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Archive - Feb 3, 2014

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Mood-Stabilizing Drug Could Treat Inherited Liver Disease, Study Finds

In a study published online on January 31, 2014 in the open-access journal PLOS ONE, researchers from Children's Hospital of Pittsburgh of the UPMC and the University of Pittsburgh (Pitt) School of Medicine (UPMC) used a primitive worm model to show that a drug typically used to treat agitation in schizophrenia and dementia has potential as a treatment for alpha-1 antitrypsin (AT) deficiency, an inherited disease that causes severe liver scarring. In the classic form of AT deficiency, which affects 1 in 3,000 live births, a gene mutation leads to production of an abnormal protein, dubbed ATZ, that, unlike its normal counterpart, is prone to clumping, explained David H. Perlmutter, M.D., physician-in-chief and scientific director, Children's Hospital of Pittsburgh, and Distinguished Professor and Vira I. Heinz Endowed Chair, Department of Pediatrics, UPMC. "These protein aggregates accumulate in liver cells and eventually lead to scarring of the organ or to tumor formation," Dr. Perlmutter said. "If we could find a drug that slows or stops this process, we might be able to prevent the need for liver transplantation in these patients." To find that drug, Dr. Perlmutter's team worked with Pitt's Stephen Pak, Ph.D., assistant professor of pediatrics, and Gary Silverman, M.D., Ph.D., Twenty-Five Club Professor of Pediatrics, Cell Biology and Physiology, who developed a model of AT deficiency in Caenorhabditis elegans, or C. elegans, a harmless microscopic worm or nematode typically found in soil. Previous experiments conducted by Drs. Pak and Silverman, in which more than 2,000 compounds were screened, showed that fluphenazine, a drug approved for human use as a mood stabilizer, could reduce ATZ accumulation in the worm, so the team studied it further.

IDH1 Gene Mutation Defines Brain Tumors That Benefit from Aggressive Surgery; Longer Lifespans Support Molecular Genetics Approach

Astrocytomas are the most common malignant brain tumors. While most patients' tumors prove to be quite aggressive, outcomes overall can vary widely, with some patients surviving for many years. Now a new study has found that malignant astrocytoma patients whose tumors carry a specific genetic mutation benefit greatly from surgical removal of the largest possible amount of tumor. Preliminary results of the study were reported at the 2012 American Society of Clinical Oncology meeting, and the team's full report appears in the January 2014 issue of the journal Neuro-Oncology. A type of glioma, astrocytomas include the highly aggressive glioblastoma and the less aggressive, but still dangerous anaplastic astrocytoma. "We found that the benefit of surgery and how aggressively the surgery should be done depend, in large part, on whether or not patients' tumors have the mutated form of the IDH1 gene," says Daniel Cahill, M.D., Ph.D., of the Pappas Center for Neuro-Oncology in the Massachusetts General Hospital (MGH) Cancer Center, who led the study. "Under the prior system of categorization, these tumors were considered the same diagnosis and were treated the same way; but we have found that this mutation identifies a completely different subclass of glioma that probably should be treated differently." Now an assistant professor of Neurosurgery at Harvard Medical School, Dr. Cahill was at the University of Texas MD Anderson Cancer Center when the study was initiated, and all study participants were treated at MD Anderson. Ian McCutcheon, M.D., professor of Neurosurgery at the MD Anderson Cancer Center, who co-led the study with Dr.

Enhancing “Grasp” Gene Function Could Offer New Avenue to Cancer Therapies

Researchers at Oregon State University (OSU) and Oregon Health & Science University have discovered a genetic function that helps one of the most important “tumor suppressor” genes (p53) to do its job and prevent cancer. Finding ways to maintain or increase the effectiveness of this gene function – attributable to a gene is called Grp1-associated scaffold protein, or Grasp – could offer an important new avenue for human cancer therapies, scientists said. The findings were published online on January 6, 2014 in Photochemical and Photobiological Sciences, a journal of the Royal Society of Chemistry. The Grasp gene was studied in the skin of mice in this research, but is actually expressed at the highest levels in the brain, heart, and lung, studies have shown. It appears to play a fundamental role in the operation of the p53 tumor suppressor gene, which is a focus of much modern cancer research. The p53 gene is involved in repair of DNA damage and, if the damage is too great, causing a mutated cell to die before it can cause further problems, up to and including cancer. Dysfunction of p53 genetic pathways have been linked to more than half of all known cancers - particularly skin, esophageal, colon, pancreatic, lung, ovarian, and head and neck cancers. “DNA mutations occur constantly in our bodies just by ordinary stresses, something as simple as exposure to sunlight for a few seconds,” said Dr. Mark Leid, professor of pharmacology and associate dean for research in the OSU College of Pharmacy, and one of the lead authors on this study. “Just as constantly, the p53 gene and other tumor suppressors are activated to repair that damage,” Dr. Leid said. “And in cases where the damage is too severe to be repaired, p53 will cause the apoptosis, or death of the mutated cell.

Male’s Silk Wrapping of Courtship Gifts Key to Female Spider’s Mating Response

It’s not only what’s inside the nuptial gift that a potential suitor brings to a female Paratrechalea ornata spider that counts. It’s the whole package, white silk wrappings and all, that can give one male spider the edge over another. So say Drs. Mariana Trillo, Valentina Melo-González, and María José Albo of the Instituto de Investigaciones Biológicas Clemente Estable in Uruguay, who carried out the first study to look at the role of silk wrappings during the courtship and mating of this South American semi-aquatic spider. The findings were published online on January 15, 2014 in Springer’s journal Naturwissenschaften – The Science of Nature. The Paratrechalea ornata spider is one of many animals, and especially invertebrates, that use nuptial gift-giving during courtship and mating. During mate searching, males of this species walk with vibrating forelegs and feeler-like pedipalps, while carrying prey wrapped in white silk in their mouth parts. To find out more about this ceremony, Dr. Trillo’s team collected spiders from the Santa Lucia River in Uruguay and ran a set of experiments in their laboratory in Montevideo. In one experiment, the mouth parts of some males were painted white, and others not. Females exposed to males with white mouth parts were more active, showed more physical contact and spent more time in front of them. They also accepted the matings earlier, and with more frequency than those exposed to males without paint. The researchers therefore believe that the white coloring of the silk itself holds the big appeal for female spiders. This highlights the importance of visual cues during courtship and mate choice in Paratrechalea ornata. Also, Dr. Trillo’s team does not believe that white is just a random choice for this spider.