August 11, 2006, 0:07 AM CT

Bisphosphonates In Treatment Of Multiple Myeloma

Mayo Clinic's multiple myeloma (MM) research team has jointly issued a consensus statement regarding the use of bisphosphonates to prevent or treat bone disease in MM. Their recommendations address several controversial issues, including the type of bisphosphonate to be used and the duration of such treatment, and are available in the recent issue of Mayo Clinic Proceedings.

"It was imperative that we address the issue that has been under recent intense debate due to patient safety concerns," said Martha Lacy, M.D., Mayo Clinic hematologist and lead author of the statement. "These drugs have far-ranging effects that raised concerns in the medical field, so we brought together the relevant specialists to develop a set of best practice recommendations. We published them in Mayo Clinic Proceedings in order to provide other physicians the benefit of our shared knowledge".

The Mayo Clinic team provided recommendations for the myeloma patients for whom bisphosphonates are indicated. They said pamidronate should be the bisphosphonate of choice for patients who are starting treatment, over the newer, more potent drug zoledronic acid, which is more frequently linked to serious damage to jaw bones. Also in the interest of safety, the team recommended that patients without active disease stop bisphosphonate treatment after two years, and patients with active disease reduce the frequency at which the drugs are given.........

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August 10, 2006, 7:06 AM CT

Predictors Of Breast Cancer

Breast cancer scientists at the University of North Carolina at Chapel Hill have identified many activity patterns in the genes of individual tumors that make them biologically different from others. These findings could provide valuable clinical information such as how likely the tumors are to be invasive, how well they might respond to different therapys and how likely they are to recur or spread.

Currently, doctors treating patients with breast cancer make therapy decisions and predictions based largely on the location and size of the tumor and if the cancer has spread, or metastasized, to lymph nodes and distant sites of the body.

But not all patients who are similar in terms of these clinical indicators get the same benefits from therapy.

These new findings could remedy that situation. Such differences in gene activity may be used as biomarkers to identify which therapys can be individually matched.

Over the past five years, gene expression profiles have been identified that appear to be predictive for cancer patients, particularly for breast cancer patients. But these tests show very little overlap in their gene lists, and thus it is not known just how distinct these different assays might be.

As per Dr. Charles M. Perou, assistant professor of genetics and pathology at the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center, some of the predictive assays are available commercially and others are under study in clinical trials in which therapy decisions, including whether or not to use chemotherapy, are being made based on them.........

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August 8, 2006, 0:11 AM CT

more effective smoking cessation

Results of a new imaging study, supported in part by the National Institute on Drug Abuse (NIDA), National Institutes of Health, show that the nicotine received in just a few puffs of a cigarette can exert a force powerful enough to drive an individual to continue smoking. Scientists observed that the amount of nicotine contained in just one puff of a cigarette can occupy about 30 percent of the brain's most common type of nicotine receptors, while three puffs of a cigarette can occupy about 70 percent of these receptors. When nearly all of the receptors are occupied (as a result of smoking at least 2 and one-half cigarettes), the smoker becomes satiated, or satisfied, for a time. Soon, however, this level of satiation wears off, driving the smoker to continue smoking throughout the day to satisfy cigarette cravings.

"Imaging studies such as this can add immensely to our understanding of addiction and drug abuse," says Elias A. Zerhouni, M.D., Director of the National Institutes of Health. "These findings suggest that drug therapies or vaccines for smoking cessation need to be extremely potent to compete with nicotine, which binds so readily to these receptors."

The study is reported in the August 2006 issue of the Archives of General Psychiatry.

"This study illustrates the powerfully addictive impact of even small amounts of nicotine. Every time a smoker draws a puff from a cigarette, they inhale numerous toxic chemicals that promote the formation of lung cancer, and contribute in a significant way to death and disability worldwide," says NIDA Director Dr. Nora D. Volkow. "Eventhough a number of smokers endorse a desire to quit, very few are able to do so on their own, and fewer than half are able to quit long-term even with comprehensive therapy. This study helps explain why".........

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August 4, 2006, 0:05 AM CT

Links between DNA damage and breast cancer

Scientists from the Pacific Northwest Research Institute (PNRI) and the National Institute of Standards and Technology (NIST) have uncovered a pattern of DNA damage in connective tissues in the human breast that could shed light on the early stages of breast cancer and possibly serve as an early warning of a heightened risk of cancer.

In the United States, breast cancer is the second leading cause of cancer-related death in women. Breast cancer detection and treatment generally target epithelial cells, the primary locus of breast cancers, but in recent years evidence has accumulated that genetic mutations that develop into cancer may occur initially in a deeper layer of breast tissue, called the stroma. Genetic changes in this connective tissue that supports the breast's network of glands and ducts have been reported to precede the cancerous conversion of tumor cells, but the actual role of stromal cells in the early stages of breast cancer initiation and progression is not well understood.

In two recent papers*, the PNRI/NIST team explored the occurrence of damage to stromal DNA caused by free radicals and other oxidants. NIST scientists used a high-precision chemical analysis technique (liquid chromatography/mass spectrometry with isotope dilution) to identify specific DNA lesions, while the PNRI team used a spectroscopic technique (Fourier transform-infrared spectroscopy) to reveal subtle conformational changes to DNA base and backbone structures. Such alterations to the molecular structure can change or disrupt gene expression.........

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August 3, 2006, 11:49 PM CT

Protector Of DNA, Enemy Of Tumors

A single gene plays a pivotal role launching two DNA damage detection and repair pathways in the human genome, suggesting that it functions as a previously unidentified tumor suppressor gene, scientists at The University of Texas M. D. Anderson Cancer Center report in Cancer Cell.

The advance online publication also reports that the gene - called BRIT1 - is under-expressed in human ovarian, breast and prostate cancer cell lines.

Defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression, the authors note, and further understanding of its function may contribute to novel, therapeutic approaches to cancer.

"Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in the Department of Molecular Therapeutics at M. D. Anderson. Genomic instability fuels the initiation, growth and spread of cancer.

A signaling network of molecular checkpoint pathways protects the human genome by detecting DNA damage, initiating repair and halting division of the damaged cell so that it does not replicate.

In a series of laboratory experiments, Lin and his colleagues show that BRIT1 activates two of these checkpoint pathways. The ATM pathway springs into action in response to damage caused by ionizing radiation. The ATR pathway responds to DNA damage caused by ultraviolet radiation.........

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August 2, 2006, 11:03 PM CT

Uterine Cancer May Yield Clues To Genetics

A new study suggests that women with endometrial cancer should be screened for inherited mutations that could lead to a high risk of several other cancers.

The study showed that 1.8 percent, or about one in 50, of newly diagnosed endometrial cancer patients have mutations for Lynch syndrome, an inherited condition also known as hereditary nonpolyposis colon cancer, or HNPCC.

People with Lynch syndrome mutations are at high risk for colon, endometrial, ovarian and gastric cancer. Endometrial, or uterine, cancer is the most common cancer in women with this condition.

The study, led by scientists at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), is reported in the Aug. 1 issue of Cancer Research.

The study is the first to comprehensively screen a large number of women with uterine cancer for Lynch syndrome mutations, said Heather Hampel, a genetic counselor in the clinical cancer genetics program and first author of the study.

"It's important to identify women with one of these mutations because they have a very high risk for developing colon cancer, and they may not be aware of that risk," said Hampel. "Because this is hereditary, half of her siblings and children may also be at risk for the syndrome.........

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August 1, 2006, 7:02 AM CT

Reduce Prostate Cancer Growth Rate

UCLA scientists observed that altering the fatty acid ratio found in the typical Western diet to include more omega-3 fatty acids and decrease the amount of omega-6 fatty acids may reduce prostate cancer tumor growth rates and PSA levels.

Reported in the Aug. 1 issue of the journal Clinical Cancer Research, this initial animal-model study is one of the first to show the impact of diet on lowering an inflammatory response known to promote prostate cancer tumor progression and could lead to new therapy approaches.

The omega-6 fatty acids contained in corn, safflower oils and red meats are the predominant polyunsaturated fatty acids in the Western diet. The healthier marine omega-3 fatty acids are found in cold-water fish like salmon, tuna and sardines.

"Corn oil is the backbone of the American diet. We consume up to 20 times more omega-6 fatty acids in our diet in comparison to omega-3 acids," said principal investigator Dr. William Aronson, a professor in the department of urology at the David Geffen School of Medicine at UCLA and a researcher with UCLA's Jonsson Cancer Center. "This study strongly suggests that eating a healthier ratio of these two types of fatty acids may make a difference in reducing prostate cancer growth, but studies need to be conducted in humans before any clinical recommendations can be made".........

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August 1, 2006, 6:58 AM CT

No Cancer Without Cell Walls

Cancer cells, like houses, need building materials for their walls. And as with a house, the cell wall needs to be built at just the right moment to protect and allow the construction of internal components. A team from the Uppsala Branch of the global Ludwig Institute for Cancer Research (LICR) has not only shown how the cell gets this timing right, but has also conducted proof-of-principle studies that indicate taking away the cell's bricks and mortar is a potential strategy for cancer control.

"New cells are created by the duplication of existing cells through a highly-organized process known as the cell cycle," explains lead author, Dr. Maite Bengoechea Alonso. "Last year we discovered that a protein called SREBP1 that regulates the synthesis of lipids needed for new cell walls was regulated during the cell cycle. Now we show that the SREBP1 protein actually controls the cell cycle".

Senior author, LICR's Dr. Johan Ericsson, realized that disrupting the function of SREBP1 might prevent the lipid synthesis mandatory for new cell walls. "In fact, we literally stopped the cell cycle in its tracks by removing SREBP1 from cells. It seems that if you don't have SREBP1 activity, you can't make lipids, and if you don't have lipids, you can't make new cells".

As per Dr. Ericsson, who is also a Research Fellow of the Royal Swedish Academy of Sciences, this approach might one day form the basis of a new strategy for the long-term control of cancer. "Cancer cells divide uncontrollably, so their need for lipids is more urgent and continuous than normal cells. Treatment with an inhibitor of SREBP1 might reduce the rate of cancer cell proliferation to slow down tumor growth, or might enhance the effect of targeted therapies that aim to actually kill cancer cells".........

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August 1, 2006, 6:53 AM CT

Curry And Onions May Prevent Colon Cancer

A small but informative clinical trial by Johns Hopkins researchers shows that a pill combining chemicals found in turmeric, a spice used in curries, and onions reduces both the size and number of premalignant lesions in the human intestinal tract.

In the study, reported in the recent issue of Clinical Gastroenterology and Hepatology, five patients with an inherited form of premalignant polyps in the lower bowel known as familial adenomatous polyposis (FAP) were treated with regular doses of curcumin (the chemical found in turmeric) and quercetin, an antioxidant in onions, over an average of six months. The average number of polyps dropped 60.4 percent, and the average size dropped by 50.9 percent, as per a team led by Francis M. Giardiello, M.D., at the Division of Gastroenterology, The Johns Hopkins University School of Medicine, and Marcia Cruz-Correa, M.D., Ph.D., at Johns Hopkins and the University of Puerto Rico School of Medicine.

"We believe this is the first proof of principle that these substances have significant effects in patients with FAP," says Giardiello.

Typically familial adenomatous polyposis is a disorder that runs in families and is characterized by the development of hundreds of colorectal adenomas (polyps) and eventual colon cancer. Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to treat some patients with this condition, but these compounds often produce significant side effects, including gastrointestinal ulcerations and bleeding, as per Giardiello.........

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July 31, 2006, 6:51 AM CT

Malignant Melanoma Secretes Embryo Protein

A Northwestern University research group has discovered that aggressive melanoma cells secrete Nodal, a protein that is critical to proper embryo formation.

An article describing this research was published recently in the advanced online issue of the journal Nature Medicine.

The scientists identified the potent and highly unstable embryonic growth factor by injecting aggressive melanoma cells into developing zebrafish embryos, which were used as "biosensors" for tumor cell-derived signals, and were consequently able to induce ectopic (abnormal) embryonic skull and backbone (axes) formation.

"This finding highlights the convergence of tumorigenic and embryonic signaling pathways. From a translational perspective, Nodal signaling provides a novel target for therapy of aggressive cancers such as melanomas," said Mary J. C. Hendrix, the corresponding author, of Children's Memorial Research Center where the discovery was made.

Hendrix is president and scientific director of the Children's Memorial Research Center, professor of pediatrics at Northwestern University Feinberg School of Medicine and a member of the executive committee of The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Jolanta M. Topczewska and Lynne-Marie Postovit, from Children's Memorial Research Center, co-led the study.........

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