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)是不治之症。这个多学科项目的目标是阐明CAP从局部和雄激素敏感的肿瘤向播散性和雄激素非依赖性肿瘤进展过程中的信号转导机制。该计划汇集了富有成效和经验丰富的研究人员，他们具有与该计划所述目标和信号转导背景相关的互补专业知识(J.T.Parsons，S.J.Parsons， 核受体生物学(Paschal)、骨生物学(Chirgwin，Gise)和前列腺癌基础与临床转移研究(Theodresu)。在项目1中，D.Theodresu和J.T.Parsons建议评估VEGF和FAK在确定CAP转移到骨的趋向性中的作用；项目2，T.guise和J.Chirgwin将研究肾上腺髓质素在骨转移中的影响；项目3，M.Weber研究RAS介导的信号级联影响配体非依赖性雄激素受体活性；项目4，B.Paschal 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这些细胞对整体肿瘤对雄激素的依赖的影响；项目6，M.Schwartz致力于研究抑制细胞黏附信号与化疗之间的协同作用，作为提高后者在雄激素非依赖性CAP中的治疗指数的新方法。这个互动项目严重依赖于 来自所有调查人员的协同技术和科学专长。个别项目的生产力是由高度集成的核心所催化的，这些核心由H.Frierson，专门从事CAP的外科病理学家，T.Guise，他在骨组织学和组织形态计量学方面拥有丰富的经验，J.T.Parsons，他在活细胞显微镜方面经验丰富，M.Conaway，专家生物统计学家和D.Theodresu领导，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。这些项目结合了不同的技能和专业知识，专注于我们了解肿瘤的基础领域。 在CAP方面取得进展，目的是加快开发这种毁灭性疾病的治疗方法的进展。