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June 5, 2006, 11:19 PM CT

New Way to Fight Brain Cancer

New Way to Fight Brain Cancer
Taking advantage of a large assortment of chemical inhibitors produced by the pharmaceutical industry as potential drugs, Howard Hughes Medical Institute scientists have synthesized and characterized a panel of compounds that may lead to new therapy strategies for targeting glioblastoma, a common type of brain tumor that commonly thwarts therapy. The compounds have also revealed new information about insulin signaling, and could be a powerful tool to evaluate cellular enzymes as potential targets for drug design.

The work is detailed in two papers reported in the journals Cell and Cancer Cell. HHMI investigator Kevan M. Shokat at the University of California, San Francisco, is the senior author on the Cell paper, published on-line April 27, 2006, which describes a pharmacological map of the family of enzymes known as PI3-kinases. Zachary A. Knight, an HHMI predoctoral fellow in Shokat's lab, is the first author of the study, which was conducted in collaboration with colleagues from UCSF. The second paper, reported in the May 15, 2006, issue of the journal Cancer Cell, describes the effects of inhibiting these kinases in glioblastoma cells. Shokat and Knight collaborated on the Cancer Cell paper with senior author William A. Weiss at UCSF.

Researchers have devoted a great deal of research to kinases because they may provide the key to better understanding of a wide array of fundamental biological processes. Kinases are a huge family of enzymes that regulate intracellular communication by tagging key molecules with a small, energy-packed chemical group known as a phosphate. Their influence over processes ranging from cell growth and survival to learning and memory makes kinases desirable targets for new drugs, and progress in this area of research depends on the careful definition of the roles of individual enzymes.........

Posted by: Daniel      Permalink         Source


June 5, 2006, 11:17 PM CT

A New Way to Build Bone

A New Way to Build Bone
Howard Hughes Medical Institute (HHMI) scientists at Stanford University have found that they can increase bone mass in mice by tweaking the shape of a regulatory protein.

HHMI investigator Gerald Crabtree and HHMI predoctoral fellow Monte Winslow report that slightly increasing the activity of a protein called NFATc1 causes massive bone accumulation, suggesting that NFATc1 or other proteins that regulate its activity will make good targets for drugs to treat osteoporosis. They report their findings as per a research findings reported in the June 6, 2006, issue of Developmental Cell.

In vertebrates, bone is constantly being formed and being broken down throughout life. Cells called osteoclasts continuously degrade bone, while cells called osteoblasts replenish it.

"Ideally, they are perfectly balanced," said Crabtree, the senior author of the study. "Over the course of a lifetime, if everything goes well, we'll maintain almost exactly identical bone mass." However, if the balance is upset, and more bone is destroyed than formed, osteoporosis results, increasing the risk of fractures.

The new study arose from the researchers' curiosity about reports that patients who were treated with the drug cyclosporine-often given to suppress the immune system before organ transplants-tend to lose bone mass. Those patients were also at increased risk of bone fractures, said first author Winslow, who led the study as an HHMI predoctoral fellow in Crabtree's lab. Winslow is now working as a postdoctoral fellow in the lab of HHMI investigator Tyler Jacks at the Massachusetts Institute of Technology.........

Posted by: Scott      Permalink         Source


June 5, 2006, 9:17 PM CT

New Predictor For Lung Cancer

New Predictor For Lung Cancer
Research from the Ireland Cancer Center of University Hospitals of Cleveland has found a promising, novel biomarker that may be used to predict the survival of patients with advanced lung cancer and their response to therapy. Afshin Dowlati, MD, hematologist/ oncologist at the Ireland Cancer Center, presented this study June 5 at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Dowlati found that patients with a low level of the biomarker ICAM had a better chance of survival and an increased response to chemotherapy. Dr. Dowlati analyzed data from a major national study, released at ASCO in 2005, that found the monoclonal antibody Bevacizumab (Avastin), in addition to standard treatment, was more effective than standard therapy alone for patients with advanced, non-squamous non-small cell lung cancer.

The analysis indicated that patients with low levels of ICAM (intercellular adhesion molecule -1), had a higher response rate to therapy (29% versus 13%) than patients with high ICAM levels. Patients with low ICAM levels also had a significantly better overall survival rate.

"We believe this research confirms a significant new prognostic marker in lung cancer," says Dr. Dowlati, who is also assistant professor at Case Western Reserve University School of Medicine. "Previously, it has been a challenge to identify those patients that will respond best to therapy and what their outcomes will be. This biomarker appears to serve as a much better predictor than gender, patients' overall health and sites of metastases." These findings confirm a pilot study performed three years ago at Ireland Cancer Center by Drs. Dowlati, Scot Remick and Keith McCrae, an expert in blood vessel disorders found in cancer.........

Posted by: Scott      Permalink         Source


June 5, 2006, 9:12 PM CT

Camptosar Important In Metastatic Colorectal Cancer

Camptosar Important In Metastatic Colorectal Cancer
Data presented today at the annual meeting of the American Society of Clinical Oncology (ASCO) demonstrated that CAMPTOSAR® (irinotecan HCL injection), when given in the infusional regimen FOLFIRI , provided statistically significant longer progression free survival (PFS) compared to bolus mIFL and CapeIRI , two alternative chemotherapeutic regimens containing CAMPTOSAR used to treat metastatic colorectal cancer (mCRC). The study also demonstrated a statistically significant benefit in overall survival (OS) for patients treated with FOLFIRI plus bevacizumab when compared with those who received mIFL plus bevacizumab. These new data highlight the central role of FOLFIRI in the first line setting of mCRC to maximize patient benefit with CAMPTOSAR.

The predefined analysis of the primary endpoint showed FOLFIRI provided a statistically significant benefit in PFS (8.2 months) when compared with mIFL (6.0 months) or CapeIRI (5.7 months). In addition the median OS for FOLFIRI was 23.1 months, for mIFL - 17.6 months and for CapeIRI - 18.9 months. Though it did not reach statistical significance, there was a trend favoring FOLFIRI. OS benefit reflects all therapies patients may have received, including 2nd and 3rd lines. The most frequent grade 3/4 adverse events in all arms were diarrhea and neutropenia. In general the toxicity profile favored the FOLFIRI arm. Each arm had a secondary randomization to celecoxib or a placebo. In general, celecoxib neither improved efficacy nor reduced chemotherapy toxicity.........

Posted by: Sue      Permalink         Source


June 5, 2006, 9:04 PM CT

A Fundamentally New Approach To Chemotherapy

A Fundamentally New Approach To Chemotherapy
A new strategy for getting anti-cancer drugs to kill cancer cells, without causing serious harm to normal cells in the body, is published in the current [June] issue of ACS Chemical Biology, a monthly peer-reviewed journal of the American Chemical Society.

The approach, tested in laboratory experiments with several existing anti-cancer drugs, could offer substantial benefits for cancer patients, as per Jeffrey P. Krise, Ph.D. Krise led a group of pharmaceutical and medicinal chemists at the University of Kansas at Lawrence who did the research.

The new approach would allow anticancer drugs to accumulate in both normal and cancerous cells. The drugs, however, would be tweaked by giving them "basic" chemical properties. In chemistry, "basic" means an alkaline substance like baking soda or laundry detergent, which has properties opposite those of acidic substances.

Normal cells simply isolate anti-cancer drugs with basic properties, greatly reducing the toxic effects. Cancer cells, in contrast, have an impaired ability to isolate basic substances, and get hit with a full blast of toxicity.

"It could allow cancer patients to tolerate higher and more effective doses of chemotherapy before normal cells are damaged to an extent that causes serious side effects and cessation of treatment," Krise said. "The approach is completely different from prior attempts that were designed to deliver drugs only to cancer cells and not normal cells."........

Posted by: Janet      Permalink         Source


June 5, 2006, 8:53 PM CT

Exercise In Childhood And Adolescence Prevent Osteoporosis

Exercise In Childhood And Adolescence Prevent Osteoporosis
Recent studies indicate that exercise can help build and maintain healthy bones. But just how early should one start? At the IOF World Congress on Osteoporosis in Toronto, Canada this week, several studies highlighted the importance of exercise in children and adolescents for building peak bone mass that will help protect against osteoporosis in later life.

Scientists at Wright State University School of Medicine in Ohio, U.S.A., have found that leisure activity has a significant impact on the rate of bone mass increase in both girls and boys. Lead author Miryoung Lee and colleague followed a group of 99 children, aged 8 to 18, to determine how changes in physical activity affects their bone mineral density, a measure of bone strength. For both sexes, the rate of bone accumulation was found to be higher with increasing leisure activity level (see conference Abstract No. P191).

In girls, more intense physical activity that is associated with sports also leads to greater increases in bone density. Similar effects were not seen in boys taking part in sports. "During childhood and adolescence, children's bodies grow rapidly and bone mass is accumulated quickly. The amount of bone built during adolescence and early adulthood is one of the most important factors correlation to the risk of developing osteoporosis in later years. These findings confirm that physical activity is important for optimal bone accrual during childhood, consequently leading to higher peak bone mass," said Lee.........

Posted by: JoAnn      Permalink         Source


June 5, 2006, 7:09 AM CT

Post-operative Combination Therapy For Pancreatic Cancer

Post-operative Combination Therapy For Pancreatic Cancer
Adding the cancer-fighting drug gemcitabine to standard treatment after surgery significantly improves survival for patients with the most common form of pancreas cancer, as per a new multicenter study led by a University of Maryland radiation oncologist. The results of the four-year Phase III clinical trial were presented June 4 at the American Society of Clinical Oncology annual meeting in Atlanta.

More than 500 patients at 128 institutions across the country, including the University of Maryland Marlene and Stewart Greenebaum Cancer Center, were enrolled in the federally funded study from 1998 to 2002.

Thirty-two percent of study participants with "pancreatic head adenocarcinoma" (cancer of the head, or wider part, of the pancreas) were still alive three years after diagnosis after having surgery and being treated with gemcitabine, another chemotherapy drug called 5-fluorouracil (5-FU) and radiation treatment. That compares to a 21 percent three-year survival rate for patients who received 5-FU and radiation therapys alone following their surgery.

"The addition of gemcitabine to the standard postoperative therapy increased patients' survival by 50 percent, which is a significant improvement. We believe these findings will provide a new standard for treating patients with this devastating disease," says the principal investigator, William F. Regine, M.D., professor and chairman of the Department of Radiation Oncology at the University of Maryland School of Medicine and chief of radiation oncology at the University of Maryland Medical Center.........

Posted by: Sue      Permalink


June 4, 2006, 8:51 AM CT

New Drug Combo For Kidney Cancers

New Drug Combo For Kidney Cancers
By using a new combination of two anticancer drugs, scientists at Duke University Medical Center have dramatically improved response rates of patients with metastatic kidney cancer, which is now generally considered incurable.

The results suggest that combining the two drugs may slow the disease's progression in significant numbers of patients, eventhough the drug combination is not a cure, said the researchers.

In the study, 40 percent of patients who received the newly approved drug sorafenib together with the established drug interferon-alpha experienced "major shrinkage" of their kidney tumors and tumors that had metastasized, or spread elsewhere. A "major" response is generally is defined as 30 percent or greater shrinkage of all tumors in the body.

In comparison, only 5 percent of patients who receive sorafenib alone show a major response, recent studies have shown. Similarly, just 10 percent to 15 percent of patients who receive only interferon alpha, considered the standard therapy for kidney cancer, show a major response.

"By combining the drugs, we are seeing more major responses in greater numbers of patients, but we don't yet know how long the responses will last," said Jared Gollob, M.D., associate professor of medicine and immunology at Duke. "There are great new drugs on the market with relatively low toxicity, but the question physicians now face is how to make them work better for patients."........

Posted by: Mark      Permalink         Source


June 4, 2006, 8:48 AM CT

Type of Stress, Not Duration, Key to Heart Enlargement

Type of Stress, Not Duration, Key to Heart Enlargement
When judging whether or not an enlarged heart is healthy or potentially at risk for heart disease, the nature of the physiological stress that produced the enlargement is more important than the duration of the stress, as per a new study led by Duke University Medical Center investigators.

This distinction has significant clinical implications, the scientists said. While enlargement of the heart can be a natural and beneficial response to exercise training, it can also be an early warning sign for such harmful conditions as heart failure.

These findings, based on a series of experiments in mice, could help settle a long-running controversy among cardiologists concerning heart enlargement, or cardiac hypertrophy, as per Duke cardiologist Howard Rockman, M.D., who led the team of Duke and University of North Carolina-Chapel Hill researchers.

The scientists published their findings on June, 1, 2006, in the Journal of Clinical Investigation. The study was supported by the National Institutes of Health.

"If you look at the hearts of athletes, they are larger than normal," Rockman said. "Conversely, patients with hypertension also tend have larger-than-normal hearts. So why are some cardiac overloads, such as exercise, good for the heart, while others, such as high blood pressure, not?".........

Posted by: Daniel      Permalink         Source


June 4, 2006, 8:42 AM CT

Overweight And Obesity Enlarges Teenagers' Hearts

Overweight And Obesity Enlarges Teenagers' Hearts
The effects of excess weight on heart health can be seen even in adolescents, with abnormal enlargement and impaired pumping function evident in subjects by age 20, as per a new study in the June 6, 2006, issue of the Journal of the American College of Cardiology.

"Heart damage starts very early in the natural history of obesity. We need to work on our young people, to prevent catastrophic effects later on," said Giovanni de Simone, M.D., F.A.C.C. from the New York Presbyterian Hospital-Weill Medical College of Cornell University in New York, New York and the Federico II University Hospital School of Medicine in Naples, Italy.

The Strong Heart study (SHS) is a longitudinal study of cardiovascular risk factors and cardiovascular disease that enrolled 4,549 people in American Indian communities in Arizona, Oklahoma, and North and South Dakota. This analysis included data from examinations of 460 participants age 14 to 20 years (245 girls and 215 boys). The scientists used ultrasound and other methods to measure the size, shape and pumping function of the teenagers' hearts.

The left ventricles of the hearts of both overweight and obese teenagers were larger and heavier than those of normal weight participants; but the obese teenagers also showed signs of impaired heart function. The changes were not entirely explained by changes by high blood pressure.........

Posted by: JoAnn      Permalink         Source



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Did you know?
Studies in monkeys and women suggest that unlike traditional estrogen therapy, a diet high in the natural plant estrogens found in soy does not increase the risk of uterine cancer in postmenopausal women, according to Mark Cline, D.V.M., Ph.D., an associate professor of comparative medicine at Wake Forest University Baptist Medical Center.

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