Growth Control in Multiple Myeloma

多发性骨髓瘤的生长控制

• 批准号: 7078603
• 负责人: BART BARLOGIE
• 金额: $ 349.94万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-05 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7078603
• 关键词: cellular oncology; clinical research; human subject; molecular oncology; multiple myeloma; neoplasm /cancer genetics; cellular oncology; clinical research; human subject; molecular oncology; multiple myeloma; neoplasm /cancer genetics

DESCRIPTION (provided by applicant): Currently in its 10th year of funding, this P01's objective is to achieve durable growth control in multiple myeloma (MM) through highly integrated translational research conducted by clinical and basic scientists. The overall hypothesis will be pursued that various components of the bone marrow microenvironment (ME) contribute to eventual treatment failure by providing (in a MM genotype-specific manner) a plethora of survival and proliferation signals, and that novel therapeutic strategies, coincapacitating MM and ME, will augment growth control. Through a combination of autotransplantsupported high-dose melphalan and therapies that co-target MM and ME, therapeutic strategies will be employed to maximize sustained complete responses. Novel immunotherapeutic approaches are aimed at augmenting autologous host responses via cancer/testis antigen vaccination and employing allogeneic natural killer cells and cytotoxic T lymphocytes. Gene expression profiling (GEP) should improve prognostic models and identify, in concert with Project 4, genes involved in pathogenetic cross talk between MM and ME. Because soluble syndecan-1 has cytokine-trapping properties, studies will determine if blocking heparan sulfate function or its bioavailability may inhibit tumor growth and dissemination. To successfully implement these Projects, 4 Cores are required: A) Admin., Data Mgmt., and Biostatistics; B) Functional Imaging; C) Molecular Genetics; and D) Cell Analysis/Tissue Banking. With access to a large patient population with MM, treated in a hypothesis-driven clinical trial setting with comprehensive follow-up, this P01 will shed light on the molecular and biological mechanisms of disease development/ progression and the current obstacles to sustaining complete remission.

描述（由申请人提供）：目前，该P01的目标是通过临床和基础科学家进行的高度综合的翻译研究来实现多发性骨髓瘤（MM）的持久增长控制。 总体假设将被提出，骨髓微环境（ME）的各种组成部分通过提供（以MM基因型特异性方式）提供了多种生存和增殖信号，以及最终的治疗信号，以及新型的治疗策略，将MM MM和ME增强生长控制。通过自动替代的高剂量Melphalan和我共同目标MM和我的疗法的结合，将采用治疗策略来最大程度地提高持续的完整反应。新型免疫治疗方法旨在通过癌症/睾丸抗原疫苗来增强自体宿主反应，并采用同种异体天然杀伤细胞和细胞毒性T淋巴细胞。基因表达谱分析（GEP）应改善预后模型，并与MM和ME之间的致病交叉聊天相关的基因鉴定。由于可溶性syndecan-1具有细胞因子捕获特性，因此研究将确定阻断硫酸乙酰肝素功能或其生物利用度是否可以抑制肿瘤的生长和传播。要成功实施这些项目，需要4个核心：a）管理员，数据管理和生物统计学； b）功能成像； c）分子遗传学； D）细胞分析/组织库。 随着在假设驱动的临床试验环境中接受MM的大量患者人群，该P01将阐明疾病发育/进展/进展的分子和生物学机制以及当前持续完全缓解的障碍。