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Archive - Nov 20, 2018

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Enzyme on Surface of Some Lung Cancers Enhances Cancer Growth & May Be Target for Treatment

University of Texas (UT) Southwestern researchers have found that an enzyme on the surface of some lung cancer cells helps feed the cancer, making it a tempting treatment target. The enzyme, transmembrane serine protease 11B (TMPRSS11B), is described in a report published in the November 20, 2018 issue of Cell Reports. The open-access article is titled “Transmembrane Protease TMPRSS11B Promotes Lung Cancer Growth by Enhancing Lactate Export and Glycolytic Metabolism.” In addition to being found in squamous cell lung cancer and prostate cancer, the enzyme also has been identified in squamous cell head, neck, and cervical cancers, said Dr. Kathryn O’Donnell (photo), Assistant Professor of Molecular Biology. Her team identified TMPRSS11B while searching for genes that can convert precancerous lung cells into malignant cells that can form tumors. “In this study, we found that the enzyme strongly promoted the growth of certain types of lung cancer cells. We uncovered a new mechanism that expands our understanding of how cancer cells reprogram their metabolism to provide energy for rapid growth as they form tumors,” Dr. O’Donnell said. The researchers noticed that the enzyme was expressed at increased levels in human squamous cell lung cancers – a common type of non-small cell lung cancer – and that suppressing the levels of TMPRSS11B through gene editing or RNA interference reduced tumor growth in mouse models, she said. The research focused on TMPRSS11B’s ability to encourage the movement of lactate, a byproduct of cell metabolism long thought to be a waste product. Ground-breaking research last year from UT Southwestern Professor Dr. Ralph DeBerardinis’ laboratory found that, in fact, lactate provides fuel for growing tumors. Dr.

DNA Vaccine Reduces Both Toxic Proteins (Beta-Amyloid & Tau) Linked to Alzheimer’s in Mouse Model

A DNA vaccine tested in mice reduces accumulation of both types of toxic proteins associated with Alzheimer’s disease, according to research that scientists say may pave the way to a clinical trial. A new study by the University of Texas (UT) Southwestern’s Peter O’Donnell Jr. Brain Institute shows that a vaccine delivered to the skin prompts an immune response that reduces buildup of harmful tau and beta-amyloid – without triggering severe brain swelling that earlier antibody treatments caused in some patients. “This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer’s disease,” said Dr. Roger Rosenberg, founding Director of the Alzheimer’s Disease Center at UT Southwestern. “I believe we’re getting close to testing this therapy in people.” The research, published online on October 20, 2018 in Alzheimer’s Research and Therapy, demonstrates how a vaccine containing DNA coding for a segment of beta-amyloid also reduces tau in mice modeled to have Alzheimer’s disease. In addition, the vaccine elicits a different immune response that may be safe for humans. The open-accessa article is titled “Active Full-Length DNA Aβ42 Immunization in 3xTg-AD Mice Reduces Not Only Amyloid Deposition But Also Tau Pathology.” Two previous studies from Dr. Rosenberg’s lab showed similar immune responses in rabbits and monkeys. The vaccine is on a shortlist of promising antibody treatments aimed at protecting against both types of proteins that kill brain cells as they spread in deadly plaques and tangles on the brains of Alzheimer’s disease patients. Although earlier research established that antibodies significantly reduce amyloid buildup in the brain, Dr. Rosenberg’s team needed to find a safe way to introduce them into the body.