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Archive - Jul 19, 2015

Whole Exome Sequencing Permits “Personalized Medicine” Approach to Thoracic Aortic Aneurysms

Researchers at the Aortic Institute at Yale-New Haven, Yale University School of Medicine have tested the genomes of more than 100 patients with thoracic aortic aneurysms, a potentially lethal condition, and provided genetically personalized care. Their work will also lead to the development of a "dictionary" of genes specific to the disease, according to researchers. The study was published online on July 15, 2015 in The Annals of Thoracic Surgery. The article is titled “Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting.” Experts have known for more than a decade that thoracic aortic aneurysms -- abnormal enlargements of the aorta in the chest area –tend to run in families and be caused by specific genetic mutations. Until recently, comprehensive testing for these mutations has been both expensive and impractical. To streamline testing, the Aortic Institute collaborated with Allen Bale, M.D., of Yale's Department of Genetics to launch a program to test whole genomes of patients with the condition. Over a period of three years, the researchers applied a technology known as whole exome sequencing (WES) to more than 100 individuals with these aneurysms. This technology sequences that part (~1%) of the human genome that codes for proteins. "To our knowledge, it's the first widespread application of this technology to this disease," said lead author and cardiac surgeon John A. Elefteriades, M.D., Director of the Aortic Institute. The researchers detected four mutations already known to cause thoracic aortic aneurysms. "The key findings are that this technology can be applied to this disease and it identifies a lot of patients with genetic mutations," said Dr. Elefteriades.

Co-Administration of High Levels of Resveratrol and Quercetin May Significantly Reduce the Cardiac Toxicity of Doxorubincin, Allowing Increased Use of This Highly Effective Anti-Cancer Drug

Resveratrol (image) and quercetin, two polyphenols that have been widely studied for their health properties, may soon become the basis of an important new advance in cancer treatment, primarily by improving the efficacy and potential use of an existing chemotherapeutic cancer drug. Resveratrol, a powerful antioxidant found in red wine and other foods, has already received much attention as a possible explanation for the "French paradox," a low incidence of cardiovascular disease despite a diet often high in fats. The new research suggests that resveratrol may soon have value far beyond that. In laboratory experiments, researchers at Oregon State University have developed a system to increase the bioavailability of these compounds in the body by using "copolymers" that make the compounds water soluble and allow their injection into the blood stream, creating levels that are far higher than could ever be obtained by diet or oral intake. The resveratrol and quercetin then appear to reduce the cardiac toxicity of a very widely used cancer drug, Adriamycin (doxorubicin). Although highly effective in the treatment of lymphomas, breast, ovarian, and other cancers, Adriamycin can only be used for a limited time in humans because of its cardiotoxicity. The co-administration of these polyphenols might allow much more extensive use of this drug, while at the same time improving its efficacy and demonstrating the polyphenols' own anti-cancer properties, scientists said. This research has been published online by the Journal of Controlled Release and will appear in the September 10, 2015 print issue of this journal. The authors are scientists from the College of Pharmacy at Oregon State University (OSU) and the School of Pharmacy at Pacific University. Both institutions supported the research.

Olfactory, Visual, and Thermal Cues Lead Mosquitoes to Targets; New Information May Result in Better Mosquito Traps, But Offers Little Hope for Reducing Bite Incidence

On summer evenings, we try our best to avoid mosquito bites by dousing our skin with bug repellents and lighting citronella candles. These efforts may keep the mosquitoes at bay for a while, but no solution is perfect because the pests have evolved to use a triple threat of visual, olfactory, and thermal cues to home in on their human targets, a new Caltech study suggests. The study, published by researchers in the laboratory of Dr. Michael Dickinson, the Esther M. and Abe M. Zarem Professor of Bioengineering, was published online on July 16, 2015 in Current Biology. The article is titled “"Mosquitoes Use Vision to Associate Odor Plumes with Thermal Targets." When an adult female mosquito needs a blood meal to feed her young, she searches for a host--often a human. Many insects, mosquitoes included, are attracted by the odor of the carbon dioxide (CO2) gas that humans and other animals naturally exhale. However, mosquitoes can also pick up other cues that signal a human is nearby. They use their vision to spot a host and thermal sensory information to detect body heat. But how do the mosquitoes combine this information to map out the path to their next meal? To find out how and when the mosquitoes use each type of sensory information, the researchers released hungry, mated female mosquitoes into a wind tunnel in which different sensory cues could be independently controlled. In one set of experiments, a high-concentration CO2 plume was injected into the tunnel, mimicking the signal created by the breath of a human. In control experiments, the researchers introduced a plume consisting of background air with a low concentration of CO2. For each experiment, researchers released 20 mosquitoes into the wind tunnel and used video cameras and 3-D tracking software to follow their paths.

Remarkable Advance: MIT Scientists Engineer Common Gut Bacterium to Sense and Report on Gut Conditions

The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders. In an article published online on July 9, 2015 in the journal Cell Systems, researchers at MIT unveil a series of sensors, memory switches, and circuits that can be encoded in the common human gut bacterium Bacteroides thetaiotaomicron. These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer. The article is titled “Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota.” Researchers have previously built genetic circuits inside model organisms such as E. coli. However, such strains are only found at low levels within the human gut, according to Dr. Timothy Lu, an Associate Professor of Biological Engineering and of Electrical Engineering and Computer Science, who led the research alongside Dr. Christopher Voigt, a Professor of Biological Engineering at MIT. “We wanted to work with strains like B. thetaiotaomicron that are present in many people in abundant levels, and can stably colonize the gut for long periods of time,” Dr. Lu says. The team developed a series of genetic parts that can be used to precisely program gene expression within the bacteria. “Using these parts, we built four sensors that can be encoded in the bacterium’s DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron,” Dr. Voigt says.

Low-Methionine Diet Primes Triple-Negative Breast Cancer Cells for Surface Antigen Targeted Therapy

A diet that starves triple-negative breast cancer cells of an essential nutrient primes the cancer cells to be more easily killed by a targeted antibody treatment, University of Wisconsin (UW) Carbone Cancer Center scientists report published in the June 15, 2015 issue of Clinical Cancer Research. The article is titled “Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.” This article was choses as a highlighted study by the journal its June 15 edition. The study's senior author, Dr. Vincent Cryns, Professor of Medicine at the UW School of Medicine and Public Health, says the study lays the foundation for a clinical trial to see if a low-methionine diet will help improve outcomes in women with "triple-negative" breast cancer. Methionine is an essential amino acid that is present in low concentrations in some vegan diets. Patients with triple-negative breast cancer have limited treatment options because their tumor cells lack the three receptors -- estrogen, progesterone, and human epidermal growth factor receptor 2 (HER-2) -- commonly targeted in hormone or chemotherapy. Scientists have known for decades that methionine deficiency can block the growth of many types of cancer, but the underlying mechanisms have puzzled researchers. "We've shown that removing methionine can have a specific effect on a molecular pathway that regulates cell death to increase the vulnerability of cancer cells to treatments that target this pathway," Dr. Cryns says. "What's particularly exciting about our findings is that they suggest that a dietary intervention can increase the effectiveness of a targeted cancer therapy."