异黄酮 G-2535 （金雀异黄素）对术前膀胱癌症患者进行2 期癌症化学预防生物标志物试验_爱德华

针对病种：膀胱癌

发表时间：2012年4月

发表国家：美国

登载刊物：癌症预防研究

研究单位：美国纽约罗切斯特大学医学中心等

研究人员：爱德华梅辛，杰森 R 吉，丹尼尔 R 萨尔茨坦等

主要结论：临床前期观察大豆组分金雀异黄素抑制膀胱肿瘤生长的潜在机制是抑制表皮生长因子受体磷酸化 (p-EGFR) 。金雀异黄素表示出对膀胱癌组织 EGFR 磷酸化可能的双峰作用（在更低剂量更有效），并且应该进一步，可能与其他试剂相结合进行评估.

Cancer Prevention Research, 2012, 5(4):621-30.

A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients

Edward Messing, Jason R. Gee, Daniel R. Saltzstein, et al

University of Rochester Medical Center, Rochester, New York, USA; et al

The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.

美国《癌症预防研究》，2012年4月

异黄酮 G-2535 （金雀异黄素）对术前膀胱癌症患者进行2 期癌症化学预防生物标志物试验

爱德华梅辛，杰森 R 吉，丹尼尔 R 萨尔茨坦等

美国纽约罗切斯特大学医学中心等

临床前期观察大豆组分金雀异黄素抑制膀胱肿瘤生长的潜在机制是抑制表皮生长因子受体磷酸化 (p-EGFR) 。随机II期，空白对照试验考察了每天，在手术前口服金雀异黄素（300 或 600 mg/d纯化大豆提取物 G-2535） 14 到 21 天，改变了被诊断出患有尿道上皮膀胱癌细胞的膀胱上皮组织中的分子途径（中位年龄，71 岁）。G-2535 治疗的耐受性良好；观察到对中部胃肠道或代谢的毒性非常轻微并且通常不归因于研究药物。检测金雀异黄素在接受 G-2535的受试者的血浆及尿液中的浓度大于空白对照组，但是没有剂量依赖性。在膀胱癌组织中对照组和联合金雀异黄素组之间的p-EGFR 染色的降低在指定协议0.10水平段比较明显(P = 0.07)。当比较 300 毫克组与空白对照组 (P = 0.015)时这种差异最突出，但是600 毫克组和空白对照组之间的p-EGFR 染色没有明显减少。在治疗组之间正常膀胱上皮细胞的 p-EGFR 染色没有差异。观察到治疗组之间的肿瘤组织环氧合酶-2，Ki-67，活化的半胱氨酸蛋白酶-3，Akt，p-Akt，丝裂原活化蛋白激酶 (MAPK)，或 p-MAPK等染色没有明显差异。观察到治疗组之间的尿道生存素或 BLCA-4 水平无明显差异。金雀异黄素表示出对膀胱癌组织 EGFR 磷酸化可能的双峰作用（在更低剂量更有效），并且应该进一步，可能与其他试剂相结合进行评估。