PATHOGENISIS OF KAPOSI'S SARCOMA

这项建议的目的是阐明卡波西的发病机制。 有或无IEV感染的肉瘤(KS)，基于 糖皮质激素和某些细胞因子/单因子的假说(IL-L， 肿瘤坏死因子、白介素6、新型生长因子)直接或间接作用于 促进KS的生长。将采用病例对照研究 免疫功能相对完整的男同性恋者中的HIV相关KS 系统(CD4)，200/dl，无AMS-定义机会性感染)。案例 将从LAC/南加州大学医疗中心的KS诊所应计 160例。每个病例将确定三个年龄匹配的对照。第I组 对照将是临床上呈EIV阳性的无症状同性恋朋友 控制组；第2组控制组将是HIV阴性的同性恋朋友 对照；第3组对照将是HIV阴性的异性恋者 邻里控制。将从洛杉矶确定典型的KS病例 洛杉矶县基于人口的癌症登记(CSP)(n=272)。控制 对于这些病例，将确定与年龄匹配的邻里控制 使用预定的算法。流行病学调查问卷、血液 所有参与者的尿样都将被采集。此外，KS 将在所有A.MS-KS病例和临床样本上获得组织 KS病例。我们将测定(1)血浆ACTH、血清皮质醇和 KS患者尿游离皮质醇较对照组升高； 血清和短期外周血单核/巨噬细胞培养上清 细胞因子/单核细胞因子水平(TNF、EL-1、EL-6)和尿IL-6水平为 与对照相比，病例中的水平更高；(3)如果 流行病学特征是KS危险因素，如使用 类固醇，某些性传播疾病的病史， 改变免疫功能等。该提案的次要目标是 建立血清和组织库，以供未来研究使用。

The goal of this proposal is to elucidate the pathogenesis of Kaposi sarcoma (KS) in the presence or absence of IEV infection, based on the hypothesis that glucocorticoids and certain cytokines/monokines (IL-l, TNF, IL-6, novel growth factors) act directly and indirectly to induce and enhance the growth of KS. A case-control study will be employed for HIV-related KS among homosexual men with a relatively intact immune system (CD4),200/dl, no AMS-defining opportunistic infections). Cases will be accrued from the KS clinics at the LAC/USC Medical Center (N=160). Three age-matched controls will be identified per case. Group I controls will be EIV-positive clinically asymptomatic homosexual friend controls; Group 2 controls will be HIV-negative homosexual friend controls; Group 3 controls will be HIV-negative heterosexual neighborhood controls. Classic KS cases will be identified from the Los Angeles County population based cancer registry (CSP) (n=272). Controls for these cases will be age-matched neighborhood controls identified using a predetermined algorithm. An epidemiologic questionnaire, blood and urine specimens will be obtained on all participants. In addition KS tissue will be obtained on all A.MS-KS cases and on a sample of clinic KS cases. We will determine (1) if plasma ACTH, serum cortisol and urinary free cortisol are elevated in KS cases compared to controls; (2) if serum and short term blood monocyte/macrophage culture supernatant cytokine/monokine levels (TNF, EL-1, EL-6) and urinary IL-6 levels are present at higher levels in cases compared to controls; (3) if certain epidemiologic characteristics are KS risk factors, such as use of steroids, history of certain sexually transmitted diseases, indices of altered immune function, etc. A secondary objective of the proposal is to establish a serum and tissue bank for use in future studies.