real-time monitoring of tumorigenesis, dissemination, drug response in a preclinical model of lymphangioleiomyomatosistuberous sclerosis complex实时监测肿瘤发生、传播、与药物反应lymphangioleiomyomatosistuberous硬化的临床前模型复杂.pdfVIP

Real-Time Monitoring of Tumorigenesis, Dissemination, Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex 1 2 3 1 1 4 Fangbing Liu , Elaine P. Lunsford , Jingli Tong , Yoshitomo Ashitate , Summer L. Gibbs , Jane Yu , 1 4 1,5 Hak Soo Choi , Elizabeth P. Henske , John V. Frangioni * 1 Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Longwood Small Animal Imaging Facility, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 4 Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to