title: [Current understanding and perspectives of lymphangioleiomyomatosis].
abstract: Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease characterized with proliferation of abnormal smooth muscle-like cells (LAM cells) in the lungs and along axial lymphatics. Proliferation of LAM cells are considered to be driven by dysregulated mTORC1 signaling, that is caused by mutations in either the TSC1 or TSC2 gene in LAM cells. The MILES trial has successfully demonstrated that sirolimus, a mTORC1 inhibitor, can stabilize pulmonary function in LAM, but its effect disappears once sirolimus is discontinued. Limited ability of sirolimus may be due to concomitant activation of autophagy in LAM cells when mTORC1 activity is suppressed by sirolimus. Recently animal models for LAM have been independently established by several groups, which may provide a platform for developing drugs interfering various steps in disease progression.
authors.affiliation: Division of Respiratory Medicine, Juntendo University, Faculty of Medicine and Graduate School of Medicine.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Hoshika
authors.forename: Yohei
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takekawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D018192:Lymphangioleiomyomatosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins