GENERAL

Next Era of Cancer Therapy Aims to Separate Cancer From Blood Supply -(M.D. Anderson Cancer Center-16/05/2003)

With cancer, it's all about the body's bounty of blood. If all the blood vessels in the body were lined up end-to-end, they would form a line that could circle the earth twice. Yet the body produces still more blood vessels on demand, such as to heal wounds or grow embryos. This task of forming new blood vessels -a process called angiogenesis - is also critical to the development of cancer. In order for a rapidly growing tumor to maintain its growth, a tumor "signals" already existing blood vessels to sprout new branches to feed it - and new tiny vessels develop in short bursts. Given the thousands of miles of blood flow already in place in a human body, vessels usually don't have far to grow to hook up to a tiny tumor that cries for blood. But scientists know that unless a tumor connects to a supply of blood, it will grow to a mere 1,000 cells and then stop. Separating cancer from its blood supply - or keeping them from linking in the first place - is the goal of clinicians and researchers at The University of Texas M.D. Anderson Cancer Center and other leading research institutions.

Teams of multidisciplinary investigators are working to understand the factors that bind blood vessels to cancer and then to perfect "anti-angiogenic" therapies that prevent further blood vessel growth. They are examining the problem from all angles and situations. Tumor angiogenesis occurs when cancer cells begin sending signals to surrounding tissue, activating proteins that encourage the growth of new blood vessels - so researchers are investigating ways to shut down those signals to stop a tumor from becoming rooted. They also are studying what to do if the cancer already has an established blood vessel network and how to give blood vessels themselves the power to resist a cancer. M.D. Anderson's focus on the blood vessel-cancer paradigm has garnered scientific praise from around the world, as well as millions in funding for research - for example, $9.2 million was awarded to the institution in 2002 from the National Cancer Institute for anti-angiogenic research. That grant supports four different angiogenic research projects that provides a backbone to ongoing clinical research. Among other areas, researchers are examining markers of angiogenesis and the specific signaling pathways through which angiogenic proteins are controlled. They are developing methods, including non-invasive imaging, to detect tumor cell death and blood vessel damage from new anti-angiogenic therapies. "Founded on the hypothesis that interim measures will enable early and accurate clinical assessment of anti-angiogenic therapies, this program is an important example of the outstanding translational research being conducted," says Waun Ki Hong, M.D., head of M.D. Anderson's Division of Cancer Medicine. "We must move beyond conventional approaches, combining targeted therapeutic strategies with established regimens of chemotherapy, radiotherapy, and surgery to develop effective cancer treatment and cancer prevention strategies."

More than 60 different anti-angiogenesis compounds are in human testing around the world, and one estimate has it that at least 6,500 cancer patients worldwide have been treated with some form of experimental anti-angiogenic therapy. While the development of drugs that inhibit angiogenesis as a means of controlling cancer is moving forward, the progress is slow, Ellis says. "Researchers are just beginning to understand this complicated process," he explains. Many of these "baby steps" have to do with the nature of the treatment. Most traditional cancer treatments, like chemotherapy, exert a toxic punch on cancer cells, and therefore their effect can be readily measured; either tumors quickly shrink or they don't. Biologic drugs, like anti-angiogenesis agents, however, are designed to rather quietly interrupt a molecular process that leads to cancer development or growth. It can be hard to know if the drugs are working - they may not shrink a tumor immediately but slow its growth, or stop it from spreading. And that is difficult to measure, especially in comparison to the short-term timeframe used to evaluate chemotherapy effects. Such is the case with endostatin, the naturally occurring protein known to inhibit tumor growth in animals. It was discovered by Michael O'Reilly, M.D., an assistant professor in radiation oncology at M.D. Anderson, when he was a researcher at Harvard Medical School in the 1990's.

Endostatin was one of the first specific anti-angiogenic drugs to be tested and M.D. Anderson was one of three centers chosen in 1999 to conduct a clinical trial using the agent, which had received wide publicity even before it had ever been tested in humans. But results of that trial, published in September, 2002, show endostatin, although safe to use, is only minimally effective when given as a single agent in the treatment of advanced cancer. Still, extensive testing hinted that some biologic activity may be going on, although that is a subject of debate. "We saw several tumors shrink for a short time, so it appears endostatin may be having an effect," says the study's co-leader, Roy Herbst, M.D., Ph.D., associate professor of medicine in the Department of Thoracic/Head and Neck Medical Oncology. The fact that endostatin didn't show dramatic clinical activity is not unusual, says James Abbruzzese, M.D., professor and chairman of the Department of Gastrointestinal Medical Oncology at M.D. Anderson. It takes time to understand how a new agent, especially a biologic drug, may be working, and then to tweak it, he says. "For first-generation drugs, progress is often incremental, but research should go on," says Abbruzzese.

As an example of how difficult it is to test these new drugs, Ellis and other colleagues at M.D. Anderson have found that using an anti-angiogenesis inhibitor may initially increase blood flow to a tumor rather than decrease it. "Ironically, it may reduce leakiness in blood vessels, and allow small vessels to open up," he says. But as the agent works over time, a tumor may shrink or stop growing. "We are into testing the third generation of anti-angiogenesis therapies," says Ellis. "The agents are constantly being refined to be more effective."

One class of angiogenesis inhibitors being tested in cancer patients at M.D. Anderson are molecules designed to stop the growth of blood vessels cells. Included in this category is endostatin, but also thalidomide, a drug developed in Germany which was marketed in the 1950's as a sleep aid and reliever of morning sickness, until it was realized that thalidomide inhibited limb development during the first trimester of pregnancy. Although a widely feared drug, thalidomide is currently used as an anti-inflammatory agent, particularly to treat some symptoms of leprosy. It also has been reported to be beneficial as a treatment of skin lesions and some diseases associated with AIDS. In the mid-1990's, researchers wondered if the very qualities that damaged the growth of limbs in neonates - angiogenesis - might be helpful in preventing tumors from promoting blood vessel formation. Today, at M.D. Anderson, thalidomide is being tested in a number of different cancers, including prostate cancer, multiple myeloma, brain and ovarian cancer.

Another group of angiogenesis inhibitors being tested in human clinical trials at M.D. Anderson are molecules that interfere with steps in the angiogenesis "signaling cascade" - the biochemical pathway that leads to new vessel development. Included in this category are drugs that block the binding of the growth factor known as vascular endothelial growth factor (VEGF) to cells lining the blood vessels (also known as endothelial cells). VEGF is produced by tumor cells and initiates the process of angiogenesis, promoting the development of a new network of blood vessels that sprout and grow toward a tumor. By blocking the binding of VEGF, these drugs help deprive the tumor of necessary nutrients to grow.

Among such experimental drugs being tested at M.D. Anderson is AE-941 (Neovastat), a naturally occurring product extracted from shark cartilage. Charles Lu, M.D., an assistant professor in Thoracic/Head and Neck Medical Oncology is leading a nationwide, Phase III trial of Neovastat in advanced lung cancer. Another agent, bevacizumab (also known as Avastin, anti-VEGF, RhuMabVEGF), is undergoing extensive review at M.D. Anderson, in a variety of cancers - lung cancer, malignant mesothelioma, carcinoid tumors, myeloid leukemia and pancreatic cancer. Like other molecularly targeted drugs, bevacizumab is designed to specifically interfere with a biological process that promotes tumor growth or survival. This drug is an antibody that neutralizes the VEGF protein by "sticking" to it, preventing it from triggering blood vessel growth.

Researchers are also investigating the power of a common arthritis medication to impede angiogenesis. They have already found that celecoxib (Celebrex) can reduce the number of colon polyps that develop in a rare genetic form of colon cancer - a discovery which led to FDA approval of the medication for that cancer therapy. Now, other ongoing M.D. Anderson clinical trials with celecoxib include studies on its effectiveness in prevention of Barrett's esophagus (a precursor to esophageal cancer), and superficial bladder cancer. It is also being tested with locally advanced lung cancer and cervical cancer, in combination with other treatments.

Other M.D. Anderson researchers are going back to the lab to pick apart what works and what doesn't - and why. Using mouse models, O'Reilly is finding that the order in which new cancer therapies are delivered is crucial. For example, chemotherapy has to get into cancer cells to be effective, but anti-angiogenesis drugs are designed to block off access to cancer cells - and may render chemotherapy ineffective if used first, he says. On the other hand, chemotherapy treatment may leave behind cells that are hard to kill with anti-angiogenesis therapy, O'Reilly says. "Sequencing matters, and that has been a surprise," he says, "But it helps us understand a lot about tumor biology."

What researchers are discovering about anti-angiogenesis is helping them put together the pieces of a grand plan - a way to deliver anticancer drugs efficiently and effectively to a single tumor site in the body, and nowhere else. Just as the post office uses street addresses and zip codes to deliver a letter to one home out of millions, researchers at M.D. Anderson have discovered that blood vessels have a vascular address system of their own. That's how blood cells circulating in the blood stream know where to go, according to the researchers who made the discovery, Renata Pasqualini, Ph.D., and Wadih Arap, Ph.D., associate professors in the Department of Genitourinary Medical Oncology and Cancer Biology. "Scientists have long thought that blood vessels are uniform and generic, much like plumbing in a house," says Arap. "Recently, we recognized that blood vessels that feed various organs are actually strikingly different, and blood vessels in tumors stand out as being particularly unusual," adds Pasqualini.

This diversity, signified by different vascular zip codes, can be used to target the delivery of diagnostic and therapeutic agents to specific organs and to sites of disease such as tumors and metastasized cancer cells, says Pasqualini. Physicians in the future may be able to deliver a cornucopia of anti-angiogenesis drugs, each of which works in different vascular zip codes, says Abbruzzese. He adds it may even prevent cancer development in susceptible patients using these agents. "We still have much to learn," says Abbruzzese. "But with such promising research, we now have some real opportunities to make progress."

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Study: Radiation Starves Cancer While Killing It-(HealthScoutNews-15/05/2003)

Radiation kills cancer cells in more than one way, says a new study that lends support to a sometimes controversial theory. In addition to killing cells directly, radiation also stops angiogenesis, the growth of blood vessels that are essential for a tumor's growth, says a report in Science. This is the first genetic evidence that damage to the blood vessels that feed a cancer can cause that cancer to shrink, say researchers from the Memorial Sloan-Kettering Cancer Center in New York City. Dr. Judah Folkman of Harvard Medical School proposed the theory several years ago that stopping angiogenesis could be an effective way to treat cancer. However, that theory remains controversial because a number of trials aimed at stopping angiogenesis in cancer patients have produced mixed results.

Radiation kills cancer cells directly. But working with genetically engineered mice, the researchers showed that it damages cells other than those of the cancer -- the delicate endothelial cells that line blood vessels and are essential to their function. The mice were manufactured to be deficient in an enzyme called acid sphingomyelinase, which regulates apoptosis, the process of natural endothelial cell death. Cells of two kinds of cancer, melanoma and fibrosarcoma, were implanted in those mice. The tumors grew at twice the rate seen in normal mice. And the cancers did not shrink when the mice were exposed to radiation, as would normally happen.

The new study arose from previous work indicating that damage to small blood vessels played a role in the injury caused to the gastrointestinal tract caused by radiation, says a statement by Dr. Richard Kolesnick, head of Memorial Sloan-Kettering's signal transduction laboratory and a leader of the research team. "It was unclear that this would also happen in tumors," Kolesnick says. "Our new study shows that damaging the angiogenic blood vessels of the tumor does indeed contribute to tumor regression." There are several ways the finding could be used to improve cancer treatment, says Dr. Carlos Cordon-Cardo, director of the Memorial-Sloan Kettering division of molecular pathology and a member of the research team. "Knowing that these blood vessels respond to specific factors, we can aim therapy at those factors," he says. And it may be possible to combine anti-angiogenesis therapy with radiation therapy that is aimed not at the cancer cells themselves but at the factors that promote blood vessel growth, Cordon-Cardo says. But more research is needed to determine such important factors as the exact role radiation treatment would play in such combined therapy and the most effective radiation doses, the researchers say.

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Study Links Obesity To Certain Cancers-(ET-23/04/2003)

New research suggests carrying extra pounds could increase the risk of certain cancers. NewsCenter 5's Liz Brunner reported that a study published in New England Journal of Medicine shows that not only does being overweight increase the likelihood of diabetes and heart disease, it also increases the risk of cancer. "This is really important," said Dr. Graham Colditz, of the Harvard School of Public Health. "We can unequivocally say 14 percent of cancer in men and 20 percent in women is due to being overweight and obesity." That's 90,000 deaths each year that could be prevented if Americans maintained a normal weight.

Colditz said putting on an extra pound here and there can be dangerous over time. "Typically we've been looking at a 20- to 40-pound gain over the weight at the end of high school as indicating an increase in risk of cancer," Colditz said. The study also suggests that certain cancers not previously linked with obesity actually are, including cervical, ovarian, pancreatic, and liver cancer, as well as non-Hodgkin's lymphoma. "It's going to give us a much more powerful motivation to work at avoiding weight gain in adulthood because the payoff across many cancers is going to be substantial," Colditz said. Previously, researchers linked breast, colon and gallbladder cancer with obesity. Doctors said it's not clear what the connection is, although the theory is being overweight changes hormone levels, which somehow affects cancer cell growth.

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WHO: Cancer May Rise 50 Percent by 2020-(ET-04/04/2003)

The number of new cancer cases worldwide is expected to increase by 50 percent over the next 20 years, partly because poor nations are adopting unhealthy Western habits, the World Health Organization said. The World Cancer Report is the first comprehensive examination of cancer around the globe, covering the current understanding of its causes, prevention and treatment. "The overall message is that we can prevent a third of cancers," one of the report's editors, Australian cancer specialist Bernard Stewart said.

Worldwide, about 10 million people are diagnosed with cancer every year and 6 million people die from it. The report projects that the annual number of diagnoses will reach 15 million by 2020, based on current trends in smoking, diet and exercise. Although one-third of the cases theoretically were preventable, that does not mean the coming increase realistically could be slashed by that amount, said WHO's cancer chief, Dr. Paul Kleihues. "I think what we can do is slow down the increase. Anything more is not realistic," said Kleihues, director of WHO's International Agency for Research on Cancer.

Rich nations have more cancer than poor ones, mostly because of tumors tied to bad habits such as smoking and drinking, eating too much or the wrong kinds of foods, and lack of exercise. "If we want to go back to a lifestyle associated with a low incidence of cancer, small changes to our lifestyles would not be sufficient. We would really have to go down to a very restricted diet, no overfeeding, starting in childhood. I don't think that's realistic expectation," Kleihues said. From one angle, the task of stemming the impending rise in cancer is easier in poor countries, Kleihues said, because 23 percent of tumors there are due to infections that can be prevented now or soon. "We already have a first-class vaccination against hepatitis B virus and there is no question that soon the rates of hepatitis B-induced liver cancer will come down in many countries," he said.Eradication of the helicobacter pylori bug, which causes stomach cancer, also would help, as would the advent of a vaccine against the human papillomavirus, which causes cervical cancer.

However, officials are especially concerned about the trend toward unhealthy lifestyles in the developing world, where early detection and treatment of cancer is not as good as in rich nations. In developing countries, 80 percent of cancer patients die, compared with 50 percent in rich nations. "It's quite disturbing. Many of them are taking up smoking and striving to get the Western lifestyle. That's very hard to stop. They will unfortunately miss this unique chance of maintaining a low cancer burden," Kleihues said. WHO plans to update the 350-page cancer report every few years. The report attempts to condense the wealth of knowledge about cancer into one book, offering governments an important resource in their efforts to tackle the disease. "This book has the advantage of putting between two relatively slim covers all of the facts that otherwise amount to a stack of textbooks about 5 feet tall," said Stewart, director of cancer services for the Southeastern Sydney area health service.

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Making sure the chemo isn't worse than the cancer-(Seattle Post Intelligencer Reporter-31/03/03)

Getting cancer is hard enough. Getting treatment shouldn't make it worse. But for a small percentage of patients, chemotherapy is more terrible than the disease itself, causing organ failure and even death. It's not just a bad-luck lottery that determines which patients do poorly with chemo. There are biological differences between them that, once better understood, could help doctors tailor "custom chemo" regimens for patients and eliminate treatment-induced deaths. That's the goal of Dr. George McDonald, a Fred Hutchinson Cancer Research Center scientist who, along with a team of colleagues, recently published work that marks a significant first step in such a strategy.

Since the 1950s, chemo doses have been determined in a relatively crude manner. "You increased it until the toxicity was too high or there was no evidence of benefit," said McDonald. "You'd push and push until you cured much of the cancer, but not at the expense of the patient dying." But some patients still died, even though they got doses that were tolerated by many others. And some got significantly sicker than others.

Kathleen Summers didn't die, but nearly five years after receiving treatment for leukemia, she is still recovering from the effects and has to be careful of her liver. Summers, now 34, found out she had leukemia in the same phone call that confirmed she was pregnant. The Woodinville woman waited to undergo treatment until she delivered her son. Then, only days after recovering from a Caesarean section, she started an intensive regimen in preparation for a bone marrow transplant. "Over a four-day period I got completely lambasted with chemo and radiation," she said. "I felt like they had completely fried my brain and insides." At one particularly frightening point, her body started to quit. "Everything shut down," she said. "I wasn't breathing. I had seizures." Summers is grateful, though. Everyone else on her floor died, either from cancer or from treatment. She vowed to do something to improve the odds for others. Summers was one of 147 patients who participated in McDonald's research to determine how different people handle chemo."We've been doing this for 30 years," said McDonald. "And even with a finely worked out recipe, 10 to 15 percent of patients suffer organ damage."

As a hematologist, McDonald has spent his clinical career studying the aftermath of treatment by oncologists. A fortuitous test-tube observation, however, led McDonald and his colleagues to dream of a new approach. Dr. Laurie DeLeve at the University of Southern California, an old friend of McDonald's, was looking at how Cytoxan, one of the oldest and most widely used chemo drugs, affected liver cells in test tubes. For decades, doctors had believed that Cytoxan didn't harm the liver. The drug itself isn't toxic, but is broken down in the liver into various components, one of which has an anti-cancer effect. That active component destroys DNA in cancer cells, which is how chemo works. But in the process of breaking down the drug to produce the active component, the liver also creates another byproduct, and this one is toxic to a specialized cell that lines parts of the liver.

"A liver is like a sponge with holes and blood percolates through the holes," he said. The holes are lined with endothelial cells. When DeLeve put Cytoxan in a test tube with liver cells, nothing bad happened. But when she put it in with both liver cells and endothelial cells, something attacked and destroyed the endothelial cells. That was one of the first indicators that the breakdown of Cytoxan by the liver cells was creating some end product that could cause organ damage, said McDonald. More important, it was a clue that could change the way cancer drugs were given. "How you metabolize (the drug) is a clear predictor of whether you are in the 10 to 15 percent of people with organ damage," he said.

McDonald's research, published this month in Blood, the journal of the American Society of Hematology, showed there was a wide range in how people metabolized the same dose and that this difference was reflected in who died. "If you're a high-toxin generator, your risk of dying is roughly sixfold greater," he said. In the initial study, for example, 15 of the 147 patients died of treatment-related complications, but it was not known at the time they received the treatment who among them would be at risk. "How you metabolize the drug is critical," he said. Researchers are now using the data to try to deduce a formula for giving the high

est dose with the least possibility of damage. Chemo doses prior to bone marrow or stem cell transplants are normally divided into two equal parts. But McDonald plans to test whether adjusting the second dose, based on the body's response to the first one, will help patients better tolerate the treatment. The hope is that a customized approach could reduce deaths during treatment by as much as 20 percent, said McDonald. Indeed, customizing drug delivery is a very hot topic in medical circles today, said John Slattery, a professor of pharmaceutics at the University of Washington. "This issue of understanding the different disposition of drugs in the body is extremely important in terms of optimizing therapy," he said. Down the road, however, an even more tantalizing approach could exist. If scientists can figure out the genetics underlying the differences, they may be able to devise a genetic test that would tell in advance who would do poorly with chemotherapy. The National Cancer Institute has just funded a study to "ask the question, is this wide variation (in metabolism) due to a genetic difference," said McDonald. "We're going gene hunting."

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Eating Less Meat Boosts Longevity, Report Says-(Reuters-10/03/2003)

People who eat little or no meat can expect to live significantly longer than the general population, a new report from the Center of Cancer Research in Germany (DKFZ) says. Between 1978 and 1999, the DKFZ monitored almost 2,000 people who ate either no meat or less than average. The group was comprised of vegans, who eat no meat, fish, eggs or dairy products, vegetarians, who eat eggs and dairy products, but no meat or fish, and occasional meat eaters, aged between 10 and 70. The monitored group had an average of 59 deaths for every 100 deaths in the general population during the period, results obtained from age-specific comparisons with the general population over five-year intervals showed.

But the study also revealed that completely avoiding meat does not make for the healthiest diet: within the group, for every 100 deaths among vegans, there were 66 among vegetarians and 60 among occasional meat eaters. "Essentially, the key issue here is having a properly balanced diet," said Jenny Chang-Claude from the DKFZ. Smokers in the group showed increased mortality rates of 70 percent compared with non-smokers. And those taking the most exercise reduced their mortality rates by more than 30 percent. No clear conclusions could be drawn on the influence of moderate alcohol consumption on longevity, the DKFZ said.

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Study suggests stress before cancer diagnosis can raise death risk-(USA TODAY-11/03/03)

Early-stage breast cancer could be most likely to kill women who had severe stress -- a family death, divorce, financial crisis -- in the year before diagnosis, a study says. The research tracked 80 patients over seven years, starting within a year of their diagnosis. There were 20 recurrences and 15 deaths. ''It's a very small study to be making any sweeping conclusion. But it does pose questions that need to be followed up on,'' says Frances Visco, president of the National Breast Cancer Coalition, an education and advocacy group in Washington, D.C. The women, all diagnosed with Stage 2 cancer that had not been detected beyond the lymph nodes, filled out questionnaires about stressors in their lives. Severe stress after their cancer diagnosis had no relation to recurrence or death, says psychiatrist Karen Weihs of George Washington University School of Medicine in Washington, D.C. But major troubles in the year before diagnosis nearly tripled the women's odds of having a recurrence or dying from the disease, Weihs says. She and co-author Diane Blyler reported at the American Psychosomatic Society meeting here.

Breast cancer is so stressful that it can swamp any other troubles, blurring the differences in life stress among the women after diagnosis, Weihs speculates. But terrible jolts in the year before diagnosis could affect the body's ability to fight off disease, Weihs says. For example, post-traumatic stress disorder impairs the immune system. Women in the study had sons who were fighting AIDS , had lost their jobs and faced other traumas. ''Their immune system may already be maxed out,'' says Weihs, so they could be vulnerable to more lethal forms of cancer.

Psychologist Steven Tovian has counseled breast cancer patients for 25 years. He says he sees no tie between life stress before diagnosis and dying, ''but it would be difficult to prove either way.'' ''We are learning more and more that stress does affect the immune system, though we're not at a point yet to say it causes cancer,'' says Tovian, director of the health psychology program at Evanston Northwestern Healthcare in Illinois. ''There are so many individual differences in immune function, and stress affects people differently,'' he says. Weihs says she intends to repeat the study with 500 patients to see whether the findings hold up.

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U.S. To Adopt Stricter Cancer Guidelines for Kids-(Environment News Service-04/03/2003)

The final draft of revised U.S. federal guidelines for cancer risk assessment assumes that children are more vulnerable to the effects of certain carcinogens than adults. It is the first time the U.S. government has officially accepted this position The move could change the way the federal government devises rules and policies to limit the American public's exposure to environmental pollutants. "This is a really big step and has far reaching implications for protecting children's health," said Jane Houlihan, vice president of research for Environmental Working Group, a non profit environmental research organization. "The government's message is simple. Children are at greater risk from exposure to carcinogens than adults."

The U.S. Environmental Protection Agency's (EPA) final draft of new guidelines for cancer risk assessment, released Monday, "explicitly recognizes that variation exists among people in their susceptibility to carcinogens." The final draft considers children aged two and younger to have 10 times the cancer risk of adults when exposed to mutagenic carcinogens, which cause cancer through direct damage to DNA. Children aged two through 15 would be considered to have three times the risk of adults.

Mutagenic carcinogens include arsenic, benzene, formaldehyde, mutagen X, brominated organics and polycyclic aromatic hydrocarbons. EPA's guidelines for carcinogen risk assessment are the framework for agency scientists to assess possible cancer risks from exposures to environmental pollutants. They are used throughout the federal government to evaluate risks from environmental pollutants. These guidelines have not been updated since they were first issued in 1986 and the current review is intended to make greater use of the increasing scientific understanding of risks from carcinogens. The proposed updates to these guidelines could prompt reevaluation of existing standards.

For its review, EPA analyzed 23 peer reviewed studies of cancer incidence from the past 50 years. Environmentalists and public health advocates said the new guidance is a good first step, but some are concerned it does not consider gender differences in cancer risks and worried that it could allow new guidelines for adult risks to carcinogens to be weakened. And EPA has evidence that supports increasing the risk standard for children even further, Houlihan said. The figure of 10 times used by EPA for children under two years of age is the average of its analysis, but some mutagenic carcinogens have been shown to be some 65 times more potent when exposure occurs during childhood. EPA data shows that half of lifetime cancer risk accumulates in the first two years of life, Houlihan said, and the agency should extend its guidance to cover carcinogens that act through other mechanisms than mutagenicity, such as phthalates and atrazine. "The guidelines need to extend to all carcinogens," said Houlihan.

EPA's review finds not enough available data to determine cancer risk assessment from non mutagenic carcinogens for specific segments of the population. It suggests that a variety of approaches still need to be developed and additional research is required. The increasing scientific evidence that children face higher risks from exposure to carcinogens prompted the agency to release for public review and comment draft supplemental guidance for assessing early life exposure to carcinogens. The supplemental guidance is part of the agency's response to a 1994 recommendation by the National Research Council that "EPA should assess risks to infants and children whenever it appears that their risks might be greater than those of adults." The final draft guidelines on risk assessment, according to EPA, reflect many of the comments and suggestions provided to EPA by public and independent scientific peer reviews. The public can submit comments on the proposed guidelines through May 1, 2003. They will take effect after a final review by an independent scientific advisory board.

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Possible cancer causer appears in nutritious food as well as in fast food-(AP-25/02/2003)

A possibly cancer-causing substance appears not only in popular fast foods, but in everyday, nutritious staples, too, U.S. government scientists say. Acrylamide, a substance that at very high doses causes cancer in animals, made headlines last spring when Swedish scientists discovered it lurking in popular foods like french fries and chips. High-carbohydrate foods cooked at very high temperatures seem to contain far more acrylamide than other foods. But products with lower levels that are eaten more frequently than junk-food snacks - from vitamin-packed breakfast cereal to toast and coffee - increase the U.S. population's overall exposure, the Food and Drug Administration said.

That means someone who dislikes fries but guzzles coffee or eats cereal every morning might eventually absorb as much as a fry-lover, suggests the FDA's new computer model. Don't change your diet, FDA scientists stressed. Cereals, for instance, are fortified with vitamins and minerals that make them a far better choice than many breakfast options - especially since no one knows yet if acrylamide really poses a cancer risk to people. But as manufacturers hunt for ways to remove the chemical from popular foods, "the point of this is ... no one food is contributing to the majority of the acrylamide" in the U.S. diet, said FDA scientist Donna Robie.

"There are going to be no quick fixes," added Robert Brown, a nutritionist at Frito-Lay Inc., which is experimenting with acrylamide-lowering techniques. "We have a very complex problem involving the entire food supply." Frito-Lay and Procter & Gamble outlined some simple steps that might eventually remove acrylamide from at least some foods, without risking safety or taste. Options include adding the amino acid cysteine or minerals such as calcium that may block acrylamide formation, or changing cooking techniques. "The research, through preliminary, looks very encouraging," said FDA food chief Joseph Levitt.

The FDA and safety regulators worldwide are studying how acrylamide gets into food and if enough is there to pose any risk to people. Scientists have discovered that it forms when a naturally occurring amino acid called asparagine is heated to very high temperatures - baking or frying, not boiling or microwaving - with certain sugars such as glucose. Potatoes are especially rich in both asparagine and glucose, leading to the high acrylamide levels in chips and fries. Cooking increases the level in some other foods. Soft bread, for instance, contains very little acrylamide, but toasting more than quadruples the chemical level. Other foods, such as milk, frozen vegetables and meat, contain little or no acrylamide.

The FDA, extrapolating from national diet studies, estimates that seven food types probably account for most exposure. Fries and chips had the highest levels, from 16 to 48 micrograms per serving. Other foods made the list with far lower levels because so many people eat so much of them: _Toast, at 9.8 micrograms per serving, and soft bread, at 2.2. _Breakfast cereal, 7.3 micrograms. _Cookies, 6.6 micrograms. _Coffee, 2 micrograms. Other popular foods, including pizza, have yet to be measured for acrylamide.

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Delaying Radiation Treatment Leads To Cancer Recurrence-(ET-25/02/2003)

Many cancer patients hope to wait to begin their radiation treatments until after they've fully recovered from their surgery. But it hasn't been clear until now whether waiting has any unfavorable effects on the progression of the disease. Researchers from Canada, reporting in the Journal of Clinical Oncology (Vol.21, Issue 3, 2003; 555-563) now say that delaying radiation leads to a higher chance the cancer will come back. Canadian doctors have a reason to be concerned about delays in radiation. Canada, along with several other countries, may have too few radiation oncology facilities. This means patients have to wait their turn in spite of having a life threatening disease.

Local Recurrence Seen In Breast Cancer Patients:To better understand the hazards of this delay, the researchers, led by William Mackillop at the Queen's Cancer Research Institute, reviewed studies in which the outcomes of early radiation therapy were compared with those of later treatment. The only cancers for which there was enough information were breast cancer that had been treated with lumpectomy, and head and neck cancer (cancers of the throat, voice box, mouth, nasal passages). In both types of diseases, radiation is commonly used to prevent the cancer from returning in the area in which it started. Lumpectomy - removing only the cancer - is the preferred surgery for most women with breast cancer. This allows the woman to keep her breast and maintain a normal appearance. But because the cancer will often recur in the breast, radiation therapy is used as a preventive. Most of the time it is successful.

The researchers found that if radiation is delayed, the treatment is less successful. They divided breast cancer patients who had been treated with lumpectomy into 2 groups: those receiving radiation within 8 weeks of surgery and those treated after 8 weeks. They found the cancer came back in the breast 60% more often if radiation was delayed by more than 8 weeks.

Chemotherapy May Add To The Delay: Often, after surgery for breast cancer, other treatment such as tamoxifen and/or chemotherapy is recommended. These are mainly aimed at stopping the cancer from traveling to distant sites such as the bones, lungs, or liver. Because chemotherapy can increase the side effects of radiation, the radiation is often delayed until chemotherapy is complete. So even though the patient is receiving chemotherapy, this delay still leads to a doubling of the local recurrence rate, according to the Canadian study. If the cancer does come back in the breast, it can almost always be treated with surgery. Although a mastectomy will usually be needed, the woman isn't in any greater danger of dying from the cancer. The researcher couldn't find any evidence that women whose radiation was delayed were more likely to die of their cancer.

Delay Also Troubling For Head And Neck Cancers: The same thing held true for head and neck cancer. Delaying radiation treatment after surgery - this time by more than 6 weeks - lead to a tripling of the recurrence rate. Once again, it wasn't clear that this delay led to a greater chance that the patient would die of their cancer. This study by Canadian physicians was likely initiated because of their difficulty in obtaining prompt treatment for their patients. On average, most patients in the US receive treatment about 10 days after being referred for radiation. In Canada it takes more than a month to begin treatment.

Still, the problem of delay poses a dilemma for doctors and their patients in the US as well. Often, chemotherapy is recommended immediately after surgery. There is a body of literature demonstrating that it can lead to a higher cure rate. Many times, radiation is put off to avoid the side effects of the combined treatment. Now it appears that there may be a trade-off between long-term cure and the problems that can arise if the cancer comes back in the local area. Often, in women with breast cancer, this means they will lose their breast. But in the absence of chemotherapy, there should be no dilemma, according to the study. "The longer radiotherapy is delayed, the poorer the outcome is likely to be," write the study authors. "We recommend that delays in initiating radiotherapy should be as short as reasonably achievable."

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New Molecule May Help Enhance Cancer Treatments-(Reuters-26/02/2003)

Scientists have identified a molecule they believe could improve cancer treatments and help protect people from the lethal effects of high levels of radiation in a nuclear attack. The molecule, MDC1, acts like an emergency service in cells to detect and repair DNA damage caused by radiation. Scientists believe its discovery will improve understanding of how cells respond to radiation and how defects in those responses lead to mutations that cause cancer. "Understanding what happens within our cells when they're pounded with radiation is important for a whole range of reasons, not least for predicting the effects of cancer radiotherapy," said Professor Steve Jackson. "In addition, it may suggest how the effects of radiation might be curtailed following a possible nuclear attack," the molecular biologist at the University of Cambridge in England added.

MDC1 is one of several molecules that work together to prevent cells from dividing unless all DNA damage has been repaired. Jackson and colleagues in Britain and Denmark believe the molecules act together like an engine to repair damage that can lead to cancer. Blocking the activity of MDC1 makes cells more susceptible to genetic damage caused by radiation. "It is becoming clear that drugs based around this kind of knowledge do have the potential in the clinic, particularly in the cancer area, to enhance existing cancer therapies," Jackson, whose research is funded by the charity Cancer Research UK, explained in an interview.

The scientists believe a drug that blocks MDC1 could make radiotherapy treatments, which cause lethal damage to DNA in cancerous cells, more effective. Radiotherapy may not kill all cancerous cells so increasing their vulnerability could prevent the cancer from recurring. By contrast, if scientists could find a method to enhance the activity of the molecule, which Jackson concedes would be much more difficult, it may theoretically be possible to spare people the effects of high doses of radiation in a nuclear accident or attack. Jackson and his team, who reported their findings in the science journal Nature, are now trying to determine how much MDC1 is found in cancerous tumors. "There is the potential of using this information in a diagnostic way, for example identifying which patients have MDC1 could help to predict response to treatment," he added.

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Gene Found for Cancer's Spread-(HealthScoutNews-28/02/2003)

An American research team has discovered a gene responsible for the spread of cancer through the body -- a process that ultimately kills the cancer patient. The researchers are hopeful that the discovery will lead to new, less-toxic drug therapies for the disease. Their strategy hinges on "knocking out" the cancer-spreading gene in order to halt the movement of cancer cells from the primary tumor site. "We've found a gene that is essential for the migration of cells. And potentially, by blocking the action of this gene product, we can control the cancer and manage the disease," says lead author Dr. Richard Pestell, who is now chairman of Georgetown's department of oncology. The work was done at the Albert Einstein College of Medicine, before Pestell went to Georgetown. It will appear in the May issue of Molecular Biology of the Cell.

Pestell's team was tipped off that the cyclin D1 gene might play a role in metastasis after learning that patients with spreading cancer also had an over-expression of the gene. The scientists tested this curious phenomenon in the laboratory by examining the progression of cancer in mice that were missing the cyclin D1 gene. Using a high-powered microscope, they observed that the cancer cells were missing an outer "ruffle" layer that would typically enable them to migrate. Without this structure, the cancerous cells were immobilized and the disease was held in check. Current therapies for cancer halt the disease's spread by hobbling the cell division process. As a result, patients suffer from hair loss and other side effects. If the researchers can determine exactly how cell migration differs from cell proliferation, new therapies could focus on just the cells that migrate, which would eliminate many of the debilitating symptoms that come with chemotherapy.

While suggestive, the findings are not conclusive, says Dr. Danny Welch, a professor of pathology at University of Alabama-Birmingham. "The data show that mice without the cyclin D1gene ... tend to develop tumors at a much lower rate. And if you couple those observations with the clinical observation that cyclin D1 is associated with more aggressive tumor spread, the implication is that it may control metastasis," he says. "But they haven't tested that theory directly in this paper. It's a great lead-in for a big number of future experiments," he adds. While such a treatment would not eliminate a cancerous tumor, it would control the disease and prevent the cancer from attacking other parts of the body, Pestell says. "Like diabetes, patients could live normally with the cancer in place," he adds.

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Some Cancer Patients Benefit from Online Support-(Reuters Health-19/02/2003)

Many breast cancer patients who go online for emotional help find Internet support groups helpful, according to new study findings. This may be particularly good news for women who live in rural areas, or those otherwise less able to access social services than their peers. The findings "proved the feasibility of providing high quality professional service to women with breast cancer (and) demonstrated that real and deep relationships, necessary for productive groups, can be established online," study author Dr. Morton A. Lieberman of the University of California at San Francisco told Reuters Health. "The women in the groups maintained close relationships long after the groups ended," he added.

The study involved 32 women--divided into four groups--who met online for one-and-a-half hours weekly for 16 weeks. Half of the women lived in rural areas or small towns and the others lived in medium-sized or large cities. Most (56%) of the women were in the early stages of the disease. Roughly two-thirds of the women said they benefited from the Internet support groups, Lieberman and his colleagues write in the journal Cancer. The women reported less depression, and while they said their pain was as intense as ever, they had fewer negative reactions to it. For example, they found the pain more tolerable and less agonizing than they did previously. These women also tended to express more "zest for life" and increased spirituality, according to the researchers. Yet, they seemed to be more likely to suppress their emotions after they participated in the support groups than they were beforehand. The reason for this latter finding is unknown, according to Lieberman. "This is an issue for further study," he said.

Six (20%) women withdrew from the study--a rate nearly comparable to that for group face-to-face psychotherapy, Lieberman and his team note. These women appeared to be less able to cope with their anxiety and more likely to report suppressing their cancer-related thoughts and feelings than those who continued in the study. They were less likely, however, to say that their pain interfered with their daily life, study findings indicate. "Those who began and did not finish may be a different kind of woman," the researchers write. For example, their reports of less pain "may be an indicator of less need for a support group." On the other hand, Lieberman and his team speculate, this may also "represent an aspect of suppression." Altogether, in light of the findings, "the rapid spread of internet use...suggests that internet delivered support groups can be made available to diverse populations," Lieberman said, such as those who live in areas that lack social resources for dealing with cancer and other illnesses.

Another benefit of the online intervention is that it was much less costly than traditional face-to-face support groups, he added. Lieberman is currently involved in a study comparing Internet and face-to-face support groups and another evaluating the benefit of Internet support groups for people with Parkinson's disease and other illnesses. A recent report by the Pew Charitable Trust found that 52 million adults in America obtain health or medical information online and nearly 5 million participate in online support groups. The California Breast Cancer Research Program funded the study.

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Breaking the Bad News When the Word Is 'Cancer'-(Reuters Health-18/02/2003)

Hearing the word "cancer" is never easy, but a new study suggests that patients are less likely to be depressed later on if their doctor doesn't tiptoe around the word when breaking the news. Patients are also less likely to be depressed later if doctors discuss their diagnosis in a forthright manner, talk about the severity of the situation and encourage patients to be involved in treatment decisions. "Without a doubt, people are far more well-informed about cancer," said Dr. Penny Schofield. "In general, people want to find out everything they can about their disease and treatment options." The findings are from a study of 131 Australian patients newly diagnosed with melanoma, the most rare but dangerous type of skin cancer. Most were male and the average age was 58, according to the report in the journal Annals of Oncology.

The patients filled out a questionnaire about four months after their diagnosis, and then two more in the 13 months following the first survey. Patients who said they had been told all the options or as many as they wanted to hear, reported the highest levels of satisfaction. Those who felt they had a "major say" in their course of treatment were less likely to be depressed 17 months later. Most patients in the study were satisfied with their doctors' communication strategies because they listened to their needs, said Schofield, who is at the Peter MacCallum Cancer Institute in Victoria, Australia. "Encouraging patients to express their feelings and actively listening to their responses are skills which are pivotal in the communication training programs that are now becoming widely available for health professionals working with cancer," she said.

Patients who felt their doctor was reassuring and prepared them for their diagnoses, and who received clear and complete information when they requested it, had the highest levels of satisfaction. Having family members present, or people who the patient asked to have in the office when their doctor broke the news, resulted in a higher level of patient satisfaction as well. Schofield said family members play a very important role to the cancer patient. "The type of support wanted varies from person to person, and can vary from day to day in the same person," she said. "The best advice I can give," said Schofield, "is for relatives and family to try to understand how their loved one wants to be supported."

There has been little research done on communicating with children who have cancer. Schofield says that they should be treated the same as adults, and that every person has a right to know the truth about their illness. She says children should be given opportunities to ask questions about cancer and be given "truthful responses in words they can understand."

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Developing World Has Most Cases of Child Cancer-(Reuters-14/02/03)

British cancer experts called for an international campaign to improve the treatment of childhood cancers in the developing world where 72,000 youngsters die of the illness each year. Seventy percent of children with cancer in Britain and the United States are alive five years after diagnosis, but because of poverty, malnutrition and a lack of medical facilities and drugs it's often a death sentence in poor countries. "What is required is an international campaign...to improve the supply and reduce the cost of drugs used to treat cancer in these countries, and a commitment from those more privileged to help those in the developing world to help themselves," said Vaskar Saha, the head of the charity Cancer Research UK's children's cancer group.

Childhood cancer is comparatively rare but 84% of the 166,000 children under the age of 15 who are diagnosed with the disease worldwide live in poor countries. Saha told a news conference to mark International Childhood Cancer Day on Saturday that partnerships forged between hospitals in the developed and developing world have made strides in improving treatments for children with cancer in poor countries but more needs to be done. "We have the technology to cure seven out of 10 children with cancer," he said.

Advances in chemotherapy drugs, which are now more effective and less toxic, and a better understanding of how to treat cancer in children have resulted in improved survival rates, but most children in the developing world do not have access to the best treatments. "We should try to get the cost of these drugs reduced," said Saha, adding that a campaign to reduce the costs of drugs, similar to what is being done to improve access to AIDS treatments in poor countries, would be a good step. World trade negotiators have been trying to hammer out a formula that will improve access in developing countries to cheaper or generic drugs. Earlier this week they agreed to allow more time to reach a decision.

Leukemia is the most common childhood cancer and accounts for nearly one third of all cases of the disease. It is followed by brain and spinal tumors. Fifty-four percent of childhood cancers are in Asia, where 55% of deaths occur, followed by Africa with 20% of cases and 25% of deaths, according to the charity.

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Group to Focus on Cancer, Genes' Function-(Reuters04/02/03)

British and Dutch scientists launched an international initiative to uncover the function of genes and to determine how new drugs can be designed to fight cancer. The ambitious project will use data from the human genome project, which mapped the estimated 35,000 genes in humans, to try to pinpoint which ones are involved in cancer and could be potential targets for new therapies. "This is the first time such an undertaking has been made," Dr Julian Downward, of the British charity Cancer Research UK which is funding the project, told a news conference.

Together with Dr Rene Bernards and scientists at the Netherlands Cancer Institute, Downward and his colleagues will use a technique called RNA interference to systematically find out which genes are linked to cancer. RNA is a messenger system that carries instructions to other parts of the cells. RNA interference (RNAi), which has been dubbed the biggest scientific breakthrough in a decade, silences a targeted gene. The natural mechanism was discovered in the nematode worm which uses tiny pieces of RNA to switch off rogues genes that could harm it. Scientists have already used RNAi to switch off genes one by one in the worm in an effort to pinpoint those linked to fat storage and obesity.

The Anglo-Dutch consortium plans to use RNA interference to initially de-activate and look at the function of 300 genes that have been linked to cancer. If the technique is successful, they will continue the process with another 8,000 genes and hope to eventually extend the initiative to cover the 35,000 genes in humans. The scientists will also use RNA interference on 30,000 cancer cells to find common genetic components. "Using RNA interference, we should be able to find out precisely what we need to take away from a cancerous cell in order to make it normal again -- essentially we will be dismantling cancer at the level of its genes," Downward said. The function of most of our genes is still unknown, so the big challenge for scientists is to discover what they all do. "Such an endeavor has never before been possible, because dissecting out the function of a single gene from around 35,000 is extremely difficult," said Paul Nurse, chief executive of Cancer Research UK. "But thanks to the incredible discovery of RNA interference, we think we should now be able to crack the problem," he s

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Older Cancer Patients Fare Well with Chemotherapy-(Reuters Health-07/02/03)

People over age 70 who have cancer appear to be able to handle chemotherapy treatment, a small study suggests. While the bulk of cancer patients are over the age of 65, previous research has found that older patients are less likely to be given chemotherapy compared to younger cancer patients. Doctors may avoid chemotherapy treatment in older patients because they underestimate a patient's life expectancy or they fear the toxic side effects may be too much for older people, according to the report. However, despite experiencing the general toxicity associated with chemotherapy drugs, older patients with cancer who are otherwise healthy appear to tolerate the treatment, report lead study author Dr. Hongbin Chen and colleagues from the University of South Florida in Tampa.

The study included 37 patients, 70 years or older, with a variety of cancers including breast, lung, colon, ovary, prostate and uterine, among others. All of the cancer patients were followed for about 130 days and were assessed for various aspects of their physical and mental health and quality of life, according to the report in the journal Cancer. The patients all received various chemotherapy regimens. Thirteen (35%) had a beneficial response, either partially or completely, nine remained stable, and in seven patients the cancer became worse. Seven patients required additional chemotherapy. While many of those in the study experienced decreases in physical and emotional functioning, "changes in most (test) scores were small in magnitude clinically," the authors report. "Older cancer patients undergoing chemotherapy may experience toxicity but generally can tolerate it with limited impact on independence, comorbidity (other illnesses) and quality of life levels, write Chen and colleagues. "It is important to recognize and monitor these changes during geriatric oncology treatment," they conclude.

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Study Doubts Acrylamide in Food Causes Cancer-Reuters-28/01/03)

Fried foods such as potato chips and French fries may contain a substance that can cause cancer in animals, but the levels do not appear high enough to increase the risk of the disease in humans, researchers said. Swedish scientists sparked a worldwide food scare last year when they found high levels of acrylamide, a suspected human carcinogen, in high-carbohydrate foods including crackers, certain cereals and cooked potatoes. But new research by scientists at the Harvard School of Public Health in Boston, Massachusetts, and the Karolinska Institute in Sweden--the first to look at acrylamide in terms of human diet and cancer risk--suggests it may not be as dangerous as people have been led to believe.

"There was a lot of concern in the public that was raised from the initial findings of acrylamide in food," said Dr. Lorelei Mucci of Harvard. "This study provides some evidence that the amount of acrylamide people are taking in is probably not sufficient to increase the risk of cancer," she told Reuters.Although conclusions about the health risks of acrylamide cannot be drawn from one study, Mucci said the research is a starting point that could help to address some of the concerns raised by Sweden's National Food Administration, a government food safety agency.

Acrylamide, a colorless compound used in manufacturing processes, in laboratories and in water purification, is labelled as a probable carcinogen based on data from animal research. But Mucci said doses given in animal studies were several times higher than what humans would be exposed to through diet or other sources. "These data suggest the doses of acrylamide people are taking in can be effectively detoxified," she said, referring to her research, which is published in the British Journal of Cancer.

The American and Swedish researchers studied the diets of 987 patients with either cancer of the colon, bladder, rectum or kidney, as well as more than 500 healthy people, to determine whether levels of acrylamide could be a factor in the development of the disease. They calculated participants' dietary acrylamide intake by asking them how often they ate a range of different foods, including items--such as fried potatoes, bread and biscuits--that have been found to have medium or high levels of acrylamide. The researchers found no link between the compound in food and the risk of bladder or kidney cancer, and high amounts of acrylamide were associated with a reduced risk of bowel cancer.

However, the scientists said the lower bowel-cancer risk could be due to other factors, such as the high fibre content in the foods. "This study provides preliminary evidence that there's less to worry about than was thought," Mucci said. Scientists believe acrylamide is formed during the cooking process, when starchy foods like potatoes, rice and cereals are fried or baked at high temperatures. "We know that acrylamide can be carcinogenic to animals, but this study suggests that either the levels in food are too low to affect cancer risk, or that the body is able to deactivate the chemical in some way," Sir Paul Nurse, chief executive of the charity Cancer Research UK, said in a statement.

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Genetic Switch Discovery Offers New Cancer Hope-(Reuters-31/01/03)

Scientists have discovered how a genetic switch that allows cancerous cells to divide and spread works, in a finding that could open up a new avenue to treat many of the most common cancers. The switch controls an enzyme called telomerase. In normal cells, the gene that regulates it is tightly packaged and coiled and the switch is off, so the enzyme is not produced and the cells can only divide a finite number of times. But British and Swiss researchers found that cancer cells manage to unravel the gene and flip the telomerase switch back on, and that blocking the process cuts off the enzyme and cancerous cells stop multiplying. "The discovery of how the switch works is what we have done and of course that has implications for therapies because there is a great interest in new drugs that will modify the way genes express (or work)," Professor Robert Newbold, of Brunel University north of London, told Reuters.

Cancer develops when the control signals in a cell go wrong and it mutates. Instead of destroying itself, the cell multiplies uncontrollably and forms a tumour. Although there are more than 200 types of cancer, they all start in the same way. Newbold and scientists from the Swiss Cancer Research Institute in Lausanne flipped off the telomerase switch in cancerous cells in the laboratory by adding genes from normal cells that made the telomerase gene recoil into its compact form. "We have shown that when we add back these repressor genes from normal cells the switch flips and the gene rapidly flips back to its compact, silent form," said Newbold. "We know that if we stop telomerase working in cancer cells they stop dividing. The question is how we go about stopping it," he added.

The scientists, whose findings are reported in the journal Cancer Research, believe that a drug that targets the gene and the way it is packaged could switch off telomerase in cancerous cells. Because telomerase is active in about 85-90 percent of cancers, a drug that blocks its production could potentially be effective against many different types of cancer. Newbold is setting up a European-wide collaboration between research institutes and pharmaceutical companies to design drugs to block the production of telomerase. In normal cells it switches off when a fetus is about 20 weeks old and still in the womb. Newbold believes the shutting down is a protective process to prevent the development of cancer because without the enzyme cells have a finite lifespan -- they can only divide a certain number of times. Newbold thinks the mechanism evolved to protect humans against cancer. "If evolution has used this route to protect us from cancer. The logic goes that it should be the route to use to treat it," he added.

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Targeting Cancer Cells-(HealthScoutNews-27/12/2002)

A new method that uses ultrasound to deliver chemotherapy drugs to specific body areas affected by cancer could help reduce side effects and enhance the potency of anti-cancer drugs, says a study in the Cancer Research. Brigham Young University researchers tested the new technique in laboratory animals.

In this approach, a drug is packaged in tiny molecules of water-soluble plastic. That prevents the drug from interacting while passing through the bloodstream. Ultrasound is then used to release the drug from the package once the package reaches the specific area of the body affected by cancer. The tests using this method on laboratory animals produced significant reductions in tumor size, but it will be several years before this technique might be used on humans. People with cancer who are being treated with chemotherapy often suffer painful side effects as the powerful chemotherapy drugs course though their bodies, damaging healthy tissue as well as tumors.

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EU Experts Confirm Safety of Aspartame-(Reuters Health-24/12/2002)

The much-studied artificial sweetener aspartame is indeed safe, according to scientific advisors to the European Union. The EU's Scientific Committee on Food (SCF) conducted a review of scientific research published about aspartame since 1988, when it last reviewed the sweetener's safety. Issues raised in the past include possible toxicity from methanol, which is formed when aspartame is broken down in the body, and a possible link with epilepsy and brain tumors, which has been disputed. All these areas have been addressed in scientific studies and reviews of evidence, the committee notes.

The sweetener has also been investigated by bodies such as the US Food and Drug Administration, Britain's Committee on Toxicity and the French health regulator, AFSSA, the EU scientists note. In their report, the committee quotes the French agency on the cancer-causing potential of aspartame: "Taking into account all the studies that have been conducted...it was concluded that aspartame had no carcinogenic potential on the brain in experimental animals." On the subject of behavioral or neurological changes, the report states that a number of well-designed studies in healthy individuals "failed to highlight any treatment-related adverse effects on behavior."

Other studies show that aspartame is no more likely than a dummy-pill to trigger headaches. The review highlights a range of studies showing no link between aspartame and epilepsy. In particular, it notes that the Epilepsy Institute in the US concluded in 1986 that aspartame is not the cause of epileptic seizures. As for brain cancer, the committee looked at the one study purporting a link. "The SCF considered this report and concluded that the data did not support the proposed...increase in the incidence of brain tumors," they write. "The Committee concluded that on the basis of its review of all the data in animals and humans available to date, there is no evidence to suggest that there is a need to revise the outcome of the earlier risk assessment or the acceptable daily intake previously established for aspartame," the report concludes.

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Dignity Crucial During Last Months of Life: Report-(Reuters Health-20/12/2002)

Interviews with dying patients suggest that most feel they have not lost a great deal of dignity during their final days. However, those who do experience a loss of dignity say that loss is accompanied by hopelessness, psychological stress and feeling dependent on others, new research reports.

In a sample of 213 cancer patients with a life expectancy of less than 6 months, only 16 said they felt they had a moderate to strong sense of a loss of dignity. However, that minority was also more likely than others to report feeling anxiety, depression, and that they had lost their will to live. Those with a so-called "fractured" sense of dignity also reported more feelings of hopelessness, of being a burden to others, and a low quality of life. Those who felt a loss of dignity were also more likely to say they needed help with a variety of activities, such as bathing and dressing, and felt more dependent on others. While most terminally ill patients do not appear to experience a loss of dignity, these findings demonstrate that when they do, it can have seriously detrimental effects, study author Dr. Harvey Max Chochinov of the University of Manitoba in Winnipeg told Reuters Health.

As such, preserving terminal patients' dignity may prevent other unwanted feelings and experiences, Chochinov noted, and should therefore become an integral aspect of caring for dying patients. "Making dignity at the end of life needs to be accepted as the only gold standard in providing end-of-life care," Chochinov said. He and his colleagues report their findings in The Lancet.

In an accompanying editorial, experts write that the current study gives some cause to celebrate. The "finding that 93% of patients in the study reported no loss of dignity is remarkable," according to Drs. Manish Agrawal and Ezekiel J. Emanuel of the National Institutes of Health in Bethesda, Maryland. However, the editorialists note that the high levels of dignity among terminal patients could also stem from flaws in the study design, such as in evaluating dignity. Chochinov and his colleagues also excluded patients with especially painful symptoms, Agrawal and Emanuel write, and those with more pain may be more likely to experience a loss of dignity. Alternatively, the authors suggest that end-of-life care could simply have improved. "These data suggest that death and dying in the modern world are not inherently undignified," Agrawal and Emanuel conclude.

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Chemotherapy for Pediatric Cancer Does Not Affect Subsequent Pregnancy- (Reuters Health-06/11/2002)

Female survivors of childhood cancer who were treated with chemotherapeutic agents do not have an increased risk of adverse pregnancy outcomes, according to a report in the American Journal of Obstetrics and Gynecology. However, pelvic irradiation does seem to increase the likelihood of having a low birth weight infant.

Dr. Daniel M. Green, of Roswell Park Cancer Institute, Buffalo, New York, and colleagues examined the effect of prior radiation therapy or chemotherapy for childhood cancer on pregnancy loss, live births, and birth weight. They reviewed medical records and pregnancy outcomes of females in the Childhood Cancer Survivor Study (CCSS) who completed questionnaires. The researchers note that 4029 pregnancies were reported by 1915 women. Sixty-three percent resulted in live births, 1% in stillbirths, 15% miscarriages, 17% abortions, and 3% unknown or in gestation. "The rate of live birth was not lower and the rate of stillbirth was not higher for the patients treated with any particular chemotherapeutic agent in comparison to those who had not been treated with the agent," Dr. Green and colleagues report.

The offspring of women who received pelvic irradiation were more likely to weigh less than 2500 g at birth (RR 1.85). There was an increased risk of miscarriage among women whose ovaries were in the radiation therapy field (relative risk [RR] 1.86) or near the field (RR 1.64). However, none of these differences were statistically significant. The risk was not increased in women whose ovaries were shielded (RR 0.90) compared with patients who did not receive radiation therapy. The investigators believe that the findings "are reassuring and generally support the conclusion that prior treatment with chemotherapeutic agents does not adversely affect pregnancy outcome." However, they add that patients and their physicians should be aware of potential complications related to prior pelvic irradiation.

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Wisconsin Research Sheds New Light on Cancer Metastasis-(cancerpage.com-07/11/2002)

University of Wisconsin researchers believe they may have discovered a key ingredient cancer cells need to metastasize or spread throughout the body. Once cancer has spread beyond its primary tumor site, it is much more difficult to control and a cure is less likely. "The real, life-threatening problem with most cancers is that they migrate away from the initial site," Richard Anderson, a UW-Madison pharmacology professor and senior author of the paper tells cancerpage.com. Anderson and colleagues have identified an enzyme, PIPKIć661, that all cells use to build "focal adhesions," structures cells use to hitch rides on other cells for transport elsewhere in the body. "Researchers have been looking for this enzyme for years," Anderson says. "There is not another enzyme like this that plays this role, that's why we think this is so key."

The discovery could lead to determining a method of turning off the production of the enzyme in cancer cells and thus depriving them the ability to metastasize. But the research, Anderson says, also demonstrates the enzyme's role in other crucial activities during a cancer cell's life cycle. "This enzyme is the first step in a process that leads not only to a cell's ability to move but to enhance proliferation as well and enhance its own survival," Anderson says. Anderson likens the enzyme's functions to the supporting function of a tree trunk. If you eliminate the trunk, all the branches - growth, reproduction and movement - aren't possible. The question Anderson and his colleagues are trying to answer now is how to selectively turn off cancer's ability to produce and utilize this enzyme.

They are also examining the DNA structure of metastatic cells to see if cancer cells that have spread from the primary tumor have somehow altered the enzyme in a way that allows them to utilize it more efficiently than normal cells. Earlier this year, scientists at the Beatson Institute in Glasgow, Scotland identified a molecule that breaks down the natural adhesion in solid tumors allowing cancer cells to move away from the primary tumor. The Anderson team research examined the next step; how those loosened cells use PIPKIć661 to construct the vehicles (the focal adhesions) needed to migrate. "Improving our understanding of how cancer spreads should help in the development of drugs to block the process," Professor Margaret Frame of the Beatson Institute said in August. "If we could confine cancer cells to the original tumor it would give surgery a much greater chance of success and reduce the risk of the disease reappearing in other parts of the body." The Anderson team's research is published in the journal Nature.

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Austrian Scientists Working on Cancer 'Vaccine'-(Reuters Health-25/11/2002)

Austrian researchers are developing a new cancer treatment that involves "vaccinating" patients against their own tumor by stimulating the immune system. In a 3-year pilot study carried out at St. Anna's Children's Hospital in Vienna, 20 children in the final stages of cancer underwent treatment with the new approach. Results were promising enough to prompt a larger study.

In the study, doctors first removed the patients' tumors by surgery. They then took a sample of white blood cells, out of which dendritic cells were cultured. Dendritic cells alert the immune system to the presence of cancer or other unwanted materials by displaying small parts of the foreign substance on their surface. Researchers think that activating dendritic cells might prevent secondary tumors from developing by stopping cancer cells from slipping past the immune system.

The Austrian group took the children's own dendritic cells and exposed them to tumor cells, prompting them to display tumor antigens. After a final quality check, the vaccine was administered to the children in the form of an injection over a 4.5-month period. The new treatment, the first to use this specific type of in-vitro manipulated dendritic cell in childhood cancer, was found to have very mild side effects, with only slight itching on injection and a mild fever. Although the preliminary study was not designed to look at the effectiveness of the treatment, researchers found that, in some cases, the disease stabilized and tumor growth slowed, Dr. Heinrich Kovar, scientific director at Vienna's Children's Cancer Research Institute, told Reuters Health. "This is the first time this type of anti-tumor vaccine has been used in pediatric malignancies. The goal of the pilot study was to determine whether vaccination using antigen pulsed dendritic cells was feasible in children and whether there would be any toxicity," Kovar said.

The team at the Children's Cancer Research Institute, which is led by Dr. Thomas Felzmann, is now planning a second phase of trials. These will include adult patients who have responded to chemotherapy but still have tumor cells in their bodies. The trials will involve hospitals in Austria, Germany and the Czech Republic. "The long-term aim is to use the anti-tumor immune therapy to help patients with minimum residual disease," Kovar said. He added that the treatment could be in use within 5 to 10 years. The research is unpublished, although Felzmann told Reuters Health the group expects to submit patient data for publication early next year

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Possible Cancer Chemical Varies in Foods-(AP-04/12/2002)

The longer french fries and certain other starchy foods are fried or baked, the higher their level of a possible cancer-causing substance, new federal research suggests. The substance, called acrylamide, made headlines last spring when Swedish scientists discovered that it forms in fries, potato chips and other high-carbohydrate foods cooked at high temperatures. Several other European countries confirmed Sweden's discovery - and now the latest batch of tests, revealed Wednesday by the U.S. Food and Drug Administration, shows that acrylamide levels vary widely even within the same brand of food. For example, FDA scientists bought french fries at four different Popeye's restaurants and found a three-fold difference between the batches with the highest and lowest acrylamide levels. In tests of 25 seemingly identical bags of Lay's Classic Potato Chips, only two bags contained the exact same acrylamide level.

Acrylamide forms during traditional cooking methods - whether you buy a ready-made food or fry or bake from raw ingredients in your own kitchen - and it seems that the longer certain foods are cooked at especially high temperatures, the more acrylamide appears. What does all this mean for consumers? Acrylamide causes cancer in test animals, but has never been proved to do so in people - meaning no one knows if higher levels in one food than another is a problem. FDA scientists stressed that there's no reason yet for Americans to start avoiding certain foods for fear of acrylamide - a message echoed by the food and restaurant industries. Instead, concentrate on eating "a variety of foods that are rich in high-fiber grains and fruits and vegetables," said FDA food safety chief Janice Oliver.

Because acrylamide forms during traditional cooking methods, dietary exposure "is something that's been going on a long time," noted FDA senior scientist Bernard Schwetz. But the big variability suggests acrylamide levels can be lowered in foods, FDA scientists told a meeting of the agency's food advisory board. Scientists in FDA chemist Steven Musser's laboratory bought frozen french fries that, before baking, contained almost no acrylamide. Baking them for 10 to 15 minutes as the package directs caused a very slight acrylamide increase - but none of the six scientists considered the fries done enough to be appetizing, so they stuck them back in the oven. After 30 minutes of baking, the fries were golden brown - and contained 120 times as much acrylamide. After 45 minutes, the now extra-crispy fries contained 400 times as much acrylamide as a mere 15-minute baking produced.

It's not just an issue for french fries. Even toasting bread increased acrylamide levels six- to 10-fold, the FDA testing showed. In contrast, microwaving frozen french fries produced no acrylamide, Musser said. Likewise, other scientists say the chemical doesn't appear to form when foods are boiled. Nobody knows why, but perhaps those cooking methods aren't hot enough to produce the chemical reaction thought necessary to form acrylamide. Acrylamide is used to produce plastics and dyes and to purify drinking water. Although traces have been found in water, no one expected high levels to be in basic foods. Now scientists know it apparently forms when a naturally occurring amino acid called asparagine is heated with certain sugars such as glucose. Potatoes are especially rich in both asparagine and glucose, although foods from grains to even asparagus also contain it. Indeed, roasting asparagus produced very high acrylamide levels.

In contrast, the FDA tested hundreds of food samples and found products from infant formulas and baby food to frozen vegetables and meats acrylamide-free - foods that either contain little asparagine or aren't cooked at super-high temperatures. Food manufacturers insist their products aren't risky, but they're working with the FDA to understand acrylamide formation and to lower levels if possible, said Henry Chin of the National Food Processors Association. It may not be easy, he cautioned. For example, if frying temperatures are lowered too much potato chips turn out soggy. Also, levels of asparagine and glucose vary in different potato batches according to growing conditions and how long the tubers are stored raw, Chin said.

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Detecting Cancer's Spread (HealthScoutNews-05/12/2002)

A combination of positron emission tomography (PET) and computed tomography (CT) detects the spread of cancer better than PET alone. That's the finding of a new study by researchers at Johns Hopkins Medical Institutions. The research, presented today at the Radiological Society of North America's annual meeting in Chicago, found PET-CT was better able to distinguish cancerous from normal tissue and better able to locate where metastases have spread in the body.

The researchers used a scanner that fuses CT and PET technology. CT provides anatomical detail, while PET detects the metabolic activity of tumors. They performed 10 PET and 33 PET-CT scans on 28 people with ovarian cancer that was suspected to have spread to the abdominal cavity. PET alone produced three true positive and two true negative results, while PET-CT produced 14 true positives and 10 true negatives. The PET produced two false positives, while PET-CT produced no false positives. PET-CT produced five false negatives, and PET alone produced no false negatives. PET-CT was able to distinguish cancer from non-cancer 100 percent of the time), compared to 50 percent for PET. The researchers caution this was a limited study, and more research is needed to properly compare PET-CT to PET or CT alone.

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Painkillers May Be Source of New Anti-Cancer Drugs-(Reuters Health-05/12/2002)

By tinkering with the structure of a class of popular anti-inflammatory drugs designed to be easier on the stomach than aspirin and other arthritis drugs, it may be possible to develop new anti-cancer medications, new research suggests. The drugs, known as COX-2 inhibitors, "can be used as a molecular starting point to generate a new class of antitumor agents," Dr. Ching-Shih Chen of Ohio State University in Columbus, the study's lead author, told Reuters Health. Chen said that he and his colleagues have started trying to develop such drugs.

COX-2 inhibitors, like older drugs such as ibuprofen and naproxen, are nonsteroidal anti-inflammatory drugs, or NSAIDs. Older NSAIDs reduce inflammation by blocking an enzyme called COX-2, but they also block an enzyme called COX-1. This enzyme helps protect the lining of the stomach, so blocking COX-1 can cause stomach irritation. COX-2 inhibitors only block COX-2, leaving the stomach-protecting COX-1 alone. Although COX-2 inhibitors were designed to relieve pain, there have been several reports that the medications, along with other NSAIDs, may offer some protection against cancer, especially colon cancer, since the drugs' approval in the late 1990s.

According to Chen, researchers first suspected that blocking COX-2 enzymes encouraged cancer cells to kill themselves, a process called apoptosis. But in a previous study, Chen and his colleagues demonstrated that the effect of celecoxib and other COX-2 inhibitors on apoptosis was independent of their effect on COX-2. In fact, even though the drugs celecoxib (Celebrex) and rofecoxib (Vioxx) both block COX-2, celecoxib has a much more powerful effect on cancer cells. The new research, Chen said, "extends this concept" that COX-2 inhibitors affect cancer in some other way than by blocking COX-2. According the Ohio State scientist, the experiments were aimed at identifying the structures on celecoxib and rofecoxib that trigger cell death in prostate cancer cells.

In the research, which was not funded by drug companies and is reported in the Journal of the National Cancer Institute, Chen's team first scrutinized the make-up of celecoxib and rofecoxib. Then the researchers, using COX-2 inhibitors as the base, developed a new class of compounds that target prostate cancer. The research confirmed that COX-2 inhibitors affect cancer cells independently of their effect on COX-2. "Our data indicate that celecoxib also inhibits other cellular targets that are crucial to the survival of cancer cells," Chen told Reuters Health. "Disruption of the functions of these cellular targets," he said," leads to cancer cell death." Likewise, the investigators found that the compounds derived from these drugs also did not influence cancer cells by blocking COX-2. Instead, these derivatives targeted signaling pathways within prostate cancer cells. The research "is a tour-de-force in chemical synthesis," according to Dr. Raymond N. DuBois at Vanderbilt University Medical Center in Nashville, Tennessee. He cautions in an accompanying editorial, however, that these compounds need to be studied much more extensively. The development of new drugs "is extremely important for the success of the entire field of cancer prevention," according to DuBois, but he notes that "these new agents must be studied and tested in a systematic way to ensure their safety and efficacy."

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Red Wine Component to Be Studied Against Cancer-(Reuters Health-05/11/2002)

Scientists in Britain and the US announced plans to begin studying a possible new cancer prevention drug based on resveratrol, a natural compound found in red wine. Researchers at the University of Leicester in England and the University of Michigan will begin testing tablets of pure resveratrol in healthy volunteers early next year, the British university said in a statement. The US National Cancer Institute (NCI) is funding the research. Leicester's Professor Will Steward said resveratrol is found in peanuts and several berries, as well as grape skins and wine--particularly red wine. "Consumption of resveratrol has been proposed as one possible explanation for the low incidence of cardiovascular disease in Southern European countries with high red wine consumption, and resveratrol has been shown to possess anti-inflammatory and anti-cancer activity in experimental models. Since resveratrol may be of value in preventing cancer, the NCI are funding early clinical studies of pure resveratrol capsules in healthy volunteers and patients with early cancer," Steward added.

The 20 or so healthy volunteers in the study will initially be given one tablet containing 0.5 grams of resveratrol--equivalent to the amount in dozens and dozens of bottles of wine, Leicester researcher Professor Andreas Gescher told Reuters Health. Later trials will look at repeated doses. The point of these preliminary studies is to analyze how long the compound stays in the body and how much circulates in the blood. The researchers will also look for evidence of biochemical changes that might suggest a protective effect. "You obviously have to know that you're taking enough to get to the places that you want to prevent cancer," Gescher said. Several studies have found that wine drinkers seem to be less likely to develop cancer. Resveratrol has been suggested as one possible reason, but the benefits of wine may be due to a combination of reasons. "It is quite possible that after all this work we find resveratrol isn't active alone," Gescher said. "But first you have to look at what these single agents do and then you look at the next step."

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Thalidomide-Like Drugs Have Anti-Cancer Properties-(Reuters-29/10/2002)

Drugs similar to thalidomide, which was taken off the market four decades ago after causing severe birth defects, have cancer-fighting properties, scientists said. In a study reported in The British Journal of Cancer, researchers at St. George's Hospital in London said thalidomide-like drugs can reduce inflammation, prime the immune system to attack cancer and reduce blood flow to the tumor. "This group of thalidomide-like drugs seem to have very complex and yet exciting properties," said Dr Keith Dredge, the author of the study.

Thalidomide was used in the 1950s and early 1960s as an anti-nausea drug for pregnant women until doctors realized it was causing limb deformities in unborn children by limiting blood supply. Cancer experts believe the same property that caused the deformities could be harnessed to starve a tumor of its blood supply. Dredge and his team looked at different versions of compounds called IMiDs and SelCIDs in laboratory studies. They found that both were 10 times as potent as thalidomide in preventing the growth of blood vessels. New Jersey-based biotechnology company Celgene Corp, which funded the research study, has developed the thalidomide-like drugs. Dredge said the new compounds have the potential to stimulate the immune system which could help to prevent cancer. "Conversely, inflammation, which also occurs naturally in the body, may contribute to the development of cancer and our research shows that thalidomide-like drugs can reduce inflammation," he added in a statement. Scientists are also looking into the effectiveness of using thalidomide in treating lung, skin, kidney and breast cancer.

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Chinese Herbs for Cancer Care Put to 'Western' Test (Reuters Health-21/10/2002)

Researchers in Hong Kong are putting Chinese herbal medicines to the test using Western scientific methods, in the hope that they can offer solid advice to the many cancer patients who consider using the traditional remedies. Many people take Chinese medicines, particularly to reduce chemotherapy symptoms, said Dr. Tony Mok from the Chinese University of Hong Kong. "We just don't know whether it is effective or safe to use at the same time as conventional medicine," he said. "We tend, therefore, to advise against it--but we should know for sure."

Chinese herbal medicine uses combinations of around 250 possible herbs to restore an individual's internal harmony and fight illness. Because the approach is so different from Western medicine, comparing them is difficult, Mok said. "It is a different concept to conventional medicine, which is based on 'one drug for one disease,"' he explained.

At the European Society for Medical Oncology conference here, the doctor described a study that looked at whether the capacity of Chinese herbs to reduce the side effects of chemotherapy could be studied in so-called double-blind, placebo-controlled trials. Such studies are considered the best way to determine whether or not a treatment is effective. These trials compare a treatment with an inactive substance, or placebo. Only at the end of the study is it revealed--to doctors and patients alike--which patients received the treatment and which the placebo. The researchers studied 40 breast cancer patients and 13 colon cancer patients who had not previously been treated with chemotherapy. The participants were treated either with a powdered form of Chinese herbs prescribed by a traditional herbalist, or a placebo powder. Half of the treatments lasted at least 84 days and the Chinese remedies included an average of 17 different herbs. The trial has not finished, but early results suggest a small reduction in nausea, vomiting and loss of appetite, Mok said. "We have already demonstrated the feasibility of capturing the information from clinical research on Chinese herbal medicine with this methodology," he said. "And we could find something really useful that could point where we should look for better treatment."

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Studies show elderly can tolerate strong cancer drugs (AP Medical Writer-20/10/2002)

Many elderly patients can tolerate powerful cancer drugs better than doctors think, according to new research. Half of all cancers are diagnosed after the age of 65 and experts predict that 30 years from now, elderly people will comprise 70 percent of cancer diagnoses. However, there is no clear treatment strategy for cancer in the elderly. Most cancer drug trials exclude patients over 70 and doctors are subsequently reluctant to give the medications to older patients because they fear the side effects may be too harsh for them. Studies presented at a meeting of the European Society of Medical Oncology indicate that, at least in some cancers, elderly patients can be treated more aggressively. "Elderly patients must be offered the same treatment options as younger patients, even if treatment of the elderly is less cost-effective," said Dr. Silvio Monfardini, president of the International Society of Geriatric Oncology who was not connected with any of the studies. "It is wrong and unethical to discriminate against a patient because of their age.The whole problem of cancer in the elderly cannot be (avoided) because of the progressively aging population."

Experts agreed that researchers must start including elderly patients in clinical trials, given that as the population in many countries continues to age, people over 70 will make up an increasing proportion of cancer patients. People are co