INFLAMMATION AND ATROPHY IN PROSTATE CARCINOGENESIS

制定合理的预防前列腺癌的新策略 癌症(CAP)依赖于发现靶向于 前列腺。我们正在探索一种假设，类似于 肝脏、大肠和胃、前列腺癌的发生可能通过以下方式加速 免疫介导的氧化应激。高级别前列腺上皮内瘤变 (HGPIN)被认为是许多前列腺癌(CAP)的先兆。 增生性炎性萎缩(PTA)是一种常见的病变，发生在 炎性细胞。我们推测PTA可能是HGPIN的前体，原因如下：1) PTA中的上皮细胞增殖率升高；2) PTA细胞表型与未成熟分泌细胞表型一致 细胞-类似于HGPIN和癌细胞；3)PIA、HGPIN和CAP 均发生在外周地带，发病率高，发病率低。 在人类前列腺的中央区域；4)PTA和Hopin密切相关 接近，它们之间有频繁的形态转换。我们致力于 假设PTA导致HGPIN/CAP通过设计实验来回答 以下问题：1)在以下情况下，是否有更大程度的PTA HGPTN/CAP与未使用HGPIN/CAP的对照相比？2)在 东南亚人和北美人之间的CAP发病率与 PTA含量的差异？3)是否存在相似的分子遗传 PIA患者8号染色体短臂上HGPIN和HGPIN基因的改变 染色体8q和8q的遗传物质是否也有类似的收获 PTA中的其他染色体，同样在HGPIN和CAP中也是已知的，可以 大鼠前列腺自发性和诱导性HGPIN和CAP的预防作用 抑制宿主炎症反应？如果这些研究的结果 涉及宿主炎症反应和PIA在前列腺癌发生中的作用 然后，可以设计出前列腺癌化学预防的合理试验 抗炎药和PTA是评估前列腺癌的新生物标志物 癌症风险。最后，新的重点将集中在找出 前列腺的慢性炎症，目的是根除这种炎症。

The development of rational new strategies to prevent prostate carcinoma (CaP) relies on discovering the carcinogenic agents that target the prostate. We are exploring the hypothesis that, similar to cancers of the liver, large bowel, and stomach, prostatic carcinogenesis may be accelerated by immune-mediated oxidant stress. High grade prostatic intraepithelial neoplasia (HGPIN) is held to be the precursor to many prostatic adenocarcinomas (CaP). Proliferative inflammatory atrophy (PTA) is a common lesion occurring near inflammatory cells. We postulate that PTA maybe a precursor to HGPIN since: 1) Epithelial cells in PTA have an elevated proliferative fraction; 2) The phenotype of PTA cells is consistent with that of immature secretory cells-similar to that for cells of HGPIN and carcinoma; 3) PIA, HGPIN, and CaP all occur with high prevalence in the peripheral zone, and with low prevalence in the central zone of the human prostate; 4) PTA and HOPIN occur in close proximity, with frequent morphological transitions between them. We address the hypothesis that PTA leads to HGPIN/CaP by designing experiments to answer the following questions: 1) Is there a greater extent of PTA in cases containing HGPTN/CaP as compared to controls without HGPIN/CaP? 2) Do the differences in incidence of CaP between South East Asians and North Americans relate to differences in the amounts of PTA? 3) Are there similar molecular genetic alterations on the short arm of chromosome 8 in PIA as is known for HGPIN and CaP? 4) Are there similar gains of genetic material from chromosome 8q and other chromosomes in PTA as, again, is known in HGPIN and CaP? 5) Can spontaneous and induced HGPIN and CaP in the rat prostate be prevented by inhibiting the host inflammatory response? If the results of these studies implicate the host inflammatory response and PIA in prostatic carcinogenesis, then rational trials for prostate cancer chemoprevention could be devised based on anti-inflammatory agents, and PTA be a new biomarker for assessing prostate cancer risk. Finally, new emphasis would be focused on finding the cause of chronic inflammation in the prostate with an aim towards its eradication.