DEVELOPMENT OF ANTIMETASTATIC THERAPY AND MODELS

抗转移疗法和模型的开发

• 批准号: 3184584
• 负责人: RALPH James BERNACKI
• 金额: $ 9.83万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184584
• 关键词: antineoplastics; basement membrane; biological models; calcium channel blockers; calcium transporting ATPase; calmodulin; carcinoma; cell adhesion; cell bank /registry; cell membrane; corneal endothelium; cytoskeleton; extracellular matrix; female reproductive system disorder; glycosides; laboratory mouse; lymph node neoplasm; metastasis; neoplastic cell; neoplastic growth; nucleotides; oligosaccharides; reproductive system neoplasm; urinary tract neoplasms; xenotransplantation

The major objective of this study is the evaluation of agents which inhibit the attachment to or degradation of basement membrane components by human metastatic carcinoma cells. Emphasis will be given on studying those agents which affect the metabolism or structure of tumor cell plasma membrane glycoconjugates and/or cytoskeleton as inhibitors of cellular attachment to extracellular matrix (ECM). This includes testing a series of synthetic sugar analogs, oligosaccharides, nucleotide-sugar derivatives, calcium channel blockers and calmodulin inhibitors for their effects on tumor cell attachment and growth. In addition, a number of potential glycosidase inhibitors will be evaluated for their inhibitory effects on tumor cell induced degradation of ECM components. Previous studies with a number of freshly isolated human gynecological and urological tumors have demonstrated that ECM, produced by bocvine corneal endothelial cells, can serve as a good model substrate for studying these phenomena in vitro. a human ovarian tumor cell line established on ECM from a lymph node metastases has been observed to avidly degrade ECM in vitro. Agents with biological activity, selected with this or other human carcinoma cells in vitro, will then be evaluated for therapeutic activity using human tumor xenographs in mice. Alterations in tumor growth rate, metastases and mouse lifespan will be monitored. It is anticipated that the proposed studies will increase our knowledge concerning mechanisms of tumor cell attachment and invasion and perhaps lead to the discovery and development of new and unique drugs having antitumor and antimetastatic activity.

本研究的主要目的是评估抑制药物 人类对基底膜成分的附着或降解 转移性癌细胞。 将重点研究那些 影响肿瘤细胞血浆代谢或结构的药物 膜糖缀合物和/或细胞骨架作为细胞抑制剂 附着于细胞外基质（ECM）。 这包括测试一系列 合成糖类似物、寡糖、核苷酸糖衍生物、 钙通道阻滞剂和钙调蛋白抑制剂的作用 肿瘤细胞附着和生长。 此外，还有一些潜在的 将评估糖苷酶抑制剂的抑制作用 肿瘤细胞诱导 ECM 成分降解。 以前的研究与 新鲜分离的人类妇科和泌尿科肿瘤数量 证明牛角膜内皮细胞产生的 ECM 可以 作为体外研究这些现象的良好模型基质。 一个 基于淋巴结 ECM 建立的人卵巢肿瘤细胞系 已观察到转移在体外会强烈降解 ECM。 代理商与 生物活性，与该或其他人类癌细胞一起选择 体外，然后将使用人类肿瘤评估治疗活性 小鼠异种移植术。 肿瘤生长率、转移和小鼠的变化 寿命将受到监控。 预计拟议的研究 将增加我们对肿瘤细胞附着机制的了解 和入侵，也许会导致新的和新的发现和开发 具有抗肿瘤和抗转移活性的独特药物。