USE OF LH-RH AGONISTS AND ANTAGONISTS IN PROSTATE CANCER

促黄体生成素释放激素类似物(黄体生成素-RH)单独给药和 联合应用将在携带Dunning R-3327H的大鼠身上进行测试 激素依赖型前列腺肿瘤Noble和Pollard大鼠模型的建立 人前列腺癌移植瘤与裸鼠或裸鼠的关系 台词。我们的研究将包括对前列腺癌生长的调查。 基于(1)连续受控给药系统的抑制效应 激动型类似物D-色氨酸-6-黄体生成素-RH的微囊制剂 可生物降解聚(D，L-丙交酯-乙交酯)(PLGA)每月一次 (2)D-色氨酸-6-黄体生成素-RH微囊联合给药方案 A)其他多肽，特别是生长抑素类似物，以及b) 抗雄激素RU-23908(Anandron)和氟他胺(SCH 13521)，以及c) 化疗药物，如环磷酰胺，米托蒽醌和 (3)基于双苯并三烯的连续控制给药系统 微囊(PLGA)制剂 N-Ac-D-p-Cl-Phe-1，2，D-Trp-3，D-Arg-6，D-Ala-10-Lh-RH(拮抗剂I)， Ac-β-D-Nal(2)-1，D-p-Cl-Phe-2，D-Trp-3，D-Arg-6，D-Ala-10-Lh-RH(拮抗剂 Ii)或另一种拮抗剂；(4)促黄体生成素-促性腺激素释放激素拮抗剂联合方案 使用生长抑素类似物、抗雄激素和化疗药物； 含细胞抑制自由基的D-色氨酸-6-黄体生成素-RH类似物的合成 (烷化剂麦法兰[附着于苯丙氨酸的氮芥末]) 及其在前列腺癌动物模型中作为激素的评价 化疗药物的载体。一些生化研究，如DNA， RNA和蛋白质的合成及蛋白质磷酸化的测定 以及前列腺胞浆和胞核中的蛋白激酶活性。 将进行肿瘤和组织学评估以提供数据 与肿瘤的消退有关。该项目的目标将是 联合用药改善前列腺癌对促黄体生成素释放激素激动剂的反应 与其他药物进行治疗，并提供关于药物有效性的新数据 单独或联合应用促黄体生成素释放激素拮抗剂的抑制作用 这个肿瘤的。

Analogs of luteinizing hormone-releasing hormone (LH-RH) given alone and in combination will be tested in rats bearing Dunning R-3327H hormone-dependent prostate tumors, Noble and Pollard rat models of prostate tumors and nude mice or nude rats with transplanted human prostate tumor lines. Our studies will include the investigation of prostate tumor growth inhibition induced by (1) continuous controlled delivery system based on the microcapsule formulation of the agonistic analog D-Trp-6-LH-RH in biodegradable poly(D,L-lactide-co-glycolide) (pLGA) for once a month administration; (2) combination regimens of D-Trp-6-LH-RH microcapsules with a) other peptides, especially somatostatin analogs, as well as with b) antiandrogens RU-23908 (Anandron) and Flutamide (SCH 13521), and c) chemotherapeutic agents such as cyclophosphamide, Mitoxantrone and Bisantrene; (3) continuous controlled delivery system based on the microcapsule (pLGA) formulation of N-Ac-D-p-Cl-Phe-1,2,D-Trp-3,D-Arg-6,D-Ala-10-LH-RH (Antagonist I), Ac-Beta-D-Nal(2)-1,D-p-Cl-Phe-2,D-Trp-3,D-Arg-6,D-Ala-10-LH-RH (Antagonist II) or another antagonist; (4) combination regimens of LH-RH antagonists with somatostatin analogs, antiandrogens, and chemotherapeutic agents; (5) synthesis of an analog of D-Trp-6-LH-RH containing a cytostatic radical (alkylating agent Melphalan [nitrogen mustard attached to Phenylalanine]) and its evaluation in animal models of prostate cancer as a hormonal carrier for chemotherapeutic agent. Some biochemical studies such as DNA, RNA and protein synthesis and measurement of protein phosphorylation as well as protein kinases activities in cytoplasma and nuclei of prostate tumors and histological evaluations will be performed to provide data to correlate with tumor regression. The aim of this project will be to improve the response to LH-RH agonists in prostate cancer by combined therapy with other agents and provide new data on the usefulness of the LH-RH antagonist given alone or in combination regimens for the inhibition of this tumor.