Signaling and Progression in Prostate Cancer

前列腺癌的信号传导和进展

• 批准号: 7284160
• 负责人: DAN THEODORESCU
• 金额: $ 176.02万
• 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/7284160
• 关键词: Affect; American; Androgen Receptor; Androgens; Area; Attention; Biology; Cell Adhesion Inhibition; Cells; Clinical; Dependence; Disease; Event; Goals; Histology; Hormones; Incidence; Individual; Life; Ligands; Localized; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Metastatic Neoplasm to the Bone; Microscopy; Neoplasm Metastasis; Neuroendocrine Cell; Nuclear; Nuclear Receptors; Operative Surgical Procedures; PTK2 gene; Pathologist; Productivity; Public Health; Receptor Activation; Regulation; Research; Research Personnel; Role; Signal Transduction; Technology; Therapeutic Index; Tropism; United States; Vascular Endothelial Growth Factors; Work; Xenograft Model; adrenomedullin; anticancer research; bone; cell growth; chemotherapy; day; experience; men; mortality; multidisciplinary; novel; programs; skills; tumor; tumor progression

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。这个多学科的计划项目的目标是阐明的信号转导机制的基础上逐步的事件与进展的CaP从本地化和雄激素敏感的肿瘤扩散和雄激素非依赖性的。该计划汇集了富有成效和经验丰富的调查人员与互补的专业知识有关的既定目标的计划和背景的信号转导（J。Parsons，S. J·帕森斯， 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建议评估VEGF和FAK在决定CaP向骨转移的向性中的作用; Guise和J. Chirgwin将研究肾上腺髓质素在骨转移中的作用; Weber研究Ras介导的信号级联，因为它们影响配体非依赖性雄激素受体活性;项目4，B。Paschal 建议研究雄激素受体激活与其核定位控制之间的关系;帕森斯研究了晚期前列腺癌中神经内分泌细胞生长的调节以及这些细胞对肿瘤对雄激素依赖性的影响; Schwartz致力于开发细胞粘附信号抑制和化疗之间的协同作用的新方法，作为增强后者在雄激素非依赖性CaP中的治疗指数的一种方式。这一互动计划在很大程度上依赖于 所有研究人员的协同技术和科学专门知识。由H.专门研究前列腺增生的外科病理学家弗里尔森说，Guise在骨组织学和组织形态计量学方面具有丰富的经验。帕森斯在活细胞显微镜方面经验丰富。Conaway是一位生物统计学专家，D.他熟悉前列腺癌的生物学和前列腺癌研究中使用的异种移植模型。总之，这些项目整合了各种技能和专业知识，专注于我们了解肿瘤的基础领域 我们的目标是加速开发治疗这种毁灭性疾病的方法。