REGULATORY MECHANISMS OF PROSTATE TUMOR PROGRESSION

前列腺的异常状况构成了一个主要的医疗问题， 美国的 前列腺炎、良性增大（BPH）和恶性 前列腺（CaP）的生长将影响大多数男性的生活。 65岁。 BPH是一种令人烦恼的异常生长， 容易通过各种选择来治疗。 前列腺癌，如果发现 早期是可以治愈的，但转移性疾病可能是致命的，因为没有 目前可用于转移性前列腺癌的治愈性疗法。 在 此外，由于生物学方面的极端异质性， 前列腺癌的最佳治疗方法存在争议。 即使是局部疾病也要治疗。 缺乏共识， 可行的管理和治疗方法。 这反映了我们缺乏 对这一系列生物学决定因素的了解， 行为的水平，将提供适当的治疗 干预 本奥布莱恩泌尿外科中心提案将重点关注 确定与所述细胞表型相关的细胞表型的变化， 从正常到癌前病变到局部病变的疾病进展 癌症转移到远处扩散的癌症。 在这个初始应用中，我们 将侧重于与增长因素相关的方案拟订的三个领域 在恶性转化表型中。 项目一将研究酪氨酸激酶相关的改变， 项目二将研究PKC同工酶的改变 信号通路的进展，项目三将检查 转铁蛋白受体样前列腺特异性膜抗原PSM和 转铁蛋白受体在前列腺肿瘤进展中的作用 这些项目和相关项目将被确定和招募 随着时间的推移，该中心将提供对生物学的理解， CaP的进展，并为新的介入治疗制定强有力的理由 战略布局

Abnormal conditions of the prostate constitute a major medical problem in the United States. Prostatitis, Benign enlargement (BPH), and malignant growth of the prostate (CaP) will effect the lives of most men over the age of 65. BPH is a bothersome abnormal growth that fortunately is readily treated by a variety of options. Prostatic cancer, if detected early is curable, but metastatic disease can be fatal as there is no currently available curative therapy for metastatic prostatic cancer. In addition, because of the extreme heterogeneity with regard to biologic potential of prostatic cancer there is debate on the best approach to therapy even with localized disease. There is a lack of consensus and viable approaches to management and therapy. This reflects our lack of knowledge of the biologic determinants responsible for this spectrum of behavior at a level that would provide appropriate therapeutic intervention. This O'Brien Urology Center Proposal will focus its attention on determining changes in the cellular phenotype that is associated with the progression of disease from normal to premalignant lesions to localized cancer to distant disseminated cancer. In this initial application we will focus on three areas related to growth factor associated programming in the malignant transformed phenotype. Project One will examine the alterations in tyrosine kinase associated growth factors, Project Two will examine alterations in PKC isoenzymes signal pathways in progression, and Project Three will examine the transferrin receptor like prostate specific membrane antigen PSM and transferrin receptor in prostatic tumor progression. These projects and related projects which will be identified and recruited to the Center will with time provide an understanding of the biology of progression of CaP and develop strong rationales for new interventional strategies.