ROSIGLITAZONE TREATMENT IN PATIENTS WITH CUSHINGS DISEASEROSIGLITAZONE TREAT

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。 具体目标 具体目标：PPAR-？配体是治疗分泌促肾上腺皮质激素的垂体瘤(库欣S病)的有效和安全的药物。由于分泌ACTH的垂体瘤表现出丰富的过氧化物酶体增殖物激活受体-γ(PPAR-？)表达和PPAR-？配基罗格列酮在体外和体内的促肾上腺皮质激素肿瘤模型中具有强大的抗激素和抗增殖作用，罗格列酮对垂体肿瘤生长的影响以及对垂体肿瘤ACTH和肾上腺类固醇激素分泌的影响将被检测。 PPAR的潜在作用是什么？配体罗格列酮治疗库欣S病将在第二阶段临床试验中进行，涉及15名新诊断的促肾上腺皮质激素分泌垂体瘤(库欣S病)患者。本研究将检测：(1)罗格列酮治疗对消除皮质醇增多症的作用，以及(2)罗格列酮治疗对阻止垂体促肾上腺皮质激素细胞生长的作用。此外，还将检查罗格列酮治疗对血浆ACTH水平和炎症标志物(C反应蛋白、IL-6、血清唾液酸、可溶性细胞内和血管黏附分子(sICAM-1和sVCAM-1)和淀粉样蛋白A)的影响。

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. SPECIFIC AIMS Specific Aim: PPAR-? ligands are a useful and safe medical therapy for Adrenocorticotrophic Hormone (ACTH)-secreting pituitary tumors (Cushing s disease). As ACTH-secreting pituitary tumors exhibit abundant peroxisome proliferator activated receptor-gamma (PPAR-?) expression and the PPAR-? ligand rosiglitazone exerts potent anti-hormonal and anti-proliferative effects in in vitro and in vivo corticotroph tumor models, the effects of rosiglitazone on pituitary tumor growth, and pituitary tumor ACTH and adrenal steroid hormone secretion will be tested. The potential role of the PPAR-? ligand rosiglitazone in treating Cushing s disease will be examined in a Phase II clinical trial involving 15 patients with ACTH-secreting pituitary tumors (Cushing s Disease), who are newly diagnosed. The study will examine: (1) effects of rosiglitazone treatment on abrogating hypercortisolism, and (2) effects of rosiglitazone treatment on abrogating pituitary corticotroph growth. Additionally the effects, if any, of rosiglitazone treatment on abrogating plasma ACTH levels and inflammatory markers (C-reactive protein, IL-6, serum sialic acid, soluble intracellular and vascular adhesion molecules (sICAM-1, and sVCAM-1), and amyloid A) will be examined.