March 29, 2007, 10:39 PM CT
Protein Averts Cell Suicide
Researchers have discovered how an unusual protein helps a cell bypass damage when making new DNA, thereby averting the cell's self-destruction.
But they also discovered that this protein, an enzyme called Dpo4, often makes errors when copying the genomic DNA sequence that later might cause the cell to become malignant.
The findings by scientists with Ohio State University 's Comprehensive Cancer Center are described in two back-to-back papers in The Journal of Biological Chemistry.
"Unrepaired DNA damage presents a big roadblock for the DNA replication machinery, which cannot go around it," says Zucai Suo, assistant professor of biochemistry. "This damage will trigger cell death because the DNA is not replicated.
"This protein bypasses the damage and saves cells from self-destructing, but it is very error prone, which suggests that it may also play a role in cancer."
Dpo4 is one of a family of enzymes called Y-family DNA polymerases that were first discovered about 10 years ago and are only now becoming understood.
"These enzymes provide a survival mechanism for cells," says first author Kevin Fiala, a graduate student in Suo's laboratory. "They allow DNA replication to continue, so the cell doesn't die. But they don't repair the DNA damage that exists."........
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March 29, 2007, 5:05 AM CT
Immune Suppression Paves Way For Cancer Trials
A natural mechanism pirated by tumors and HIV to evade the immune response is opening the door to better therapy for these conditions, scientists say.
The National Cancer Institute and Iowa biopharmaceutical company NewLink Genetics are pursuing FDA approval to move forward with cancer trials of a drug that inhibits the mechanism, an enzyme called indoleomine 2,3-dioxegenase, or IDO, says Dr. Andrew Mellor, director of the Immunotherapy Center at the Medical College of Georgia.
He will deliver seminars about the biology and immunology of the mechanism at the Keystone Symposium on "The Potent New Anti-Tumor Immunotherapies," in Alberta, Canada, March 28-April 2 and the World Immune Regulation Meeting April 10-16 in Switzerland.
Immune cells, especially those in the mucosal surfaces of the gut, lungs and eyes, express IDO to mediate inflammation triggered by the constant assault of substances from outside the body.
Now, researchers know cancer in humans and mice also attract cells that express IDO, which degrades tryptophan, an amino acid essential to survival of immune system orchestrators called T-cells. MCG scientists are still exploring how IDO interacts with other cells to amplify immune suppression.
A team of MCG scientists, led by Dr. Mellor and his colleague, MCG pediatric oncologist Dr. David Munn, showed in 1998 that the fetus also expresses IDO to help avoid rejection by the mother's immune system. When they used an orphan drug known to suppress IDO in pregnant laboratory mice, fetuses were rejected.........
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March 29, 2007, 4:53 AM CT
Preventive health exams and cancer screening
Health plan members who receive preventive health examinations, as opposed to going to a doctor only when they are sick, appear more likely to undergo testing for colorectal, breast and prostate cancers, as per a report in the March 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Preventive or periodic health examinations-also called well visits, health maintenance visits or general medical examinations-have been part of medical practice since at least the middle of the 19th century, as per background information in the article. These examinations generally include a medical history and a physical examination and may also include screening, counseling or immunizations. "The preventive health examination may be an auspicious time to promote cancer screening," the authors write. "The preventive health examination may afford primary care physicians the opportunity to discuss and recommend cancer screening when indicated, and physicians' recommendations have been consistently linked to timely cancer screening".
Joshua J. Fenton, M.D., M.P.H., University of California, Davis, Sacramento, and his colleagues assessed the association between preventive health examinations and screening for colorectal, breast or prostate cancer in 64,288 enrollees of a Washington State health plan in 2002 to 2003. This included 39,475 patients eligible for colorectal cancer screening, 31,379 women eligible for breast cancer screening and 28,483 men eligible for prostate cancer screening. The patients were between the ages of 52 and 78, and all visited their primary care doctor at least once during the study period.........
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March 29, 2007, 4:45 AM CT
Tequila ingredient to treat colon diseases
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn's disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they've had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.........
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March 29, 2007, 4:30 AM CT
MRI screening of opposite breast in breast cancer patients
Women with a recent diagnosis of cancer in one breast should have MRI screening of the opposite breast, concludes a multi-center study involving University of North Carolina at Chapel Hill researchers.
The international research team observed that MRI, or magnetic resonance imaging, detected cancer in the opposite breast in 30 of 969 women (3.1 percent) who had recently been diagnosed with cancer in one breast only. The cancers in the opposite breast were missed by prior mammography and clinical exam.
The authors recommend MRI screening for women at high risk for breast cancer - those who already have the disease, have been recently diagnosed or have a family history of breast cancer. The results appear in the March 29, 2007, issue of The New England Journal (NEJM).
"This study is pretty definitive evidence that the opposite breast needs to be reviewed with MRI," said co-author of study Dr. Etta Pisano, a principal investigator and Kenan professor of radiology and biomedical engineering at the UNC School of Medicine. "But no one is recommending that we give up mammography. MRI screening is a very expensive tool that should be used judiciously for high risk populations. The last thing we would want is for every woman to think she should get an MRI," Pisano said.........
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March 25, 2007, 8:17 PM CT
Blueberries to prevent colon cancer
A compound found in blueberries shows promise of preventing colon cancer in animals, according to a joint study by scientists at Rutgers University and the U.S. Department of Agriculture. The compound, pterostilbene, is a potent antioxidant that could be developed into a pill with the potential for fewer side effects than some commercial drugs that are currently used to prevent the disease. Colon cancer is considered the second leading cause of cancer death in the United States, the researchers say.
While recent studies have identified a growing number of antioxidants in fruits, vegetables and whole grains that show potential for fighting colon cancer, this is believed to be the first study to demonstrate the cancer-fighting potential of pterostilbene against the disease, the scientists say. Their findings were described today at the 233rd national meeting of the American Chemical Society. March is National Colorectal Cancer Awareness Month.
This study underscores the need to include more berries in the diet, especially blueberries, says study leader Bandaru Reddy, Ph.D., a professor in the Department of Chemical Biology at Rutgers in Piscataway, N.J. Although the blueberry compound wont cure colon cancer, it represents a potential new and attractive strategy for preventing the disease naturally, says Reddy, a leading expert on nutritional factors that influence colon cancer development.........
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March 25, 2007, 8:07 PM CT
Kiwis prove that green is good
In one of the most comprehensive and definitive studies of its kind to date, a team of researchers at the University of California, Davis have proven that organically grown kiwifruit contain more health-promoting factors than those grown under conventional conditions. The research is reported in the SCIs magazine Chemistry & Industry. The debate over the relative health benefits of organic versus conventional food has raged for years, with UK environment secretary David Miliband declaring in January that buying organic is just a lifestyle choice.
The Davis scientists, led by Drs. Maria Amodio and Adel Kader, showed that organically grown kiwifruit had significantly increased levels of polyphenols, the healthy compounds found in red wine and coloured berries. They also had a higher overall antioxidant activity, as well as higher levels of ascorbic acid (vitamin C) and important minerals compared with their conventionally grown counterparts (Journal of the Science of Food and Agriculture DOI 10.1002/jsfa.2820). Their work differed to previously inconclusive studies, as they were able to compare like-for-like with kiwis grown next to each other on the same farm at the same time, in the same environmental conditions. Kader added: [previous] studies did not include phenolic compounds in the comparison.........
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March 20, 2007, 10:10 PM CT
Small Molecule Cancer Therapeutics
A small molecule derived from the spacer domain of the tumor-suppressor gene Rb2/p130 has demonstrated the ability to inhibit tumor growth in vivo and could be developed into an anti-cancer therapeutic, as per scientists at Temple University's Sbarro Institute for Cancer Research and Molecular Medicine.
The researchers reported their findings, "A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo," in the March 22 issue of the journal Oncogene http://www.nature.com/onc.
Rb2/p130 was discovered in the early 1990s by Antonio Giordano, director of the Sbarro Institute http://www.shro.org and the Center for Biotechnology in Temple's College of Science and Technology, who headed the study.
The scientists discovered that within Rb2/p130's spacer domain--a sequence of 212 amino acids located in the pocket or middle section of the gene--was a small portion that resembled an amino-acidic sequence contained in the protein p21, which acts as a cdk (cyclin dependent kinase) inhibitor. Cdks play a critical role in cell cycle regulation.
"What we tested was the ability of the Rb2/p130 spacer region to inhibit the kinase activity of cdk2, which is the same kinase p21 inhibits," said Giordano, one of the study's lead authors. "And to our surprise, it happened".........
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March 19, 2007, 9:36 PM CT
Biosand filter reduces diarrheal disease
A simple, affordable household filtration device can reduce the occurence rate of diarrhea, one of the leading causes of disease and death in developing countries, by up to 40 percent, scientists at the University of North Carolina at Chapel Hill have shown.
"This technology has the potential to bring safe drinking water to a number of people in developing countries around the world who don't have access to it now," said Mark Sobsey, Ph.D., professor of environmental sciences and engineering at UNC's School of Public Health. "We can tremendously improve people's health and quality of life if we can help them get a reliable source of clean drinking water. Our study shows that simple biosand filters actually do improve water quality and consequently improve the health of everyone in the home".
Sobsey and scientists in UNC's School of Public Health compared rates of diarrhea and the condition of drinking water in homes in two villages near Bonao, Dominican Republic. They monitored about 150 households without filters for four months, assessing the rate of illness. Then, about half the houses were given biosand filters - concrete containers that hold gravel and sand. All households were monitored for another six months. The team's initial analysis showed the filter reduced diarrheal disease among household members by an estimated 30 percent to 40 percent, including in highly vulnerable young children less than 5 years old. At the end of the study, filters were given to all participating homes.........
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March 19, 2007, 5:11 AM CT
Smart Therapies For Breast, Ovarian Cancer
New non-toxic and targeted therapies for metastatic breast and ovarian cancers may now be possible, thanks to a discovery by a team of researchers at the University of British Columbia.
In a collaboration between UBC stem cell and cancer scientists, it was found that a protein called podocalyxin which the researchers had previously shown to be a predictor of metastatic breast cancer changes the shape and adhesive quality of tumour cells, affecting their ability to grow and metastasize. Metastatic cancer is invasive cancer that spreads from the original site to other sites in the body.
The discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The findings were recently published online by the Public Library of Science.
"We believe weve found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research," says Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. "The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing "smart" molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments very different from the standard slash and burn chemotherapy".........
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