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Archive - Apr 11, 2018

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Antibacterial Treatment for Translocated Gut Bacterium May Have Relevance for Systemic Lupus & Autoimmune Liver Disease, Yale Study Suggests

Bacteria found in the small intestines of mice and humans can travel to other organs and trigger an autoimmune response, according to a new Yale study. The researchers also found that the autoimmune reaction can be suppressed with an antibiotic or vaccine designed to target the bacteria, they said. The findings, published in the March 9, 2018 issue of Science, suggest promising new approaches for treating chronic autoimmune conditions, including systemic lupus and autoimmune liver disease, the researchers said. The article is titled “Translocation of a gut pathobiont drives autoimmunity in mice and humans.” Gut bacteria have been linked to a range of diseases, including autoimmune conditions characterized by immune system attack of healthy tissue. To shed light on this link, a Yale research team focused on Enterococcus gallinarum, a bacterium they discovered is able to spontaneously “translocate” outside of the gut to lymph nodes, the liver, and spleen. In models of genetically susceptible mice, the researchers observed that in tissues outside the gut, E. gallinarum initiated the production of auto-antibodies and inflammation — hallmarks of the autoimmune response. They confirmed the same mechanism of inflammation in cultured liver cells of healthy people, and the presence of this bacterium in livers of patients with autoimmune disease. Through further experiments, the research team found that they could suppress autoimmunity in mice with an antibiotic or a vaccine aimed at E. gallinarum. With either approach, the researchers were able to suppress growth of the bacterium in the tissues and blunt its effects on the immune system. “When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity,” said senior author Martin Kriegel, MD.

Double-Drug Strategy Blocks Escape Route for Most Lung Cancers—"Finding Has Possibility of Dramatically Altering How We Treat Lung Cancer”

A one-two combo punch using two currently available drugs could be an effective treatment for the majority of lung cancers, a study by scientists with the University of Texas (UT) Southwestern’s Simmons Cancer Center shows. Researchers found that a combination of drugs – one targeting epidermal growth factor receptor (EGFR) and one targeting tumor necrosis factor (TNF) – effectively blocks the cancer from using TNF as an escape route. Using a mouse model, the researchers showed that when TNF is also blocked, the cancer becomes sensitive to EGFR treatment. “There has been a tremendous effort over the past several years to block EGFR as a treatment for lung cancer, but this therapy only works in a small subset of patients. The cancer fights back with a bypass pathway,” said senior author Dr. Amyn Habib (photo) with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and a staff physician at the Dallas Veterans Affairs Medical Center. “Blocking both of these proteins could be a treatment that is beneficial for the majority of lung cancer patients,” said Dr. Habib, Associate Professor of Neurology and Neurotherapeutics with UT Southwestern’s Peter O’Donnell Jr. Brain Institute. Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute and, in 2017, lung cancer caused 26 percent of all cancer deaths. Non-small cell lung cancer (NSCLC), the type of lung cancer for which the EGFR/TNF inhibitor combination would be effective, comprises approximately 85 percent of all lung cancers. The latest findings build on previous work by Dr. Habib’s lab showing that the same combination of drugs was successful in a mouse model of glioblastoma, a deadly type of brain cancer.

World First--Drug to Treat Skin Lesions in Tuberous Sclerosis Complex Approved

Scientists at Osaka University in Japan have developed a new drug treating skin lesions in tuberous sclerosis complex (TSC), a rare intractable disease, a world first. Following the physician-led clinical studies I and II by Osaka University, and Phase III clinical trials by a pharmaceutical company, the drug was approved within 6 months of the drug application by the SAKIGAKE Designation System, an early approval system led by the Japanese government, on March 23, 2018 and was then commercialized. This drug is the first drug designated by the SAKIGAKE system. The details of physician-led clinical studies I and II were published in JAMA Dermatology on January 1, 2017. The open-access article is titled: “Efficacy and Safety of Topical Sirolimus Therapy for Facial Angiofibromas in the Tuberous Sclerosis Complex A Randomized Clinical Trial.” TSC is an inherited autosomal dominant disease caused by mutations in TSC1 (hamartin) and TSC2 (tuberin) genes. Mutations in the TSC1 and TSC2 tumor suppressor genes cause hyperactivation of the mTORC1 (mammalian target of rapamycin complex 1), developing neoplastic lesions called hamartomas in numerous organs, such as the brain, skin, kidneys, and lungs. The symptoms of TSC include epilepsy, learning disabilities, developmental delays, and autism spectrum disorder in addition to hamartoma. Of the various symptoms, skin problems, such as facial angiofibromas, develop in more than 90 percent of patients with TSC. Hemorrhage, secondary bacterial infection, pain, and functional disorder associated with lesions inflict suffering on patients, severely compromising their quality of life for cosmetic reasons.