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Archive - Nov 6, 2012

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Inhibition of NOX4 Enzyme Prevents Liver Fibrosis

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona, Spain, have led a study published on September 26, 2012 in the online journal PLoS One showing that the inhibition of a family member of NADPH oxidase enzyme, NOX4, plays an important role in liver fibrosis. The researchers studied the function of a cytokine called transforming growth factor-beta (TGF-beta) in the pathophysiology of the liver, which is one of the main research lines of the Biological Clues of the Invasive and Metastatic Phenotype research group at the IDIBELL, led by Dr. Isabel Fabregat. This paper is related to the processes of liver fibrosis, an illness caused by the overproduction of extracellular matrix proteins in the liver tissue. During fibrosis, levels of TGF-beta are increased, and there is an activation of the extracellular matrix producing the activation of protecting cells of the extracellular matrix and other possible events leading to the death of hepatocytes. The TGF-beta is a complex cytokine. It is a prominent tumor suppressor in early stages of tumor formation, but, in advanced stages, the cells adapt to escape from the growth inhibitory signals and, under these conditions, the TGF-beta is able to potentiate tumor progression, contributing to metastasis. The study published in PLoS One is a collaboration between IDIBELL and the research group of Dr. Wolfgang Mikulits, co-author of the study, at the Cancer Research Institute of the Medical University of Vienna (Austria), that has provided cellular and animal models. The analysis in patient samples has been possible thanks to the collaboration with the University Hospital Alcorcon Foundation and the Complutense University of Madrid.

Second Species of Mole Rat Has Different Anti-Cancer Mechanism

Biologists at the University of Rochester have determined how blind mole rats fight off cancer—and the mechanism differs from what they discovered three years ago in another long-lived and cancer-resistant mole rat species, the naked mole rat. The team of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, found that abnormally growing cells in blind mole rats secrete the interferon beta protein, which causes those cells to rapidly die. Drs. Seluanov and Gorbunova hope the discovery will eventually help lead to new cancer therapies in humans. Their findings were published November 5, 2012 in PNAS. Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only mammals never known to develop cancer. Three years ago, Drs. Seluanov and Gorbunova determined the anti-cancer mechanism in the naked mole rat. Their research found that a specific gene—p16—makes the cancerous cells in naked mole rats hypersensitive to overcrowding, and stops them from proliferating when too many crowd together. "We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous cells," said Dr. Seluanov. "Instead, we discovered they've evolved their own mechanism." Drs. Gorbunova and Seluanov made their discovery by isolating cells from blind mole rats and forcing them to proliferate in culture beyond what occurs in the animal. After dividing approximately 15-20 times, all of the cells in the culture dish died rapidly. The researchers determined that the rapid death occurred because the cells recognized their pre-cancerous state and began secreting a suicidal protein, called interferon beta.