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In a series of recently published papers - including studies now appearing in the July 2006 issues of two separate scientific journals - American Institute for Cancer Research (AICR) grantee Gilda Hillman, Ph.D. has shown that under certain conditions, soy makes prostate cancer cells more sensitive to radiation therapy. Dr. Hillman is part of a growing movement of scientists investigating how dietary factors might improve the treatment of cancer.

In labs and clinics across the country, many AICR researchers like Hillman are investigating how specific changes such as adding soy, garlic, fish oil or other foods to the diet may make it easier for conventional cancer therapies to target cancer cells, rendering treatment more safe and effective.

The process of making tumors more susceptible to the effects of therapy is called sensitization. It appears that specific foods or food components have the potential to make cancer cells more radiosensitive (susceptible to radiation) or chemosensitive (susceptible to chemotherapeutic agents).

Dr. Hillman has developed several cellular and animal models to study the interaction of soy and cancer therapy at the Karmanos Cancer Institute at the Wayne State University School of Medicine in Detroit, Michigan.

Dr. Hillman’s work revealed that a combination of soy and radiation therapy is more effective against prostate cancer cells in laboratory experiments than radiation therapy alone. Dr. Hillman began looking at the issue of cancer treatment by studying the radiosensitization effects of genistein, a single soy component.

But when her experiments revealed that under specific conditions, isolated genistein showed a troubling potential to stimulate the spread of tumor cells (metastasis) from prostate tumors to lymph nodes, Dr. Hillman switched to a dried powder of whole soy. She found that whole soy produced the same positive effects of genistein (radiosensitization) without the negative effect on tumor spread.

“It’s intriguing that whole soy did not stimulate prostate cancer cells to metastasize while a single soy component did,” said Hillman. “We’ve confirmed it in different prostate cancer models, we’ve pinpointed the likely biomolecular mechanism responsible, and we are beginning to incorporate our findings into ongoing clinical trials with prostate cancer patients under rigorously controlled conditions with fellow Karmanos clinicians Dr. Omer Kucuk and Dr. Jeffrey Forman.”

Initial Findings With Isolated Genistein Aroused Concern

In a paper featured in the July 2006 issue of online scientific journal BMC Cancer, Dr. Hillman and her colleagues report that genistein alone seems to work in vitro by inhibiting a protein called Nuclear Factor Kappa B (NF-kB), which is activated to help cells recover from damage, such as the kind of damage that occurs when cancer cells are exposed to radiation treatment. (This study provides strong confirmation of previous findings by Dr. Hillman’s colleague, Dr. Fazlul Sarkar.)

In fact, Hillman and her colleagues determined the optimal dose and timing to maximize this anti-cancer effect in vitro. Cancer cells exposed to genistein before and after radiation therapy show the strongest likelihood to have their growth arrested during a phase of the life cycle - just prior to cell division - during which cells are known to be most susceptible to radiation.

In another paper appearing in the July issue of the journal Radiation Research, Hillman and her colleagues have found that this combination of genistein and radiation therapy is effective against different models of prostate cancer in mice. Treating established prostate tumors with genistein first, followed by radiation, and finishing up with continuous treatment with genistein, effectively controlled tumor growth. The combination inhibited the growth of prostate tumors and kept cancer from spreading to lymph nodes

Dr. Hillman found, however, that pairing genistein with radiation therapy was crucial. In mice that were fed pure genistein alone, without undergoing radiation therapy, the soy phytochemical seemed to increase the rate at which prostate tumors spread to the lymph nodes.

“The increase in metastatic spread observed with pure genistein given alone concerned us, because we needed to establish that any participants in clinical trials with soy would not be exposed to risks, no matter how small,” she said.

The finding was of particular interest to Dr. Hillman’s colleague Dr. Omer Kucuk, who had previously shown that soy components such as genistein could be safely administered for more than 6 months in Phase I clinical trials.

Whole Soy Provides Benefits Without Risks, Study Finds

Dr. Hillman and her colleagues repeated their prostate cancer experiments using soy powder - a dried form of whole soy - instead of the isolated genistein soy component. They observed that soy exhibited the same anti-cancer effect: it sensitized prostate cancer cells to the effects of radiation by halting cellular growth.

Importantly, feeding whole soy was not associated with the increased metastasis of cancer into the lymph nodes that was observed with genistein, even when whole soy was administered by itself, without radiation treatment. These findings were published earlier this year in the journal Radiotherapy and Oncology and in the Proceedings of the American Association for Cancer Research.

“This is an important finding with great promise for people undergoing prostate cancer treatment,” said Dr. Hillman. “But this work is just beginning, and it is still too early to make practical recommendations about soy foods and soy supplements to cancer patients.”

Diet as Combination Therapy?

In addition to its ongoing mission to support research on diet and cancer prevention, AICR also provides funding for researchers exploring the interaction of conventional cancer therapies and a host of dietary factors, including:

* Quercetin (a phytochemical found in apples and onions)
* Glutamine (an amino acid found in meat, fish, beans, dairy)
* Curcumin (a component of turmeric, mustard, curry powder)
* Selenium (a mineral found in many plants and animals)
* Silymarin and Silibinin (both from the plant known as milk thistle)
* Vitamin D (from dairy foods)
* Phytic Acid (found in berries, seeds, broccoli)
* Fish Oil
* Garlic

Hundreds of researchers are now investigating diet’s role during the very specific set of conditions that occur during cancer treatment. They are finding evidence that common dietary components can help conventional therapy halt cancer growth, cut off blood supply to tumors, prevent cells from spreading to other areas of the body, or simply encourage cancer cells to “commit suicide.” Their work suggests that dietary factors may soon come to be regarded as vital parts of cancer treatment and recovery - tools to be employed with precision and care.

Treatment And Prevention Not the Same

But Hillman is quick to point out that findings from research on diet during cancer treatment do not speak directly to cancer prevention.

“With cancer patients, we have a clearly defined and measurable goal - get rid of the cancer. We can quantify the cause and effect relationship between dietary factors and existing tumors under specific sets of conditions, and repeat those experiments to verify our results.”

Because many different but interconnected factors influence cancer risk, and these factors take place over a lifetime, it’s more difficult for scientists who study cancer prevention to isolate the effects of specific dietary factors. In order to arrive at scientific consensus about the prevention of cancer, researchers instead pool many different studies of varying design to find commonalities among population, laboratory, and clinical data.

[Note: The advice for lowering cancer risk from the cancer prevention experts at AICR includes eating a varied diet rich in vegetables, fruit, whole grains and beans and low in animal fat, getting regular physical activity, and maintaining a healthy weight.]

Promising Research, but Still Preliminary

Dr. Hillman cautioned individuals who are currently undergoing prostate cancer therapy against loading up on soy foods or soy supplements without alerting their oncologists. More clinical data in human subjects are needed before advice about soy and supplements during treatment can be made, she said.

She noted that participants in clinical trials are only exposed to soy in forms and amounts that are rigidly controlled by researchers, unlike individuals who consume whole soy foods or unregulated, store-bought soy supplements. “The phytochemical profiles of whole foods vary widely, as do the components of supplements available commercially,” said Hillman. “That’s another reason we can’t yet generalize our results to the world at large.”

Until these ongoing clinical trials are completed, Dr. Hillman said, prostate cancer patients should always keep their doctors fully informed about their diet. “It’s clear that dietary factors can play a very important role - perhaps never more important than during cancer treatment,” Hillman said.

“It’s our goal to find ways to make this often painful and debilitating process less toxic, and more effective.”

Researchers have identified a novel gene that facilitates the spread of malignant melanoma, a life-threatening skin cancer, using a technique they say can speed the discovery of hard-to-find cancer genes.

A team of scientists from Dana-Farber Cancer Institute, led by Lynda Chin, MD, report that the gene, NEDD9, is abnormally abundant in more than a third of melanomas that have metastasized, but not in primary melanomas that have not spread.

The protein made by the NEDD9 gene allows the cancer cells to migrate beyond the initial skin tumor, to invade surrounding tissues and ultimately to metastasize to distant organs. While the protein itself does not lend itself to targeting by cancer drugs, say the researchers, insights gained in this study suggest that disrupting genes and proteins associated with NEDD9 may be fruitful in halting spread of melanoma.

“This is clinically important,” said Chin, “because primary skin melanoma doesn’t kill patients – metastases are the major problem. So understanding the events that drive metastasis may lead to identifying the most relevant targets for therapy, and potentially, for preventing metastasis.”

More than 62,000 cases of melanoma will be diagnosed in the United States this year, according to American Cancer Society estimates, and about 7,900 people will die of the cancer.

WOMEN who work at night, like those employed in call centers, could be prone to breast cancer and menstrual problems, according to an Institute for Occupation Health and Safety Development official.

Noting the increasing number of women working the graveyard shift — usually from 6 p.m. to 6 a.m. — in the ubiquitous call centers, the institute’s executive director, Noel Colina, said this type of working arrangement could pose health risks for women.

He cited a study by the US-based Fred Hutchinson Cancer Research Center which found that women who work the graveyard shift may face up to 60 percent higher risk of breast cancer compared to those who never work at night.

The study showed that exposure to light at night may affect the production of melatonin, a hormone which is mainly produced by the pineal glands during the night, Colina said.

“Nighttime sleep deprivation or exposure to light at night somehow interrupts melatonin production, which in turn stimulates the ovaries to kick out extra estrogen, a known hormonal promoter of breast cancer,” he said.

Aside from the increased risk of breast cancer, night time work may also interfere with the menstrual cycle.

“Painful menstruation (dysmenorrhea), absence of menstruation (amenorrhea), and heavy menstruation (menorrhagia) are conditions associated with women taking the graveyard shift,” Colina said.

He noted that this was the main reason pregnant women are not allowed to work at night as it can adversely affect the health of both mother and child.

“Although the study isn’t conclusive, it provides us [with] pointers on how to address and protect the occupational health and safety of working women at call centers,” Colina said.

He said call center companies should provide free and regular breast cancer screening for their employees as well as seminars on how to prevent breast cancer.

They should also sponsor regular seminars on health and safety in the workplace and set up health and safety committees, he added.

Ever stayed out too long in the sun? Missed a spot with the sunscreen and got sunburn?

Soon, there may be something new you can do about it.

A “morning after” lotion called Dimericine, which is being developed by AGI Dermatics, has under gone a number of studies and is currently being considered for approval by the FDA. That approval is expected to come through in the next two years.

Dimericine is basically an enzyme cream that repairs the skin’s damaged DNA. The body does this process naturally, but this cream would significantly speed it up.

So, does this mean someone can bake all day out in the sun and then use Dimericine the next day and not have to worry?

“No, you still need to use SPF,” said Dr. Doris Day, a dermatologist and author of “Forget the Facelift.” “This does not protect against the most dangerous kind of melanoma and only protects to some extent against the others.”

Melanoma causes only four percent of all skin cancer but is responsible for 75 percent of all deaths from skin cancer, according to the CDC. Basal cell and squamous cell carcinomas are known to be caused by excessive sun exposure alone, so Dimericine could help prevent those cancers. But melanomas are caused by a number of factors, so Dimericine wouldn’t be able to protect against it.

The “morning after” cream also won’t protect people from wrinkles or lessen the pain or redness of the sunburn, Day said.

“This isn’t a cure for sunburn,” she said. “It simply helps you repair the damage of that sunburn. But you’re still going to have to live through the unpleasantness of that burn.”

Skin cancer is the most common form of cancer, and 1.3 million Americans are diagnosed each year, according to the Centers for Disease Control. Day offered some tips on how to protect yourself against sun damage.

“You want to apply an SPF of 15 or higher,” she said. “You want to reapply at least every two hours, more often if you are sweating and swimming. And you also want to physically protect. You have to be sun smart. That means you wear a hat with a big brim … and sunglasses.”

Drinking an eight-ounce glass of pomegranate juice daily could slow the progress of prostate cancer, minimise cell damage and could also kill cancer cells, a new study has found out.

Researchers led by Allan Pantuck at the University of California, Los Angeles, studied 50 men who had undergone surgery or radiation treatment for prostate cancer - but had shown signs that the disease was rapidly returning, reported the online edition of BBC News.

The presence of prostate cancer cells is monitored by measuring levels of a chemical they produce called prostate-specific antigen (PSA). The researchers measured how long it took for PSA levels to double in individual patients — a short doubling time indicates that the cancer is progressing quickly.

The average doubling time is about 15 months, but in patients who drank pomegranate juice, this increased to 54 months. Pomegranates contain a cocktail of chemicals including isoflavones, which are believed to play a role in cancer cell death.

In the first large-scale, prospective study to examine possible links between chronic, low-dose exposure to pesticides and Parkinson’s disease (PD), researchers at the Harvard School of Public Health (HSPH) have shown that individuals reporting exposure to pesticides had a 70 percent higher incidence of PD than those not reporting exposure. No increased risk of PD was found from reported exposure to other occupational hazards, including asbestos, coal or stone dust, chemicals, acids, or solvents. The study will appear in the July issue of Annals of Neurology and also appears online via Wiley Interscience.

Previous studies had suggested a link between PD and low-level exposure to pesticides, though the data remains inconclusive. The researchers, led by Alberto Ascherio, associate professor of nutrition and epidemiology at HSPH, looked at data from the Cancer Prevention Study II Nutrition Cohort, a prospective study begun in 1992 by the American Cancer Society. Some 143,325 participants who responded to a follow-up survey in 2001 were included in the HSPH study. Researchers then contacted those individuals in the 2001 survey who reported a diagnosis of PD to ask if their medical records could be reviewed to confirm the diagnosis. Ultimately, Ascherio and his colleagues included in their study a total of 413 cases of PD with onset of symptoms and diagnosis after 1992.

The researchers used exposure data collected in 1982 from the CPS II mortality study, a study from which the Nutrition Cohort was drawn. Exposure to pesticides was reported by 5,203 men (8.2 percent) and 2,661 women (3.3 percent). Among those reporting exposure, after adjusting for age, sex, and other risk factors for Parkinson’s disease, there was a 70 percent higher incidence of PD than among people who reported no exposure. Those reporting exposure were more likely to be male than female to report their occupation as farmer, rancher or fisherman and to be blue-collar workers, but none of these factors could account for the increased risk of Parkinson’s disease, which was similar in men or women, and in non-farmers as well as farmers. The significant association between pesticide exposure and Parkinson’s disease among individuals who are not farmers is most likely explained by use of pesticides at home or in gardening.

Future studies will need to examine which specific pesticides or classes of pesticides are likely to cause Parkinson’s disease.

Researchers here have learned how a derivative of vitamin E causes the death of cancer cells. The researchers then used that knowledge to make the agent an even more potent cancer killer.

The compound, called vitamin E succinate, or alpha tocopheryl succinate, is taken by some people as a nutritional supplement, mainly for its antioxidant properties. In addition, it has a weak ability to kill cancer cells, and it has been tested as a cancer chemopreventive agent.

The substance kills cancer cells by causing them to undergo a natural process known as programmed cell death, or apoptosis. Until now, no one knew how the agent caused this to happen.

These findings answer that question and also indicate that the molecule’s antitumor activity is separate from its antioxidant effect.

The study, led by researchers with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), is published in the April 28 issue of the Journal of Biological Chemistry.

“Our findings could lead to a potent chemopreventive agent that has both strong anticancer and antioxidant properties,” says principal investigator Ching-Shih Chen, professor of pharmacy and of internal medicine and a researcher with the OSUCCC-James.

“Such an agent might help reduce the risk of prostate, colon and other cancers.”

Chen and his collaborators found that vitamin E succinate works by blocking a protein called Bcl-xL. The protein, which is made by healthy cells, is often present at abnormally high levels in cancer cells and protects them from dying when they should.

Using computer modeling, the researchers found that the vitamin E derivative works because it lodges in a groove in the structure of the Bcl-xL protein, disabling it.

However, the vitamin E molecule has a long, coiled, protruding tail that keeps the molecule from fitting tightly, and more effectively, into the groove.

“Once we identified how the agent and the protein interact, we asked how we could improve that interaction,” Chen says.

The scientists found that a relatively simple process of altering the molecule’s structure – basically cutting the tail short – allowed a tighter fit and improved the agent’s ability to kill cancer cells by five- to ten-fold in laboratory tests.

“Overall, out findings are proof of the principle that this drug can kill cancer cells very effectively but does very little damage to healthy cells,” Chen says.