively exposed to tobacco. Subsequently she led the largest study of lung cancer in nonsmoking women, a U.S. multi-center study that provided critical information on the association between passive smoking and lung cancer risk. Dr. Fontham has also published extensively on premalignant lesions leading to gastric cancer, modifiable factors associated with progression, and chemoprevention of this cancer.

Dr. Fontham has served as a member of the National Cancer Institute Board of Scientific Counselors. She was Treasurer and member of the Board of Directors of the American College of Epidemiology of which she is a Fellow. She was a member of the inaugural Editorial Board of Cancer Epidemiology Biomarkers and Prevention, Chairman of the Scientific Editorial Board of the North American Association of Central Cancer Registries and has been a co-author of both the Surgeon General's Report and International Agency for Cancer Research Carcinogenesis Monograph series. She is recipient of the C.L. Brown Award for Leadership Excellence in Tobacco Prevention, the Leadership and Distinguished Service Award of the American College of Epidemiology, and the Pfizer Award for Excellence in Research, Education and Patient Care.

Dr. Fontham is a long time active volunteer in the American Cancer Society at the local, division and national levels. She has served as President of the Greater New Orleans Unit Board, Chairman of the Board of the Mid-South Division, and is a member of the ACS National Board of Directors where she serves as the First Vice President. She was a member of the ACS Cancer Action Network Board of Directors and has served on many ACS committees. She currently chairs the national Reduction of Cancer Incidence and Mortality Committee and co-chairs the International Affairs Advisory Committee. Other current committee/workgroup memberships include Research and Medical Affairs Committee and Advocacy and Public Policy Committee. She is a recipient of the ACS Capitol Dome Award and the St. George Medal as well as Life Saver Awards from both her unit and division.

Dr. Fontham has been and continues to be a leader in the building of our Stanley S. Scott Cancer Center at LSU Health Sciences Center New Orleans and the Louisiana Cancer Research Consortium, as the co-director for Population Sciences, notes Augusto Ochoa, MD, Director of the LSUHSC Stanley S. Scott Cancer Center. She is also an example for our cancer researchers for her continued commitment to propose novel research projects that continue to help us understand the impact of cancer on the population of Louisiana and the United States in general.

Researchers aim to over-stress already taxed mantle cell lymphoma cells

Mon, 10 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) AUGUSTA, Ga. - Cancer cells are already stressed by the fast pace they require to grow and spread and scientists believe a little more stress just may kill them.

Think about an assembly line in a factory that is working five times faster than normal, said Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center. There is a lot of stress but you need workers to keep going. Some of them fall out, some get bent out of shape.

His research team believes they can disrupt the over-stressed assembly line of mantle cell lymphoma and possibly similar cancers such as pancreatic, liver and breast, by taking away support needed for rapid protein turnover and by clogging up the mechanism for eliminating poorly made ones.

Mantle cell lymphoma, an aggressive cancer of the lymphatic system that mostly occurs in middle age, responds initially to chemotherapy and antibiotics, but often returns, said Dr. Bhalla. Patients have a median survival of three to four years. This cancer affects b lymphocytes, immune cells which make antibodies to fight infection. Ironically, in the process of rearranging genes to make antibodies to a specific invader, mistakes happen, and a would-be protector becomes cancer.

MCG researchers found that to keep their fast pace, these now-malignant cells need increased activity of heat shock protein 90. Cancer cells require hsp90 for keeping their proteins in active conformation to do their job. That is what cancer is addicted to, said Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. Hsp90 is one of the more common molecular chaperones, which help proteins get made, moved, folded and function. Its levels and activity are upregulated in response to stress.

They also found that the usually busy endoplasmic reticulum of these cells, which is supposed to be making normal antibodies, is stressed by making hyperactive, cancer-associated proteins. Stepped-up protein production also means more misfolded proteins that the proteasome must deal with. It's all stressed-out machinery, Dr. Bhalla said.

To help push cancer cells over the edge, the researchers are inhibiting hsp90, so the cells lose the molecular chaperone function required to maintain their fast pace. This also puts more stress on the endoplasmic reticulum. Independently hsp90 inhibitors are known to selectively kill cancer cells. But researchers also are clogging up the proteasome, the machinery for chopping up misfolded proteins, recycling some products and eliminating what's left. Much like a sink won't work with a clogged garbage disposal, mantle cell lymphoma cells will start backing up. When a cell detects excessive misfolded proteins, it first has a protective response, but if the problem persists, it commits suicide.

With support from a five-year, $1.5 million grant from the National Cancer Institute, the researchers are using hsp90 and proteasome inhibitors to study protective versus lethal endoplasmic reticulum stress as a way to get rid of mantel cell lymphoma cells. The laboratory studies are being done in human mantle cell lymphoma cells as well as an animal model the researchers developed.

The drugs they are using already are in early clinical trials for a variety of cancers but have not yet been packaged together, Dr. Bhalla said. We kill cancer cells and a lot of them with this strategy. Still, at least one more inhibitor may get added to the mix. After the rather brutal attack at the cancer's molecular underpinnings, the immune system comes in to essentially mop the floor, but researchers have found cancer cells can still get a pass from an enzyme called IDO. A team of MCG researchers led by Dr. David Munn is exploring IDO's therapeutic potential in cancer. Fetuses use IDO to avoid rejection by the mother's immune system and tumors appear to use it as well. Dr. Bhalla suspects an IDO inhibitor, already under study for lung cancer and other tumors, likely will get a shot at mantle cell lymphoma as well.

Stopping hormone therapy did not reduce cancer risk for African-Americans

Tue, 15 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The decreased incidence of invasive breast cancer in the United States seen in 2002 and 2003 did not extend to women of African ancestry, researchers from the University of Chicago Medical Center report at the 2008 annual meeting of the American Association for Cancer Research in San Diego.

Breast cancer incidence rates in U.S. women over 50 declined sharply during 2002 and 2003. But this decline, the researchers report, was confined to Caucasians.

For Caucasian women aged 50 to 69, the rate of invasive breast cancer, which was stable from 2000 to mid-2002, decreased by more than two percent every three months during the second half of 2002 and all of 2003, then stabilized in 2004. For African Americans there was virtually no change.

The benefit was not equal across racial groups, said Dezheng Huo, PhD, research associate (assistant professor) of health studies at the University of Chicago Medical Center. Only Caucasians saw this reduced incidence of invasive cancers.

In mid-2002, many women who had been taking replacement hormones stopped taking them in response to the Women's Health Initiative trial, which showed that the supplements increased coronary heart disease and breast cancer risk.

Saturation of screening may also account for part of the decline. Screening mammogram use increased substantially during the 1990s, which temporarily raised the rates of new cancer diagnosis. But mammography use stabilized and then slightly decreased after 2000.

Much of the racial disparity, the researchers suspect, may have resulted from differences in biology. We suspect, Huo said, that the widespread discontinuation of menopausal hormone use had a greater effect on Caucasians.

African Americans are less likely to use hormone replacement therapy and less likely to develop breast cancers that are receptive to estrogen, Huo said, so they were harmed less by taking hormones and benefited less by discontinuing them.

African Americans had a similar magnitude of reduction in hormone therapy use, he added, yet it did not lead to any benefit, suggesting that genetic variations in estrogen and progesterone metabolism may play a role in how women of African ancestry respond to hormonal therapies. Alternatively, the causes of breast cancer may vary in different populations.

Almost 80 percent of breast cancers in Caucasians are estrogen receptor positive, a type of tumor that depends on estrogen to grow, said Huo, compared to about 60 percent in African Americans. That proportion drops to about 30 percent among Nigerian women.

For this study, the researchers looked at rates of breast cancers that were invasive as well as breast cancer in situ--early lesions that have not invaded surrounding tissues--in women aged 50 to 69. They used data from 17 large cancer registries, covering about 26 percent of the U.S. populations.

They found that the incidence rate of invasive breast cancers for Caucasians declined soon after April 2002, when many women stopped taking replacement hormones after studies showed that HRT increased cancer risk. Invasive cancer rates for Caucasian women fell from about 86 cases per quarter per 100,000 women in mid-2002, to about 74 per 100,000 by the end of 2003.

African American women had fewer invasive cancers, about 71 per 100,000 per quarter, but their numbers did not decline in 2002-2003. Rates for Asian women, lower still, declined slightly, but stayed in the mid-60s per 100,000. Native American invasive breast cancer rates remained quite low, about 33 per 100,000, but did not decline.

Rates for early, non-invasive breast cancers, did not follow the same patterns. They remained nearly steady for all ethnic groups, except Asian women, for whom the rates increased from 2000 to mid-2002 then slowly declined, probably because of slowly growing use of mammography in this population.

The finding that the rate of invasive breast cancer, but not in situ cancer, decreased suggests that estrogen serves as a promoter rather than an initiator of breast cancer, say the study authors.

Age affects motivation for quitting smoking

Mon, 22 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) (Chicago, IL, October 22, 2007) � A new study shows that obstacles to smoking cessation and motives for quitting smoking vary with age. The study presented at CHEST 2007, the 73rd annual international scientific assembly of the American College of Chest Physicians (ACCP), found that smokers over age 65 reported quitting smoking due to physician pressure and stress due to a major health problem, while smokers under age 65 reported cigarette cost and tobacco odor as reasons for quitting.

�The current common perception among the medical community is that if smokers age 65 and older haven�t quit by now, they can�t or won�t quit � a perception which may lead physicians to focus less on their older patients� smoking habit,� said lead study author Virginia Reichert, NP, Center for Tobacco Control, North Shore-LIJ Health System, Great Neck, New York. �Our results show that older smokers are motivated to quit smoking by very different factors compared with younger smokers. If these factors are addressed, we may see cessation rates improve for both age groups.�

Ms. Reichert and colleagues from the Center for Tobacco Control at North Shore-LIJ compared health status and motives and obstacles for quitting smoking between 1,909 smokers under age 65 (younger smokers) and 143 smokers over age 65 (older smokers) who were attending a 6-week comprehensive cessation program. Older smokers were more likely than younger smokers to have a recent hospitalization (23% vs 13%), comorbid cardiac disease (78% vs 38%), cancer (20% vs 7%), and/or chronic obstructive lung disease/asthma (37% vs 23%). Regarding motivation, older smokers cited pressure by their physician and stress of a major health problem as main reasons for quitting. Younger smokers attributed their reasons for quitting to the cost of cigarettes, tobacco odor, and general health concerns.

�If the cost of cigarettes hasn�t made the older smoker quit by now, they are not as likely to be affected by the rising costs as much as younger smokers may be,� said Ms. Reichert. �On the other hand, younger smokers may not have experienced health effects from their smoking, but they may have felt the impact of the cost of cigarettes/cigars.�

Obstacles to smoking cessation also varied by age group. Younger smokers were more likely than older smokers to report concerns of weight gain (30% vs 15%), stress management (59% vs 45%), fear of failure (15% vs 8%), handling social situations (24% vs 7%), and cravings (44% vs 36%) as obstacles to quitting smoking. Furthermore, 54% of older smokers and 69% of younger smokers reported not wanting to give up their first cigarette in the morning as an obstacle to quitting smoking. Young smokers also believe that trying to quit �cold turkey� is best, when in reality, only 7% of smokers achieve long-term abstinence without professional help.

�To be most effective, treatment plans and education should be relevant to each group�s concerns,� said Ms. Reichert. She suggests that health-care providers offer weight management programs and stress management strategies as part of the treatment and relapse prevention programs for younger smokers, while older smokers may be more successful with physician encouragement and knowledge of how smoking is influencing their current health conditions.

�Tobacco-related diseases are major causes of death in the United States,� said Alvin V. Thomas, Jr., MD, FCCP, President of the American College of Chest Physicians. �The more we know about what motivates smokers to quit their habit and what personal obstacles they face in doing so, the more we can tailor smoking cessation programs to fit the individual needs of our patients.�

Hypnosis for smoking cessation sees strong results

Mon, 22 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) (Chicago, IL, October 22, 2007) � Hospitalized patients who smoke may be more likely to quit smoking through the use of hypnotherapy than patients using other smoking cessation methods. A new study presented at CHEST 2007, the 73rd annual international scientific assembly of the American College of Chest Physicians (ACCP), shows that smoking patients who participated in one hypnotherapy session were more likely to be nonsmokers at 6 months compared with patients using nicotine replacement therapy (NRT) alone or patients who quit �cold turkey�. The study also shows that patients admitted to the hospital with a cardiac diagnosis are three times more likely to quit smoking at 6 months than patients admitted with a pulmonary diagnosis.

�Our results showed that hypnotherapy resulted in higher quit rates compared with NRT alone,� said Faysal Hasan, MD, FCCP, North Shore Medical Center, Salem, MA. �Hypnotherapy appears to be quite effective and a good modality to incorporate into a smoking cessation program after hospital discharge.�

Dr. Hasan and colleagues from North Shore Medical Center and Massachusetts General Hospital compared the quit rates of 67 smoking patients hospitalized with a cardiopulmonary diagnosis. All patients were approached about smoking cessation and all included in the study were patients who expressed a desire to quit smoking. At discharge, patients were divided into four groups based on their preferred method of smoking cessation treatment: hypnotherapy (n=14), NRT (n=19), NRT and hypnotherapy (n=18), and a group of controls who preferred to quit �cold turkey� (n=16). All patients received self-help brochures. The control group received brief counseling, but other groups received intensive counseling, free supply of NRT and/or a free hypnotherapy session within 7 days of discharge, as well as follow up telephone calls at 1, 2, 4, 8, 12, and 26 weeks after discharge. Patients receiving hypnotherapy also were taught to do self-hypnosis and were given tapes to play at the end of the session.

At 26 weeks after discharge, 50 percent of patients treated with hypnotherapy alone were nonsmokers, compared with 50 percent in the NRT/hypnotherapy group, 25 percent in the control group, and 15.78 percent in the NRT group. Patients admitted with a cardiac diagnosis were more likely to quit smoking at 26 weeks (45.5 percent) than patients admitted with a pulmonary diagnosis (15.63 percent).

�Patients admitted with coronary symptoms may have experienced �fear and doom� and decided to alter a major health risk to their disease when approached about smoking cessation,� said Dr. Hasan. �In contrast, pulmonary patients admitted for another exacerbation may not have felt the same threat. They likely felt they can live for another day and continue the smoking habit.�

The researchers note that hospitalization is an important opportunity to intervene among patients who smoke.

�Doctors and other health personnel should use this occasion to firmly recommend smoking cessation and emphasize the impact of smoking on their disease process and hospital admission,� said Dr. Hasan. �Pulmonologists, in particular, should make a stronger case and more passionate message to their patients, and efforts should be coordinated with counseling.�

�As physicians, we are constantly reviewing new approaches for smoking cessation and revisiting existing approaches to confirm their effectiveness,� said Alvin V. Thomas, MD, FCCP, President of the American College of Chest Physicians. �The results of this study and many others confirm that using a multimodality approach to smoking cessation is optimal for success.�

Leading researchers to reveal comprehensive dos and don'ts for prostate cancer

Sat, 13 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Lake Tahoe, CA, October 13, 2007�Today at the Prostate Cancer Foundation�s Annual Scientific Retreat, researchers will share new findings on how eating common foods such as tomatoes and fish, maintaining a healthy weight, and avoiding meats cooked at high temperatures may help prevent prostate cancer, and help men live healthier and longer after diagnosis. One in six men will be diagnosed with prostate cancer in their lifetime, and an estimated 218,890 cases will occur in The United States this year.

Since the 1980s, researchers have hypothesized that nutrition choices could be connected to prostate cancer. Today, those ideas are being substantiated by more widespread studies, in combination with newer technologies in gene research.

�There are strong indicators in our research that diet and lifestyle are very important with this particular form of cancer,� said Meir Stampfer, M.D., Professor of Epidemiology and Nutrition, Harvard School of Public Health. �When we look at men from other cultures like in Asia, the rates of prostate cancer are significantly lower than in the U.S. Yet when these same men move here, within one generation, the rates increase very rapidly. We believe there is a clear correlation to how we live and eat.�

June Chan, ScD, of the University of California San Francisco, has been studying the potential impact of fish oil and tomato extracts on the prostate gland prior to and after exposure. �What we�re trying to determine is if men with low grade prostate cancer can manage their disease with these kinds of nutritional interventions and delay or avoid the need for more aggressive treatments, all of which carry a risk of side effects that can adversely affect physical function and quality of life,� said Chan. �In combination with other studies, the potential we see for these everyday supplements or foods to help men avoid or delay treatment is promising.�

This type of approach, often deemed �active surveillance,� is a prostate cancer disease management option that monitors prostate-specific antigen (PSA) levels as well as the grade and stage of the tumor until a more aggressive treatment option may become necessary. One-quarter to one-half of all cases of diagnosed prostate cancer in the U.S. and Europe are considered candidates for this kind of approach, which researchers hope leads to better outcomes for patients with low-risk disease. One aspect of this management approach may include specific dietary modifications such as minimizing intake of red, processed or well-done meats.

Angelo De Marzo, M.D., Ph.D., along with colleague William G. Nelson M.D., Ph.D. of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, have been studying one of the most high profile issues around diet and prostate cancer: don�t overheat your meat. �We�ve known since the 1980s that ingesting meat cooked at very high temperatures can cause cellular mutations, some of which can lead specifically to prostate cancer. What we�ve found now in the rodent prostate is that the specific areas within the organ that develop cancer after exposure to the meat compounds also first become inflamed and develop a form of atrophy that resembles damaged areas in the human prostate that are likely a very early indicator of a problem.� According to De Marzo, if scientists can develop markers of damage and dietary exposures it may be possible for doctors to intervene before cancer ever develops in the prostate.

De Marzo also has some practical advice: �If you�re going to eat meat cooked at high temperatures, like I still enjoy, flip your hamburgers more often so the outside does not burn, marinate the meat in ingredients (such as teriyaki sauce) that don�t create a crust, precook it in the microwave, or at the least scrape off the charred material.� De Marzo also suggests replacing chicken, beef, veal or lamb with soy protein or fish, taking a page from the Asian diet where disease rates are very low. �We need to be realistic: you can help reduce your chance of developing prostate cancer without becoming a vegetarian.�

With more widespread testing for prostate cancer using the common PSA test, increasing numbers of new cases are being tracked. The resulting volume of patients, many of whom may have less virulent forms of prostate cancer, is creating a challenge for physicians determined to provide patients with the most appropriate advice � which may not always include aggressive treatment.

�Thanks to funding from the Prostate Cancer Foundation and others like the National Cancer Institute, we�re getting closer every day to developing the best protocols for thousands of men with this diagnosis,� said Stampfer. Our goal is that any man with low risk prostate cancer can make simple changes that will extend his life and that healthy men can avoid it altogether.�

Oncolytics Biotech Inc. reports positive interim results of UK phase Ia/Ib trials

Fri, 28 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CALGARY, AB, --- September 28, 2007 - Oncolytics Biotech Inc. (�Oncolytics�) (TSX:ONC, NASDAQ:ONCY) announced that an oral presentation covering interim results from a U.K. Phase Ia/Ib combination REOLYSIN� and radiation clinical trial for patients with advanced or metastatic cancers is scheduled to be presented at the National Cancer Research Institute (NCRI) conference on October 2, 2007 in Birmingham, U.K. The presentation, entitled �Biological Approaches to Radiosensitisation: Viruses, Gene Therapy and Novel Radiosensitisers� will be presented by Dr. Kevin Harrington of The Institute of Cancer Research, London and one of the principal investigators for the trial. The conference runs from September 30 through October 3, 2007 in Birmingham, U.K.

�We are very pleased with the results of this trial to date,� said Dr. Brad Thompson, President and CEO of Oncolytics. �We continue to evaluate the data and look forward to announcing final results.�

To date, 22 patients have been treated with 15 having completed the study. Five patients withdrew from the study, and two patients are still on study.

A total of 11 patients in the Ia portion of the trial received two intratumoural treatments of REOLYSIN� at dosages of 1x108, 1x109, or 1x1010 TCID50 with a constant localized radiation dose of 20 Gy given in five fractions. Of these 11 patients, three patients (oesophageal, squamous skin carcinoma and squamous cell scalp) experienced significant partial responses.

One month following treatment, the oesophageal patient experienced a 28.5% reduction in the target tumour, with stable disease noted in four, non-treated tumours. At two and three months, the target tumour had shrunk 64%, with stable disease continuing in the four non-treated tumours, including a 15% volume reduction in non-treated mediastinal disease that was maintained for more than six months. The squamous skin cancer patient experienced a 50% reduction in the target tumour, as well as stable disease in two, non-treated tumours at one, two and three months post treatment.

The squamous cell scalp patient experienced stable disease in the target tumour for two months which then became a partial response at three months. This patient also experienced stable disease in one non-treated tumour measured at three months post-treatment. Patients in the Ib portion received either two, four or six intratumoural doses of REOLYSIN� at 1x1010 TCID50 with a constant localized radiation dose of 36 Gy given in 12 fractions. Of the six patients who have completed the study to date, three patients (colorectal, melanoma and lung cancer) experienced tumour regression in the target tumour, as well as stable disease in non-treated tumours.

The colorectal patient experienced a partial response with a more than 50% regression in the target tumour as well as stable disease in four, non-treated tumours measured at one month following treatment. A melanoma patient experienced minor regression in the target tumour as well as stable disease in two, non-treated tumours at one and two months following treatment. A lung cancer patient experienced minor regression in the target tumour, as well as stable disease in three, non-treated tumours at two months following treatment.

The treatment has been well tolerated, with mostly Grade 1 or 2 toxicities noted including fatigue, lymphopenia, fever, and neutropenia. Grade 3 toxicities including cellulitis, dysphasia and diarrhoea were related to disease progression and not to the combination treatment. Viral replication was unaffected by cellular irradiation.

The primary objective of the Phase Ia/Ib trial is to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), and safety profile of REOLYSIN� when administered intratumourally to patients receiving radiation treatment. A secondary objective is to examine any evidence of anti-tumour activity. Eligible patients include those who have been diagnosed with advanced or metastatic solid tumours that are refractory (have not responded) to standard therapy or for which no curative standard therapy exists.

Ancient mechanism for coping with stresses also gives cancer a boost

Thu, 20 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An ancient mechanism for coping with environmental stresses, including heat and toxic exposures, also helps cancerous tumors survive, reveals a new report in the Sept. 21, 2007, issue of Cell, a publication of Cell Press. The findings could lead to a new way to treat cancer and may also have implications for the treatment of neurodegenerative and other diseases, according to the researchers.

The scientists found that loss of the master controller of the heat-shock response dramatically limited the spontaneous formation of tumors in mice genetically predisposed to developing cancer, and those exposed to cancer-causing chemicals. Most importantly, they reported, depletion of the so-called heat-shock factor 1 (HSF1) in diverse previously established human cancer cell lines strongly impaired their growth and survival, while having little effect on normal cells.

At a fundamental level, the ability of HSF1 to enable lethal malignancies is an unfortunate legacy of its ancient role in enhancing the survival of normal cells exposed to diverse acute and chronic stresses, said Susan Lindquist, a Howard Hughes investigator at the Whitehead Institute for Biomedical Research. We expected it would have some effect on cancer, but we were surprised at the degree.

The heat-shock response is one of the most ancient and evolutionarily conserved protective mechanisms found in nature, the researchers said. While environmental insults provoke a variety of adaptive physiological responses to help organisms cope with specific stressors, the dramatic induction of heat-shock proteins (HSPs) is an essential unifying component of most of them.

The HSPs, which are under the control of a small family of heat-shock factors (HSFs), guard against the abnormal activity of other proteins in the face of stressors such as heat and oxygen starvation. Although less well understood, Lindquist said, HSFs also influence an array of other genes involved in cell metabolism and other basic cell functions. Scientists had also long noted that HSP levels increase in many cancer cells.

The odd thing is, apparently no one thought it was that interesting, Lindquist said. Therefore, whether the stress management proteins played a causal, supportive, or inhibitory role in cancer remained an unanswered question. On the one hand, given its prominent role in helping cells cope with stressful insults, HSF1 might promote [cancer's formation] by facilitating cellular adaptation to the malignant lifestyle, she explained. On the other hand, given its general role in enhancing longevity, HSF1 might assist organisms in combating malignancy.

To find out, the researchers first looked to a common mouse model of skin cancer, in which the animals' are exposed to cancer-causing chemicals. Mice unable to switch on the heat-shock response were far more resistant to tumor formation than normal mice were under those conditions, they found. It took the mutant mice five weeks longer to develop tumors. They were less likely to develop cancer and, when they did, had fewer and smaller tumors. The HSF1-deficient mice also lived longer.

The researchers next examined mice predisposed to develop cancer due to a deficiency of the tumor suppressor p53, the most frequently mutated gene in human cancers. Again, they found, the HSF1-deficient animals lived tumor-free for dramatically longer. Indeed, even cancer-prone animals lacking just one working copy of HSF1 lived longer than normal animals did. Through studies in cultured mouse cells, they found further evidence that HSF1 supports the transformation to cancer by orchestrating a variety of basic cell functions, including proliferation, survival, protein synthesis, and glucose metabolism.

They then examined the role of HSF1 in normal and cancerous human cells, including those derived from the breast, prostate, and cervix. In every case, they found that the cancerous cells, but not the normal cells, were strongly affected by HSF1's inhibition. Those findings led them to conclude that HSF1 function helps to maintain the growth and survival of human cancer cells with diverse underlying malignant defects.

The results may have therapeutic implications, the researcher said, as an expanding array of small, drug-like compounds with potent effects on HSF1 are now becoming available. Indeed, drugs that ramp up the heat-shock response are being explored for treating ischemic injury and neurodegenerative diseases, including Huntington's and Parkinson's diseases.

The new findings raise concern that such therapies might increase the risk of cancer, Lindquist said. On the other hand, treatments designed to block HSF1 might provide a multifaceted and broadly effective cancer chemopreventative as well as chemotherapeutic strategy.

The results also point to the delicate balance between aging, longevity, and cancer risk, she added.

Strikingly, our data now make clear that HSF1 plays opposite roles in the complex diseases that plague aging populations, she said. It powerfully potentiates the development of cancers. But it has also been implicated in protection against ischemia/re-perfusion injury, neurodegenerative disorders and in other broad-ranging physiological processes affecting lifespan. We are poised on the balance between aging and degeneration [on one side] and the active, youthful cell growth, [which can lead to cancer], on the other. If we pay more attention and learn how to manipulate these systems properly, we could have a huge impact on human disease.

Liver cancer marker could yield blood test for early detection

Tue, 18 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ATLANTA � In the face of an emerging liver cancer crisis in Asia, researchers at the Chinese University of Hong Kong have developed a test that could help millions. Due to widespread hepatitis B virus (HBV) infection, nearly 10 percent of China�s population is at high risk for hepatocellular carcinoma (HCC), a liver cancer with low survival rates if not detected and treated early. Researchers report on a new blood screening technique that could make it possible to detect early-stage liver cancer and predict how well a patient will do following treatment. They present their data today at the American Association for Cancer Research�s Second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, in Atlanta, Georgia.

According to their report, the Chinese team has detected an altered version of RASSF1A, a tumor suppressing gene, in the blood of HCC patients and in 58 percent of HBV-infected test subjects. Healthy subjects showed no signs of the altered gene. They also found that patients treated for HCC with high blood levels of the gene were more likely to have a relapse of the disease.

�A large portion of the population throughout Hong Kong and China are carriers of hepatitis B, so many people are at risk for hepatocellular carcinoma,� said K.C. Allen Chan, MBBS a professor at the Chinese University of Hong Kong. �And we hope that this will form the basis of an effective clinical test for early detection of hepatocellular carcinoma.�

Hepatocellular carcinoma is one of the deadliest forms of cancer in China and throughout Asia, according to the researchers. In the West, liver cancer is usually a secondary cancer, caused by the spread of tumor cells from elsewhere in the body. In China, however, liver cancer mainly manifests as HCC, a primary cancer, which has been linked to hepatitis B and C infection and cirrhosis. Noticeable symptoms do not usually appear until the cancer has progressed, so it is rarely caught early, when intervention would be most effective, and survival rates are typically low, said Chan.

Currently, ultrasound and CT scans are the gold standard for detecting HCC. However, they are too expensive to be an effective mass screening tool, the researchers said. About 70 percent of patients exhibit a detectable increase in bloodstream amounts of alphafetoprotein, but a screen for this protein would miss many potential patients. �We need a new biomarker for hepatocellular carcinoma, something that can be used to screen large populations of at-risk people for follow-up studies,� Chan said.

RASSF1A is a good candidate, according to Chan. Researchers have known that the DNA of HCC tumor cells lack a functioning copy of RASSF1A. In these cells, RASSF1A is �hypermethylated,� meaning the RASSF1A gene has been physically altered by cancer-related processes that added clusters of carbon and hydrogen atoms, called methyl groups, to portions of the DNA within the gene. Hypermethylation is epigenetic � the gene is altered by environmental circumstances and is not inherited. Since the cell�s protein making system can�t access the gene, hypermethylation effectively knocks out the tumor-suppressing RASSF1A gene, which is then unable to stop cells from becoming cancerous.

While hypermethylated RASSF1A would make a useful biomarker for HCC, methylation-specific PCR � the polymerase chain reaction used to specifically amplify and detect methylated DNA � destroys about 85 to 93 percent of the DNA in a blood sample. Together with the fact that tumoral DNA is only present at very low concentrations in blood during early stages of HCC, this method has not been sensitive enough to detected altered RASSF1A in blood for the purpose of early cancer detection, Chan said.

To compensate, Chan and his colleagues invented a new technique that they call �methylation-sensitive enzyme-mediated real-time PCR,� which combines real-time PCR, a technique that enables researchers to simultaneously detect and amplify a given gene, with an enzyme that breaks unmethylated DNA apart. With this new technique, Chan�s team was able to separate out the altered methylated DNA, thus developing a more sensitive technique for detecting and quantifying hypermethylated RASSF1A derived from cancer cells in blood.

To test the relationship between altered RASSF1A and HCC � as well as test the new detection technique -- Chan and his colleagues conducted two studies involving HCC patients. In the first, they matched 63 pairs of patients, one with HCC and the other a chronic HBV carrier by age and sex, along with 30 healthy volunteers. They detected hypermethylated RASSF1A in 93 percent of the HCC patients, 58 percent of the HBV carriers and none of the healthy patients. The median RASSF1A levels for the HCC patients were 770 copies per milliliter and 118 copies per milliliter for HBV carriers.

�The respective levels of the gene for HCC patients and HBV carriers, is consistent with what we already know about the progression of the disease,� Chan said. �The gene is altered very early in the procession of malignant transformation, and so we can see that the levels of the altered gene increase as the cancer process progresses.�

In the second study, the researchers looked at 22 pairs of sex- and age-matched patients who had been enrolled in a HCC surveillance program involving 1018 HBV carriers. For the 22 HBV carriers who subsequently developed HCC, there was a significant increase in circulating RASSF1A levels from the time of enrollment to the time of cancer diagnosis. On the contrary, there was no significant change in RASSF1A levels over the same period for the 22 matched subjects enrolled in the same program who didn�t develop HCC.

�As we refine the process of detecting hypermethylated RASSF1A, we hope to have a functioning test for hepatocellular carcinoma,� Chan said. �A significant number of people will develop this cancer and it is only through early screening and detection that we can hope to help them.�

Blood protein detects lung cancer, even at earliest stage

Tue, 18 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ATLANTA - Biopharmaceutical researchers have found a protein in blood they say is linked to all stages of lung cancer but which rarely shows up in the blood of people without the disease. Testing for this protein might help physicians decide whether smokers or others at high risk for lung cancer should be referred for lung imaging, say investigators, who presented their findings today in Atlanta, Georgia at the American Association for Cancer Research�s second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

A diagnostic blood test to screen high-risk individuals for lung cancer could be both practical to use and cost-effective, say investigators from Panacea Pharmaceuticals, Inc., of Gaithersburg, Md.

�A positive test for this protein marker, followed by CT scanning, may help identify individuals with lung cancer at a stage in which treatment is more effective, possibly even curative,� said research scientist Mark Semenuk, who is presenting results of a study testing the specificity and sensitivity of the blood test.

Currently, there are no approved blood tests available to help detect lung cancer, which is expected to be diagnosed in 213,000 people in the U.S. this year, and will be responsible for more than 160,000 deaths, according to the National Cancer Institute. Typically, CT scanning or chest x-rays are performed on people who have developed symptoms of lung cancer, but by the time a patient is symptomatic the disease is often well advanced. These two methods are not often used in early screening for potential lung cancer given such issues as price and whether radiological methods are appropriate for routine screening on a large scale.�

The protein targeted in the blood test is Human Aspartyl (Asparaginyl) �-Hydroxylase (HAAH), which Panacea Pharmaceutical researchers say is abnormally expressed on the surface of cancer cells, compared to normal cells, where it resides inside the cell body. HAAH is also found in the serum of individuals with cancer. The protein recognizes cell surface growth factors and modifies them, Semenuk says, pushing the cells into uncontrolled growth. It is likely that increased expression of HAAH is an early step in cancer development, since all stages of lung cancer express roughly the same level of the protein compared to adjacent normal cells.

Thus detection of HAAH in the bloodstream can detect lung cancer before it becomes symptomatic, he says.

Staining of normal versus cancer cells has found that HAAH is expressed in a wide range of carcinomas, including lung cancer, Semenuk reports. In this study, researchers found that 99 percent of 160 patients who represented all stages and various types of lung cancer, had high levels of HAAH protein in their blood, but only nine percent of 93 non-smokers without lung cancer had a positive HAAH blood test.

In a group of 50 smokers not known to have cancer, four patients had levels of HAAH that were higher than the projected �cut-off� line established between cancer development and no disease, Semenuk says. It is not known, however, whether these four people did eventually develop lung cancer, because the samples were provided for study without access to patient records, and further tests may change that cut-off point, he adds.

�These results are very encouraging, because it points to those patients who are most likely to need further testing,� Semenuk said. �Elevated levels of HAAH cannot confirm whether a person has lung cancer, but can be used as a routine screening test for recommending further diagnostic evaluation. That is the way most cancer biomarker tests, like the PSA or CEA, are meant to work, and this may be one of the most effective to date.�

Cancer stem cell subpopulation drives metastasis of human pancreatic cancer

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Scientists have identified a distinct subpopulation of cancer stem cells (CSCs) that is responsible for metastasis of a deadly human pancreatic cancer. The research, published by Cell Press in the September issue of the journal Cell Stem Cell, provides insight into the role of CSCs in cancer initiation, progression, and metastasis and suggests new directions for development of more effective therapeutics.

Pancreatic adenocarcinoma ranks as the fourth leading cause of cancer death and is relatively incurable due to early metastatic spread and high resistance to radiation and chemotherapy. In order to better understand the pathology of this deadly cancer, scientists have recently begun to explore the role of CSCs in pancreatic tumors. CSCs are thought to be a small population of tumor cells that have similar properties to normal stem cells in that they are self-replicating and capable of giving rise to populations of differentiated cells. Dr. Christopher Heeschen from the Department of Surgery at Ludwig-Maximilians-University in Munich, Germany led a study to examine the role of CSCs in pancreatic cancer.

The researchers discovered that human pancreatic cancer tissue contains tumorigenic and chemotherapy resistant stem cells defined by expression of CD133, a surface marker expressed by a variety of normal and malignant stem cells. They identified a distinct subset of cells expressing both CD133 and the chemokine receptor CXCR4, which plays a key role in blood cell migration, in the invasive front of the tumor. Implantation of isolated CD133+/CXCR4+ cells into mice resulted in metastatic tumor development, identifying them as CSCs. Cancer metastasis was abolished by inhibiting CXCR4 or by transplanting CD133+/CXCR4- cells instead, underlining the importance of CXCR4 for the invasive cell behavior. Clinical studies revealed that tumor samples with a high number of CXCR4+ cells were more migratory and came from patients that suffered from more advanced metastatic disease. This important correlation may provide more accurate individual prognoses, allowing for improved selection of therapeutic agents.

These findings demonstrate for the first time that a specific CD133+/CXCR4+ cancer stem cell population present at the tumor-host interface is critically involved in pancreatic tumor metastasis. �The further molecular characterization of the pancreatic CSCs identified in the present study will be crucial for the development of new therapeutic strategies to eliminate these tumorigenic and metastatic cells. This may eventually provide a more effective treatment for our patients suffering from this deadly disease. In this respect, the demonstrated possibility of expanding pancreatic CSCs in vitro will dramatically help us in the evaluation of drug efficacy,� offers Dr. Heeschen.

Diesel exhaust may increase risk in patients with heart disease

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Air pollution could be putting patients with heart disease at risk by affecting blood vessels and clotting, researchers warn.

A study by the University of Edinburgh and Ume� University measured the effects of diesel exhaust on heart and blood vessel function in men who have previously experienced a heart attack.

The research, funded by the British Heart Foundation and published in the New England Journal of Medicine, found that inhalation of diesel exhaust caused changes in the heart�s electrical activity, suggesting that air pollution reduces the amount of oxygen available to the heart during exercise.

Dr Nicholas Mills, of the University�s Centre for Cardiovascular Sciences, said: �This study provides an explanation for why patients with heart disease are more likely to be admitted to hospital on days in which air pollution levels are increased. Most people tend to think of air pollution as having effects on the lungs but, as this study shows, it can also have a major impact on how our heart functions.�

Twenty men who had suffered a previous heart attack were carefully screened to ensure they did not suffer from angina or heart rhythm problems and that their heart condition was stable and appropriately treated. The men were exposed for one hour to either filtered air or dilute diesel exhaust while intermittently riding a stationary bicycle in a carefully monitored exposure chamber in Ume� University. Heart function was monitored continuously and blood tests taken six hours after leaving the chamber.

Electrical monitoring of the heart showed that inhalation of diesel exhaust caused a three-fold increase in the stress of the heart during exercise. In addition, the body�s ability to release a �guardian� protein known as t-PA (tissue plasminogen activator), which can prevent blood clots from forming, was also reduced by more than one third following exposure.

The link between air pollution and heart disease is strongest for the fine exhaust particles produced by road traffic. Researchers are particularly interested in diesel engines because they generate 10-100 times more pollutant particles than petrol engines. The number of diesel-powered automobiles is increasing in Europe and other parts of the world.

�Diesel exhaust consists of a complex mixture of particles and gases. Before we can recommend the widespread use of particle traps in diesel engines, we need to show that particles are the responsible component,� Dr Mills said.

�If we do that, then it is likely that devices to filter particles from exhaust, will reduce exposure and benefit public health.�

Professor Peter Weissberg, Medical Director of the British Heart Foundation (BHF), said: �There is already evidence that air pollution can make existing heart conditions worse. This research is helping us work out why. It shows that in patients with coronary heart disease, diesel exhaust can reduce the amount of oxygen available to the heart during exercise, which may increase the risk of a heart attack.

�Because of the overwhelming benefits of exercise on heart health, we would still encourage heart patients to exercise regularly, but preferably not when there is a lot of local traffic around. Heart patients can look out for pollution levels on their local weather forecasts.�

Safe water: simpler method for analyzing radium in water samples cuts testing time

Tue, 28 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A simpler technique for testing public drinking water samples for the presence of the radioactive element radium can dramatically reduce the amount of time required to conduct the sampling required by federal regulations. The U.S. Environmental Protection Agency (EPA) has approved use of the new testing method.

The technique � developed by Bernd Kahn, director of the Georgia Tech Research Institute�s (GTRI) Environmental Radiation Center (ERC), and GTRI senior research scientist Robert Rosson � became advantageous when the EPA established new radionuclide drinking water standards in 2000.

While radium is found at low concentrations in soil, water, plants and food, the greatest potential for human exposure to radium is through drinking water. Research shows that inhalation, injection, ingestion or body exposure to relatively large amounts of radium can cause cancer and other disorders. Since radium is chemically similar to calcium, it has the potential to cause harm by replacing calcium in bones.

As a result, drinking water systems are now required to sample and report on the amounts of two isotopes, radium-226 and radium-228, that are sometimes found in drinking water supplies.

�The Georgia Department of Natural Resources recognized the applicability and benefits of our method because of the new rules and proposed it to the EPA in 2002,� said Kahn.

The new method developed at GTRI requires only two steps. First, hydrochloric acid and barium chloride are added to a sample of water and heated to boiling. Then concentrated sulfuric acid is added and the radium precipitate is collected, dried and weighed. The samples are then counted with a gamma-ray spectrometry system to determine the content of radium-226 and radium-228.

A gamma-ray spectrometer determines the energy and the count rate of gamma rays emitted by radioactive substances. When these emissions are collected and analyzed, an energy spectrum can be produced. A detailed analysis of this spectrum is used to determine the identity and quantity of radioisotopes present in the source.

�The old method took four hours for each type of radium you needed to test�totaling eight hours for radium-226 and radium-228,� said Rosson. �Our method does the two tests simultaneously and it takes about half an hour of actual technician time.�

Previously approved EPA methods for measuring radium required several isolation and purification steps involving sequential precipitations from large sample volumes and sometimes liquid-liquid extractions. They all ended with a complicated final preparation step before measurement with an alpha scintillation detection system. The scintillation detector detects and counts the flashes of light that are produced when a radioactive substance interacts with a special coating on the inside of the detection container.

The EPA�s December 2007 deadline requiring every water supply be tested for radium-228 and gross alpha radioactivity greatly increased the number of radium-228 measurements required, as well as the likelihood both radium-226 and radium-228 must be measured in the same sample, also increasing the number of measurements required.

If the total radium concentration measured is above five picocuries per liter, then the water supply is out of compliance and radium-226 and radium-228 must be measured quarterly. This may require the water source to be replaced or treated to reduce the radium concentration. If the amount of radioactivity measured is less than five picocuries per liter, samples may be collected at three-, six- or nine-year intervals.

Since the EPA approved this new testing procedure in July 2006, GTRI�s ERC has been able to use the testing method they developed to analyze water samples from Georgia�s Department of Natural Resources.

�We analyze about 1,200 samples per year for them. With 3,000 to 6,000 water supply entry points in Georgia, we�re not done yet,� noted Rosson.

Pitt study finds inequality in tobacco advertising

Mon, 20 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Aug. 20 � Compared with Caucasians, African-Americans are exposed to more pro-tobacco advertising, according to a University of Pittsburgh School of Medicine study published in this month�s Public Health Reports.

Smoking remains the leading cause of preventable death and disease in the United States, causing more than 440,000 deaths annually and costing more than $150 billion in direct and indirect costs each year; African-Americans currently bear the greatest burden of this morbidity and mortality. Although exposure to pro-tobacco media messages is now known to be a potent risk factor for tobacco use, whether African-Americans are in fact exposed to more pro-tobacco advertising has been unclear until now.

�This review and meta-analysis demonstrates that African-Americans are indeed disproportionately exposed to pro-tobacco mass media messages in terms of both concentration and density,� said Brian A. Primack, M.D., Ed.M., senior author of the study and assistant professor of medicine and pediatrics at the University of Pittsburgh School of Medicine. �These findings will help us develop interventions and further research aimed at reducing tobacco-related health disparities.�

In the study, Dr. Primack and colleagues evaluated data from both predominantly African-American and Caucasian markets using studies from peer-reviewed journals. By extracting the number of total media messages the number of tobacco-related messages, and the number of residents living in each market area, they were able to calculate the concentration and density of tobacco advertising in each market.

Concentration of tobacco advertising can be defined as the number of tobacco advertisements divided by the total number of advertisements. �According to our data, the concentration of pro-smoking signage is approximately 70 percent higher for African-Americans ,� said Dr. Primack. �Our results also showed that there are about 2.6 times as many advertisements per person in African-American areas as compared to Caucasian areas.�

The findings, Dr. Primack notes, suggest that African-Americans may be special targets of the tobacco industry.

�This population may require specific public health interventions to counter the effect of unbalanced pro-tobacco promotion. Knowing that they may be targeted could motivate African-Americans to refuse to fall prey to industry tactics and help them avoid smoking,� he said.

The study authors point out important limitations worth noting. In particular, the studies that met criteria for inclusion in this review focused on older forms of advertising and promotion such as billboards and magazines. This suggests that additional research is needed on current media portrayals of smoking, such as tobacco promotions and smoking in films.

Compounds that color fruits and veggies may protect against colon cancer

Sun, 19 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio Understanding the molecular structures of compounds that give certain fruits and vegetables their rich colors may help researchers find even more powerful cancer fighters, a new study suggests.

Evidence from laboratory experiments on rats and on human colon cancer cells also suggests that anthocyanins, the compounds that give color to most red, purple and blue fruits and vegetables appreciably slow the growth of colon cancer cells.

The findings also bring scientists a step closer to figuring out what exactly gives fruits and vegetables their cancer-fighting properties.

These foods contain many compounds, and we're just starting to figure out what they are and which ones provide the best health benefits, said Monica Giusti, the lead author of the study and an assistant professor of food science at Ohio State University.

Giusti presented the findings, which represent the collaborative efforts of Giusti and her colleagues, on August 19 at the national meeting of the American Chemical Society in Boston.

Giusti and her colleagues found that in some cases, slight alterations to the structure of anthocyanin molecules made these compounds more potent anti-cancer agents.

In their studies on human colon cancer cells grown in laboratory dishes, the researchers tested the anti-cancer effects of anthocyanin-rich extracts from a variety of fruits and vegetables. They retrieved these anthocyanins from some relatively exotic fruits and other plants, including grapes, radishes, purple corn, chokeberries, bilberries, purple carrots and elderberries.

The plants were chosen due to their extremely deep colors, and therefore high anthocyanin content. Some of these plants are also used as a source of food coloring.

The researchers determined the amount of extract needed from each plant to cut the growth of human colon cancer cells in half. Altering pigment structures slightly by adding an extra sugar or acid molecule changed the biological activity of these extracts.

The researchers added different extracts to flasks that contained colon cancer cells. They used an analytical technique called high-performance liquid chromatography mass spectrometry in order to determine the exact chemical structure of each compound. They used biological tests to determine the number of cancer cells left after anthocyanin treatment.

The researchers found that the amount of anthocyanin extract needed to reduce cancer cell growth by 50 percent varied among the plants. Extract derived from purple corn was the most potent, in that it took the least amount of this extract (14 micrograms per milliliter of cell growth solution) to cut cell numbers in half. Chokeberry and bilberry extracts were nearly as potent as purple corn. Radish extract proved the least potent, as it took nine times as much (131 µg/ml) of this compound to cut cell growth by 50 percent.

All fruits and vegetables that are rich in anthocyanins have compounds that can slow down the growth of colon cancer cells, whether in experiments in laboratory dishes or inside the body, Giusti said.

In additional laboratory studies, she and her colleagues found that anthocyanin pigments from radish and black carrots slowed the growth of cancer cells anywhere from 50 to 80 percent. But pigments from purple corn and chokeberries not only completely stopped the growth of cancer cells, but also killed roughly 20 percent of the cancer cells while having little effect on healthy cells.

In animal studies, rats induced with colon cancer cells were fed a daily diet of anthocyanin extracts either from bilberries and chokeberries, which are most often used as flavorings or to make jams and juices. The dietary addition of the anthocyanin extracts reduced signs of colon tumors by 70 and 60 percent, respectively, when compared to control rats.

Giusti says the results suggest that anthocyanins may protect against certain gastrointestinal cancers.

Very little anthocyanin is absorbed by the bloodstream, Giusti said. But a large proportion travels through the gastrointestinal tract, where those tissues absorb the compound.

In fact, other researchers at Ohio State have found that black raspberries may help reduce the growth of esophageal and colon cancers tumors.

Still, Giusti stops short of recommending one kind of fruit or vegetable over another. She and her colleagues are continuing to study how the chemical structure of anthocyanins contributes to the potential health benefits of food as well as how changes to these structures may affect the body's ability to use the compounds.

There are more than 600 different anthocyanins found in nature, she said. While we know that the concentration of anthocyanins in the GI tract is ultimately affected by their chemical structures, we're just beginning to scratch the surface of understanding how the body absorbs and uses these different structures.

She pointed out that her team is also evaluating how these pigments interact with other compounds in foods such interactions could ultimately affect the health benefits of the food or the anthocyanin itself.

It is possible to use natural, anthocyanin-based food colorants instead of synthetic dyes, Giusti said. Doing so still maintains the wonderful colors of foods while enhancing their health-promoting properties.

Tumors use enzyme to recruit regulatory T-cells and suppress immune response

Thu, 16 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) One way tumors fly under the radar of the immune system is by using IDO, an enzyme used by fetuses to help avoid rejection, to recruit powerful regulatory T cells that turn down the immune response, researchers say.

It was known tumors assemble a protective barrier of regulatory T cells, or Tregs, but how they are such able recruiters was an unknown, says Dr. David Munn, pediatric hematologist/oncologist at the Medical College of Georgia Cancer Center.

People have been very interested in how the tumor gets so many of these cells and how they get activated so they tend to be very aggressive, more suppressive in the tumor than they appear to be elsewhere in the body, Dr. Munn says of Tregs, major players in preventing autoimmune diseases such as arthritis and type 1 diabetes, where the immune system attacks body tissue.

Research published online Aug. 16 in The Journal of Clinical Investigation shows IDO, which seems to play a powerful role in tumor survival despite the relatively few number of cells in the tumors draining lymph nodes, directly activates existing Tregs which become strongly suppressive within a day. The number doesnt change a lot, but their activation state changes hugely, says Dr. Munn, corresponding author.

Studies in a tumor animal model show this rapid conversion occurs only in lymph nodes connected to tumors.

The findings further define a tumors survival strategy of first recruiting IDO, which helps recruit Tregs. Tregs then up-regulate the PD-L1/PD-L2 pathway, which has been shown to play an important role in the immune suppression caused by AIDS.

For the first time it creates a link between IDO, regulatory T cells and this novel pathway we dont know much about, says Dr. Munn. Interestingly its a link that appears to come full circle because, as researchers at the University of Perugia in Italy showed in 2003, in the test tube at least, Tregs also help recruit more IDO.

IDO appears to be a sort of linchpin; its a crossroads where a number of mechanisms, some of which are more powerful than IDO itself, come together, says Dr. Munn. Tregs, for example, are much more powerful than IDO. If you take a mouse and remove IDO, it compensates just fine. If you remove Tregs, the mouse dies. But if the tumor uses IDO to recruit and activate Tregs, that is a leverage point.

Therapies aimed at these new leverage points will be most effective when packaged with other emerging and existing treatments, he says.

The FDA has approved early clinical trials of the IDO inhibitor, 1MT, in coming months. A team, led by longtime collaborator Dr. Scott Antonia, hematologist/oncologist and co-leader of the Immunology Program at the H. Lee Moffitt Cancer Center and Research Institute, will begin phase 1 trials of 1MT in patients with lung and other tumors shortly. MCG is pursuing FDA approval to begin trials of the combination of 1MT and chemotherapy in breast cancer patients. Dr. Munn notes that while the IDO inhibitor seems to be a safe drug that doesnt cause autoimmune disorders in mice, it wont be used in patients with autoimmune disorders because it could worsen the disorders.

By combining IDO with chemotherapy, researchers hope to wipe the slate clean of the tumors manipulation of the immune response, says Dr. Munn. We have found that once the tumor gets a hold of the immune system, just giving an IDO inhibitor does not restore everything to normal. The tumor has too much influence on the immune system at that point.

Standard doses of chemotherapy reduce immune system function, creating a window where IDO likely can be more effective. That window may work for cancer vaccines too, which are still under study and getting mixed reviews. Recent reports indicate vaccines can actually increase the number of Tregs in mice with tumors, a problem when fighting cancer but a possible opportunity in which an IDO inhibitor might improve efficacy, Dr. Munn says. An antibody to the PD-L1/PD-L2 already under study in cancer may be another component of a total anti-tumor package.

We have data from a mouse model that while 1MT works modestly by itself, it works significantly better when combined with chemotherapy, says Dr. Munn. I think immunotherapy needs to learn from the finding with multi-agent chemotherapy, which is you need to orchestrate more than one approach. If you give one drug over and over again, the tumor invariably figures out a way to escape, so you always have to combine different strategies. Multiple approaches also reduce the chance of needing toxic levels of any of them.

Early clinical trials of the IDO inhibitor ideally will benefit patients for whom more standard therapies have failed and enable scientists to verify laboratory findings in people, Dr. Munn says. Scientists will carefully monitor Tregs to see if they show evidence of being activated by IDO now that they know what that looks like and de-activated by the IDO inhibitor. Theyll also have to see if Tregs circulating in the bloodstream are good indicators of whats happening or whether tumor biopsies will be needed.

IDO inhibitors potential against tumors as well persistent viruses such as HIV arose out of work MCG scientists, led by Dr. Munn and his long-time collaborator Dr. Andrew L. Mellor, director of the MCG Immunotherapy Center and Georgia Research Alliance Eminent Scholar in Immunogenetics. Their work published in Science in 1998 showed fetuses use IDO indoleamine 2,3-dioxygenase to locally disable a pregnant womans immune system and avoid rejection. They showed then that one way IDO suppresses the immune response is by degrading tryptophan, a natural amino acid important to T cells.

Later, they found that tumors and certain viruses such as HIV also appear to use IDO for protection from the immune response. However, the fact that IDO-expressing cells make up less than 1 percent of the cells in a tumor or its draining lymph node led MCG researchers to look for a population of powerful allies within the immune system that could explain the suppressive impact. Tregs seemed like a good choice. The 2003 paper by Italian scientists, followed by a 2006 paper that showed naïve T-cells exposed to IDO differentiated into Tregs, helped cement that some sort of relationship existed, prompting MCG researchers to further explore the relationship in a tumor animal model.

Its only been in the last year or two that people have begun to realize Tregs spend most of their time in a sort of resting state where they have the potential to be suppressive but are not at that moment, says Dr. Munn. That would make sense, because you dont want your immune system always shut off.

Green tea holds promise as new treatment for inflammatory skin diseases

Mon, 06 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Green tea could hold promise as a new treatment for skin disorders such as psoriasis and dandruff, Medical College of Georgia researchers say.

Researchers studied an animal model for inflammatory skin diseases, which are often characterized by patches of dry, red, flaky skin caused by the inflammation and overproduction of skin cells. Those treated with green tea showed slower growth of skin cells and the presence of a gene that regulates the cells life cycles.

Psoriasis, an autoimmune disease, causes the skin to become thicker because the growth of skin cells is out of control, says Dr. Stephen Hsu, an oral biologist in the MCG School of Dentistry and lead investigator on the study published in the Aug. 18 edition of Experimental Dermatology. In psoriasis, immune cells, which usually protect against infection, instead trigger the release of cytokines, which causes inflammation and the overproduction of skin cells.

Other autoimmune diseases with similar side effects include lupus, which can lead to skin lesions, and dandruff.

Green tea, already shown to suppress inflammation, helps by regulating the expression of Caspase-14, a protein in genes that regulates the life cycle of a skin cell.

That marker guides cells by telling them when to differentiate, die off and form a skin barrier, Dr. Hsu says. In people with psoriasis, that process is interrupted and the skin cells dont die before more are created and the resulting lesions form.

Animal models treated with green tea also showed reduced levels of proliferating cell nuclear antigen, a gene expressed when skin cells multiply. In psoriasis, the gene is over-expressed and speeds production of skin cells.

Before treatment, the antigen, PCNA, was present in all layers of the skin, Dr. Hsu says. Typically, PCNA is only found in the basal layer, the innermost layer where skin cells continually divide and new cells push the older ones to the skin surface, where they eventually slough off. After being treated with green tea, the animal models showed near-normal levels of PCNA in only the basal layers.

This research is important because some treatments for psoriasis and dandruff can have dangerous side effects, he says.

The traditional treatment of ultraviolet light and medication, while it can control the lesions and be used long term, may cause squamous cell carcinoma the second most common form of skin cancer, Dr. Hsu says. Some of the most effective anti-dandruff shampoos also have carcinogens in them. While the U.S. Food and Drug Administration allows that in small amounts, the bottom line is that we dont know the long-term effects of using those products continuously.

Green tea, which is plant-derived, may be an alternative, he says. But scientists must work to overcome some barriers with the treatment.

The chemicals in green tea are so active that they are oxidized too quickly when mixed with other ingredients. They also dissolve in water, which cannot penetrate the skins barrier.

Researchers are looking for a balanced formula that can dissolve in fats, which can permeate the skin, Dr. Hsu says.

There are no cures for autoimmune diseases. But it is possible that this is a non-toxic way to regulate them. We need further study on humans to determine the full effects.

American Cancer Society to hold third annual Virtual Relay For Life in Second Life

Thu, 26 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) On July 27 and 28, the American Cancer Society and Second Life will team up once again to celebrate survivorship and raise money for the fight against cancer by holding the Societys third annual virtual Relay For Life® in the Second Life virtual world.

This years event, supported by the Societys Futuring and Innovation Center, is expected to attract nearly 2,500 global participants. Volunteer organizers have already shattered their goal of raising $75,000 by raising nearly $90,000 (or $24 million Linden dollars, the official Second Life currency) to support cancer research and programs.

The Societys virtual Relay For Life began in 2005 when Society volunteers in the Second Life community contacted Society staff to discuss the idea of creating a Relay event in the virtual world. In 2006, the event raised more than $41,000 and attracted more than 1,100 participants to a track that included real-world representations of New York City, Paris, Mexico, Sweden and South Africa. During this years event, as in past years, avatars will gather to donate money and walk on a custom-built track that encompasses a 512-acre park.

Using the theme Quest for a Cure, volunteers are planning to use action adventure movies as inspiration for the games, scenes and activities that will greet participants during this years Relay.

The Second Life community continues to show unwavering support, dedication and inexhaustible creativity as we draw close to another record breaking event, said Randal Moss, the Societys manager of futuring and innovation-based strategies.

In addition to the Relay For Life event, the Society also is celebrating the recent opening of its virtual headquarters in Second Life. The new virtual building, which opened on June 1, is designed to provide the same cancer information and services to people in the virtual world as the organization provides in the non-virtual world. The building includes presentation and meeting rooms for cancer education sessions and fundraising meetings, and will soon feature a staffed link to the Societys National Cancer Information Center that provides free cancer information 24 hours a day, seven days a week, 365 days a year. The headquarters also features green space and gardens to showcase user-created art that expresses the personal fight against cancer.

Already we have existing peer-to-peer Second Life cancer support groups coming to us to use the facility and our resources. We are certain that going forward the community will find untold uses for our office space in terms of education, advocacy, fundraising and community support, said Moss.

Cancer research summaries

Fri, 20 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Individuals who receive blood transfusions from donors with undiagnosed cancers are at no higher risk of developing malignant disease than people who receive blood from donors without cancer, according to the results of a retrospective study published in The Lancet last month.

Before donated blood can be used in a clinical setting, it must go through a rigorous battery of tests to ensure that no diseases are passed between the donor and recipient. However, whereas the risk of transmission of infectious agents is well established and appropriate precautions are routinely taken, establishing whether there is also a possibility of transmission of chronic diseases such as cancer through blood transfusions has been more difficult.

There is some evidence to support the theory that cancers might be transmissible through blood. Even if a tumour is too small to be detected, it will shed millions of cells into the circulation every day that may have the potential to establish new malignancies within the donor or blood recipient. Reports of transmission of cancer cells from needles or surgical instruments demonstrate that tumours cells have the capability to be transplanted to, and develop in, healthy recipients. And there is some data to show that transfused patients are at increased risk of cancers, particularly non-Hodgkin lymphoma.

To test some of these ideas, Gustaf Edgren and colleagues set out to investigate whether there is a history of increased cancer diagnoses among individuals that receive blood transfusions from people who donate blood while unaware of their cancers. Using registry data from Sweden and Denmark , the authors created a database from which they identified a group of exposed individuals, who had received donated blood from a person who was diagnosed with cancer less than 5 years after giving blood.

The study population comprised all individuals with no history of malignant disease who had received at least one unit of whole blood, erythrocytes, plasma or platelets between 1968 and 2002. All blood donors who contributed to these transfusions were traced through population and health registers and donors who were subsequently diagnosed with a malignancy within 5 years of the blood donation were deemed to harbour a sub-clinical malignancy at the time of donation. The resulting group of exposed individuals numbered 12 012; 342 082 people who received blood from non-precancerous donors were classed as unexposed.

Recipients of blood from people with a known history of cancer were excluded from the analysis as were those for whom 5 years of follow up was not available. All recipients were followed for cancer occurrence using the Swedish and Danish cancer registries. Any recipients diagnosed with cancer within 6 months of transfusion were excluded.

The researchers identified 978 cases of cancer among all the blood recipients but after statistical analysis they found no excess risk of cancer overall among individuals who had received one or more blood products from a precancerous blood donor. The relative risk was not substantially affected by sex age, calendar period, or number of transfusions. What is more, there was no excess risk when patients who received blood from people with cancers at sites that are thought to have the highest risk of metastasising through blood---the lung, liver, skeleton, and central nervous system---were combined.

An additional finding was that the cancer incidence among the 9377 recipients of blood from donors with a previous diagnosis of cancer who were excluded from the main analysis did not differ from that among recipients of blood from non-cancerous donors. Since we found no increased cancer risk associated with transfusions from an admittedly limited number of donors with a previous history of cancer, it would seem that long-term cancer survivors might be a fairly safe donor group, concluded the authors.

Enzyme eliminated by cancer cells holds promise for cancer treatment

Wed, 18 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An enzyme that cancer cells eliminate, apparently so they can keep proliferating, may hold clues to more targeted, effective cancer treatment, scientists say.

In a high-stakes tit for tat, protein kinase G enables healthy cells to stay on task to proliferate, differentiate then provide a useful function. Cancer somehow reduces or eliminates PKG and cells get stuck proliferating.

The bottom line is, in normal tissue, you can see PKG being expressed; but tumors or cell lines that correlate with those tissues dont have nearly as much, says Dr. Darren Browning, cancer researcher at the Medical College of Georgia.

Cell lines used for all types of research appear to support his hypothesis. Many are actually cancer cells because of their proclivity to keep producing; Dr. Browning and others have shown PKG is lost in these cells. You split them once or twice and they kind of lose their character, he says.

The same appears true for tumors in people, says Dr. Browning, whose lab has found dramatic differences in PKG levels in tumors compared to even nearby, healthy tissue removed in surgery to ensure a cancer-free margin.

The findings made him wonder if the change in PKG level was just an artifact or was critical to cancer survival. A lot of proteins are lost by cancer cells, so we asked, What happens if we put PKG back into the cancer cells

He took metastatic colon cancer cells, created a system for reintroducing PKG, then put the cells into mice without an immune system. He admits he was disappointed that the PKG-enhanced cells grew but became very interested in how they grew.

Cancer cells without PKG created hard, solid tumors that spread. PKG-enhanced cells created a soft, non-invasive tumor that literally fell apart on contact and seemed to grow in little islands. After consultation with pathologists and others, he realized the PKG-enhanced cells were congregating around the few blood vessels. We know that cancer cells, particularly colon cancer cells, are very aggressive at bringing blood vessels into the tumor, he says. Cells poor at recruiting blood vessels dont grow well, which seems to be the case for PKG-enhanced colon cancer cells.

Now he wants to know how PKG nullifies aggressive metastatic cancer cells. We think PKG inhibits cancer by getting rid of a cancer-promoting gene called beta-catenin, which slows growth and blocks the tumors ability to recruit blood vessels that are needed to grow bigger, says Dr. Browning, who recently received a $720,000 American Cancer Society grant to pursue his hypothesis. His proposal was ranked number one by the ACS Cell Structure and Metastasis Study Section.

Hes already shown that PKG can reduce vascular endothelial growth factor, or VEGF; anti-VEGF drugs are the focus of numerous anti-cancer trials underway in the country because of VEGFs critical role in development of new blood vessels. Maybe by activating PKG or increasing PKG expression in tumors, we are going to reduce the amount of VEGF they produce, he says. We dont know whether PKG has a role in going from normal tissue to the initiation of a tumor, but we think its important to the tumor both in terms of angiogenesis and blocking metastasis. He points to one of his studies in which colon cancers spread to the lungs a common path for metastatic colon cancer was completely blocked by PKG expression.

A big part of the magic of PKG may be its impact on a gene called beta-catenin, which enables many stem cells, including those in the skin, bone marrow and colon, to proliferate throughout life. Little pits called crypts in the wall of the colon contain Wnt hormone which stimulate nearby stem cells, causing an increase in beta-catenin. The net effect is the colon makes new cells to replace cells lost to the ongoing grind of absorbing water and minerals from food and forming and eliminating waste.

As cells start moving out of the crypt, away from the Wnt hormone, beta-catenin levels go down so cells should stop dividing and start maturing. Essentially all colon cancers have an aberration in this beta-catenin system that prevents normal degradation and allows cell to keep proliferating.

In the normal cells that line the colon, you dont see very much beta-catenin. We think PKG in these cells keeps it that way to keep the cells from continuing to proliferate and spread, says Dr. Browning, who has already shown that in the test tube at least, adding PKG lowers beta-catenin levels. Interestingly, beta-catenin also is known to regulate VEGF expression in colon cancer.

In a nutshell, the first and most important genetic lesions leading to colon cancer cause increased beta-catenin levels, says Dr. Browning. We found PKG can knock down beta-catenin levels by up to 80 percent in some colon cancer cells and we think that is part of the mechanism by which PKG is able to block tumor angiogenesis and metastasis.

Hes excited by the implications and is involved in extensive collaborations to understand how PKG regulates beta-catenin and how it might be used in cancer therapies.

Evidence of PKGs effectiveness in fighting colon cancer in humans may already be available. Colon and rectal cancer is the third most common cancer in men and women in the United States but its rare in developing countries where residents eat less processed food and ingest more bacteria. Some of these bacteria make a protein, STa, which appears to prevent and even kill colon cancer cells. Dr. Browning believes that PKG is responsible for STas anti-cancer effects.

Tobacco industry efforts to derail effective anti-smoking campaigns

Wed, 11 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Anti-smoking ads that reveal the tobacco industrys deceptive practices have been aggressively quashed through various methods found Temple University Assistant Professor Jennifer K. Ibrahim, co-author of an analysis in the August issue of the American Journal of Public Health.

In the article, Ibrahim tracks the rise and fall of state and national efforts to curb smoking for the past 40 years. She chronicles industry strategies to prevent a campaigns creation, steer messages to smaller audiences, limit the content of the message, limit or eliminate the campaigns funding, and pursue litigation against the campaign. Ibrahim looks at campaigns in Minnesota, California, Arizona, Oregon, Florida, and a national campaign from the American Legacy Foundation.

It tells the story behind the smoke. People often judge these ads and now you know what the tobacco industry was doing trying to undermine them, Ibrahim said.

Research has found ads that reveal the deceptive practices of the tobacco industry are the most effective media campaigns that reduce smoking rates, she said.

For example, one billboard in California read Tobacco is legal, profitable, and kills people featuring an alligator labeled big tobacco with a smirk saying Two out of threes not bad.

However, these messages arent always getting out there because of the money spent by the tobacco industry to eliminate them, said Ibrahim, an assistant professor of public health.

State health departments face an uphill battle when dealing with the political clout of the industry with its lobbying, campaign contributions and specials events, Ibrahim said.

One tactic also involves the industry producing its own ineffective campaigns in order to portray state programs as duplicative and a waste of public dollars. Campaigns designed by the tobacco companies patronize youth in their early teen years, with messages like Think, Dont smoke, Ibrahim said.

In contrast, Floridas truth anti-smoking campaign empowered them by giving them information about how the tobacco industry tried to manipulate by marketing.

The tobacco industry has spent more money in advertising in light of successful media campaigns that target large audiences.

From 1975 to 2003, tobacco industry expenditures in advertising and promotion grew from $491 million to $15.5 billion. During this period, the percentage of smokers in the United States fell from about 37 percent to 22 percent, according to the Behavioral Risk Factor Surveillance System.

Attitudes are changing as the public is becoming more aware about the dangers of smoking, secondhand smoke, and the deceptive practices of the industry, Ibrahim said.

While the numbers offer some promise, more initiatives are needed to keep anti-smoking efforts alive.

Its naïve to think the industry is still not following these practices and preparing tactics to respond, Ibrahim said.

The Master Settlement Agreement in 1998 marked an important step when seven tobacco companies agreed to change the way tobacco products are marketed, release previously secret industry documents, dispand trade groups, and pay the states an estimated $206 billion. The tobacco companies also agreed to finance a $1.5 billion public anti-smoking campaign.

States attorney generals continue to enforce the provisions of the agreement, Ibrahim said.

A recent product that has created uproar is Camels No. 9s pink cigarettes that public health advocates say target teenage girls not women. In June, congress sent a letter to the editors of 11 major magazines, from Glamour to Cosmopolitan, requesting them to stop running the ads for the cigarettes.

Aggressive efforts to battle current marketing efforts and litigation from the tobacco industry are vital to keep the best media campaigns from disappearing, Ibrahim said.

The efforts put forth by California and the American Legacy Foundation as they pursued legal battles with tobacco companies provide a good example of the tenacity needed to successfully defend and promote tobacco control campaigns, said Ibrahim. Persistence can pay off. We need to go with campaigns that work,

Polish journalist scoops first prize in prestigious European award

Mon, 09 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) 9 July 2007 - Pawel Walewski, a correspondent with Polands biggest selling weekly magazine Polityka, has been awarded the European School of Oncologys Best Cancer Reporter Award for 2007. The Award was established by the European School of Oncology (ESO) in 2006 to encourage better quality media coverage of cancer and recognise the many examples of outstanding cancer reporting by journalists across Europe.

The standard of this years entries was very high, with nominations received for journalists from Belgium, Czech Republic, Ireland, Italy, Kosovo, Poland, Portugal, Spain, Switzerland and the UK. Walewski, who will receive a prize of 10,000, said he felt honoured to be given this Award I have been writing about oncology and cancer survivors for ten years but every time I sit at my computer or reach for a pen I have a dilemma: how to reconcile competent information, based on facts and science. I am delighted the judging panel recognised it as the important issue.

Linda Geddes a correspondent with the New Scientist magazine and Maria Valerio Sainz who writes for the online version of Spanish newspaper El Mundo were joint runners up and will receive a prize of 5,000 each. When told that she had received a Best Cancer Reporter Award Geddes said that It is good to know that this kind of investigative health reporting is still valued and rewarded. I hope I have helped to raise awareness of the desperation some cancer patients feel, and the need for their doctors to listen to them and help them make the right decisions for their health.

Sainz flagged the important role that journalists play in educating the public about cancer and said I think that journalists have an important social responsibility, even more so when talking about health and illnessI feel that we should show the human courage of all those who live and survive a tumour that's why I try to use a simple language, a human tone, far from unrealistic expectations and false alarms.

A further two journalists were specially commended by the Best Cancer Reporter Award jury for the courage in writing their own cancer story in order to raise awareness about the challenges faced daily by cancer patients: Eric Baumann of TagesAnzeiger, Switzerland and Iva Skochova from the Prague Post, Czech Republic.

The journalists will be presented with their prizes at a ceremony that will take place during ESOs forthcoming media event Cancer: Time for a Reality Check that will be held on Friday October 26 2007 in Rome, Italy.

In order to further promote excellence in cancer journalism ESO is pleased to announce the launch of its Cancer Media Service (CMS) at

Patients with soft tissue sarcomas should be treated at high volume centers

Mon, 09 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Soft tissue sarcomas---rare tumours of the connective tissue---should be treated at the few centres which see most cases, in order to give patients the best chance of good outcomes, concludes an analysis of sarcoma management in Florida, published in the Annals of Surgery last month.

STS [soft tissue sarcomas] are rare. This paucity leaves most health care institutions with low case volumes and outdated or inadequate resources, which impede the ability to offer optimal treatment of these rare and often complicated tumours, the authors explain.

Using an analysis of a large population-based state cancer registry in Florida, the Juan Gutierrez and colleagues tested the hypothesis that soft tissue sarcomas are better treated at institutions with higher volumes of cases. They used the Florida cancer data system, a prospective database of all cancer cases in the state of Florida since 1981, to identify all records of soft tissue sarcomas up to 2001. A total of 6259 cases were extracted and, after duplicates were removed, the researchers arrived at a total of 5564 unique cases. A final study sample of 4205 cases was created by excluding individuals who had non-surgical treatments.

Next, the researchers looked at the medical facilities where each persons treatment was done. A total of 256 institutions in Florida performed at least one resection of a soft tissue sarcoma between 1981 and 2001; these were grouped into percentile ranges by surgical procedure volume. Of 4673 surgical procedures recorded (including repeat procedures, which were excluded from the main analysis), 7 institutions performed 1504 cases (32.2%) and were classified as high volume centres. The remaining two thirds of institutions did 3169 cases (67.8% of the total) and were classed as low volume. Our analysis of 20 years surgical management of STS in Florida[showed that] volumes in 213 facilities amounted to less than 1 case per year and less than 2 cases per year were managed at an additional 79 health care institutions, reported the authors.

Patients at high volume centres were generally younger, with a higher proportion of women, were more likely to have high-grade tumours and were more likely to receive radiation therapy and chemotherapy. When the authors looked at outcomes, they found that 30-day mortality rates were twice as high in low volume centres than in high volume institutions; there was a similar disparity with the 90-day mortality rate. Median 5-year and 10-year survival was significantly better for patients treated at high volume centres (40 months versus 37 months); however, survival of patients with extremity tumours was equal among the two groups of institutions. There was a slight selection bias in favour of the low volume centres because tumours managed at high volume places were higher grade and larger in size but despite this, higher volume centres achieved superior outcomes in patients with high grade lesions and those with tumours over 10 cm in size.

In an additional analysis, the researchers examined outcomes from treatment of extremity tumours alone to establish whether the volume of surgeries done at a centre affected the likelihood of patients keeping their limbs. A total of 1937 extremity tumours were analysed. At high volume centres, 90.6% of procedures for these tumours were limb sparing operations compared with 86.2% at low volume centres, suggesting that physicians at low-volume centres were more likely to resort to amputation to protect the patients survival chances.

This analysis reveals a direct correlation between hospital surgical volume and both short-term and long-term treatment outcomes for STS. While the observations reported here require confirmation with additional independent data sets they argue persuasively for exclusive referral of patients with STS to high volume specialised centres for optimal treatment, survival, and functional outcomes, conclude the authors.

Scientists follow familiar TRAIL to new cancer therapy

Mon, 09 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new study identifies a combination therapy that may sensitize human cancer cells to a promising treatment currently being used in clinical trials. The research, published in the July issue of the journal Cancer Cell, published by Cell Press, provides a pharmacological method for enhancing the potency and effectiveness of a tumor necrosis factor (TNF) death receptor ligand against a variety of human cancers.

Potency and lack of toxicity to normal tissues make activation of TNF-a-related apoptosis-inducing ligand (TRAIL) death receptor signaling an attractive and exciting target for cancer therapy, and it is currently being tested in clinical trials. However, most cancer cells have defects in their ability to die via a cell death pathway called apoptosis, and unfortunately, TRAIL therapy is not effective in cells that have certain defects in apoptotic pathways. Dr. Wafik S. El-Deiry from the University of Pennsylvania School of Medicine and colleagues designed a series of studies to gain a better understanding of TRAIL-associated cell signaling pathways in cancer cells and to look for ways to pharmacologically optimize TRAIL therapy.

Dr. El-Deirys group had previously established that c-Myc is a key mediator of TRAIL-induced apoptosis and that cancer cells lacking c-Myc and a functional apoptotic pathway were resistant to TRAIL. In the current study, the researchers demonstrated that expression of c-Myc in TRAIL-resistant human colon cancer cells sensitized the cells to TRAIL, even when the cells had intrinsic apoptotic defects. The researchers observed that TRAIL induced expression of two potent antiapoptotic molecules, Mcl-1 and cIAP2, and that c-Myc repressed both molecules.

The researchers also discovered that the multikinase inhibitor sorafenib prevented TRAIL-mediated induction of Mcl-1 and cIAP2, and although it had little effect on the killing of TRAIL-resistant cells when administered alone, combination with TRAIL caused significant death of previously TRAIL-resistant cancer cells in culture and TRAIL-resistant tumors in mouse models. Sorafenib was recently approved by the FDA for treatment of renal cancer and is currently undergoing investigation in over 30 clinical trials for use against a wide range of human cancers, including melanoma, prostate, ovarian, pancreatic, lung cancers, and others.

Like c-Myc, sorafenib appears to work through a mechanism that involves repression of TRAIL-induced expression of Mcl-1 and cIAP2. These results also establish the clinical potential for combining TRAIL or other death receptor agonists with an orally bioavailable, low-toxicity multikinase inhibitor, sorafenib/Nexavar, thus providing an exciting approach for attacking cancers that harbor defective intrinsic apoptotic machinery, explains Dr. El-Deiry.

Gene variations directly link inflammation to an increased risk for lung cancer

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Variations in two genes related to inflammation may be a major risk factor for developing lung cancer, according to a team of scientists from the National Cancer Institute and the University of Texas M. D. Anderson Cancer Center. The effect of these genes is especially strong among heavy smokers, suggesting that the inflammatory response is important in modulating the damage caused by tobacco smoke.

Their study, published in the July 1 issue of Cancer Research, a publication of the American Association for Cancer Research, is the first to pinpoint the mechanism by which damage to the lung might trigger an overzealous inflammatory response by the immune system, leading to lung cancer. The variants, or polymorphisms, were found in genes for interleukin 1A and interleukin 1B, two signaling molecules that immune system cells secrete in response to infection or tissue damage.

Our findings help explain how heavy smoking, for example, combines with a genetic predisposition to create a besieged environment within the lungs, said lead author Eric Engels, M.D., MPH, researcher at the Viral Epidemiology Branch of the NCIs Division of Cancer Epidemiology and Genetics. Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA.

Inflammation is part of the immune systems arsenal to combat the effects of infection and cell damage. However, prolonged or intense inflammation could lead to conditions within the lung environment that foster cancer, Engels said. Previous studies have shown that diseases associated with lung damage, such as tuberculosis and asthma, increase the risk of developing lung cancer. Likewise, exposure to tissue-damaging substances like silica and asbestos, inhaled into the lungs, has also been shown to increases lung cancer risk.

Inflammation has long been thought to be a factor in many cancers, including lung cancer, and could provide an explanation how damage to lung tissue leads to cancer, Engels said. Knowing more about the downstream effects of these polymorphisms, and discovering others like them, will increase our understanding of how some people are predisposed to developing cancer.

To examine the relationship between inflammation and lung cancer risk, the researchers compared differences in genes related to inflammation between more than 1,500 lung cancer patients and 1,700 controls at M. D. Anderson Cancer Center in Houston, Texas. More than 80 percent of the cancer patients in the study were current or former smokers. Among the 59 variations in 37 inflammation-related genes studied, the researchers discovered that some variants in the genes for interleukin (IL) 1A and 1B, are found more frequently in patients with lung cancer -- and especially among heavy smokers. The effect was most profound in polymorphisms in IL1B, which is central to the inflammation process, the researchers said.

According to Engels, the IL1B protein is an integral part of the chemical cascade by which cell signals moderate the response to inflammation. Variations in the gene may lead to greater expression of the protein, which is more likely to turn on the cascade and sustain the damaging effects of inflammation. Over time, the constant damage of inflammation could lead to genetic damage and cancer, Engels said.

The researchers believe their findings will provide the basis for further lung cancer research as well as a model for examining the nature of inflammation in other types of cancer.

While smoking is still the greatest risk factor, we still do not understand how other factors play a role, Engels said. A better understanding of the risks involving inflammation will lead to a better understanding of cancer prevention.

Inhaling from just 1 cigarette can lead to nicotine addiction

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WORCESTER, Mass. -- A new study published in the Archives of Pediatric and Adolescent Medicine shows that 10 percent of youth who become hooked on cigarettes are addicted within two days of first inhaling from a cigarette, and 25 percent are addicted within a month. The study found that adolescents who smoke even just a few cigarettes per month suffer withdrawal symptoms when deprived of nicotine, a startling finding that is contrary to long-held beliefs that only people with established smoking habits of at least five cigarettes per day experience such symptoms.

The study monitored 1,246 sixth-grade students in six Massachusetts communities over four years. Students were interviewed frequently about smoking and symptoms of addiction, such as difficulty quitting, strong urges to smoke, or nicotine withdrawal symptoms such as cravings, restlessness, irritability, and trouble concentrating. Of those who were hooked, half were already addicted by the time they were smoking seven cigarettes per month. As amazing as it may seem, some youth find they are unable to quit smoking after just a few cigarettes. This confirms an earlier study by the same researchers.

Interim analysis of anti-cancer vaccine, BiovaxID, to be conducted

Wed, 13 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Tampa, FL--June 13, 2007 -- Biovest International, Inc. (OTCBB: BVTI), a majority owned subsidiary of Accentia Biopharmaceuticals, Inc. (NASDAQ:ABPI) announces a milestone in its effort to gain accelerated conditional approval for BiovaxID. The independent Data Monitoring Committee (DMC) has requested an interim analysis of all primary and secondary endpoints. The DMC is the independent committee that is responsible for safety and efficacy reviews of the BiovaxID Phase 3 Clinical Trial. Further, the DMC has requested data lock to occur in September 2007 to facilitate this interim analysis.

Additionally, the DMC has informed the Company that, after its review of unblinded data for the BiovaxID Phase 3 Clinical Trial, there are no identifiable safety concerns related to this therapy. The company believes that BiovaxIDs strong safety record will be supportive of its planned application for accelerated conditional approval of BiovaxID.

BiovaxID is an anti-cancer vaccine that is in pivotal Phase 3 Clinical Trial for the indication of non-Hodgkins lymphoma (NHL). BiovaxID is a personalized, patient specific vaccine designed to stimulate the patients own immune system to recognize and destroy cancerous B-cells that may remain in the body or may arise after the patient has been treated with chemotherapy. Unlike many other approaches to treating NHL, BiovaxID is designed to kill only cancerous B-cells. The BiovaxID Phase 3 clinical trial is being conducted at fourteen oncology centers within the United States and nineteen centers in Russia.

The Chairman of the DMC, Dr. Gerry Messerschmidt, MD, FACP, stated, There are no identifiable safety concerns in the current BiovaxID Phase 3 pivotal Clinical Trial at this time in our data review. To facilitate Biovests regulatory agency discussions and petitions based on its announced decision to seek accelerated conditional approval of BiovaxID, the DMC has requested that the database be fully updated and appropriate analyses of all enrolled/randomized patients to-date be performed for DMC-only closed session review at the Committees next scheduled meeting in September 2007.

At that time, the independent committee will explore possible mechanisms of unblinded data review with regulatory agencies.

Dr Messerschmidt further stated, The DMC recommends continuation of the Trial with the following changes: that the CHOP-R induction chemotherapy arm (the current Standard of Care) remain open and active; the PACE therapy arm of the study be discontinued, with protocol- defined follow-up of all current PACE patients enrolled.Applications for accelerated conditional approval of BiovaxID are planned to be submitted to both the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by mid-2008. The DMC has agreed to serve as a liaison between the Company and the FDA and the EMEA. If conditionally approved by the target date of mid-June 2008, BiovaxID would be commercially available in early 2009.

Dr. Steven Arikian, Chairman and CEO of Biovest, stated that The Phase 2 efficacy and safety data, combined with the Phase 3 safety data, blinded disease progression data, and third-party published data, reinforce our confidence that this anti-cancer vaccine is effective and the risk-benefit of BiovaxID in defeating NHL will be proven. Our follow-up data, which was generated during the National Cancer Institute (NCI) Phase 2 Clinical Trial, is now 10 years mature and our initial Phase 3 Clinical Trial patients will be 7 years mature at the data lock scheduled for September of this year. We believe that our robust and lengthy follow-up data, which covers over 200 patients in the Phase 2 and Phase 3 Clinical Trials to date, will be helpful in supporting our application for accelerated conditional approval of BiovaxID.

Pursuant to the DMCs request, we plan to submit a comprehensive interim analysis to the DMC in September 2007. Dr. Arikian added that, We are pleased with the independent confirmation of BiovaxIDs overall safety profile in its ongoing Phase 3 Clinical Trial. We are committed to getting BiovaxID to NHL patients as soon as possible. The support being offered by the DMC in upcoming discussions with the FDA and EMEA is of the utmost importance in achieving this goal.

Choice is a key element in success for smokers who want to quit

Thu, 24 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Smokers who have a say in how they quit are more likely to try kicking the habit and are more successful, according to new research at the University of Rochester.

Rochester researcher Dr. Geoffrey Williams associate professor of medicine at the University of Rochester School of Medicine and Dentistry, will unveil new findings at a Toronto conference this month that demonstrate patient involvement in a quit plan leads to smokers who are more motivated to quit because they genuinely want to, not because they are being nagged or bullied.

Williams will be one of more than 300 researchers from 25 countries to gather at the University of Toronto this weekend to discuss their work within Self-Determination Theory. This groundbreaking psychological theory of human motivation was developed by University of Rochester psychologists Edward Deci and Richard Ryan.

Williams' team of researchers found that smokers who were counseled in a manner that encouraged them to reflect on whether they wanted to smoke or not, and if not why they were trying to quit, were more likely to maintain their abstinence for two years than those who received usual care.

Participants in the control group were simply given a list of quit resources in the community and were encouraged to visit their doctors for help, while participants in the special program received one-on-one counseling and more.

Williams said patients in the cessation program were asked about their willingness to and confidence in quitting, their history with tobacco, general medical history, and even their life aspirations. Smokers in the program were also encouraged to take part in developing a personalized quit plan by providing input and perspective on how smoking fit into their lives and which aspects of quitting were most daunting.

The support and choice patients received in the program resulted in a greater motivation to quit, willingness to try medications, higher levels of commitment to quit plans, and ultimately, more successes. Williams said the cessation plan offered additional support to smokers that a typical doctor's office doesn't.

I don't think they get enough time and I don't think they get enough input and choice into the quit plan, Williams said. Our findings showed it was particularly important to promote patient choice and active participation in the plan.

Williams said the method has also proved successful for patients managing diabetes, weight loss, and dental care.

Along with Ryan, who is a professor of psychology, psychiatry, and education, Deci, the Gowen Professor in the Social Sciences, and Williams, Rochester research assistant professor Heather Patrick will also present at the conference. She has applied Self-Determination Theory to a common conundrum of romantic relationships: If you do something positive for your mate, does it matter why The answer is yes according to Patrick's research. She found that both small sacrifices, like doing the dishes for your partner, and big ones, like moving across the country for a new job he or she really wants, mean more if you do them because you genuinely want to.

Both Patrick's and Williams' research illustrates the crux of Self-Determination Theory: A self-motivated person derives more satisfaction in completing a given task, and is more likely to do it well. The research presented at the conference will explore motivation in human development, education, work, relationships, sports, health, medicine, virtual environments, psychotherapy, and cross-cultural applications.

Deci and Ryan hosted the first SDT conference at the University in 1999.

Panel offers guidelines on skin reactions to new class of cancer drugs

Wed, 23 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DURHAM, N.C., May 22 -- Skin reactions to a powerful new class of anti-cancer drugs are frequent, but manageable through a simple and rational treatment approach usually without the need to reduce the dose or interrupt treatment with potentially life-prolonging chemotherapy, according to an article in the May issue of The Oncologist.

The special article presents the first recommendations on skin reactions to the new drugs, called Epidermal Growth Factor Receptor Inhibitors (EGFRIs). The guidelines were developed at an international multidisciplinary meeting, including medical oncologists, dermatologists, nurses, and pharmacists. One important goal is to ensure that healthcare professionals and patients see EGFRI-associated dermatologic toxicity as manageable, thereby optimizing clinical benefit from continued and uninterrupted use of EGFRIs when possible, according to lead author Dr. Thomas J. Lynch, Jr., of Massachusetts General Hospital, Boston.

Treatment with EGFRIs has been shown to improve survival in patients with several types of cancer, including lung, pancreatic, and colorectal cancers. The drugs including erlotinib (Tarceva), cetuximab (Erbitux), and panitumumab (Vectibix) work by interfering with cell-signaling abnormalities that contribute to cancer development and growth.

Unfortunately, the EGFRIs carry a substantial risk of skin reactions more than half of treated patients have some type of skin toxicity, most commonly an acne-like rash. The reactions most likely occur because the receptor blocked by the drugs also performs key functions in normal skin. There is even evidence that the rash may be a sign that EGFRI anti-cancer treatment is working in some studies, patients with more severe skin reactions had better survival. The skin reactions are rarely so severe that the dosage is reduced or treatment stopped. Until recently, there was no strong scientific data to guide the treatment of skin reactions to EGFRIs.

To address this issue, the authors propose a simple system for classification and treatment of skin reactions. To start, all patients receiving EGFRIs are advised to use a moisturizer and protect against exposure to sunlight the rash may be more severe in sun-exposed areas.

If skin reactions occur, a structured approach is recommended to keep the rash under control and avoid cancer treatment interruptions. Reactions are classified as mild, moderate, or severe, based on the area of the rash, itching or other symptoms that interfere with the patient's activities, and the risk of infection. Treatment is targeted to severity: mild steroids and/or antibiotics for mild reactions, stronger medications for moderate reactions. If the rash becomes severe, the guidelines call for reduction in the EGFRI dose, along with other medications. Treatment should be interrupted only if the reaction still hasn't cleared within two to four weeks. Once the rash has decreased, treatment with EGFRIs can be restarted if the skin reaction returns, it will likely be manageable.

The authors underscore the need for further studies to validate their recommendations. Until then, the expert guidelines will play an important role in helping patients and cancer care professionals to understand why EGFRI-related skin reactions occur and the logic behind their management. [I]t is important to emphasize that, in the majority of cases, there is no clinical need to withdraw EGFRI treatment, Dr. Lynch and coauthors conclude. Even in worst-case scenarios, suspension of EGFRI treatment often needs only to be temporary, simply allowing for diminution of the rash.

I believe the consensus guidelines will have a significant impact on the way EGFRI-associated rash is managed, said Dr. Mario Lacouture, Assistant Professor of Dermatology at Northwestern University Feinberg School of Medicine and founding director of the SERIES (Skin and Eye Reactions to Inhibitors of EGFR and kinases) Clinic, Chicago, which focuses on early diagnosis and treatment of reactions to EGFRIs and related drugs. Currently, many patients with skin reactions to EGFRIs receive no treatment until they have a severe rash, when their dosage has to be decreased. The new classification and treatment guidelines will encourage earlier intervention, hopefully avoiding the need for dose reductions. This should help to improve the anticancer effects of the EGFRIs, while at the same time improving quality of life for patients.

Hexavalent chromium in drinking water causes cancer in lab animals

Wed, 16 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers announced today that there is strong evidence a chemical referred to as hexavalent chromium, or chromium 6, causes cancer in laboratory animals when it is consumed in drinking water. The two-year study conducted by the National Toxicology Program (NTP) shows that animals given hexavalent chromium developed malignant tumors.

Previous studies have shown that hexavalent chromium causes lung cancer in humans in certain occupational settings as a result of inhalation exposure, said Michelle Hooth, Ph.D., NTP study scientist for the technical report. We now know that it can also cause cancer in animals when administered orally.

The study findings were announced at the National Institute of Environmental Health Sciences (NIEHS) after the NTP Board of Scientific Counselors Technical Reports Review Subcommittee completed its independent peer review of the sodium dichromate dihydrate research report. Sodium dichromate dihydrate is an inorganic compound containing hexavalent chromium that was used in the NTP studies. The NTP is located at the NIEHS, part of the National Institutes of Health.

Hexavalent chromium compounds are often used in electroplating, leather tanning, and textile manufacturing and have been found in some drinking water sources.

Male and female rats and mice were given four different doses of sodium dichromate dihydrate in their drinking water ranging from 14.3 mg/l to 516 mg/l for two years. The lowest doses given to the animals in the study were ten times higher than what humans could consume from the most highly contaminated water sources identified in California.

The researchers report finding significant increases in tumors at sites where tumors are rarely seen in laboratory animals. Male and female rats had malignant tumors in the oral cavity. The studies conducted in mice found increases in the number of benign and malignant tumors in the small intestine, which increased with dose in both males and females.

We found that hexavalent chromium is absorbed from the gastrointestinal tract, said Hooth. After it is orally administered, it is taken up by the cells in many tissues and organs.

Hexavalent chromium has been brought to the publics attention in many ways, most notably in the movie Erin Brockovich. Eleven members from the California Congressional Delegation sent a letter to the NTP Director requesting the NTP conduct the studies. Nominations for studying this compound also came from the California Environmental Protection Agency and the California Department of Health Services. The NTP began work on this compound after gaining input from the public and a panel of scientific experts about the study design.

Researchers create model of cancer-preventing enzyme, study how it works

Fri, 11 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBIA, Mo. -- Researchers at the University of Missouri-Columbia recently created a model of proline dehydrogenase, an important cancer-preventing enzyme in the human body, and analyzed how it works. A paper detailing their results was published today in the Journal of Biological Chemistry.

Proline dehydrogenase is important because it plays a role in apoptosis, the process of cell death, by enabling the creation of superoxide, a highly reactive electron-rich oxygen species. Superoxide is involved in the destruction of damaged cells and therefore is important in preventing the development and spread of cancer. The protein proline dehydrogenase opens up to allow oxygen to steal electrons and create a superoxide, said Tommi A. White, an MU doctoral student in biochemistry.

White worked with John J. Tanner, professor of chemistry and biochemistry in MUs College of Arts and Science, and Navasona Krishnan, a doctoral student at the Unviersity of Nebraska-Lincoln, and Donald F. Becker, an associate professor at the University of Nebraska-Lincoln, to create the first model of proline dehydrogenase. Because the human form of this enzyme is difficult to work with, the team studied proline dehydrogenase from the bacteria Thermus thermophilus. They used bioinformatics and biochemical studies to show that this enzyme is functionally similar to the human version, so their results can be generalized to the human version, as well as the bacterial version.

Using X-ray crystallography and biochemical analysis, the team created a model of proline dehydrogenase that can tell scientists more about the molecules structure and functions.

The three-dimensional model tells us a lot about the structure of the molecules and helps us understand how they work, Tanner said. This protein is important in cancer prevention because it enables the creation of superoxide, which aid in cell death. Cells arent meant to live forever, and at some point, they need to die and be destroyed. Cells that are damaged or diseased are usually destroyed in this process. Our structure tells us how oxygen gets access to electrons stored in the enzyme. We think we've identified a gate that opens to let oxygen into the enzyme where the electrons are stored.

In this way, proline dehydrogenase is important in preventing cancer. White said its unusual for proline dehydrogenase to be involved in such a process because the usual job of this type of enzyme is to transfer electrons to the mitochondrial membrane, not allow them to be attached to oxygen to create highly reactive superoxides.

Tanner and White said they hope to continue to study proline dehydrogenase and the molecules that can inactivate it. They also plan to examine another protein they suspect works in collaboration with proline dehydrogenase to understand how that protein affects the cancer-preventing abilities of proline dehydrogenase.

Dealing deadly cancers a knockout punch

Thu, 10 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) New scientific evidence is helping to build a compelling case for oncolytic viruses as a first-line and adjunctive treatment for many cancers.

Reovirus, a non-pathogenic virus under development at Calgary, Alberta-based Oncolytics Biotech, has shown powerful anti-cancer activity against cultured tumor cells, in animal models, and in human clinical trials. Oncolytics' proprietary reovirus formulation, Reolysin®, is active against numerous cancers, including intractable sarcomas and melanomas.

Recent studies also indicate that Reolysin works synergistically with standard anti-cancer drugs, providing significantly stronger responses than either agent alone.

In addition, other studies completed in the past year have shown Reolysin has the ability to prime patients' immune systems against their particular cancer, leading to additional cancer cell killing. It is through this second inflammatory mechanism that researchers hope Reolysin will bring about long-term remissions of once-untreatable cancers.

At the Fourth International Conference on Oncolytic Viruses as Cancer Therapeutics in March 2007 in Scottsdale, Arizona, several presentations focused on reovirus efficacy alone or in combination with standard chemotherapies.

In one study, investigators examined the tumor-killing ability of reovirus plus cisplatin, a standard chemotherapy agent, in a mouse melanoma model that included both cultured cells and live animals. The results of the preclinical study showed that the combination of reovirus and cisplatin was significantly more effective than cisplatin or reovirus alone at killing melanoma cancer cells in a mouse model. The investigators intend to explore the mechanism of this promising synergistic action in further detail in future preclinical work.

Another presentation at the Arizona conference reported on the use of Reolysin plus the cancer drug cyclophosphamide in an animal model of melanoma. When treated with both agents, test animals experienced enhanced tumor regression compared with either agent alone, and without additional toxicity. Oncolytics has permission from the U.K. regulatory authorities to test Reolysin in three separate human trials in combination with the cancer drugs gemcitabine, paclitaxel/carboplatin and docetaxel.

Perhaps the most exciting findings of Reolysin combination therapy were reported at the American Association for Cancer Research Annual Meeting in April, 2007. In mice transplanted with a human colon cancer, Reolysin plus gemcitabine completely eradicated the tumors in four of five test animals. It is rare to see the virtual elimination of tumours as well as the long-lasting therapeutic effect that was observed in this study.

Combination therapy results for reovirus in animals are particularly encouraging because they suggest that Reolysin can improve the anti-tumor activity of standard chemotherapy agents in advanced cancer patients without causing additional toxicity, said Dr. Karl Mettinger, Chief Medical Officer of Oncolytics.

Physicians often prefer to treat cancer with multiple agents, but toxicity limits these approaches. Since reovirus typically is not pathogenic in humans nor associated with severe toxicity in clinical studies, its co-administration is not expected to increase a treatment's overall toxicity.

Doctors ill equipped to confront parent smoking

Tue, 01 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) With the growing concerns of childrens exposure to secondhand smoke, it has become more critical than ever to involve health care providers such as pediatricians in educating parents about the potential hazardous health consequences.

Almost 60 percent of U.S. children ages 3 to 11 -- approximately 22 million children --are exposed to secondhand smoke daily with urban children suffering the highest rates of exposure in a U.S. Surgeon General report from June 2006.

However, minimal formal medical training exists regarding how pediatricians can effectively speak to their patients about secondhand smoke-related issues, according to an article in the May issue of The Journal of Pediatrics.

Part of the issue is teaching medical residents (physicians in training) to advise smoking parents at every patient visit. Consider every message as a dose of advice that in the long run could promote lasting changes in parental smoking behavior and childrens exposure, said Brad Collins, Ph.D, the lead author and assistant professor of public health at Temple University.

The Surgeon Generals report also found secondhand smoke causes disease and death in children and nonsmoking adults. Breathing secondhand smoke can be harmful to children's health and can cause or contribute to asthma, Sudden Infant Death Syndrome (SIDS), bronchitis and pneumonia and ear infections.

The developing lungs of young children are severely affected by exposure to secondhand smoke for several reasons including that children are still developing physically, have higher breathing rates than adults, and have little control over their indoor environments.

Previous surveys by Collins team found that over 40 percent of postpartum mothers were either currently smoking or reported smoking late in their pregnancy.

The rates of postpartum smoking we found in North and West Philadelphia are consistent with other, lower income, urban communities across the countryIts alarming when considering the consequences children bear, Collins said.

Such data underscores the importance of programs like Philadelphia FRESH a free health education program from Temple University -- that helps parents create a smoke-free home, and why were interested in learning how to enhance pediatricians role in the overall process in promoting clean home air environments, Collins said.

For The Journal of Pediatrics article, Collins and his co-authors surveyed physician training needs and attitudes towards improving secondhand smoke reduction efforts at a Philadelphia hospital.

Sixty-six residents across all years of training and twenty-seven preceptors (resident supervisors) responded to the survey. Most pediatricians surveyed believed second-hand smoke exposure was a serious health concern for children, but they also believed they were not equipped to help. Almost all respondents (93 percent) reported that they received less than two hours of smoking cessation training during residency.

Survey participants cited key barriers to addressing patients second-hand smoke exposure, including lack of training, time, confidence in their tobacco intervention skills, and knowledge about appropriate tobacco intervention resources.

A recent large scale analysis from the Cochrane Collaboration showed that brief physician advice provided in primary care, hospital wards, and outpatient clinics significantly increased the odds of quitting smoking by approximately 2.5 percent compared to no advice. While the analysis called this a a small effect on cessation rates, a 2.5 percent annual improvement in promoting parental smoking cessation would result in the improved health of tens if not hundreds of thousands of children each year from a public health perspective, Collins said.

Linking brief physician advice and follow-up with more intensive behavioral smoking treatment programs, like Philadelphia FRESH, would improve the impact of physician advice more dramatically, he added.

As a result of this study, the co-authors have made recommendations for tobacco intervention training for pediatric medical residents. These include classroom lecture, strategies for problem-solving with smoking parents, patient education materials, and clinical reminders for guideline adherence.

AACR Annual Meeting showcases significant developments in understanding and targeting cancers

Tue, 10 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) LOS ANGELES -- Data demonstrating genetic differences in individuals susceptibility to certain cancers as well as differences in how people respond to specific cancer treatments will take center stage when more than 17,000 scientists from around the world gather at the Los Angeles Convention Center April 14-18 for the 2007 Annual Meeting of the American Association for Cancer Research (AACR). Key data presented at the meeting will also include findings related to the safety and effectiveness of several new, high-profile cancer therapies and vaccines.

Because of significant diagnostic and therapeutic advances such as personalized and targeted therapies that prolong patients lives, the number of people successfully managing and living with cancer continues to grow, said Geoffrey M. Wahl, Ph.D., President, AACR. By hosting the largest meeting in the world of its kind where the science behind these significant developments is shared and analyzed by researchers at the leading edge of cancer study the AACR promotes clinical exchange with the goal of ensuring research discoveries translate directly into improved patient outcomes.

The theme of this years annual meeting, A Century of Leadership in Science A Future of Cancer Prevention and Cures, commemorates the AACRs Centennial and underscores the remarkable scientific advances that researchers have achieved in the 100 years since the organizations founding, well as the critical importance of ongoing research.

The opening Centennial Ceremony will set an exciting and inspirational tone for a week of science and discovery, with a procession of young researchers bearing flags of all 70 AACR member nations, appearances by the University of Southern California (USC) Marching Band, the All-American Boys Choir and presentation of Centennial Medals and other honors to leading cancer researchers and advocates.

The opening plenary, Translating a Century of Science into a Future of Cancer Prevention and Cures featuring world leaders in the fields of cancer genetics, cellular metabolism, stem cell biology, molecular diagnostics, targeted therapies, early detection and the impact of future cancer science on public health will provide a vantage point for historical and current perspectives across the spectrum of basic and applied cancer science.Late-breaking plenary sessions in basic, translational and clinical cancer research will cover the latest advances from the laboratory and their translational potential to the clinic. Special sessions will also feature phase I and phase II studies of novel therapeutic agents in early-stage clinical trials, as well as the latest phase III clinical trial findings.

This meeting provides an unmatched opportunity to exchange information on current and emerging discoveries, forge new collaborations and identify future opportunities in virtually all areas of modern cancer research and patient care, said Ronald A. DePinho, M.D., scientific chairperson of the 2007 AACR Program Committee. In our Centennial year, this deeply reflects the intent of our founders on a scale that they could scarcely imagine.

AACRs Annual Meeting attracts attendees including leading academic, industry and government scientists, as well as clinical oncologists, students, cancer survivors, advocates and other health care professionals. Such a diverse group facilitates a cross-disciplinary exchange of new ideas and collaborations. This year, more than 6,000 abstracts were submitted for presentation, complementing an outstanding program of scientific and educational events.

Among meeting highlights, the AACR has selected more than 35 scientific abstracts for presentation by their authors in 10 press briefings, each highlighting a critical or emerging area of cancer research. Featured press briefing topics include:

Natural mechanism for immune suppression paves way for cancer trials

Wed, 28 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A natural mechanism pirated by tumors and HIV to evade the immune response is opening the door to better treatment for these conditions, researchers say.

The National Cancer Institute and Iowa biopharmaceutical company NewLink Genetics are pursuing FDA approval to move forward with cancer trials of a drug that inhibits the mechanism, an enzyme called indoleomine 2, 3-dioxegenase, or IDO, says Dr. Andrew Mellor, director of the Immunotherapy Center at the Medical College of Georgia.

He will deliver seminars about the biology and immunology of the mechanism at the Keystone Symposium on The Potent New Anti-Tumor Immunotherapies, in Alberta, Canada, March 28-April 2 and the World Immune Regulation Meeting April 10-16 in Switzerland.

Immune cells, particularly those in the mucosal surfaces of the gut, lungs and eyes, express IDO to mediate inflammation triggered by the constant assault of substances from outside the body.

Now, scientists know cancer in humans and mice also attract cells that express IDO, which degrades tryptophan, an amino acid essential to survival of immune system orchestrators called T-cells. MCG researchers are still exploring how IDO interacts with other cells to amplify immune suppression.

A team of MCG scientists, led by Dr. Mellor and his colleague, MCG pediatric oncologist Dr. David Munn, showed in 1998 that the fetus also expresses IDO to help avoid rejection by the mothers immune system. When they used an orphan drug known to suppress IDO in pregnant laboratory mice, fetuses were rejected.

The findings, published in Science, led the scientists to suspect and later prove that tumors and some viruses, including HIV, express it as well.

Cancers should evoke a response from the immune system and dont, says Dr. Mellor. That is a big question in the immunology field: Why dont they?

IDO appears to be one reason. What (cancers) do, we think, is make a protective cocoon so the immune system does not attack the tumor, so that gives you the therapeutic opportunity. If you stop IDO from blocking the response, you should allow the response, so now the specificity of the immune system is brought to bear directly on tumor cells.

Clinical trials, likely to begin this year, will determine whether a slightly modified version of the orphan drug researchers use in the lab, does just that.

NCI has produced kilogram quantities of the IDO inhibitor compound and contracted with a series of labs to do the studies required before studies can move from the laboratory to humans.

The IDO inhibitor should result and that is why we need to do the trials because we dont know for sure until we do in better immunity directed against cancer cells, Dr. Mellor says.

Investigators already have shown that the IDO inhibitor works synergistically with chemotherapy in animal models of cancer. While chemotherapy knocks out some of the immune systems suppressive pathways, the IDO inhibitor prevents cancer cells from tricking the system into ignoring them again.

Chemotherapy is toxic to cancer cells, but the problem is the cells come back so you dont completely eradicate the tumor. One of the main reasons they come back is the tumor already has established an environment which helps protect it, even after chemotherapy, Dr. Mellor says.

Although the IDO inhibitor will first be studied alone, he believes it will become part of the treatment cocktails that are becoming the standard for cancer care, possibly enabling less toxic doses of other drugs to be used.

Another goal for IDO suppression is to treat chronic infections that induce this mechanism, Dr. Mellor says.

This mechanism is induced by pathogens to protect themselves from host immunity, says Dr. Mellor. HIV certainly is a potent inducer of this mechanism. He suspects other diligent viruses and bacteria are as well.

This is obviously an evolutionary adaptation that the pathogen has to protect it from being eliminated by the host, he says. That is why the infection does not go away. In the case of HIV, we know it persists for decades, and in those decades its slowly eating away at the immune system so that it becomes unable to deal with the infection. That is where AIDS comes from. The current standard of care for HIV patients is to slow that process, that wearing-down process of the immune system.

In 2002, MCG researchers showed that dendritic cells, which present antigens to T cells, express IDO. If they express IDO, its an important control point, Dr. Mellor says of research published in the Sept. 13, 2002 issue of Science.

IDO has been known for decades, he says. What was not known was IDO activity was regulating the adaptive immune response.

Race affects tobacco absorption in children

Mon, 12 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) (NORTHBROOK, IL, MARCH 12, 2007) New research suggests that a child's race may be a factor in determining his/her susceptibility to tobacco toxins associated with environmental tobacco smoke (ETS). The study, published in the March issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP), reveals that African American children with asthma, who are exposed to ETS, have significantly higher toxin levels when compared to their Caucasian counterparts.

African American children suffer from higher rates of tobacco-related disorders, such as asthma, sudden-infant death syndrome, and low birth weight, and we need to know why, said lead author Stephen Wilson MD, University of Cincinnati. So our goal is to understand how certain populationsparticularly those groups who are most susceptiblerespond to ETS exposure.

Dr. Wilson and colleagues from the Cincinnati Children's Hospital Medical Center examined 220 tobacco-exposed children with asthma, who had previously participated in the Cincinnati Asthma Prevention study. Researchers studied a bi-racial, community-based sample (55% African American) of children ranging in ages 5 to 12. All of the children had physician-diagnosed asthma, symptoms consistent with persistent asthma, and were exposed to at least five cigarettes per day in or around the home.

Researchers tested for levels of cotinine, a nicotine metabolite, by collecting serum and hair samples at baseline, 6 months, and 1 year. Serum samples accounted for short-term tobacco exposure and hair samples accounted for long-term tobacco exposure.

Cotinine is a product of nicotine metabolism. When people inhale or ingest nicotine, the body uses proteins to convert it into cotinine, said Dr. Wilson, and, currently, measuring cotinine in various biologic specimens is a widely used method for assessing nonsmokers' exposure to ETS.

Researchers also avoided reporting parental bias by actively measuring levels of tobacco smoke in the home. Each study participant had a nicotine dosimeter placed in his or her home at baseline and at the 6-month visit. These dosimeters were removed at the 6-month and 1-year visits, and were used to objectively measure each child's level of ETS exposure.

No racial differences were reported in levels of ETS exposure outside of the home or in air nicotine levels at the 6-month or 1-year study visits. But, results indicated that while African-American children spent less time exposed to ETS, they showed significantly higher levels of cotinine compared to Caucasian children. On average, serum cotinine levels in the African-American participants were 32 percent higher than in the Caucasian participants, and hair cotinine levels were 4 times that of the Caucasian participants.

Previous studies of adult smokers, as well as cross-sectional studies of nonsmokers have demonstrated similar racial differences in serum cotinine, however, we were surprised at the magnitude of the racial differences in the hair continine, said Dr. Wilson. African-American children may handle environmental tobacco smoke differently than white children, so these results raise questions as to whether there are racial differences in other tobacco toxicants, as well.

Exposure to tobacco smoke is dangerous for everyone, regardless of age or race, said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. These findings underline the importance of eliminating environmental tobacco smoke in every setting, especially those where children are present.

Research strengthens link between smoking, pancreatic cancer

Thu, 08 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Researchers at Michigan State University have added yet another piece to the puzzle that links cigarette smoking with cancer of the pancreas, one of the deadliest forms of cancer.

In research published in the recent issue of the International Journal of Cancer, MSUs James Trosko and colleagues zeroed in on the mechanism by which a healthy cell turns cancerous.

Specifically, they found that the chemicals produced by the burning of tobacco products polycyclic aromatic hydrocarbons, or PAHs interfere with communication between the bodys cells. More importantly, the work showed that some of these chemicals dont necessarily initiate the cancer, but rather contribute to the promotion of it.

These PAH chemicals are related to the multistage, multimechanism process of carcinogenesis, not by mutating the stem cell, but by triggering the stem cell thats been previously mutated to proliferate, said Trosko, a professor of pediatrics and human development. This finding has major implications, including the possibility that dietary intervention might interrupt or even reverse the promotion of pancreatic cancers.

Until now, most scientists thought that specific PAHs produced by burning tobacco mutated genes which, in turn, triggered the cancer mechanism.

We take issue with this interpretation, Trosko said. We dont believe that the PAH chemicals cause mutations which then lead to cancer.

Pancreatic cancer is one of the more deadly forms of cancer, with an average survival rate of only about a year. Its projected that more than 37,000 Americans will be diagnosed with pancreatic cancer in 2007.

Trosko noted that PAHs are formed when any substance containing certain proteins is burned, including foods.

PAHs are all over, he said. When you grill a steak or a hamburger, for example, you get exactly the same class of chemicals.

This research is the culmination of nearly 30 years of work in Troskos lab. It was in 1979 that Trosko, colleagues and students demonstrated that tumor-promoting chemicals interfered with a cells ability to communicate with other cells. Later, this group isolated adult human pancreatic stem cells from human pancreatic tissue.

Subsequent published findings indicated that these stem cells appeared to be targets for cancer.

Since we had the system here in our lab, we decided to see if PAHs would act as a tumor promoter, he said. And sure enough they did.

The good news is that people who quit smoking can dramatically improve their chances of avoiding cancers.

If these chemicals act like cancer promoters and not initiators, Trosko said, then quitting smoking can assist in interrupting the process.

Chemo combination improves survival in asbestos-related cancer

Thu, 08 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) People with mesothelioma a form of cancer associated with asbestos exposure have a higher survival rate when treated with a combination of two cancer drugs, a large multicenter study finds.

Mesothelioma, a rare but aggressive form of cancer that occurs in the lining of the lungs, heart and abdomen, is associated with exposure to asbestos. There is no known cure.

In the study, patients receiving pemetrexed and cisplatin along with the vitamin supplements folic acid and B12 survived nearly three months longer than patients getting cisplatin alone.

Researchers led by John Green, M.D., at the Clatterbridge Center for Oncology in England, reviewed a study of 448 patients with advanced mesothelioma who were treated with either the single drug or the combination.

Pemetrexed used in combination with cisplatin significantly increases the length of survival, when compared with cisplatin alone, the researchers say. Further research is needed into the optimum treatment regimen for pleural mesothelioma.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The researchers examined data from a clinical trial of 20 treatment centers in Europe, the Americas, Australia and Asia. Eighty-one percent of the patients were men, with an average age of 61. Patients who received the combination treatment survived an average 2.8 months longer.

Patients receiving both medications also reported improved quality of life in terms of fatigue, loss of appetite, pain and cough.

During the early stages of the trial, patients receiving pemetrexed had serious symptoms of toxicity, including drug-related death. Other side effects included blood cell abnormalities, nausea and diarrhea, which decreased in both incidence and severity after the vitamins were added to the treatment.People who work trades such as shipbuilding, railway engineering, construction work and asbestos manufacture have higher rates of mesothelioma than the general public. The cancer may take 10 to 60 years to develop, and the risk does not diminish after exposure to asbestos has stopped. Family members of people exposed to asbestos at work also have an increased risk of developing mesothelioma from asbestos fibers carried home on the clothes of the people they live with.

Daniel Baram, M.D., a pulmonologist at the Lung Cancer Evaluation Center at the State University of New York, said, Most cases [of mesothelioma] are still from pre-OSHA workplace improvements. I suspect that modern asbestos abatement precautions will avoid most, if not all, future cases. The latency is over 30 years, so we are still diagnosing cases with exposure during World War II and the '40s and '50s.

Mesothelioma is difficult to diagnose, Green said, because there is a lag of many years between exposure and asbestosis, which is a nonmalignant condition, and a greater lag before the development of overt malignancy.

There is no way of diagnosing the premalignant phase during the latent period of 15 to 20 years, Green added. Many of these patients smoke and are in economically disadvantaged communities. Many individuals have moved away from heavy industries and may not admit or know they were exposed to asbestos as young men, with similar issues for their partners.

According to the U.S. Environmental Protection Agency, 10 percent to 15 percent of schools and other public buildings in the United States contain asbestos insulation.

Although safety measures for working with asbestos have been in place since the 1970s, mesothelioma is projected to account for 65,000 deaths between 2001 and 2050 worldwide, peaking between 2012 and 2015, according to background information in the review.

It is a personal matter as to whether the survival increase for patients receiving the two drugs is worthwhile, Baram said. It depends in large part on the patient. A 2.8-month mean survival increase means that some patients may get even more than that, though some people will get less. Many, if not most, patients when faced with a disease with a very bad prognosis are often willing to undergo aggressive therapy, although the toxicity is serious and potentially life-threatening.

Do cigarette warning labels work -- results from 4 countries

Tue, 06 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) As the second leading cause of death in the world, cigarette smoking is a preventable behavior. Most countries require warnings about health risks on every package, but the effectiveness of these warnings depends upon the design and the freshness of the messages. In a multi-country study published in the March 2007 issue of the American Journal of Preventive Medicine, researchers found that more prominent text messages were more effective and graphic pictures even more so in affecting smokers' behaviors. Recent changes in health warnings were also associated with increased effectiveness, while health warnings on US packages, which were last updated in 1984, were associated with the least effectiveness.

The authors analyzed data from four waves of surveys taken during 2002-2005 of adult smokers in Canada, the United States, the United Kingdom and Australia. Almost 15,000 smokers were surveyed on their awareness of the messages, any changes in understanding of the risk of smoking, their intention or motivation to quit and any behavioral changes they had noticed in themselves.

The International Tobacco Control (ITC) Four Country Survey collected the responses from the same smokers, approximately 2 months before new UK warnings were implemented, and then at 6, 18 and 32 months after implementation. Warnings on the packages ranged from graphic pictures covering half the package in Canada to small text warnings on the side of packages in the US. The first international treaty devoted to public health, the Framework Convention on Tobacco Control (FCTC), has mandated large, clear, visible and legible warnings that cover at least 30 per cent of the surface. Canada currently meets this guideline, although most countries fall short. Thus, the current study evaluated warnings that were: (1) well below the minimum FCTC standard (US and UK at baseline); (2) slightly below the FCTC minimum (Australian warnings), (3) enhanced to the FCTC standard (UK at follow-up), and (4) at the recommended FCTC standard (Canada).

Writing in the article, David Hammond, PhD, states, This study suggests that more prominent health warnings are associated with greater levels of awareness and perceived effectiveness among smokers. In particular, the findings provide strong support for the effectiveness of new health warnings implemented on UK packages that were enhanced to meet the minimum international standards...UK smokers were also more likely to report that the new warnings had led them to think about quitting, to think about the health risks of smoking, and had deterred them from having a cigarette compared to Australian and US smokers. Although the findings provide strong support for the effectiveness of prominent text warnings that meet the minimum international standards, the findings also suggest that larger pictorial warnings may have an even greater impact: data collected two and a half years after the implementation of the Canadian pictorial warnings and two and a half years after the implementation of the new UK warnings indicate that the Canadian warnings had impact levels at or above the UK warnings for each of the measures examined in the survey.

Simple diagnostic test detects genetic signs of lung cancer in a patient's sputum

Thu, 18 Jan 2007 04:59:37 PST

( from http://www.rxpgnews.com ) PHILADELPHIA -- DNA coughed up along with phlegm could point to lung cancer, say researchers at the University of Maryland School of Medicine who are developing an inexpensive and non-invasive gene probe to help diagnose early stage lung cancer in current and former smokers.

In the January 15 issue of Clinical Cancer Research, the researchers report that their fledgling test, designed to check whether two genes believed to be tumor suppressors are deleted in cells found in sputum, identified 76 percent of stage I lung cancer patients whose tumors also showed the same genetic loss. Existing sputum cytology tests, which look for changes in cell structure, identified only 47 percent of the patients, they say.

While no other simple sputum analysis has found such a high correlation with lung cancer, it is not yet good enough for the clinic, researchers say, and so they are now expanding their test to screen for up to eight genes.

There is an urgent need to develop reliable early diagnostic biomarkers for lung cancer that can be detected non-invasively, and these two genes look to be great candidate markers for such a test, said Feng Jiang, M.D., Ph.D., assistant professor of pathology at the University of Maryland School of Medicine. We need to validate our findings, of course, but we have shown that the genetic aberrations seen in sputum reflect the same genetic aberrations found in lung tumors, and that these molecular changes occur before any morphological changes can be seen in a cytology test.

Sputum cytology is still used in some clinics, but has largely been found to be insensitive, Jiang said. For that reason, he and his collaborators have been working for years on a simple, effective way to detect changes in the genes of cells in the bronchial airway that signify early cancer is developing somewhere in the lung system. Many cells within the airway exhibit a similar pattern of genetic abnormalities that leads to lung cancer development, the researchers say, but the challenge is to find altered genes that are only predictive of cancer, and not just of general cellular damage from smoking.

Most heavy smokers never develop lung cancer, even though cells in their airways show genetic damage, Jiang said. The trick is to find the genes that are only cancer related.

The research group had previously identified a set of genes that were deleted in lung cancer tumors, and in this study, they tested three of them (HYAL2, FHIT, and SFTPC) in sputum samples taken from 38 patients with stage 1 non-small cell lung cancer, 36 cancer-free smokers and 28 healthy nonsmokers.

Given that sputum contains expectorated airway cells, the researchers asked each of the participants to cough into a cup first thing in the morning for three days. Investigators then examined the sputum with both traditional cytology and with fluorescent in situ hybridization (FISH). The FISH technique uses fluorescently labeled single-strand DNA probes to bind to the complementary strand of a specific gene. The presence, or absence, of a fluorescent signal produced when the strands bind can be detected and scored with use of a special microscope.

As a diagnostic tool to identify early stage lung cancer patients who would then benefit most from curative therapies, FISH is very cheap and convenient, Jiang said. The technique may be also useful in monitoring lung cancer patients for response to treatment, disease progression and early evidence of relapse in the future.

They found that FISH could not detect deletions in the SFTPC gene in sputum, although it was absent in 71 percent of tumors. But the loss of HYAL2 and FHIT in a patient's tumor could be detected in that person's sputum. The investigators specifically found that HYAL2 and FHIT were deleted in 84 percent and 79 percent of tumors and in 45 percent and 40 percent of matched sputum, respectively. Combining both HYAL2 and FHIT deletions increased sensitivity to 76 percent (compared to 46 percent for cytology tests) and the combined probe had a specificity of 92 percent.

The false positive rate of about eight percent occurred because HYAL2 was found in sputum of four cancer-free smokers and FHIT deletions was found in three cancer-free smokers. However, the deletions were not found in the sputum of healthy non-smokers. Those deletions in cancer-free smokers could represent an early indication that lung cancer is developing that has not yet been detected, but we won't know that without longer follow-up study, Jiang said.

Doubts cast on organophosphate poisoning as cause of Gulf War Syndrome depression

Wed, 20 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Research published in the Journal of Epidemiology and Community Health casts doubt on the belief that organophosphate poisoning causes symptoms of depression among Gulf War veterans and farmers, who are exposed regularly to these chemicals.

Several previous studies have found that people who are regularly exposed to organophosphates are more likely than the general population to have symptoms of depression, including irritability, difficulty concentrating and poor sleep patterns.

But these studies do not prove that organophosphates are responsible for these symptoms.

In a bid to look at the association more closely, researchers from the University of Bristol tested out the theory among older women between the ages of 60 and 79, who would not have been habitually exposed to organophosphates in the course of their employment.

The women were already part of a long term study of women's health, involving more than 4,000 participants from 23 British towns.

They were surveyed about their levels of depression, and blood samples were taken for genetic testing.

Because an individual's genetic make-up (genotype) is randomly determined from their parents' genotype at the time of conception, genes can be used to test whether a non-genetic factor (for example, organophosphates) causes a disease.

The PON1 Q192R gene comes in three versions (QQ, QR or RR) and individuals with the RR version tend to metabolise organophosphates more slowly than those with either of the other versions.

Several previous studies have shown that Gulf War Veterans and sheep dippers with the RR genotype had a higher probability of symptoms.

In agreement with this, the results from the new study found that women in the study with the genetic variant were significantly more likely to report depression than those without the variant.

But because these women had not been exposed to organophosphates, these new findings suggest that the association of this gene with depressive symptoms is unlikely to be explained by organophosphate poisoning, because the association is the same, irrespective of exposure to organophosphates.

In fact, the authors suggest that exposure to more mundane everyday toxins or activities, rather than the specific chemical hazards found in warfare and farming, are likely to have a role.

The authors also note that recent research has suggested that rather than slowing the capacity to clear organophosphates from the body, the genetic variant actually does the opposite and speeds it up, so minimising exposure.

The authors point out that their findings do not negate the biological basis theory of the Gulf War Syndrome, but suggest that reliance on genetic vulnerability studies in specific groups is 'perhaps misplaced.'

Diet can provide protection against development of certain cancers, new studies show

Tue, 14 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) BOSTON -- With cancer, researchers don't believe you are what you eat; that disease is always a direct result of what is, or what isn't, on your dinner plate. But studies into the association between diet and cancer show that food can have an impact in preventing cancer, or in reducing the aggressiveness of the disease. At the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, investigators have found that eating fish regularly as an adult, or soy as a young girl, or using a specific vitamin if you are a smoker, can help to protect against development of certain cancers. Another study found that blood cholesterol, some of which comes from eating animal fats, doesn't control whether a man develops prostate cancer, but lower levels of these lipids may help protect against aggressive forms of the disease. The researchers say these studies provide some of the strongest links found to date between diet and cancer.

Childhood soy intake and breast cancer risk in Asian-American women

In a novel study of Asian-American women, a team of researchers led by National Cancer Institute (NCI) investigators has found that consuming soy during childhood, adolescence and adult life were each associated with a decreased risk of breast cancer, but that the strongest and most consistent effect was seen for childhood intake.

They found that women who ate the most soy-based foods (such as tofu, miso, natto) during ages 5-11 reduced their risk of developing breast cancer by 58 percent, compared to women who ate the least amount. The corresponding reductions for adolescent and adult intake were about 25 percent.

Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical, said the study's lead investigator, Larissa Korde, M.D., MPH, a staff clinician at the NCI's Clinical Genetics Branch, in the Division of Cancer Epidemiology and Prevention. Korde worked in collaboration with epidemiologists at the University of Hawaii, the Northern California Cancer Center, and the University of Southern California.

The underlying mechanism is not known. However, Korde said that one hypothesis for the decreased risk associated with childhood intake is that soy isoflavones have estrogenic effects that cause changes in breast tissue, leading to decreased sensitivity to carcinogens. A similar protective effect has been found in studies of overweight girls, perhaps because fat tissue also secretes estrogens, she added.

Hormonal exposures in adulthood, such as use of estrogen and progesterone replacement therapy, are established breast cancer risk factors. However, a growing body of evidence suggests that hormonally related exposures early in life may also modify susceptibility to breast cancer, Korde said.

Studies investigating adult soy intake and breast cancer risk have had mixed results, but the two studies that looked at adolescent consumption found that the risks of developing breast cancer later in life were cut in half. This study is the first to address the relationship between soy consumption during childhood and future risk of breast cancer.

As provocative as the findings are, the senior investigator on the study, Regina Ziegler, Ph.D, MPH, cautioned that it would be premature to recommend changes in childhood diet. This is the first study to evaluate childhood soy intake and subsequent breast cancer risk, and this one result is not enough for a public health recommendation, she said. The findings need to be replicated through additional research.

The researchers conducted a case-control study of women of Chinese, Japanese and Filipino descent who were living in the San Francisco Bay area, Los Angeles, or Oahu, Hawaii. Included were 597 Asian-American women with breast cancer and 966 women without the disease, who answered questions about their adult and adolescent diet and lifestyle. In addition, for a subset of 255 participants whose mothers were alive and living in the US, the mothers were asked about their daughter's early childhood exposures.

Soy intake was then divided into thirds, based on frequency of consumption, and by comparing the highest category to the lowest, the researchers found an inverse association between the risk of developing breast cancer and the amount of soy consumed. The childhood relationship held in all three races and all three study sites, and in women with and without a family history of breast cancer. Since the effects of childhood soy could not be explained by other measures of Asian lifestyle during childhood or adult life, researchers concluded that early soy intake might itself be protective.

A prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men

Men who ate fish five times a week or more had a 40 percent lower risk of developing colorectal cancer compared to men who ate fish less than once a week, according to a new analysis of data from 22,071 participants in the Physicians' Health Study (PHS).

The researchers say the reduction in colorectal cancer risk is substantial in comparison to other dietary components, and while they don't suggest that everyone starts eating fish daily simply because of these results, they say the health benefits of fish consumption have already been proven.

We already know that eating fish can reduce the risk of sudden cardiac death, and this might provide another reason to add fish to your diet, said Megan Phillips, a doctoral student at the Harvard School of Public Health and the lead author of this study.

The researchers believe the health effects of fish consumption in relation to colorectal cancer may lie in their content of the n-3 fatty acids that can inhibit the cyclooxygenase-2 (COX-2) enzyme. This enzyme acts as a mediator of inflammatory responses thought to be associated with cancer development.

The PHS was designed as a randomized, double blind, placebo-controlled clinical trial to examine the effect of aspirin and beta-carotene supplements on development of cancer and cardiovascular disease, and the participants filled out a one-time food questionnaire 12 months after starting the study. In this analysis, investigators were also trying to determine if fish consumption had a different effect on men who received aspirin for five years compared to men who weren't randomized to use aspirin, which is also a COX-2 inhibitor. We thought that maybe for men who received aspirin, it wouldn't matter whether they ate fish or not, Phillips said.

The researchers looked at four different categories of fish consumed- tuna fish, dark meat fish (salmon, sardines, bluefish, etc.), a general fish category, and shellfish including shrimp, lobster and scallops- and asked how many times the participants ate them on average during the previous year. They found almost 10 percent ate fish less than once a week, 31 percent ate it less than two times a week, 48 percent ate fish less than five times a week, and about 11 percent ate it five times or more a week. They then compared these figures with incidence of colorectal cancer that later developed in the men. (The average follow-up was 19.4 years).

They found that compared to men who ate the least amount of fish, the risk of developing colorectal cancer was 40 percent lower in men who ate the most fish, was 20 percent lower in men who ate fish 2-5 times a week, and 13 percent lower among participants who ate fish less than two times a week.

The relationship between fish consumption and colorectal cancer was similar for men randomized to aspirin and those who weren't, possibly because the researchers only had information on aspirin use during the first five years in the trial, and it may take more years of aspirin use to see an effect, Phillips said.

While she said the results are promising, Phillips also noted that they are based on the assumptions that the pattern of fish consumption observed in the sole food questionnaire represented a diet that the men subsequently followed for many years.

In addition, men who consumed more fish may also have a healthier lifestyle perhaps including better cancer screening. Although this study controlled for some of these factors such as cigarette smoking, vigorous exercise, and multivitamin use, the investigators do not have information on colorectal endoscopies. Thus, these findings need additional confirmation through other prospective studies with more complete information and a definitive answer might require a randomized trial, said senior author Jing Ma, M.D., Ph.D., a researcher at the Brigham and Women's Hospital-based Channing Laboratory and associate professor of medicine at Harvard Medical School.

The relationship between dietary antioxidants and oxidative damage in smokers: evidence of effect modification by lifestyle and genetic factors

Vitamin E in the diet of male smokers appears to protect against oxidative damage that can lead to cancer development, according to researchers from Columbia University's Mailman School of Public Health working with investigators from the NYU School of Medicine.

They found that male smokers who had high plasma levels of vitamin E had lower levels of oxidative-DNA damage in their white blood cells. Oxidative DNA damage is a mechanism by which tobacco smoking can increase risk of cancer. In addition, the protective effect of vitamin E was greatest among the men with a beneficial form of a common detoxifying gene, GSTM1. The investigators did not find a similar effect of vitamin E in women.

There was a dose-response relationship, in that the more vitamin E we found in the blood of the men, the less there was of this cancer-related biomarker, said the study's senior investigator, Frederica P. Perera, Dr.P.H., Professor in the Division of Environmental Health Sciences at the Columbia University School of Public Health.

This suggests that while working toward the goal of quitting smoking, which is the very best way to prevent development of smoking-related cancers, it could be helpful to eat a diet rich in vitamin E, she said, and added, we don't yet know why this relationship was not found in women, but a good diet is beneficial to health in many ways.

The most active form of vitamin E (known as alpha-tocopherol) is believed to be a strong antioxidant, capable of preventing oxidative chemical reactions that damage DNA. The vitamin is found in certain vegetable oils, nuts, whole grains, fish, green leafy vegetables and other foods. Studies that have examined the ability of vitamin E to protect against cancer have shown mixed results, however.

The present study is unusual, the researchers say, because it measured two different markers in white blood cells drawn from 280 participants - people who smoked at least 10 cigarettes a day. These markers were the amount of vitamin E in blood derived from food (those who used vitamins were excluded from this study) and the quantity of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a measure of oxidative damage to DNA.

The researchers found a protective effect of plasma alpha-tocopherol on oxidative damage among smokers, but only among men. They next looked at the interaction between vitamin E and GSTM1, a gene variant known to produce enzymes that efficiently detoxify carcinogens in tobacco smoke, and found a greater effect of the vitamin among men with this gene.

We all want to know if vitamins help protect us against disease, and measuring their effects in the blood using markers of cellular damage is the most direct way to do that, said Perera. But we have a lot of work ahead before we can fully understand the role of antioxidants in the chemoprevention of tobacco-related cancer.

Association between plasma cholesterol and prostate cancer

Prostate cancer patients who had lower levels of cholesterol in their blood had a significantly reduced chance of developing more aggressive forms of the disease, compared to patients with higher cholesterol readings.

These findings may help explain the earlier discovery, reported by the same team of researchers at the AACR annual meeting in 2005, that men who used statin drugs experienced half the risk of developing advanced prostate cancer.

Statin drugs reduce cholesterol in the blood, but they also influence a number of different pathways, said the study's lead researcher, Elizabeth Platz, ScD, MPH, an associate professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. This study suggests that the ability of statins to lower cholesterol may be important to prostate carcinogenesis, but we are continuing to examine other pathways with which statin drugs interact, such as reduction of inflammation.

The researchers looked at cholesterol levels first because cholesterol affects cell signaling and survival. Some scientists theorize that a large quantity of cholesterol in the blood could stimulate the survival of abnormal prostate cells.

They studied blood drawn from 698 men before they were diagnosed with prostate cancer and matched it to blood taken from 698 men who had not been diagnosed with the disease. All of the men participated in Harvard University's Health Professionals Follow-up Study, a group of 18,018 participants who provided a blood sample between 1993 and 1995.

They found that mean cholesterol levels did not differ between the men with prostate cancer and the control participants, suggesting that cholesterol was not involved in the initial development of prostate cancer, Platz said.

But when comparing men who had the lowest quartile of serum cholesterol to men who had the highest, they found that prostate cancer patients with lower cholesterol had the lowest risk of developing a more worrisome form of the disease. They specifically found that the risk of being diagnosed with high-grade or advanced cancer was reduced by 40 percent and 50 percent, respectively.

Platz says it is not clear at what levels serum cholesterol may stimulate the abnormal growth seen in cancer development. The findings suggest either that high cholesterol may push existing prostate cancer to become aggressive, or, alternatively, very low levels of cholesterol may provide protection against development of an aggressive cancer, she said. We just don't know which it is at this point.

She also said that because the findings come from an observational study, not a trial, it is impossible to conclude that men can lower their risk of developing an aggressive form of prostate cancer by reducing their intake of saturated fat, the type of fat that increases serum cholesterol, which some studies have linked to an increased risk of advanced prostate cancer.

It is too soon to say that such measures would be specifically beneficial to lowering such a risk, but for good health in general, it is prudent to consume a diet that contains healthful fats that do not increase serum cholesterol, she said.

Genes offer researchers a 'crystal ball' to help them prevent, diagnose and treat cancer

Sun, 12 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) BOSTON -- The science of cancer prevention has advanced to the point where researchers now say they can detect cancer genes in the breath of smokers, and can test the presence of two proteins in men they say will predict development of prostate cancer a decade in advance. All of these novel findings need much more examination, of course, but scientists at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, say these examples illustrate how it is becoming increasingly possible to use genes and their protein products to help predict and diagnose cancer, as well as choose therapy that offers the most potential for a good result. These researchers will also discuss a test that can pick out patients who have pancreatic cancer - an advance that offers hope the disease can be treated at earlier stages than it is now - and how several unique genes can predict which prostate cancer or lung cancer patients will develop aggressive tumors that need additional treatment. Cancer is a disease of genes, they say, so genes can be employed as a crystal ball to thwart the disease.

Lung carcinogenesis tracked by DNA methylation mapping in exhaled breath

For the first time, researchers have demonstrated that it is possible to detect DNA methylation in the breath of smokers and lung cancer patients, suggesting that, in theory, it may be possible to use this technique to identify people who have undiagnosed lung cancer or are at high risk of developing the disease.

Investigators at the Wadsworth Center, the public health laboratory of the New York State Department of Health, have been able to develop an assay that simultaneously detects the presence of methylation in six tumor suppressor genes - a process by which a gene is chemically silenced. The assay examines the promoter region of a gene, where certain cytosine nucleotide bases may be methylated, preventing the gene from being expressed.

The seven participants tested so far breathe for ten minutes into a commercially available handheld device, which cools the air, forming a condensed vapor, to which the methylation assay is applied. Investigators found it could detect the presence of the methylated form in all six tumor suppressor genes. For RASSF1A, the test was negative in non-smokers, and positive in both current and ex-smokers. For DAPK, methylation was more variable, given smoking status. The four other tested genes (p16, MGMT, PAX5B,CDH1) known to be methylated in various stages of lung cancer development, were minimally or not methylated, in this pilot study of predominantly cancer-free smokers.

Dr. Weiguo Han and I have shown that this approach is technically feasible, and if further research demonstrates the assay can measure DNA in such a way that it diagnoses or predicts lung cancer, this could be important for non-invasive lung cancer testing, said the study's lead author, Simon D. Spivack, M.D., M.P.H., a research physician at the Wadsworth Center, and a specialist in lung diseases. But we are a long way from that point. Han, a post-doctoral fellow in Spivacks' laboratory and the study's first author, will be presenting the findings.

Spivack said his study was only the third to date that proved DNA could be tested in condensed breath - German researchers reported the first such result in 2003, followed by an Italian group in 2005 - and the first to find methylation-silenced tumor suppressor genes in the breath of patients at risk or harboring lung cancer.

The concept of testing exhaled breath is not new - that's what breathalyzers do when they measure small volatile molecules such as alcohol, as well as inflammation molecules that are currently being assayed to test the activity of asthma and other lung diseases, said Spivack. But what is rather remarkable here is that DNA can be tested in the air that comes from the lungs and airways, and that it might be possible to use this in diagnosis of lung cancer in particular, and gene-dysregulation disorders of the lung, in general.

The DNA is believed to be released when cells turn over, or are damaged, in the lungs and airways, he said. Although it is not possible to say at this point the precise anatomic origin of the airway-derived DNA being tested, it may be that different patterns of gene methylation will themselves actually map the origin of this DNA to particular regions of the airway, Spivack said.

Our goal is early detection of lung cancer and risk stratification, he said. If all we can do is confirm that a smoker is smoking, or that a lung cancer patient has cancer, then this test will be meaningless. But we now know it is technically feasible to measure DNA methylation in breath.

Multiplexed serum markers screening for detection of pancreatic cancer

A panel of 10 blood biomarkers performed almost perfectly in picking out people who had pancreatic cancer from those who didn't, according to researchers at the University of Pittsburgh. The advance raises hopes that a test can be developed to screen for the aggressive cancer in time to treat it, they say.

Early detection of pancreatic cancer is crucial to survival, but there has been no way to diagnose it early before symptoms occur, said the lead investigator, Anna E. Lokshin, Ph.D., an associate professor of medicine and pathology at the University of Pittsburgh School of Medicine. This assay represents a new way to screen for disease that appears to be applicable to pancreatic cancer, and potentially, to other cancer types.

The assay contains the largest panel of blood-based biomarkers to be examined simultaneously in pancreatic cancer. It consists of proteins known to be secreted by pancreatic tumors as well as proteins that represent the body's response to that tumor growth, Lokshin said.

Tumors are located in the context of certain tissues, and those tissues react in their own individual ways to the cancer, she said. For example, tissue-specific proteins try to fight the cancer, and each tumor type grows blood vessels in tissue uniquely, so we believe the body responds differently to each kind of cancer.

The researchers initially evaluated a panel of 44 protein biomarkers, including cytokines, chemokines, adhesion molecules and hormones, and used blood from 100 pancreatic cancer patients and a control group of 400 healthy people to find those associated with the cancer. They used a microbead array, which can sample up to 100 different proteins simultaneously, and found 10 biomarkers that offered the highest diagnostic power, Lokshin said. Two of those biomarkers are CA125, which can detect a number of cancers but which is not very specific, and CA19-9, which has been known to correlate weakly with pancreatic cancer.

They found that this panel of markers correctly identified pancreatic cancers 97 percent of the time, with a sensitivity of 95 percent (meaning it could correctly identify cancerous lesions) and with a 98 percent specificity (the ability to detect truly negative cases).

The researchers are continuing to study, validate, and perfect the assay, and test its ability to identify pancreatic cancer at early, treatable stages. Although pancreatic cancer is relatively rare, survival is poor compared to most other forms of cancer - it is the fourth leading cause of cancer-related deaths in males and the fifth-leading cause of cancer-related deaths in females.

A diagnostic screen for pancreatic cancer would likely first be used in smokers, because use of tobacco is a known risk factor for developing pancreatic cancer, Lokshin said.

The researchers also are developing similar assays for ovarian, breast, lung, endometrial, head and neck, and esophageal cancers. So far, every panel is different for each cancer to the point where we can say with greater than 97 percent certainty which cancer it is, she said.

Surprisingly, although in theory body response could be similar for several cancers, in practice it is very different.

TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion

The presence of a gene fusion in prostate tumors is significantly associated with aggressive cancer, metastatic spread, and an increased probability of death, a team of researchers is reporting.

They say that the new gene, formed by the fusion of TMPRSS2 and ERG, may serve as a biomarker to separate patients who might benefit from radical prostate cancer therapy from those who potentially need little, if any, treatment.

We believe this gene has the potential to be used as a diagnostic and prognostic test, which could offer thousands of patients peace of mind and spare them from unnecessary surgery and therapy, said the study's lead author, Sven Perner, M.D.,, a postdoctoral fellow in the Department of Pathology at Harvard University's Brigham and Women's Hospital in Boston. He worked with researchers from the Universities of California and Michigan, Johns Hopkins University and McGill University in Montreal.

Perner and his colleagues reported the discovery of the fused gene last year and they now say that TMPRSS2-ERG occurs in about 50 percent of prostate cancers - making it the most common genetic aberration in human cancer, and the first one found in a common solid cancer. Fused genes and chromosomal rearrangements have been found in several blood cancers, such as chronic myelogenous leukemia (CML) and in soft tissue tumors, such as Ewing's sarcoma, but these diseases are rare compared to prostate cancer, which is one of the leading cancers among American men.

In this study, the researchers sought to learn whether TMPRSS2-ERG is associated with a particular prostate cancer stage, and how it might be contributing to development of the cancer. They gathered 406 prostate tissue samples, representing a range of benign, precursor, and malignant prostate lesions, and used a FISH analysis to look for TMPRSS2-ERG. They didn't find any evidence of the fused gene in non-cancerous samples, but found it was present in 48.5 percent of localized prostate cancer tumors, 30 percent of hormone-naïve metastases, and in 33 percent of hormone refractory metastasis, as well as in about 20 percent of prostatic intraepithelial neoplasias, a lesion believed to be precursor of invasive prostate cancer.

The investigators also discovered that the gene fusion could occur in two different ways. The genes, TMPRSS2, which is regulated by the male sex-hormone androgen, and ERG, which is a potential oncogene, are located close to one another on chromosome 21. When fused, TMPRSS2 drives over-expression of the ERG gene. According to Perner, fusion can occur when the piece of DNA separating the genes breaks off and the genes merge (a process described as fusion through deletion), or if parts of each gene break off and switch positions (translocation).

They found that TMPRSS2-ERG fusion through deletion was more common in the tumor samples as compared to TMPRSS2-ERG fusion through translocation. More recent work has found a significant association between TMPRSS2-ERG fusion and death from prostate cancer, although the researchers have not yet been able to determine which fusion form predicted the highest risk of death.

Perner says investigators are hoping to find a small molecule to inhibit the TMPRSS2-ERG fusion protein in the same way that the drug Gleevec has revolutionized care of CML.

Prediagnostic interleukin-6, C-reactive protein and prostate cancer incidence and mortality

Increased levels of two markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), are significantly associated with prostate cancer incidence and mortality almost a decade prior to diagnosis, say researchers at the Harvard School of Public Health.

They also found that elevated CRP in these men was associated with a two-fold increased risk of developing fatal prostate cancer, compared to men with the lowest levels of the protein.

The results of this study provide further evidence that inflammation is involved in development and progression of prostate cancer, said the study's lead author, Jennifer Rider Stark, a graduate student in epidemiology.

Stark said that IL-6 and CRP were more strongly associated with prostate cancer risk and death from prostate cancer in normal weight men. Because IL-6 is secreted from adipose (fat) tissue, levels of the cytokine are naturally higher in overweight or obese men. It is possible that high levels of IL-6 and CRP in men with a healthy body weight may be more indicative of a pro-inflammatory environment in the prostate, she said.

Some studies have already shown that high levels of IL-6 and CRP can be associated with a poor prognosis in prostate cancer patients, but this is one of only a few studies to examine whether these markers can predict risk before symptoms develop and cancer is diagnosed.

The findings come from a prospective study nested within the Physician's Health Study, and included 516 men who later developed prostate cancer and 516 matched controls who did not. The researchers examined blood taken from each participant early in the study - a median of 9.4 years before prostate cancer was diagnosed in the cases. Levels of IL-6 and CRP were compared among men who did and did not go on to develop cancer. Long-term follow-up of the cases also allowed the researchers to assess the effect of these markers on prostate cancer mortality.

They found that high levels of CRP in the blood was associated with a higher incidence of prostate cancer development among all patients and associated with a two-fold increased risk of developing lethal prostate cancer. IL-6 levels were not associated with prostate cancer risk overall. But when they separated out men by body mass index, those who had a healthy weight and high IL-6 in their blood had a 40 percent higher risk of developing prostate cancer.

Researchers suspect that abnormal amounts of IL-6 and CRP are markers of biological processes involved in development of a number of diseases, including cancer. IL-6 is secreted by immune cells in response to infection or trauma, and it, in turn, stimulates synthesis of CRP in the liver, which is believed to play a role in response to infections and cellular damage control. CRP has been found to be a marker of cardiovascular disease, diabetes and colon cancer, but its use as a cardiology screening test has been controversial.

Stark noted that the predictive power of these two markers for determining prostate cancer risk and mortality needs to be confirmed in other prospective studies. She added, Understanding the role of inflammation in prostate cancer is important because inflammatory pathways could potentially be targeted for prevention and treatment.

Characteristics of long-term lung cancer survivors

In preliminary findings from an ongoing study, researchers at Mayo Clinic have identified four different factors they say predicts long-term survival in patients diagnosed with lung cancer, and one of the strongest is inheritance of a gene variant, GSTM1 positive, which is more efficient than another allele type of the GSTM1 gene at detoxifying carcinogens.

They found that patients with a null type at this gene were four times more likely to die within two years as were matched patients who had the positive variant.

The researchers also found that patients who had surgery, who were active, and whose cancer did not come back or progress were much more likely to survive five years or longer.

Outcome varies among lung cancer patients, even within groups that have the same stage at the time of diagnosis, and so it is difficult to know how aggressively to treat and provide follow-up care for individual patients, said the study's lead investigator, Ping Yang, M.D., Ph.D., a clinical and genetic epidemiologist at Mayo Clinic.

In order to enhance both survival and quality of life, we are trying to establish a model that will identify patients who would benefit from additional clinical intervention, and the data we have accumulated to date could be enormously helpful, she said.

To derive these predictive factors, the researchers aim to compare 400 lung-cancer patients treated at Mayo Clinic and who have survived five or more years, with 400 patients who lived less than two years after treatment. The researchers match the groups by age at diagnosis, gender, tumor cell type, cancer stage and the number of primary lung cancers, and they examine blood samples and follow the progress of the patients' disease as well as their quality of life.

In an interim analysis of data on 150 patients in each group, the researchers specifically found that patients who experienced any progression or recurrence of their cancer were almost three times more likely to die within two years, compared to patients of the same cancer stage whose disease did not progress or return.

They also concluded that lung cancer patients who had surgery were three times as likely to have longer survival as matched patients who did not have surgery. This can be very useful information for patients who are undecided about whether they should risk having surgery, she said.

Patients who reported being unable to do work or could only do light work were at a 2.7-5.8 fold higher probability of dying within two years than were patients who were active, the researchers also discovered. The clinical care of these patients is a long- term process, Yang said. If, through follow-up and monitoring, we find a patient is physically inactive, we may recommend exercise and rehabilitation as appropriate to keep them stronger.

Knowing the contribution of inheriting a GSTM1 gene form to outcome is also important, she said. If our model tells us that a patient's cancer has a higher chance of recurring or progressing because of innate genetics in metabolism, we can watch them more closely, and consider treating them aggressively and promoting preventive measures, Yang said.

The GSTM1 gene is just one of many candidate genes the investigators are studying in these patients.

Research finds antioxidant therapies do not interfere with radiation treatment

Thu, 09 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Cancer patients can get the vital nutritional benefits from taking antioxidants without the risk of interfering with radiation treatment, according to research findings being presented this weekend at the Society of Integrative Oncology's Third International Conference in Boston. The Society for Integrative Oncology is a non-profit organization of oncologists and other health professionals studying and integrating effective complementary therapies in cancer care.

The study, Effect of Concomitant Naturopathic Therapies on Clinical Tumor Response to External Beam Radiation Therapy for Prostate Cancer, was conducted by researchers at Cancer Treatment Centers of America and reviewed PSA levels of prostate cancer patients after receiving radiation therapy. Researchers found no difference between patients taking antioxidants and those who did not. Antioxidants used in the study included green tea extract, melatonin, high-potency multivitamins, vitamin C and vitamin E.

Cancer Treatment Centers of America chose this study to address clinical concerns about the use of dietary supplements in conjunction with conventional cancer therapies. The study addressed the concern that antioxidants might interfere with cancer cell oxidation levels that contribute to tumor killing by chemotherapy and radiation therapy.

This study provides evidence that antioxidants as a complementary therapy in cancer treatment do not interfere with external beam radiation therapy, said Timothy Birdsall, ND, vice president of integrative medicine for Cancer Treatment Centers of America and lead author of the paper. Antioxidants are one of many complementary and alternative medicine (CAM) therapies that are crucial in today's fight against cancer.

Treating cancer with advanced radiation, chemotherapy and surgery remains the best option for patients medically. But the side effects of these treatments can devastate a patient physically and emotionally. Through a fully integrated whole person care model, combining the best of traditional medicine with scientifically supported complementary and alternative therapies, cancer patients appear to be living a better quality of life.

In cancer treatment today, we have to look beyond the traditional focus of treating only the tumor, Birdsall said.

Cancer patients will be the first to tell you that's not enough. The integrated, whole person approach to cancer is highly valued, so much so that cancer patients and their caregivers are seeking out complementary or alternative therapies on their own.

More than 80 percent of cancer patients report using some sort of CAM treatmenti, many of them without medical supervisionii. Taking supplements without supervision, however, creates a huge patient safety risk. St. John's Wort, for example, is taken by some cancer patients to help lessen feelings of depression. But St. John's Wort can interfere with the effectiveness of some forms of chemotherapy, ultimately doing patients more harm than good.

John C. Williams, Jr., a prostate cancer survivor from Reidsville, GA, credits having fully integrated cancer care with helping him get through his cancer treatment. I didn't know which was scarier, being diagnosed with cancer or when the doctor told me about the treatments, Williams said. The whole person approach at Cancer Treatment Centers of America was my choice because they used nutrition, supplements, physical therapy and other therapies to help me keep my body, mind and spirit strong.

Vaccination with embryonic stem cells prevents lung cancer in mice

Wed, 08 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Prague, Czech Republic: Researchers in America have discovered that vaccinating mice with embryonic stem cells prevented lung cancer in those animals that had had cancer cells transplanted into them after the vaccination or that had been exposed to cancer-causing chemicals.

The findings suggest that it could be possible to develop embryonic stem cell vaccines that prevent cancers in humans, such as hereditary breast and colon cancer and lung cancer caused by smoking or other environmental factors.

Professor John Eaton told a news briefing at the EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Wednesday 8 November): We found that the vaccinations were between 80-100% effective in preventing tumour growth in mice that were subsequently challenged with transplanted Lewis lung carcinoma, and it was between 60-90% effective in mice subsequently exposed to carcinogens that cause lung cancer.

Our results raise the exciting possibility of developing a prophylactic vaccine capable of preventing the appearance of various types of cancers in humans, especially those with hereditary, chronological or environmental predispositions to neoplastic disease.

However, he warned that the work was still in its early stages and that people should not think that, for instance, they could start, or carry on, smoking because a vaccine to prevent lung cancer was just around the corner.

Cancer has been prevented and even cured in mice hundreds of times. At present, all I can say is that so far it looks good, and that, unless something unexpected happens, this strategy might some day be applied to humans at high risk for development of cancer. The likelihood of this happening is more a question for the US Food and Drug Agency than for us. Given their stringent regulations I consider it quite likely that, by the time this is tried in humans, I will be pushing up daisies.

Prof Eaton is the James Graham Brown Professor of Cancer Biology and Deputy Director of the James Graham Brown Cancer Center, University of Louisville, USA. He and his colleague, Dr Robert Mitchell, tested two different vaccines in the mice. One consisted of embryonic stem cells (ESC) only, obtained from mouse blastocysts (very early, pre-implantation embryos). The other vaccine consisted of the ESCs combined with cultured fibroblast cells producing GM-CSF, a growth factor usually made by white blood cells and blood vessel-lining endothelial cells, which supercharges the immune response and appears to enhance the vaccine-induced immunity to cancer.

Prof Eaton explained: We needed a delivery vehicle for GM-CSF and chose STO fibroblasts because they are often used as a 'feeder layer' to maintain these particular mouse embryonic stem cells in their embryonic state. If we had used only ESCs expressing GM-CSF, they might have differentiated into non-embryonic cells, which, therefore, would not have worked as a vaccine.

He and his team injected mice with ESCs alone or ESCs + STO/GM-CSF. In mice that had Lewis lung carcinoma transplanted into them afterwards, ESCs were 80% effective in preventing tumour growth and ESCs + STO/GM-CSF were 100% effective. In mice subsequently exposed to a carcinogen that causes lung cancer (3-methylcholanthrene followed by repetitive dosing with butylated hydroxytoluene), ESCs resulted in 60% of mice remaining tumour free after 27 weeks and ESC + STO/GM-CSF resulted in 90% remaining tumour free. Importantly, tumours arising in vaccinated mice were, on average, about 80-90% smaller than tumours in unvaccinated mice. All the unvaccinated mice developed tumours. None of the vaccinated mice developed autoimmune disease or a showed a significant decline in adult pluripotent bone marrow stem cells both potential adverse responses to the vaccinations.

Prof Eaton said: We think the results from the carcinogen-initiated cancers are probably the most important, as they are closer to the 'real-life' model of the development of cancer than just implanting cancer cells in an animal. We are studying several different types of carcinogen-induced mouse cancers (skin, colon, breast) to determine whether the preventative effect of vaccination extends beyond our models of lung cancer (although in our state of Kentucky with its high smoking rates, lung cancer alone would be a big victory). We may also vaccinate ageing rodents, the majority of which develop endocrine tumours in old age.

In terms of human testing, if all goes well, then I think this vaccination might best be tested in women at high (genetic) risk of breast cancer, in people with high (genetic) risk of colon cancer and, perhaps, in smokers.

Our progress over the next few years will depend, to a large extent, on whether we can attract significant funding. Our work is presently supported by a pilot grant from our cancer centre and a small grant from the Kentucky Lung Cancer Research Program. US federal funding agencies such as the NIH notorious for funding predictable research have been quite disinterested.

Hecht honored with AACR-Cancer Research and Prevention Foundation Award

Mon, 06 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) PHILADELPHIA -- Stephen S. Hecht, an internationally recognized expert on cancer-causing agents in tobacco and the pathways by which they cause cancer, has been selected to receive the fifth annual American Association for Cancer Research (AACR)-Cancer Research and Prevention Foundation (CRPF) Award for Excellence in Cancer Prevention Research.

Dr. Hecht, the Wallin Professor of Cancer Prevention and the American Cancer Society Research Professor at The Cancer Center at the University of Minnesota, is being honored for more than three decades of research on tobacco and its link to cancer formation and growth.

Over this span of time, Dr. Hecht has been the most cited author on tobacco carcinogenesis, and is generally recognized as the world's leader in research on tobacco-specific human carcinogens called nitrosamines, found in cigarette smoke and smokeless tobacco. Other work in his laboratory, showing that exposure to second-hand tobacco smoke resulted in the presence of tobacco-specific carcinogens in nonsmokers has had a profound impact on clean indoor air laws critical for tobacco control.

Stephen Hecht's ground-breaking and detailed research on tobacco-specific nitrosamines has enhanced our understanding of tobacco carcinogenesis, said Dr. Margaret R. Spitz, chair of the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center and co-chair of the award selection committee.

His research has provided a strong scientific rationale for public policies on smoking restriction.

Added Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR: Dr. Hecht has been, and continues to be, among the most recognized scientists in the world studying the impact of tobacco and tobacco products on lung cancer. His critical work in this field marked by its thoroughness, breadth and extraordinary high quality -- is helping to save countless lives from this devastating disease.

It was 1974 when Dr. Hecht, along with Dr. Dietrich Hoffmann, provided the first demonstration of organic carcinogens nitrosamines -- in unburned tobacco. The two scientists identified substantial amounts of a specific nitrosamine called N'-nitrosonornicotine (NNN) in unburned tobacco, suggesting that smokeless tobacco was not a harmless substitute for cigarettes. This work ultimately led to the regulation of smokeless tobacco products.

Dr. Hecht subsequently reported the first synthesis of another nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and he demonstrated its formation from nicotine during the curing process. He further showed that exposure to NNK resulted in lung cancer in laboratory mice and rats, and then characterized how NNK caused lung cancer. In highly detailed studies, Dr. Hecht determined virtually all the known pathways of metabolism of NNK, and later showed the chemical binding of DNA to metabolically activated NNK, NNN and other tobacco-related nitrosamines steps that are critical to the initiation of cancer.

These studies led to the development of biomarkers substances that can be measured in blood or urine to help identify individuals most susceptible to the cancer-causing effects of tobacco products. Such biomarkers also can help determine exposure of non-smokers to second-hand tobacco smoke. Dr. Hecht demonstrated the presence of a metabolite of NNK in the urine of non-smokers exposed to second-hand tobacco smoke in various settings. The metabolite, NNAL, also was discovered in the fetuses and newborns of smoking mothers. Such evidence provided the rationale for tobacco control laws in public places.

Another area of research in the Hecht lab is the identification and development of naturally occurring chemopreventative agents that may help protect smokers from later disease. Current work in this area involves compounds found in cruciferous vegetables, nuts and fruit. Phase II studies to evaluate the efficacy of these agents in smokers and ex-smokers are now being planned.

Other past winners of AACR-CRPF Award for Excellence in Cancer Prevention include Scott M. Lippman, M.D. of The University of Texas M. D. Anderson Cancer Center, in 2005; David S. Alberts, M.D., of the Arizona Cancer Center, in 2004; Waun Ki Hong, M.D., also of the M. D. Anderson Cancer Center, in 2003; and Michael B. Sporn, M.D., of the Dartmouth Medical School, in 2002.

Dr. Hecht graduated from the Duke University, with a degree in chemistry. He was awarded a Ph.D. in organic chemistry from the Massachusetts Institute of Technology, where he also did postdoctoral research in mass spectrometry. Prior to moving to the University of Minnesota in 1996, for 23 years Dr. Hecht conducted research at the American Health Foundation in Valhalla, N.Y., where he was Director of Research from 1987-1996. At the University of Minnesota, he is Head of the Carcinogenesis and Chemoprevention Program at the Cancer Center, Co-director of the Transdisciplinary Tobacco Use Research Center, and a member of the Medicinal Chemistry graduate department.

Dr. Hecht, who has authored or co-authored more than 600 publications, holds a Merit Award and was previously the recipient of an Outstanding Investigator Grant, both from the National Cancer Institute. In 2000, he was named an American Cancer Society Research Professor, one of about 40 in the country. Dr. Hecht has served on several International Agency for Research on Cancer working groups, was a contributor to the 2005 Surgeon General's Report on Passive Smoking and Health, and is chapter editor for cancer in the upcoming Surgeon General's Report on How Tobacco Causes Diseases. He also has participated on numerous government and international committees including the National Cancer Institute's Board of Science Counselors, the National Toxicology Program Board of Scientific Counselors, and the National Center for Toxicological Research Science Advisory Board.

He is active in the AACR, where he has served on program committees for national and special meetings, and on the steering committee of the Chemistry in Cancer Research Working Group.

Dr. Hecht will give an award lecture titled, A Tobacco-Specific Lung Carcinogen: from Basic Research to Tobacco Control, on Tuesday, November 14, at the Fifth Annual AACR International Conference on Frontiers in Cancer Prevention Research. This premier meeting on cancer prevention research will be held November 12-15, 2006 at the Hynes Convention Center in Boston, Mass.

Smoking cessation therapy may be harmful for ICU patients

Wed, 25 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) A common smoking cessation therapy used to help reduce adverse events associated with nicotine withdrawal may actually increase the risk of death for smokers admitted to the intensive care unit (ICU). In a new study presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP), researchers found that smokers admitted to the ICU who received nicotine replacement therapy (NRT) during their stay had a higher risk of death than smokers who did not receive NRT.

In some critically ill patients, the development of nicotine withdrawal symptoms can worsen their prognosis. As a result, NRT is given to active smokers in the ICU to prevent nicotine withdrawal symptoms, said lead researcher Amy Lee, MD, Mayo Clinic College of Medicine, Minneapolis, MN. The hemodynamic effects of nicotine may lead to increased heart rate, systemic arterial blood pressure, and constriction of the coronary arteries. Although these potential adverse effects of NRT have not been shown to worsen the prognosis of healthy volunteers and patients with stable coronary artery disease, they may be detrimental in critically ill patients.

Lee and colleagues examined the safety of NRT in the ICU by reviewing the medical records of 112 smoking patients admitted to the ICU who received NRT during their stay. Researchers compared patient outcomes between the NRT group and a control group. Among the patients who received NRT, 18 deaths (16.1%) occurred, compared with the 3 deaths (2.7%) in the control group. The hospital mortality rate was 21.4% for the NRT group, compared with 5.4% in the control group. Furthermore, when researchers controlled for severity of illness, NRT was found to be an independent risk factor for mortality (odds ratio 17.0).

There were no statistically significant differences in age, gender, ethnicity, and severity of illness measured by APACHE III prognostic model between the NRT and control groups. The median ICU length of stay for the NRT group was 24.4 (16.1 63.6) hours, compared with 22.6 (14.0 42.8) hours for the control group. The median hospital length of stay was 29.6 (18.3 127.1) hours, compared with 46.2 (19.8 117.3) hours for the control group.

Although administering nicotine replacement therapy to smokers in the ICU is not a standard practice, some ICUs have nurse-driven protocols aimed at providing NRT for active smokers. We expect NRT to be more widely used in such ICUs, said senior author Bekele Afessa, MD, FCCP, Mayo Clinic College of Medicine. Common signs of nicotine withdrawal include craving, irritability, depression, restlessness, and sleep disturbances. However, researchers caution that, because of other conditions that mimic nicotine withdrawal in the critically ill, to may be difficult to make an accurate diagnosis.

Minimizing the effects of nicotine withdrawal in critically ill patients who smoke can present a significant challenge to the ICU team, said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. The findings of this study are intriguing and reinforce the need for additional research regarding the effects of nicotine replacement therapy on patients in the ICU.

Statins protect smokers from lung damage

Mon, 23 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Statins, the widely used class of drugs for cholesterol management, are now showing promising results in slowing smoking-induced lung damage. In a new study presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP), current and former smokers who used statins had lower lung function decline than those not using statins, regardless of whether patients continued or stopped smoking.

Until now, no medication has shown to slow smoking-induced lung damage, said Walid G. Younis, MD, University of Oklahoma Medical Center, Oklahoma City, OK. Our study is the first to show that statins may decrease the decline in lung function in smokers and former smokers, and, therefore, prevent millions from developing debilitating diseases that could eventually lead to death.

Younis and colleagues from the University of Oklahoma Medical Center compared the effects of statins on the management of 182 current smokers and 303 former smokers, with a mean age 66.1 ± 2.1 years, seen at the Oklahoma City Veterans Hospital. Patients had at least two pulmonary function tests, with the time between the first and the last test being 2.7 ± 1.6 years. Patients were categorized by initial level of lung impairment, with 319 having obstructive lung disease, 99 having restrictive lung disease, and 67 patients having normal lung function. Of the patients, 238 were on statin for an average of 2.7 ± 1.8 years, while the remaining patients did not receive statins (control group).

Over the study follow-up period, the decline in FEV1 was 12.8 percent in the control group and 2.5 percent in the statin group. The decline in FVC was 10.3 percent in the control and 1.3 percent in the statin group. Both differences were highly significant. This beneficial effect of statin remained significant, irrespective of the type of lung disease and regardless of whether the patient continued or stopped smoking. Furthermore, statin use in patients with obstructive lung disease led to a 35 percent decline in the rate of respiratory-related emergency department visits and hospitalizations.

Researchers note that it is not known whether decreasing the rate of decline in lung function or whether preventing emphysema, an independent risk factor of lung cancer, could translate into a reduction of lung cancer.

It is conceivable that long-term statin therapy could be used in smokers and former smokers to prevent and slow the progression of lung diseases, said Dr. Younis. Even though statins may help with lung function, they have no effect on preventing a patient from the major smoking-related killer, which is lung cancer. Therefore, smokers should never lose their incentive to quit smoking.

Smoking is the number one cause of lung cancer and chronic lung diseases in the world. Although statins may reduce the incidence of lung damage in smokers, patients must still be urged to stop smoking as the best way to maintain and improve their health, said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians.

Smoking ban associated with rapid improvement in health of bar workers

Tue, 10 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Bar workers in Scotland showed significant improvements in respiratory symptoms and lung function within 2 months following a ban on smoking in confined public places, according to a study in the October 11 issue of JAMA.

Exposure to secondhand tobacco smoke is a major worldwide public health issue, according to background information in the article. The effects on individuals has been difficult to measure, but a number of studies have established an increased risk of coronary artery disease, cerebrovascular disease and lung cancer, and the 2006 report by the U.S. surgeon general highlighted the causal relationship between secondhand smoke and premature death. In addition, for patients with preexisting respiratory conditions such as asthma, secondhand smoke leads to poorer disease control and more frequent hospital admission.

As the harmful effects of secondhand smoke become more widely appreciated, a number of countries have attempted to limit the health risks to the population at large by prohibiting smoking in public. On March 26, 2006, Scotland introduced a legislative ban on smoking in enclosed public places. One group of people most likely to benefit from this legislation is bar workers, who are exposed to high levels of secondhand smoke as part of their occupation.

Daniel Menzies, M.B.Ch.B., and colleagues from Ninewells Hospital and Medical School, Dundee, Scotland examined the effect of the recently introduced smoke-free legislation on bar workers' health in Scotland. The study, conducted in Tayside, Scotland from Feb. - June 2006, initially included 105 nonasthmatic and asthmatic nonsmoking bar workers, of whom 77 completed the study. The participants were evaluated for respiratory symptoms (wheeze, shortness of breath, cough, and phlegm) and sensory symptoms (red or irritated eyes, painful throat and nasal itch, runny nose, and sneeze), and also had pulmonary tests and blood tests performed before the ban and at 1 month and 2 months after the ban went into effect.

The researchers found that a total of 79.2 percent (n = 61) of the bar workers experienced respiratory or sensory symptoms before the introduction of the smoke-free policy, whereas 1 month afterward, 53.2 percent (n = 41) reported these symptoms, a decline of 26 percent. At 2 months after introduction of the smoke-free policy, this improvement was maintained, with 46.8 percent of participants reporting any symptom (a decrease of 32.4 percent from baseline). There were also improvements on certain measurements of lung function and reductions in serum cotinine (metabolized nicotine) levels. Asthmatic bar workers also had less airway inflammation and an increase in quality of life scores.(JAMA. 2006;296:1742-1748. Available pre-embargo to the media at

A tNOX-based protocol for early detection of lung cancer in smokers and nonsmokers

Wed, 13 Sep 2006 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- Lung cancer is a formidable disease. While it is one of the most preventable cancers, with the vast majority of 160,000 annual deaths in the United States due to smoking, it is invariably difficult to find early when it is most amenable to treatment. As a result, it remains the top cancer killer in the nation.

But a new test for the early detection of lung cancer that involves measuring levels of a certain protein may provide hope for thousands of smokers worldwide. While the findings are preliminary and involve a small group of subjects, the researchers see their early results as extremely promising.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

A team led by Dorothy M. Morre, Ph.D., professor of foods and nutrition at Purdue University in West Lafayette, Indiana, and D. James Morre, Ph.D., distinguished professor of medicinal chemistry at Purdue, wanted to come up with a robust lung cancer screening procedure for people who smoke.

We'd like to have a means of detecting lung cancer early in individuals who smoke with a low incidence of false positives, Dorothy Morre said. There's apparently no good method of finding this and there is a lot of interest at the National Cancer Institute in developing such a protocol.

The Morres -- along with colleagues at Purdue, NOX Technologies, Inc., also in West Lafayette, and at Mount Sinai Medical Center in New York -- focused their efforts on a protein called tNOX, a member of a family of proteins that are involved in cell growth. Normal cells express the NOX enzyme only when they are dividing in response to growth hormone signals. In contrast, cancer cells have gained the ability to express NOX activity at all times. This overactive form of NOX, known as tNOX for tumor-associated NOX has long been assumed to be vital for the growth of cancer cells, because drugs that inhibit tNOX activity also block tumor cell growth in culture.

The researchers compared four different protocols to determine levels of tNOX in the blood of 421 volunteer subjects, including 104 patients with lung cancer, 175 smokers who had not been diagnosed with lung cancer, 117 randomly selected outpatients and 25 healthy individuals.

Two of the protocols used rapid high-throughput screening techniques and gave a low incidence of false-positive diagnoses of lung cancer. In contrast, the researchers employed a technique using two different antibodies that they created against the tNOX protein, which they found gave a definitive indication of lung cancer.

In healthy individuals, we have 0 out of 25 false positives, noted D. James Morre. In lung cancers, 103 of the 104 patients were positive for tNOX. In smokers older than 40 years of age, 12 percent were positive, which is about the normal incidence picked up with high resolution tomography.

The researchers envision the tNOX test as serving as a screening tool for the early detection of lung cancer. Those who test positive would then be followed up with a medical examination and further tests, ostensibly including high resolution CT.

According to D. James Morre, current approaches to diagnosing lung cancer are costly and time consuming. Our findings would provide a simple blood test that would indicate whether or not additional testing would be required, he said. We could screen very large smoker populations and eliminate perhaps 90 percent of them, while encouraging the other 10 percent to go on to the next stage of testing.

This test is structured with the antibody we're using to be specific for lung cancer in one form or another, Dorothy Morre added. It's a specific diagnosis and it also distinguishes between non-small and small cell lung cancer.

The scientists are already doing similar studies in colon, ovarian, prostate and breast cancers as well. They are planning three collaborative studies in which they will correlate tNOX antibody test results with medical evidence such as high resolution CT, physician examinations of patients standard procedures for detecting early stage lung cancer.

Aspirin and other NSAIDs may not reduce the risk of colorectal cancer in long-term smokers

Sat, 01 Jul 2006 03:59:37 PST

( from http://www.rxpgnews.com ) SEATTLE -- It is widely known that the use of aspirin and other nonsteroidal anti-inflammatory drugs, or NSAIDS, may reduce the risk of colorectal cancer by up to 40 percent, but this protective effect may not extend to long-term smokers, who already face an increased risk of the disease, according to a study led by researchers at Fred Hutchinson Cancer Research Center.

In a large, population-based study comparing risk factors in people with and without colorectal cancer, the researchers found the highest risk of colon cancer to be among long-term smokers of 20 or more years who had never used NSAIDs. The researchers also found that smokers who used NSAIDs were still at an approximate 30 percent higher risk of colon cancer than nonsmokers.

The findings, which appear in the July 1 issue of Cancer Research, arise from the first study of its kind to examine the effects of NSAID use on colorectal-cancer risk among smokers, said first author Victoria Chia, a research associate in the Hutchinson Center's Cancer Prevention Program.

Smoking has been linked to a modestly increased risk of colorectal cancer, and use of NSAIDs has been shown to significantly decrease the risk of colorectal cancer. We wanted to see if NSAIDs could counteract the adverse effects of smoking with regard to colorectal-cancer risk, and whether these associations differed by tumor characteristics, she said.

In particular, Chia and colleagues were interested in examining the impact of NSAIDs on a certain type of colorectal tumor that may be associated with smoking. Such tumors display microsatellite instability, an acquired genetic characteristic that indicates defects in DNA-repair machinery. Microsatellite instability, or MSI, occurs in approximately 15 percent to 20 percent of colon cancers.

The researchers found a two-fold increased risk of microsatellite-unstable colorectal tumors among long-term smokers who took NSAIDs -- about the same risk as smokers who had not used NSAIDs.

Given the damage that smokers receive over their lifetime, even strong anti-progression agents, like NSAIDs, may be ineffective, the authors wrote. NSAIDs may not be able to counteract the long-term effects of smoking, as evidenced by our observation that long-term smokers are at increased risk of colorectal cancer, despite current NSAID use.

The link between smoking and cancer stems from the fact that cigarette smoke contains hundreds of carcinogenic metabolic products that may damage DNA. This accumulated damage might not be reversible, Chia said. NSAIDs act to suppress inflammatory processes and may help limit the progression toward cancer. However, people who have microsatellite-unstable tumors may be even more susceptible to the effects of smoking because they already have a reduced capacity to repair DNA, even in the presence of strong anti-inflammatory agents.

Funded by the National Cancer Institute and the National Institutes of Health, the study involved 3,299 Seattle-area residents between the ages of 20 and 74 (mean age 60), approximately half with a history of colon cancer and approximately half without, who served as a control, or comparison group. Cancer cases were identified through the Puget Sound Surveillance, Epidemiology and End Results Program, a population-based registry. Controls were randomly selected to match the distribution of the cases regarding age and sex. Participants were interviewed by telephone about their smoking history and use of aspirin and other NSAID use, among other risk factors. Microsatellite instability was assessed in tumors from 1,202 cases.

Smoking was more common in cancer cases than controls, and NSAID use was more common among controls than cases.

Researchers from the Mayo Clinic College of Medicine collaborated on the study.

Proteins linked to cancer prevention in humans affect aging in worms

Thu, 01 Jun 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Statistically, we know that aging is a huge risk factor for cancer, said Buck faculty member Gordon Lithgow, PhD, lead author of the study. We don't know why that is. If we look at checkpoint proteins as a gear we've known for a long time that they drive the cancer gear, now we know that they also drive a longevity gear. This discovery has exciting potential as area of inquiry into a potential cellular link between aging and cancer.

The research carried out in the Buck Institute's Lithgow Laboratory, involved genetically eliminating checkpoint proteins in the microscopic worms. This caused a 15 30% increase in their lifespan. Given the role that checkpoint proteins play in preventing the development of cancer (or in encouraging it when the proteins are defective), the findings raise the question of whether genetic variations in checkpoint proteins in humans may place some individuals at risk for cancer, but protect them against other age-associated diseases; or conversely, set a genetic course for a shorter life which would be free from cancer.

The intriguing discovery came from ongoing work in the Lithgow lab, during a screening for genes that determine stress resistance and longevity in the worm, an animal which has about 18,000 genes and does not undergo cell division once it reaches maturity. Lead researcher Anders Olsen, PhD, found an unfamiliar gene during his screening. I typed the DNA sequence into an internet database, and up came this gene we had never heard of or ever imagined would be involved in lifespan determination, said Olsen. The scientist identified two other survival-controlling checkpoint proteins which are also included in the study. Olsen's work now involves identifying additional tumor suppressor genes that impact aging in both worms and human cells, as well as screening for compounds that mimic the genetic elimination of the checkpoint proteins that took place in the lab.

We think there are many more checkpoint proteins -- in worms, in complex animals, in humans, said Olsen. Some may be more attractive than others for developing therapies for cancer and aging. The job now is to catalogue the genes and find out which ones have these dual properties. There is lot of work to be done in many labs and by many people.

This work brings a new richness and sophistication to the way we think about longevity interventions, said Dale Bredesen, MD, Buck Institute CEO and Scientific Director, who acknowledged that this area of research is in its infancy. If we're smart about it, we might be able to design strategies where you could keep checkpoint proteins active in dividing cells and knock them out in cells that no longer divide, such as neurons. Increasing the survival of neurons could provide a new avenue of treatment for neurodegenerative diseases.

Broccoli, cauliflower and genetic cancer

Wed, 17 May 2006 03:59:37 PST

( from http://www.rxpgnews.com ) A research team led by Rutgers' Ah-Ng Tony Kong has revealed that these widely consumed cruciferous vegetables so called because their four-petal flowers resemble crosses are abundant in sulforaphane (SFN). This compound had previously been shown to inhibit some cancers in rodents induced by carcinogens substances or agents external to the body. Kong's investigations, however, focused on whether SFN might inhibit the occurrence of hereditary cancers those arising from one's genetic makeup.

The American Cancer Society estimates that more than two-thirds of cancer may be prevented through lifestyle modification, and nearly one-third of these cancer occurrences can be attributed to diet alone.

Our research has substantiated the connection between diet and cancer prevention, and it is now clear that the expression of cancer-related genes can be influenced by chemopreventive compounds in the things we eat, said Kong, a professor of pharmaceutics in the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

Chemopreventive properties are those that prevent, stop or reverse the development of cancer. In a study published online in the journal Carcinogenesis, Kong and his colleagues used a mouse model for human colon cancer to demonstrate the chemopreventive power of SFN and explain how it works to thwart cancer at the biomolecular level.

The researchers employed a specially bred strain of mice (labeled Apc/Min/+) that carry a mutation that switches off a gene (Apc) that suppresses tumors. This is the same gene known to be directly implicated in the development of most colon cancers in humans. When the gene is inactivated in the mice, polyps, which lead to tumors, appear spontaneously in the small intestine. Experiments using these mice can help in designing human clinical trials that can lead to new treatments for colon cancer in humans.

Two groups of mice were fed diets supplemented with SFN for three weeks, one group receiving 300 parts per million (ppm) of SFN and the other getting 600 ppm. Our results clearly demonstrated that those mice fed with an SFN-supplemented diet developed significantly fewer and smaller tumors, Kong said.

After the three weeks, the average number of polyps in the small intestine in each mouse decreased more than 25 percent in those on the 300 ppm diet and 47 percent in the 600 ppm treatment group, as compared to control animals who had received no SFN.

Our results showed that SFN produced its cancer preventive effects in the mice by inducing apoptosis (programmed cell death) and inhibiting proliferation of the tumors; however, it was not clear what mechanism SFN employs to accomplish this, Kong said.

Using biomarkers (indicator molecules) associated with apoptosis and proliferation, Kong's team found that SFN suppressed certain enzymes or kinases that are highly expressed both in the mice and in patients with colon cancer. The researchers concluded that this enzymatic suppression activity is the likely basis for the chemopreventive effects of SFN.

Our study corroborates the notion that SFN has chemopreventive activity. Based on these findings, we feel SFN should be evaluated clinically for its chemopreventive potential in human patients with Apc related colon cancers, Kong said.

Penn professor to present research on radiation-induced cancer on 20th anniversary of Chernobyl

Wed, 12 Apr 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Just before dawn on April 26th, 1986, the Number Four nuclear reactor at Chernobyl exploded. The fallout was 400 times more radioactive than what was released over Hiroshima during World War II, and it covered an area the size of New Jersey. Numerous radioactive elements were released into the air including radioactive iodine, an element that is preferentially taken-up by the thyroid gland. As a result, there was a rise in cancer and, in particular, in thyroid cancer in children. (Since the thyroids of children are much smaller than adults, it is assumed that the relative dose of radioactive iodine these thyroids received was much larger than the adult thyroids.)

Following the accident, an international panel of experts was formed to study the after-effects of the accident. One group of specialists including pathologists who, like Dr. LiVolsi, have expertise in thyroid pathology was charged with studying the thyroid tumors that had occurred to reach a consensus diagnosis. These analyses, including samples of the tumors, have been made available to the international research community to further our understanding of thyroid-cancer development and radiation-induced tumors.

The isotopes of radioactive iodine that are suspected of causing the outbreak of thyroid cancer have a relatively short half-life of eight days, but other isotopes that were released in the explosion -- like cesium 137 and strontium 90, will last for decades. One of the interesting aspects of this research is that we are still seeing new thyroid-cancer tumors in the exposed population even though, after 20 years, there is no radioactive-iodine fallout left from the accident, LiVolsi said. In the future, it will be informative to compare tumors that appeared initially to those that are occurring now.

Chernobyl is still a threat to this day. The lead and steel sarcophagus initially built around the Number Four Reactor has decayed. A replacement structure is in the planning stages. This replacement will take four-five years to assemble, cost over $800 million and be the largest movable structure ever built.

However, information learned from the Chernobyl accident could prove valuable insofar as aiding and treating future victims of a dirty bomb a conventional explosion that scatters radioactive materials, including the longer-lasting strontium 90 and cesium 137. According to the Department of Homeland Security's National Terror Alert Resource and Information Center website, the Washington Post reported in March of 2002 that the Bush administration's consensus view is that the al-Qaeda terrorist network probably had such acquired often-stolen radioactive contaminants as strontium 90 and cesium 137, which could be used in a dirty bomb.

Media Invite: Dinner to award prize for Progress in Cancer Research

Fri, 31 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com ) ADDITIONAL INFORMATION: The Szent-Györgyi Prize Committee selected Dr. Dvorak based on his breakthrough discovery of vascular permeability factor/vascular endothelial cell growth factor (VPF/VEGF) and that contribution that has led to a series of discoveries which both elucidated the mechanisms of angiogenesis as well as the development of antibodies and small molecule therapies to inhibit VEGF.

Without Dr. Dvorak's fundamental discovery we would probably not have had the therapeutic agent bevacizumab which has had a tremendous impact on improving survival for patients with advanced colorectal cancer, breast cancer, non-cell lung cancer and renal cell carcinoma, stated Chairman of the Szent-Györgyi Prize Committee Dr. Daniel Von Hoff, Vice President of the Translational Genomics Research Institute in Phoenix. In addition, other small molecules which inhibit VEGF have also shown outstanding clinical antitumor activity with dramatic therapeutic effects for patients worldwide.

Dr. Dvorak's seminal discoveries in basic science have led to significant clinical benefits for cancer patients, perfectly fitting the unique criteria of the Albert Szent-Györgyi Prize for Progress in Cancer Research, said Sujuan Ba, Ph.D., NFCR Chief Scientific Officer and Co-Chair of the Szent-Györgyi Prize Committee. Dr. Dvorak's key VPF/VEGF discovery paved the way for researchers to better understand the mechanisms involved in tumor angiogenesis. His work is now being utilized in very real practical applications, offering hope for angiogenesis-centered treatments to halt and even reverse tumor growth.

Published in 1983 in the journal Science, Harold Dvorak, M.D. and his colleagues were the first to show that tumor cells secreted VPF and that a blocking antibody to VPF could prevent the devastating edema and fluid accumulation characteristic of ovarian, breast, and many other human cancers. This discovery laid the foundation and also provided the molecular basis for the entire angiogenesis field and what is now one of modern medicines most promising anti-cancer hopes. In 1986, Dr. Dvorak went on to demonstrate in the journal Cancer Research that VPF was secreted by a variety of human tumor cell lines and proposed that VPF was in part responsible for the abnormal vasculature seen in human tumors. As a result, he and other investigators demonstrated that VPF was capable of stimulating endothelial cell growth and angiogenesis. These fundamental discoveries led to additional research conducted by Dr. Napoleone Ferrara and his lab confirming the cloning of VPF and renaming the protein Vascular Endothelial Growth Factor or VEGF. Ferrara and his colleagues later developed an inhibiting antibody against VEGF that has demonstrated outstanding clinical anti-tumor activity.

In another 1986 paper in the New England Journal of Medicine Dvorak proposed that by secreting VPF tumors induce angiogenesis by turning on the wound healing response. He noted that wounds, like tumors, secrete VPF, causing blood vessels to leak plasma fibrinogen which stimulates blood vessel growth and provides a matrix on which they can spread. Unlike wounds however that turn off VPF production after healing, tumors did not turn off their VPF production and instead continued to make large amounts of VPF, allowing malignant cells to continue to induce new blood vessels and so to grow and spread. Thus, tumors behave as wounds that fail to heal. This work is again extremely significant for patients worldwide, as Dr. Dvorak's scientific research is leading his colleagues all over the world to examine how to treat a tumor through its blood supply.

Harold F. Dvorak, M.D. stepped down as Chair of Pathology at Beth Israel in July after 26 years to devote his life to basic science cancer research; he is emeritus Mallinckrodt Professor of Pathology at Harvard Medical School. Dr. Dvorak is a fellow of the American Association for the Advancement of Science and of the National Foundation for Cancer Research, and has served as President of the American Society for Investigative Pathology. Educated at Princeton University and Harvard Medical School, he did residency training in Pathology at the Massachusetts General Hospital and postdoctoral research training at the National Institutes of Health. He has served on the Harvard Medical School faculty since 1967 and at Beth Israel since 1979 and has written over 220 original journal reports.

When informed that he was the recipient of the award, Dr. Dvorak said I am surprised and delighted, but also humbled because of my great respect for Dr. Szent-Gyorgyi whom he had known and greatly admired for his independent spirit and outstanding contributions to science. Dvorak also noted that the award meant even more to him because NFCR had provided some of the initial funding for his work on VPF, at a time when no one else believed in the concept and grant support was hard to come by.

The Albert Szent-Györgyi Prize for Progress in Cancer Research was established by the National Foundation for Cancer Research in honor of its co-founder, Dr. Albert Szent-Györgyi, recipient of the 1937 Nobel Prize for Physiology and Medicine for his study on Vitamin C and cell respiration. Dr. Szent-Györgyi was a leading advocate for developing resources to provide scientists with the financial support necessary to pursue innovative cancer research. In 1973 he changed the face of cancer research funding by founding the National Foundation for Cancer Research with entrepreneur Franklin C. Salisbury.

The annual Albert Szent-Györgyi Prize for Progress in Cancer Research carries a $25,000 cash prize and was established to honor outstanding scientific achievement in the war against cancer and celebrate leading researchers who have made extraordinary contributions in the field of cancer research. The Prize is designed to draw attention to the continued need to support basic science cancer research.

Any scientist or individual may be nominated for the annual prize by his or her peers and the winner is selected by a prize committee of academic, scientific, business and non-profit leaders highly qualified to review and select the Prize winner. The inaugural prize committee consisted of: Daniel Von Hoff, M.D. TGen; Sujuan Ba, Ph.D., NFCR; Stanley Cohen, M.D., Stanford University; Bruce Zetter, Ph.D., Children's Hospital Boston; Stephen Sallan, M.D., Dana Farber Cancer Institute; Thea Tlsty, Ph.D., University of California, San Francisco; Dennis Carson, M.D., University of California, San Diego; and Richard Gaynor, M,D., Eli Lilly.

Genes and environment interact to promote cancer

Tue, 28 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com ) After smoking, radon is considered to be the second leading cause of lung cancer in the United States, said Avner Vengosh, Ph.D., associate professor at Duke's Nicholas School of the Environment and Earth Sciences. Western North Carolina is highly affected, and many homes exceed the EPA's recommended levels of radon.

Radon's risk is not new or unknown, but it illustrates the real danger posed by indigenous substances as well as those artificially created by humans, say Duke scientists. More than 80,000 synthetic chemicals have been introduced worldwide since World War II, with little or no knowledge as to how they affect humans or animals.

Day by day, environmental scientists identify new culprits in the cancer equation in which genes, environment and lifestyle interact to increase cancer risks in some people but not in others.

Their synergy is by no means a simple interaction, said H. Kim Lyerly, Director of the Duke Comprehensive Cancer Center. For example, vitamin A can promote lung cancer growth in some women while it maintains healthy breast cell growth and division in others, said Victoria Seewaldt, M.D., director of the Duke Breast Health Clinic. Chemicals that promote cancer in one fish species do not cause cancer in a closely related species, while populations of another species have adapted to a polluted environment, found Richard Di Giulio, Ph.D., of Duke's Nicholas School. Common nutritional supplements like folic acid, given to pregnant mice, altered their offspri! ngs' coat colors and their adult risk of cancer, found Randy Jirtle, Ph.D. professor of radiation oncology at Duke University Medical Center.

Why these differences exist, and how and when the changes are imposed, are major questions being studied in a partnership between the Duke Comprehensive Cancer Center and Duke's Nicholas School of the Environment and Earth Sciences. The two groups are hosting their joint conference March 30 to 31 to present their latest findings on how the environment impacts cancer. Collectively, their data show that the timing and dose of exposure, combined with an individual's genetic makeup, play critical roles in cancer susceptibility.

The nature-versus-nurture argument is rapidly proving to be irrelevant, because we're finding that the two forces interact in highly specific ways that alter gene behavior, said Jirtle.

Select chemicals may damage or mutate genes at any given time in the lifespan, contributing to a host of human diseases, he said. But another, more subtle, change is emerging as the trigger for many cancers, diseases and even personality traits.Called epigenetic alterations, they occur when chemicals, nutrients or even behaviors elicit a chemical change in the brain or body that activates or silences a gene without changing its fundamental genetic code. The chemical or event mobilizes groups of molecules, called methyl or acetyl groups, to attach to the control region of a gene and alter its usual activity.

Such stealth changes often occur during embryonic or fetal development, but emerging data suggests they set the stage for an adult's susceptibility to a host of diseases and behavioral responses. Moreover, epigenetic changes so named because they sit on top of the gene and leave its sequence unchanged can also be passed down from one generation to the next, said Jirtle, who has extensively studied the phenomenon. They can also be reversible. Methyl groups can be added or knocked off following exposure to various substances.

Finding methylated or acetylated genes is no small task, however. Certain genes are more susceptible to epigenetic alterations than others, but no one knows for certain which genes and when the changes occur. Second, multiple compounds may interact to halt or promote genetic or epigenetic changes. Finally, epigenetic changes may occur so early in prenatal development that gauging its effects in adulthood prove difficult.

There are critical windows of development during which compounds can have a profound impact on disease and wellness, said Lyerly. And one compound may act differently in liver tissue than in breast tissue. Testing a compound during an inactive or inert period of development, or in the wrong tissue, is akin to testing a Porche's speed in Manhattan rush-hour traffic. The device works fine, but the timing and location are wrong.

The scenario grows more complex as multiple chemicals are introduced. A single chemical that proves safe by itself and in low doses may become highly toxic in high doses or when combined with other chemicals.

And, even the lowest detectable limits of a chemical can have dire effects on an organism, said William Schlesinger, Ph.D., Dean of Duke's Nicholas School. Atrazine is a prime example. Less than one part per billion of this widely used corn herbicide de-masculinizes developing frogs or produces dual male-female genitalia. Yet the Environmental Protection Agency's instrumentation often cannot record such minute levels of chemical exposure, he said.

If atrazine is having this effect in animals, we question its effects on humans, said Schlesinger. Are the current standards of exposure high enough to protect the organisms exposed to select chemicals? Our role as environmental scientists is to assess the potential impact of each compound on native organisms and develop models that physician scientists can apply to humans.

Likewise, Duke pharmacologist Mohamed Abou Donia, M.D., has shown that insecticides that are generally safe when used alone or in small amounts can damage the brain, nervous system and testes when combined with other chemicals or certain medications.

Testing each drug alone would fail to produce the synergy that elevates toxicity, he said.

Similarly, certain drugs can sensitize cells to the effects of hormones such as estrogen, progesterone and testosterone. In 2004, Duke researchers showed that an industrial solvent (EGME) and a commonly prescribed drug, Valproic acid, potently boosted estrogen and progestin activity inside cells. The elevated hormone levels are likely responsible for the reproductive failures and breast cancers seen among women exposed to these chemicals, said Duke pharmacologist Donald McDonnell, Ph.D.

Our study demonstrates that these chemicals boost the activity of estrogens and progestins inside cells eight- to 10-fold, said McDonnell. These data should prompt caution for patients who are exposed to either of these chemical compounds while taking any estrogen- or progesterone-containing medications, such as hormone therapy, oral contraceptives or tamoxifen for breast cancer.

Teasing out which factors most influence human disease risk is difficult without conducting large scale studies, said Joellen Schildkraut, Ph.D., epidemiologist in the department of Community and Family Medicine at Duke. A prime example is the ongoing debate over the role of smoking and the NAT2 gene in promoting bladder cancer. Some studies show that people with a certain version or allele of the NAT2 gene have a 40 percent increased risk for bladder cancer. Adding tobacco smoke to the effects of this allele may increase one's risk to 300 percent, said Schildkraut, but the data sometimes conflict.

Ultimately, the knowledge we gain about gene-environment interaction will lead to new drugs and therapies to prevent or treat cancers, and improved environmental regulations that protect humans and animals against toxic exposures, said Schlesinger.

Colorectal cancer develops earlier in drinkers, smokers and men

Fri, 24 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Colorectal cancer is the second leading cause of cancer death in the United States yet it is one of the most preventable forms of the disease. Screening not only helps diagnose it at an early stage when it is most curable, it also can locate polyps before they become cancer. However, once patients experience symptoms, the disease has already spread beyond the point where it can be cured. This is why physicians recommend everyone 50 years of age and older get screened for colorectal cancer and sooner for individuals who have a family history or other risk factors.

ENH researchers examined the records of 161,172 colorectal cancer patients from 350 teaching and community hospitals nationwide to assess whether alcohol and tobacco use, should also be considered in screening decisions. They analyzed the relationship between use of these substances and age of onset of colon cancer as well as location of onset--distal or proximal colon. Distal tumors, including those in the lower left part of the colon and the rectum, can generally be detected by flexible sigmoidoscopy; while proximal tumors in the right side of the colon can be missed by methods other than colonoscopy.

The data clearly show that screening for colorectal cancer in people who smoke and drink should start earlier, said lead author of the study Hemant K, Roy, MD, Evanston Northwestern Healthcare. If confirmed after further research, these factors should guide recommendations regarding the timing of colorectal cancer screening.

The data showed that alcohol and tobacco users developed cancer an average of 7.8 years earlier than those who had never drank or smoked. Those who had never smoked but drank or who had never drank but smoked were each an average of 5.2 years younger at cancer diagnosis than those who neither smoked nor drank. The effect of smoking appeared to be particularly larger for women. Women who smoked but never drank developed cancer 6.3 years younger than those who never drank or smoked, compared with 3.7 years in men. Also, current alcohol and tobacco consumption was associated with an increased likelihood of distal colorectal cancer, although women in all categories were less likely to have distal cancer than men.

Our report provides compelling evidence that smoking and alcohol consumption are associated with an earlier age of diagnosis and likelihood for distal colorectal cancers, said Dr. Roy. This data underscores the need for tobacco and alcohol cessation as an integral part of a colon cancer prevention program.

These findings also suggest that women who do not smoke or drink may be at increased risk for proximal colon cancer and may want to consider undergoing a colonoscopy instead of flexible sigmoidoscopy. In the future, we envision the development of risk scores with exogenous factors to tailor an individual's colorectal cancer screening program, said Roy.

New compound may protect against liver cancer

Wed, 15 Feb 2006 04:59:37 PST

( from http://www.rxpgnews.com ) The compound's effectiveness at very low doses suggests it may have similar cancer-fighting properties in humans. Researchers believe it may be particularly effective in preventing cancers with a strong inflammatory component, such as liver, colon, prostate and gastric cancers. The compound could eventually play a preventive role in a wide range of other illnesses such as neurodegenerative disease, asthma and emphysema.

The study results are featured on the cover of the February 15, 2006 issue of the journal Cancer Research.

The results show that the potency of this compound is more than 100 times as great as that of other chemopreventive agents in protecting against cancer, said NIEHS Director David A. Schwartz, M.D. This protective effect, combined with the compound's anti-inflammatory properties, make it an exciting avenue for the prevention of other diseases as well.

CDDO-Im belongs to a class of cancer-fighting compounds called triterpenoids. It is a synthetic compound derived from oleanolic acid, a naturally occurring substance found in plants all over the world. Research with other oleanolic derivatives showed marked anti-tumor activity in both animals and humans.

To test the effectiveness of CDDO-Im, researchers treated laboratory rats with either 0.1, 0.3, 1.0, 3.0 or 10 micromole doses of the compound. Two days after treatment with CDDO-Im, the rats were treated with aflatoxin, a naturally occurring toxin that causes liver cancer in animals.

Evaluation of the rat livers showed that the lowest concentration of CDDO-Im led to an 85 percent reduction in pre-cancerous lesions, abnormal growths that have a greater likelihood of developing into actual cancers. This compound has a much greater effect at a far lower dose than any other compound currently used for preventing aflatoxin-induced cancer in humans, said Thomas Kensler, Ph.D., a cancer biologist with the Johns Hopkins Bloomberg School of Public Health and lead author on the study.

According to Kensler, CDDO-Im activates a protein called Nrf2 that plays a central role in protecting the cells against the toxic effects of environmental agents. Nrf2 directs certain genes to stimulate the cell's defense mechanisms, he said. The protein also stimulates key enzymes that can detoxify harmful agents like aflatoxin and remove them from the cell.

Like other compounds derived from oleanolic acid, CDDO-Im also has strong anti-inflammatory properties that make it ideally suited to the prevention of certain cancers. When cells become inflamed, they can produce reactive molecules called free radicals that can damage DNA and promote cancer development, said Kensler. CDDO-Im can also inhibit cancer formation by interfering with this inflammatory process.

Because it can stimulate the body's cancer-fighting capabilities at such low doses, Kensler believes that CDDO-Im is an excellent candidate for cancer prevention use in humans. If this compound can produce such a potent and dramatic reduction in the number of pre-cancerous growths, it should have an equally dramatic impact on the development of actual cancers, he said.

In addition to serving as a valuable tool in the development of new cancer prevention interventions, CDDO-Im may offer protection in a wide range of other disease settings. We know that the Nrf2 protein plays a role in regulating many different kinds of genes involved in protecting the cell from harmful agents, said Kensler. It follows that activation of the Nrf2 pathway with CDDO-Im could provide protection against a number of diseases where environmental agents play important roles in their causes.

First disease-specific protein library opens new drug paths

Wed, 08 Feb 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Perhaps more significantly, these researchers expressed a subset of the 1,300 protein-expressing complementary DNAs in the library into a model system mimicking cells of a human breast, allowing them to study on a broad scale how these proteins might contribute to the development of breast cancer. Through this comprehensive approach, they identified potentially novel functional activities for both well known and lesser-known breast cancer-associated proteins.

The process of carcinogenesis is complex and involves the activation of many different cellular programs, says Joan Brugge, PhD, Chair, HMS Department of Cell Biology, and co-principal investigator of this initiative, called Breast Cancer 1000. A significant limitation for breast cancer research has been the inability to distinguish whether certain proteins that are altered in breast tumor cells are the cause or the effect of conversion of normal breast cells to malignancy. The systematic approach that we've enabled and demonstrated will allow researchers to track cancer-causing proteins in simulated environments, with the goal of learning how to impede them.

The availability of this collection will enable pilot experimentation and accelerate the development of faster techniques for studying breast cancer in a mammalian setting, says Joshua LaBaer, MD, PhD, director of the Harvard Institute of Proteomics (a division of Harvard Medical School), and also co-principal investigator. To advance breast cancer research quickly, we are making the BC1000 library publicly available. It can be viewed from the Harvard Institute of Proteomics website (

Drug design teams in the pharmaceutical industry traditionally have not used proteomics approaches to screen for potential targets, primarily because systematic proteomic tools are in their infancy, said Steven Carr, PhD, who was not part of this research team, and who leads the Proteomics group at the Broad Institute (of Harvard University and Massachusetts Institute of Technology). While this work is highly in-vitro and needs further validation, the tools and approaches demonstrated in this study show a potentially valuable screening tool for drug companies, primarily as a means to triage for novel targets to design drugs around, said Carr, who prior to joining the Broad was director of Computational and Structural Sciences at SmithKline Pharmaceuticals and (now GlaxoSmithKline) and led protein science and proteomics groups at Millennium Pharmaceuticals. This study helps lay the groundwork for new and refined proteomics tools for cancer and other diseases.

The American Cancer Society estimated that 211,240 new cases of invasive breast cancer would be diagnosed among women in 2005, as well as an estimated 58,490 additional cases of non-invasive (in situ) breast cancer. The ACS also estimated that approximately 40,410 women would die from breast cancer last year. Only lung cancer accounts for more cancer deaths in women.