Signaling and Progression in Prostate Cancer

前列腺癌的信号传导和进展

• 批准号: 7115394
• 负责人: DAN THEODORESCU
• 金额: $ 177.66万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-28 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115394
• 关键词: Signaling; Progression; Prostate; Cancer

Metastatic, hormone independent prostate cancer (CAP) is incurable. The goal of this multidisciplinary Program Project is to elucidate the signal transduction mechanisms that underlie the stepwise events associated with progression of CaP from a localized and androgen sensitive tumor to a disseminated and androgen independent one. The Program brings together productive and experienced investigators with complementary expertise relevant to the stated goal of the Program and backgrounds in signal transduction (J. T. Parsons, S. J. Parsons, Schwartz, Weber), nuclear receptor biology (Paschal), bone biology (Chirgwin, Guise) and basic and clinical prostate cancer metastasis research (Theodorescu). In Project 1, D. Theodorescu and J. T. Parsons propose to evaluate the roles of VEGF and FAK in determining the tropism of CaP metastasis to bone; Project 2, T. Guise and J. Chirgwin will study the impact of adrenomedullin in bone metastasis; Project 3, M. Weber studies Ras-mediated signaling cascades as they affect ligand independent androgen receptor activity; Project 4, B. Paschal proposes to study the relationship between androgen receptor activation and the control of its nuclear localization; Project 5, S. J. Parsons studies the regulation of neuroendocrine cell growth within advanced prostate cancers and the impact of such cells on overall tumor dependence on androgen; Project 6, M. Schwartz works on novel ways of exploiting synergies between inhibition of cell adhesion signaling and chemotherapy as a way to enhance the therapeutic index of the latter in androgen independent CaP. This interactive Program relies heavily on synergistic technical and scientific expertise from all investigators. The productivity of individual Projects is catalyzed by highly integrated Cores led by H. Frierson, an expert surgical pathologist who specializes in CaP, T. Guise who has extensive experience in bone histology and histomorphometry, J. T. Parsons who is highly experienced at live cell microscopy, M. Conaway an expert biostatistician and D. Theodorescu who is familiar with the biology of prostate cancer and the xenograft models used in prostate cancer research. Together, these Projects integrate diverse skills and expertise to focus on areas fundamental to our understanding tumor progression in CaP, with the objective of accelerating progress in developing a cure for this devastating disease.

转移性、激素非依赖性前列腺癌 (CAP) 是无法治愈的。这一多学科项目的目标是阐明信号转导机制，该机制是与 CaP 从局限性雄激素敏感肿瘤进展为播散性雄激素非依赖性肿瘤相关的逐步事件相关的信号转导机制。该计划汇集了富有成效和经验丰富的研究人员，他们具有与该计划既定目标相关的互补专业知识和信号转导背景（J. T. Parsons、S. J. Parsons、 Schwartz，Weber），核受体生物学（Paschal），骨生物学（Chirgwin，Guise）以及基础和临床前列腺癌转移研究（Theodorescu）。在项目 1 中，D. Theodorescu 和 J. T. Parsons 提议评估 VEGF 和 FAK 在确定 CaP 骨转移倾向中的作用；项目2，T. Guise 和J. Chirgwin 将研究肾上腺髓质素对骨转移的影响；项目 3，M. Weber 研究 Ras 介导的信号级联，因为它们影响配体独立的雄激素受体活性；项目 4，B. 逾越节 提议研究雄激素受体激活与其核定位控制之间的关系；项目 5，S. J. Parsons 研究晚期前列腺癌中神经内分泌细胞生长的调节以及此类细胞对肿瘤对雄激素的总体依赖性的影响；项目 6，M. Schwartz 致力于研究利用细胞粘附信号传导抑制和化疗之间的协同作用的新方法，作为提高后者在雄激素非依赖性 CaP 中的治疗指数的方法。这个交互式程序很大程度上依赖于 所有研究人员的协同技术和科学专业知识。各个项目的生产力由高度集成的核心催化，这些核心由专门研究 CaP 的外科病理学家 H. Frierson、在骨组织学和组织形态计量学方面拥有丰富经验的 T. Guise、在活细胞显微镜方面经验丰富的 J. T. Parsons、生物统计学专家 M. Conaway 和熟悉前列腺癌生物学和前列腺癌异种移植模型的 D. Theodorescu 领导。 研究。这些项目整合了不同的技能和专业知识，重点关注我们了解肿瘤的基础领域 CaP 的进展，目标是加快开发治疗这种毁灭性疾病的方法。