ENDOCRINE CANCER

这项提议是为了继续我们在体内和体外的 三组激素诊断标记物的研究 产生肿瘤：1)降钙素(CT)编码的多肽 吉恩。CT基因不仅编码CT本身，而且至少编码两个 其他多肽、CGRP(降钙素基因相关肽)和 卡塔卡星(PDN21)。这些多肽中的每一个都是由 甲状腺髓样癌、某些肺癌和其他 内分泌肿瘤。2)嗜铬颗粒蛋白A(CGA)及其相关 蛋白质和多肽。CgA是一种蛋白质，存在于许多 内分泌腺，并与内分泌激素共同分泌 那些腺体。它的组织和血清浓度因此可以 作为多种在位和异位内分泌肿瘤的标志物。 CGA可能代表一组蛋白质和多肽，它们具有 不同内分泌细胞的特异性。3)新奇的内分泌 由单抗和c DNA确定的肿瘤标记物 探测器。利用特异性的单抗和cDNAs探针 内分泌肿瘤，我们已经确认了至少四个额外的 可能成为肿瘤的内分泌癌的产物 记号笔。其中两种是由抗髓鞘单抗确定的。 甲状腺癌，由抗胰腺的单抗引起 胰岛细胞，并在松弛杂交下由一个cDNAto CgA 条件。我们建议研究组织特异性， 这三组内分泌的生物合成和分泌 肿瘤标志物。我们已经培育出人类内分泌细胞系 来产生和分泌这些物质。对于这些细胞系来说 我们已经开发了免疫组织化学程序来确定 肿瘤标志物重组DNA的组织特异性 方法研究它们的基因转录和免疫分析。 研究它们的分泌物的程序。对于临床研究，我们有 开发了免疫组织学程序来确定组织 这些肿瘤标志物和免疫分析系统的特异性 研究它们在内分泌癌患者中的分泌。 这些研究应该阐明调节细胞周期的机制 我们已建立的和新的推定的生物合成和分泌 人类内分泌细胞系肿瘤标志物的研究。此外， 研究应该导致免疫组织学的发展和 可以在临床上有价值的免疫分析程序 异位激素的分类、诊断和处理 产生肺癌和原位激素产生等肿瘤 基本上所有内分泌细胞类型的肿瘤。简而言之，这些 研究应该有助于开发新的生物学工具和 内分泌癌患者的治疗。

This proposal is designed to continue our in vivo and in vitro studies of three groups of diagnostic markers for hormone- producing tumors: 1) Peptides encoded by the calcitonin (CT) gene. The CT gene not only encodes CT, itself, but at least two additional peptides, CGRP (calcitonin-gene-related-peptide) and Katacalcin (PDN21). Each of these peptides if produced by medullary thyroid carcinoma, certain lung cancers,and other endocrine tumors. 2) Chromogranin A (CgA) and its related proteins and peptides. CgA is a protein that is present in many endocrine glands and is co-secreted with the resident hormones of those glands. It's tissue and serum concentration can thus serve as markers for a variety of eutopic and ectopic endocrine tumors. CgA may represent a family of proteins and peptides that have specificity for different endocrine cells. 3) Novel endocrine tumor markers defined by monoclonal antibodies and cDNA probes. Using monoclonal antibody and cDNA probes specific to endocrine tumors, we have identified at least four additional products of endocrine cancers that have potential as tumor markers. Two are defined by monoclonal antibodies to medullary thyroid carcinoma, one by a monoclonal antibody to pancreatic islet cells, and one by a cDNA to CgA under relaxed hybridization conditions. We propose to study the tissue specificity, biosynthesis, and secretion of these three groups of endocrine tumor markers. We have developed human endocrine cell lines that produce and secrete these substances. For these cell lines we have developed immunohistochemical procedures to determine the tissue specificity of the tumor markers, recombinant DNA methods to study their gene transcription, and immunoassay procedures to study their secretion. For clinical studies, we have developed immunohistology procedures to determine the tissue specificity of these tumor markers and immunoassay systems to study their secretion in patients with endocrine cancer. These studies should elucidate the mechanism that regulate the biosynthesis and secretion of our established and novel putative tumor markers by human endocrine cell lines. In addition, the studies should lead to the development of immunohistology and immunoassay procedures that can be clinically valuable in the classification, diagnosis, and management of ectopic hormone- producing tumors like lung cancer and eutopic hormone-producing tumors of essentially every endocrine cell type. In short, these studies should help to develop new tools for the biology and management of patients with endocrine cancer.