METABOLISM OF AUTOCRINE PEPTIDES--SMALL CELL LUNG CANCER

自分泌肽的代谢--小细胞肺癌

• 批准号: 3187694
• 负责人: THOMAS Paul DAVIS
• 金额: $ 9.04万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-15 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187694
• 关键词: antineoplastics; bombesin; carcinogenesis inhibitor; high performance liquid chromatography; hormone inhibitor; hormone related neoplasm /cancer; neoplasm /cancer chemotherapy; neoplastic growth; neurotensin; peptide hormone metabolism; protease inhibitor; protein sequence; small cell lung cancer; synthetic peptide; tissue /cell culture; tissue /cell preparation

Small cell lung cancer (i.e. small oat-cell carcinoma) accounts for approximately 25% of all identifiable human lung cancers. This malignant neoplasm has a rapid growth rate and shows a propensity to metastasize and grow rapidly. In Arizona alone, there are 2,400 new cases of lung cancer diagnosed each year. Of these 2,400 cases, 600 are new cases of small cell lung cancer (SCLC). This proposal is designed to study and develop potential inhibitors of small cell lung cancer growth by inhibiting the formation of certain peptide hormones produced by the SCLC cells. These peptide hormones are known to affect SCLC by increasing its potential for abnormal growth. The hypothesis that we will test is that SCLC produces metabolic "byproduct" peptide hormones by proteolytic metabolism of larger "parent" proteins, and that these peptides cause SCLC to grow. If we can control the production of these peptide hormones by inhibiting the enzymes responsible for their formation, then we may be able to control SCLC growth. Our research approach can be seen as attempting to disrupt a cascade of events responsible for SCLC growth by altering the formation of the necessary catalysts (peptides) responsible for many of the symptoms of the disease. Our long term objective is to develop a drug (peptidase inhibitor) capable of acting on peptides produced from SCLC. In this way we will be controlling the growth of SCLC, and also controlling the formation of peptide hormones which have serious and deleterious side effects due to their hypersecretion from SCLC cells.

小细胞肺癌（即小燕麦细胞癌）占 约占所有可识别人类肺癌的 25%。 这 恶性肿瘤生长速度快，表现出 转移和快速生长的倾向。 仅在亚利桑那州， 每年新诊断出 2,400 例肺癌病例。 的 这2400例中，600例是小细胞肺癌新发病例 （小细胞肺癌）。 本提案旨在研究和开发潜力 通过抑制小细胞肺癌生长的抑制剂 SCLC 产生的某些肽激素的形成 细胞。 已知这些肽激素通过以下方式影响 SCLC： 增加其异常生长的潜力。 假设 我们将测试 SCLC 产生代谢“副产物”肽 通过较大“母体”蛋白质的蛋白水解代谢产生激素， 这些肽会导致 SCLC 生长。 如果我们能控制 通过抑制这些肽激素的产生 负责其形成的酶，那么我们也许能够 控制 SCLC 生长。 我们的研究方法可以看作是 试图破坏导致 SCLC 的一系列事件 通过改变必要催化剂的形成来实现生长 （肽）导致该疾病的许多症状。 我们的长期目标是开发一种药物（肽酶抑制剂） 能够作用于 SCLC 产生的肽。 这样 我们将控制 SCLC 的增长，并控制 肽类激素的形成具有严重和 由于 SCLC 分泌过多而产生有害副作用 细胞。