Biomarkers in monitoring for efficacy of immunotherapy and chemoprevention of bladder cancer with dimethylsulfoxide.

G P Hemstreet, J Rao, R E Hurst, R B Bonner, J E Mellott, G M Rooker
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引用次数: 20

Abstract

This study correlated biomarkers expressed in tumor and epithelial field with clinical response and recurrence. Of 25 bladder cancer patients, 11 received 6 weeks of intravesical Bacille Calmette-Guerin (BCG), and 14 were treated weekly with intravesical dimethylsulfoxide (DMSO) for 4 weeks to further modulate biomarker expression. G-actin, DNA aneuploidy, and p300 tumor antigen were evaluated by quantitative fluorescence image analysis on uroepithelial cells from bladder wash samples prior to and immediately following treatment. Excluding patients who did not respond to BCG (and who had persistently abnormal p300 and DNA markers), recurrence correlated with persistent abnormal G-actin findings. Of patients who were G-actin negative following therapy, only 25% recurred during follow-up in contrast to 67% in patients who were positive (p < 0.03 by Fisher's exact test). The odds ratio for recurrence was 6.00 (95% confidence interval: 1.3-28.6). Cytosolic G-actin levels can be an important intermediate end point marker for chemoprevention.

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生物标志物监测二甲亚砜免疫治疗和化学预防膀胱癌疗效的研究。
本研究将肿瘤和上皮组织中表达的生物标志物与临床反应和复发联系起来。在25例膀胱癌患者中,11例接受6周膀胱内卡介子(BCG)治疗,14例接受4周膀胱内二甲基亚砜(DMSO)治疗,以进一步调节生物标志物的表达。在治疗前和治疗后立即对膀胱洗涤样本的尿上皮细胞进行定量荧光图像分析,评估g -肌动蛋白、DNA非整倍体和p300肿瘤抗原。排除对卡介苗无反应的患者(以及p300和DNA标记持续异常的患者),复发与g -肌动蛋白持续异常相关。在治疗后g -肌动蛋白阴性的患者中,只有25%的患者在随访期间复发,而阳性患者的复发率为67%(经Fisher精确检验p < 0.03)。复发的优势比为6.00(95%可信区间:1.3-28.6)。胞质内g -肌动蛋白水平可作为化学预防的重要中间终点标志物。
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