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，激素独立的前列腺癌（CAP）是无法治愈的。这个多学科计划项目的目的是阐明与从局部和雄激素敏感的肿瘤到传播和雄激素无关的逐步事件相关的逐步事件的信号转导机制。该计划汇集了具有与该计划的既定目标和信号转导背景有关的互补专业知识的生产和经验丰富的研究人员（J. T. Parsons，S。J。Parsons，S。J。Parsons， Schwartz，Weber），核受体生物学（Paschal），骨生物学（Chirgwin，uise）以及基本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在确定Cap转移对骨骼的最大性中的作用；项目2，T。Guise和J. Chirgwin将研究肾上腺果蛋白在骨转移中的影响；项目3，M。Weber研究RAS介导的信号级联反应，因为它们影响配体独立的雄激素受体活性。项目4，B。Paschal 建议研究雄激素受体激活与控制核定位之间的关系；项目5，S。J。Parsons研究了晚期前列腺癌中神经内分泌细胞生长的调节，以及此类细胞对雄激素总体肿瘤依赖性的影响；项目6，施瓦茨M. Schwartz致力于在抑制细胞粘附信号和化学疗法之间利用协同作用的新型方法，以此来增强雄激素独立帽中后者的治疗指数。这个互动程序在很大程度上依赖 所有研究人员的协同技术和科学专业知识。由H. Frierson领导的高度积分核心催化了单个项目的生产力，他是一位专业的手术病理学家H. Frierson，他专门从事Cap，T。Guise，在骨骼组织学和组织学方面具有丰富经验，J。T。Parsons在Live Cell Microscopight中经验丰富的经验丰富 研究。这些项目共同整合了多样化的技能和专业知识，以关注我们理解肿瘤的领域 CAP的进展，目的是加快为这种毁灭性疾病的治疗而进步。