RAPAMYCIN THERAPY OF RENAL ANGIOMYOLIPOMAS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大约每5000人中就有一人患有结节性硬化症(TSC)，在美国约有5.6万名患者，全球约有100万名患者。这一疾病过程不会聚集在族裔群体中，也没有性别偏好。据报道，肾功能衰竭是成人结节性硬化症患者死亡的主要原因，在大多数情况下，是由于健康的肾脏组织被称为血管肌脂肪瘤的脂肪肿瘤取代。 大约40%的女性TSC患者还会发展成一种称为淋巴管肌瘤病(LAM)的肺部疾病。LAM的特点是肺内平滑肌细胞浸润，导致肺组织囊性变性，气体交换障碍，呼吸衰竭和死亡。最近有证据表明，LAM可能是由血管肌脂肪瘤细胞转移到肺引起的。 血管肌脂肪瘤细胞对从TSC基因中选择正确基因产物的治疗是唯一脆弱的。TSC1的基因产物hamartin和TSC2的基因产物tuberin是调节细胞生长的关键分子。雷帕霉素模拟TSC中功能失调的tuberin/hamartin复合体的功能。雷帕霉素可抑制人、大鼠、小鼠和苍蝇的tuberin和hamartin缺陷细胞的生长，并使大鼠和小鼠的肿瘤消退。因此，这项研究的目的是确定雷帕霉素能否像在人类细胞培养和动物模型中所做的那样，减少或消除TSC和散发性LAM患者中的血管肌脂瘤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately one out of 5,000 individuals has tuberous sclerosis complex (TSC), representing approximately 56,000 patients in the United States and 1 million patients worldwide. This disease process does not cluster in ethnic groups and has no gender predilection. Renal failure has been reported to be the leading cause of death in adult tuberous sclerosis patients, in most cases due to replacement of healthy kidney tissue by fatty tumors called angiomyolipomas. Approximately 40% of female patients with TSC also develop a pulmonary disease called lymphangioleiomyomatosis (LAM). LAM is characterized by smooth muscle cell infiltration in the lungs leading to cystic degeneration of lung tissue, impaired gas exchange, respiratory failure and death. There is recent evidence that LAM may be caused by metastases of angiomyolipoma cells to the lung. Angiomyolipoma cells are uniquely vulnerable to treatments that select for the presence of the correct gene product from the TSC genes. The gene products of TSC1, hamartin, and TSC2, tuberin, are key players in a pathway that regulates cell growth. Rapamycin mimics the function of the tuberin/hamartin complex, which is dysfunctional in TSC. Rapamycin inhibits the growth of tuberin and hamartin deficient cells from humans, rats, mice and flies, and produces tumor regression in rats and mice. Thus, the aim of this study is to determine if the administration of Rapamycin can reduce or eliminate angiomyolipomas in patients with TSC and sporadic LAM as it does in human cell culture and animal models.