新辅助多烯紫杉醇治疗局部晚期前列腺癌:一个临床病理的研究。

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周Magi-Galluzzi C、M,鲁瑟,Dreicer R,克莱因EA

新辅助多烯紫杉醇治疗局部晚期前列腺癌:一个临床病理的研究。

癌症。2007年9月15日,110 (6):1248 - 54。

PubMed ID

17674353 (在PubMed

]

文摘

背景:本研究的目的是确定的组织学和分子变化发生在高风险患者,局限性前列腺癌(PCa)后新辅助多烯紫杉醇化疗。方法:患者局部晚期PCa(血清术前(初始)前列腺特异性抗原(iPSA)水平>或= 15 ng / mL,或临床> = T2b疾病,或活检格里森评分(GS) > = 8)和没有证据表明转移性疾病收到6个剂量的静脉多西他赛(40毫克/米(2))管理每周6周之后,根治性前列腺切除术(RP)。的Wilcoxon符号秩检验被用于比较预处理和后处理标记。结果:28例完成化疗和接受RP在克利夫兰诊所;没有取得病理完全缓解。综述了预处理诊断前列腺活检(PBx)在所有的病人,和清白的部分formalin-fixed组织11名患者。患者年龄中值为62岁(范围,49 - 72年),以及国际公共部门会计标准局中值为6.8 ng / mL(范围2.5 -24 ng / mL)。在平均随访49.5个月(范围,23 - 72个月),12例(43%)仍临床和生化的疾病,没有额外的治疗,和16个病人(57%)有生化失败。预处理GS 6 2例(7%),10名病人(36%)、7 8 11例(39%)和9 5例(18%)。两个病人(7.1%)有organ-confined疾病,和23个患者(82.1%)有extraprostatic扩展。 Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens. CONCLUSIONS: The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted.

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药物靶点

药物	目标	类	生物	药理作用	行动
多烯紫杉醇	bcl - 2细胞凋亡调节器	蛋白质	人类	未知的	不可用	细节