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December 8, 2008, 10:14 PM CT

An Achilles heel in cancer cells

An Achilles heel in cancer cells
A protein that shields tumor cells from cell death and exerts resistance to chemotherapy has an Achilles heel, a vulnerability that can be exploited to target and kill the very tumor cells it commonly protects, scientists from the University of Illinois at Chicago show in a new study reported in the Dec. 9 issue of Cancer Cell

Akt is a signaling protein, called a kinase, that is hyperactive in the majority of human cancers.

"Akt is perhaps the most frequently activated oncoprotein (cancer-promoting protein) in human cancer," says Nissim Hay, professor of biochemistry and molecular genetics at the UIC College of Medicine. Pharmaceutical companies have been trying to find ways to inhibit Akt to improve cancer treatment, he said, but most candidate drugs have acted too broadly and proved toxic.

"One of Akt's major functions in tumor cells is promoting cell survival," Hay said. "Tumor cells with hyperactive Akt are not only resistant to the external stresses that can induce cell death but also to chemotherapy."

But Akt is also mandatory for metabolism and the proliferation of cancer cells, and it was as a byproduct of its role in metabolism that the scientists were able to exploit Akt hyperactivity against the tumor cell.

"We observed that cells with hyperactive Akt have increased intracellular levels of reactive oxygen species (ROS) and at the same time impaired ability to scavenge ROS," Hay said. These ROS are highly reactive byproducts of metabolism that can damage the cell. Cells commonly respond to high levels of ROS by undergoing cell suicide, or apoptosis.........

Posted by: Janet      Read more         Source


December 4, 2008, 7:44 PM CT

Gene packaging tells story of cancer development

Gene packaging tells story of cancer development
To decipher how cancer develops, Johns Hopkins Kimmel Cancer Center researchers say scientists must take a closer look at the packaging.

Specifically, their findings in the December 2, 2008, issue of PLoS Biology point to the three dimensional chromatin packaging around genes formed by tight, rosette-like loops of Polycomb group proteins (PcG). The chromatin packaging, a complex combination of DNA and proteins that compress DNA to fit inside cells, provides a repressive hub that keeps genes in a low expression state.

"We think the polycomb proteins combine with abnormal DNA methylation of genes to deactivate tumor suppressor genes and lock cancer cells in a primitive state," says Stephen B. Baylin, M.D., Virginia and D.K. Ludwig Professor of Oncology and senior author.

Previous to this discovery, researchers studying cancer genes, looked at gene silencing as a linear process across the DNA, as if genes were flat, one dimensional objects. Research did not take into account the way genes are packaged.

To better understand the role of the PcG packaging, the team compared embryonic cells to adult colon cancer cells. The gene studied in the embryonic cells was packaged by PcG proteins, in a low expression state, and had no DNA methylation. When the gene received signals for cells to mature, the PcG loops were disrupted and the gene was highly expressed. However, when the same gene was abnormally DNA methylated, as is the case in adult, mature colon cancer cells, the PcG packaging loops were tighter and there was no gene expression. "These tight loops touch and interact with a number of gene sites folding it into a structure that shuts off tumor suppressor genes," says Baylin. However, when the scientists removed DNA methylation from the cancer cells, the loops loosened somewhat, back to the state of an embryonic cell, and some gene expression was restored.........

Posted by: Scott      Read more         Source


December 4, 2008, 5:26 AM CT

Novel basis identified for tamoxifen failure

Novel basis identified for tamoxifen failure
Tamoxifen may worsen breast cancer in a small subset of patients. Research published in BioMed Central's open access journal Breast Cancer Research suggests that in patients who show reduced or absent expression of the protein E-cadherin, usually used anti-oestrogen drugs such as tamoxifen may promote more harmful cancer cell behaviour.

A team of scientists co-ordinated by Dr. Stephen Hiscox, from the Welsh School of Pharmacy at Cardiff University, investigated the selective oestrogen receptor modulator (SERM) tamoxifen on human breast cancer cells, comparing it to the direct effects of oestrogen withdrawal. Dr. Hiscox said, "Anti-oestrogens, such as tamoxifen, have been the mainstay of treatment in patients with oestrogen receptor positive (ER+) breast cancer and have provided significant improvements in survival. Our experimental studies suggest that in a certain group of patients, it may be much less effective, however, as it appear to promote an aggressive cell behaviour".

The authors observed that tamoxifen can promote an invasive phenotype in ER+ breast cancer cells under conditions of poor cell-cell contact, a previously unknown effect of this drug. As per Dr. Hiscox, "This could have major clinical implications for those patients with tumours where there is inherently poor intercellular adhesion. In such patients, oestrogen deprivation with aromatase inhibitors (AIs) may be a more appropriate therapy".........

Posted by: Janet      Read more         Source


December 4, 2008, 5:17 AM CT

Angled gantry technique reduced breast radiation exposure

Angled gantry technique reduced breast radiation exposure
A novel angled gantry approach to coronary CT angiography reduced radiation exposure to the breast by more than 50%, as per Thomas Jefferson University researchers.

Ethan Halpern, M.D., associate professor of Radiology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, presented the research at the 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America.

"Radiation dose to the breast during coronary CT is particularly a concern for young women as the dose may increase the risk for breast cancer," Dr. Halpern said. "Physicians are working diligently to reduce the patient radiation dose correlation to coronary CT".

Dr. Halpern and his colleagues retrospectively evaluated 100 consecutive coronary CT angiography images that were obtained with a 64 detector helical scanner. They reviewed sagital images to: 1) define the position of the breasts and the gantry angulation mandatory to perform a CT examination parallel to the long axis of the heart; and 2) determine the reduction in breast exposure to radiation that might be accomplished by imaging the heart with an angled gantry acquisition.

The standard axial imaging plane for coronary CT angiography mandatory a 6.5cm.

1.8 cm. overlap with the lower breast. The overlap with the lower breast using the angled scan was reduced in half to 3.2 cm 1.6 cm (P<0.001).........

Posted by: Janet      Read more         Source


December 3, 2008, 5:25 AM CT

Exposure to secondhand smoke reduced

Exposure to secondhand smoke reduced
As the correlation between second-hand smoke and coronary heart disease (CHD) became clearer and legislation was passed to reduce such passive smoking, exposures have been reduced. In an article reported in the January 2009 issue of the American Journal of Preventive Medicine, scientists from the University of California, San Francisco, Partners Healthcare, Boston and Columbia University have recalibrated the CHD Policy Model to better predict future trends in CHD.

At 1999჻� levels, passive smoking caused between 21,800 and 75,100 CHD deaths and between 38,100 and 128,900 myocardial infarctions annually. Treatment costs ranged from $1.8 to $6.0 billion per year. If recent trends in the reduction in the prevalence of passive smoking continue from 2000 to 2008, scientists predict that the burden would be reduced by approximately 25%󈞊%.

The CHD Policy Model is a computer simulation of CHD incidence, prevalence, mortality and costs in the US population aged >35 years. Using data from a variety of sources, such as the US Census, the Framingham Heart Study (FHS), the Framingham Offspring Study (FOS), the National Health and Nutrition Evaluation Survey (NHANES), the National Hospital Discharge Survey (NHDS) and the Year 2000 National Health Interview Survey (NHIS), the scientists updated the Model to better predict how reduced second-hand smoke may reduce CHD.........

Posted by: Daniel      Read more         Source


December 3, 2008, 5:23 AM CT

New breast imaging technology targets hard-to-detect cancers

New breast imaging technology targets hard-to-detect cancers
Breast-specific gamma imaging (BSGI) is effective in the detection of cancers not found on mammograms or by clinical exam, as per a research studypresented today at the annual meeting of the Radiological Society of North America (RSNA).

"BSGI can identify the most difficult to detect breast cancerinvasive lobular carcinoma," said lead author Rachel F. Brem, M.D., professor of radiology and director of the Breast Imaging and Interventional Center at The George Washington University Medical Center in Washington, D.C. "It also can help us detect additional lesions of all types of breast cancer in women whose mammograms show only one suspicious lesion."

Breast cancer affects more women than any other non-skin cancer and, as per the American Cancer Society, accounts for more than 40,000 deaths annually in the U.S. Most experts agree that the best way to decrease breast cancer mortality is through early detection using mammography and clinical breast exam. However, some cancers are difficult to detect with mammography and clinical exam, especially in the earliest stage when therapy is most effective.

Typically while mammography findings are characterized by the difference in appearance between normal and suspicious breast tissue, BSGI findings are based on how malignant cells function.........

Posted by: Janet      Read more         Source


December 1, 2008, 6:22 PM CT

Eating eggs when pregnant affects breast cancer in offspring

Eating eggs when pregnant affects breast cancer in offspring
A stunning discovery based on epigenetics (the inheritance of propensities acquired in the womb) reveals that consuming choline-a nutrient found in eggs and other foods-during pregnancy may significantly affect breast cancer outcomes for a mother's offspring. This finding by a team of biologists at Boston University is the first to link choline consumption during pregnancy to breast cancer. It also is the first to identify possible choline-related genetic changes that affect breast cancer survival rates.

"We've known for a long time that some agents taken by pregnant women, such as diethylstibesterol, have adverse consequences for their daughters," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "But there's an upside. The emerging science of epigenetics has yielded a breakthrough. For the first time, we've learned that we might be able to prevent breast cancer as early as a mother's pregnancy".

The scientists made the discovery in rats by studying females whose mothers were fed varying amounts of choline during pregnancy. Different groups of pregnant rats received diets containing standard amounts of choline, no choline at all, or extra choline. Then the scientists treated the female offspring with a chemical that causes cancer of the mammary gland (breast cancer). Eventhough animals in all groups developed mammary cancer, the daughters of mothers that had received extra choline during pregnancy had slow growing tumors while daughters of mothers that had no choline during pregnancy had fast growing tumors.........

Posted by: Janet      Read more         Source


December 1, 2008, 5:54 PM CT

Curbing hormones' effects in obese patients

Curbing hormones' effects in obese patients
Once-promising drugs that were abandoned in the fight against breast cancer still could be effective in obese patients, new research suggests.

In laboratory tests, hormones produced by fat cells stimulate breast cancer cells to migrate and invade surrounding tissues, researchers at Emory University School of Medicine found. A class of drugs called epithelial growth factor receptor (EGFR) inhibitors could block the stimulatory effects of the hormones.

The researchers' results are published online and are scheduled for publication in the recent issue of the journal Cancer Research

"This group of compounds was basically written off as far as breast cancer goes," says senior author Dipali Sharma, PhD, assistant professor of oncology/hematology at Emory University School of Medicine and Emory Winship Cancer Institute.

Sharma and her colleagues have been studying the effects of leptin, a hormone produced by adipocytes (fat cells), on breast cancer cells. One of leptin's functions is to send "had enough" signals to the hypothalamus, part of the brain that controls appetite, and it also regulates bone formation, reproductive functions and the growth of blood vessels.

Most obese people appear to produce an abundance of leptin but for them, leptin"s appetite-controlling effects are muted in ways that are poorly understood. In addition to leptin, obese people also have high levels of insulin-like growth factor-1 (IGF-1), which is produced primarily by the liver.........

Posted by: JoAnn      Read more         Source


November 27, 2008, 5:21 AM CT

Encouraged by drop in colorectal cancer deaths

Encouraged by drop in colorectal cancer deaths
Colonoscopy
The American Society for Gastrointestinal Endoscopy (ASGE) heralds the recent news of a decline in U.S. cancer deaths and incidence rates, with colorectal cancer among the top three cancers with significant declines. ASGE, representing the specialists in colorectal cancer screening, is excited by the report showing that colorectal cancer deaths among men and women dropped 4.3 percent per year between 2002 and 2005. The incidence rate for colorectal cancer (the rate at which new cancers are diagnosed) dropped 2.8 percent per year among men and dropped 2.2 percent per year among women between 1998 and 2005.

The study, issued annually since 1998 by the American Cancer Society, the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, showed for the first time a simultaneous decline in both cancer death rates and incidence rates in men and women. Incidence rates for all cancers combined (15 most usually diagnosed) decreased 0.8 percent per year from 1999 through 2005 for both sexes combined; rates decreased 1.8 percent per year from 2001 through 2005 for men and 0.6 percent per year from 1998 through 2005 for women. The decline in both incidence and death rates for all cancers combined is due in large part to declines in the three most common cancers among men (lung, colon/rectum, and prostate) and the two most common cancers among women (breast and colon/rectum), combined with a leveling off of lung cancer death rates among women.........

Posted by: Sue      Read more         Source


November 24, 2008, 9:46 PM CT

Genomic signature of colon cancer may individualize treatment

Genomic signature of colon cancer may individualize treatment
Scientists in the Duke Institute for Genome Sciences & Policy have developed a model for predicting risk of recurrence in early stage patients with colon cancer, and have used the model to also predict sensitivity to chemotherapy and targeted treatment regimens.

"These findings have important implications for individualizing treatment," said Katherine Garman, M.D., a gastroenterology fellow at Duke and lead investigator on the study. "By examining gene expression in early-stage colon cancer tumors, we have found certain patterns that seem to put some patients at higher risk for recurrence. By identifying these patients up front, we may be able to treat them in a targeted and proactive manner to prevent this recurrence and help them live longer and healthier lives".

The findings are due to appear in the online edition of the Proceedings of the National Academy of Sciences, between November 24 and November 26, 2008. The study was funded by the Emilene Brown Cancer Research Fund and the National Institutes of Health.

The scientists studied gene expression data from 52 samples of early stage colon cancer tumors, looking for patterns. Then they correlated the gene expression patterns with patient progress reports to track the recurrence of cancer. The predictive power of the correlations was subsequently tested in two independent data sets from 55 and 73 tumors, respectively.........

Posted by: Sue      Read more         Source



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Cancer
Cancer is a very common disease, approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during the course of their life. Cancer is more common in the elderly and 77 percent of cancers occur in people above age 55 or older. Cancer is also common in children. Cancer incidence is said to have two peaks once during early childhood and then during late years in life. No age period is completely exempted from development of cancers. Some cancers occur predominantly in the elderly, other types occur in children, Cancer occurs in all ethnic races, however the cancer rates and rates of specific cancer types may vary from group to group. Late stages of cancer may be incurable in most cases, but with the advancement of medicine, more and more cancers are becoming curable.

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