t - JOUR T1 -塞来昔布在淋巴管平滑肌瘤病中的作用:摩根富林明I期临床试验的结果——欧洲呼吸杂志》乔和J - 10.1183/13993003.02370 -2019欧元六世- 55 - 5 SP - 1902370 AU El-Chemaly Souheil AU - Taveira-DaSilva,安吉洛盟——Bagwe Shefali盟——Klonowska Katarzyna AU -马查多,塔尼亚AU - Lamattina,安东尼·m . AU -戈德堡,希拉里·J . AU -琼斯,阿曼达·m . AU - Julien-Williams,帕特丽夏盟,毛雷尔Rie AU -罗萨斯,伊万·o . AU - Henske伊丽莎白p . AU -莫斯,乔尔盟——Kwiatkowski摘要N2 -淋巴管平滑肌瘤病(LAM)是一种伴有进行性肺部疾病的多系统疾病，几乎只发生在女性身上。LAM的病理特征是异常的平滑肌肉样细胞增生，携带突变的主要是结节性硬化症(TSC)基因TSC2，很少在TSC1[1]。LAM可偶发或与TSC相关。TSC基因突变导致雷帕霉素复合体1 (mTORC1)[2]的哺乳动物/机械靶点的激活。在具有里程碑意义的随机对照MILES(多中心国际LAM疗效的西罗莫司)试验中，mTORC1抑制剂雷帕霉素稳定了伴有中度至重度肺功能(1 s用力呼气量(FEV1) <70%)变化的LAM患者的肺功能并改善其症状。最近的体外和临床前证据显示，TSC2缺失导致COX-2和前列环素合酶(PGTIS)表达上调，而不依赖于mTORC1。用COX-2特异性抑制剂塞来昔布治疗Tsc2+/−小鼠，可使肾囊腺瘤体积减少50%，这在模型[4]中自然发生。此外，LAM结节的COX-2表达水平高于对照组的[4]。COX2抑制在轻度疾病的LAM患者中是安全的。 In the subset of patients with high VEGF-D (>800 pg per mL) COX2 inhibition appears to cause a decrease in VEGF-D levels and may provide clinical benefit. http://bit.ly/395drXsWe are indebted to patients and their families for their participation in this study. We also thank The LAM Foundation and the Tuberous Sclerosis Alliance for patient referral. We thank the Data Safety Monitoring Board Members and Medical Monitor, as well as the clinical trials support staffs at the BWH and the Office of the Clinical Director, National Heart, Lung, and Blood Institute, NIH. We are grateful to Saint George's, University London for permission to use the SGRQ. ER -