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Archive - May 2012

Date

May 3rd

New Model Suggests Low Oxygen Levels, Not Mutations, Drive Cancer Growth

Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors' findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth. If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Dr. Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences. The research team analyzed samples of messenger RNA data—also called transcriptomic data—from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published on April 20, 2012 in the early online edition of the Journal of Molecular Cell Biology. Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Dr. Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells. "Cancer drugs try to get to the root—at the molecular level—of a particular mutation, but the cancer often bypasses it," Dr. Xu said.

Scientists Analyze “Junk DNA” to Find Colorectal Cancer Clues

Two researchers at the Geisel School of Medicine at Dartmouth have helped to identify switches that can turn on or off genes associated with colorectal cancer. The finding offers clues about the development of colorectal cancer and could—potentially—provide targets for new therapies. Dr. Jason Moore, Third Century Professor of genetics and the director of the Institute for Quantitative Biomedical Sciences, and Richard Cowper-Sal.lari, a graduate student in Dr. Moore's lab, were part of a team that included researchers from Case Western Reserve University and the Cleveland Clinic. The team published its findings in Science Express, the online prepublication site for the journal Science, on April 12, 2012. Many studies of cancer and other diseases have looked for genetic variations that lead to disease. But for this study, Dr. Moore, Cowper-Sal.lari, and their colleagues examined sections of DNA that do not code for proteins—sections that have sometimes been referred to as "junk DNA." Long overlooked, junk DNA has gained more attention of late as it has become clear that it can regulate the expression of genes. "We're now starting to assign function to what historically has been known as the junk DNA—stuff in between genes that we weren't really sure what it did, if it did anything at all," Dr. Moore says. Proteins that bind to noncoding sections far away from a gene, Dr. Moore explains, can help turn that gene on or off. The researchers looked at specific sections of noncoding DNA in nine colorectal cancer samples and three samples of healthy colon tissue. They found patterns in the sections of noncoding DNA that differed depending on whether the tissue was cancerous or healthy. They refer to these sections as variant enhancer loci (VELs).

Bacteria Discovery Could Lead to Alternatives to Antibiotics

Scientists have discovered an Achilles heel within our cells that some bacteria are able to exploit to cause and spread infection. The researchers say their findings could lead to the development of new anti-infective drugs as alternatives to antibiotics whose overuse has led to resistance. University of Manchester researchers studied Listeria – a potentially deadly group of bacteria that can cause listeriosis in humans when digested – and found they are able to spread infection by hitching a ride on a naturally occurring protein called calpain. "Bacteria produce a number of chemicals that allow them to invade a host and to establish an infection," said lead researcher Dr. David Brough, who is based in Manchester's Faculty of Life Sciences. "The chemicals produced depend upon many factors, such as the species of bacteria, the type of host, and also whether the infection grows inside or outside a cell. We have investigated the growth of Listeria, a pathogenic bacterium that grows inside cells. An essential step for its growth, and thus the infection, is the bacteria's ability to move from within one compartment in a cell to another. We discovered that in order for this particular type of bacteria to move and to grow some of the host cells biology is exploited, a protein called calpain. Without calpain the bacteria cannot move within the cell and so do not grow. This discovery highlights the possibility of using drugs against these host proteins to block infections, potentially reducing the need to use antibiotics." The study, funded by the Wellcome Trust, was published April 26, 2012 in PLoS ONE. [Press release] [PLoS ONE article]

Cohesin SA1 Has Functions Relevant to Cancer and Cornelia de Lange Syndrome

Cohesin is a ring-shaped protein complex involved in the spatial organization of the genome and in mitotic chromosome structure. Vertebrate somatic cells have two versions of cohesin that contain either SA1 or SA2, but their functional specificity has been largely ignored. Researchers of the Spanish National Cancer Research Centre (CNIO) under the direction of Dr. Ana Losada have identified new functions of cohesin SA1 that are relevant for two human diseases, cancer and Cornelia de Lange Syndrome (CdLS). These results are published in two papers that appeared back-to-back in the March 13, 2012 issue of the EMBO Journal. The first study shows that SA1 is required for efficient duplication of chromosome ends, the telomeres. In its absence, aberrant telomere structures hinder chromosome segregation during cell division and aneuploid cells (i.e., those with an incorrect number of chromosomes) are generated. This aneuploidy likely contributes to accelerating the onset of tumorigenesis in SA1-deficient mice. The appearance of certain types of pancreatic tumours, extremely rare in mice, is particularly striking. This mouse model may turn out to be a very useful tool for the study of pancreatic cancer. The second study reports for the first time a precise map of the distribution of cohesin SA1 and cohesin SA2 along the mouse genome. Moreover, it uncovers an essential role of cohesin SA1 in the regulation of gene expression during embryonic development. Lack of cohesin SA1 alters the transcription of genes involved in biological processes related to CdLS. This developmental disorder affects 1:30,000 newborns and is characterized by growth and mental retardation and multiple organ abnormalities. The study offers new clues to understanding the origin of the pathologies observed in CdLS patients.

Brain Circuitry Associated with Addictive, Depressive Behaviors Identified

Scientists at the Gladstone Institutes in San Francisco, California, have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson's disease—and psychiatric disorders such as addiction and depression. [Referential website: California rehab centers http://www.allaboutcounseling.com/dir/drug-rehab-programs/california/ Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, Ph.D., discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson's. Now, in a paper published online on April 29, 2012 in Nature Neuroscience, Dr. Kreitzer and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson's symptoms—and mark an important step in finding new treatments for those who suffer from addiction or depression. “The physical symptoms that affect people with Parkinson's—including tremors and rigidity of movement—are caused by an imbalance between two types of medium spiny neurons in the brain,” said Dr. Kreitzer, whose lab studies how Parkinson's disease affects brain functions. “In this paper, we showed that psychiatric disorders—specifically addiction and depression—might be caused by this same neural imbalance.” Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake.

May 2nd

Black Pepper's Secrets As a Fat Fighter

A new study provides a long-sought explanation for the beneficial fat-fighting effects of black pepper. The research, published online on April 2, 2012 in the ACS Journal of Agricultural and Food Chemistry, pinpoints piperine — the pungent-tasting substance that gives black pepper its characteristic taste, concluding that piperine also can block the formation of new fat cells. Dr. Soo-Jong Um, Dr. Ji-Cheon Jeong, and colleagues describe previous studies indicating that piperine reduces fat levels in the bloodstream and has other beneficial health effects. Black pepper and the black pepper plant, they note, have been used for centuries in traditional Eastern medicine to treat gastrointestinal distress, pain, inflammation, and other disorders. Despite that long medicinal history, scientists know little about how piperine works on the innermost molecular level. The scientists set out to get that information about piperine's anti-fat effects. Their laboratory studies and computer models found that piperine interferes with the activity of genes that control the formation of new fat cells. In doing so, piperine may also set off a metabolic chain reaction that helps keep fat in check in other ways. The group suggests that the finding may lead to wider use of piperine or black-pepper extracts in fighting obesity and related diseases. [Press release] [Journal of Agricultural and Food Chemistry abstract]

Huge Study Finds Brain Networks Connected to Drug Abuse by Teenagers

Why do some teenagers start smoking or experimenting with drugs—while others don't? In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer. Dr. Robert Whelan and Dr. Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive. Their findings were published online on April 29, 2012 in Nature Neuroscience. This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it. "The differences in these networks seem to precede drug use," says Dr. Garavan, Dr. Whelan's colleague in the University of Vermont’s psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study. In a key finding, diminished activity in a network involving the "orbitofrontal cortex" is associated with experimentation with alcohol, cigarettes, and illegal drugs in early adolescence. (Referential web site: 60-day treatment http://www.rehabs.com/about/60-days-two-months-program/) "These networks are not working as well for some kids as for others," says Dr. Whelan, making them more impulsive. Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, "yeah, gimme, gimme, gimme!" says Dr.

May 1st

Two-Drug Combination More Effective Than Just Metformin in Youths with Type 2 Diabetes

A combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone, a study funded by the National Institutes of Health (NIH) has found. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone. The study also found that metformin therapy alone was not an effective treatment for many of these youth. In fact, metformin had a much higher failure rate in study participants than has been reported in studies of adults treated with metformin alone. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study is the first major comparative effectiveness trial for the treatment of type 2 diabetes in young people. TODAY was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH. Study results appeared in the New England Journal of Medicine on April 29, 2012. "The results of this study tell us it might be good to start with a more aggressive drug treatment approach in youth with type 2 diabetes," said Philip Zeitler, M.D., Ph.D., the TODAY study chair and a pediatric endocrinologist at Children's Hospital Colorado, Aurora. "We are learning that type 2 diabetes is a more aggressive disease in youth than in adults and progresses more rapidly, which could be why metformin alone had a higher than expected failure rate." The TODAY study tested how well and for how long each of three treatment approaches controlled blood glucose levels in youth enrolled from ages 10 to 17 with type 2 diabetes.