Effects of short-term celecoxib treatment in patients with invasive transitional cell carcinoma of the urinary bladder.
Effects of short-term celecoxib treatment in patients with invasive transitional cell carcinoma of the urinary bladder.
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DOI：
10.1158/1535-7163.mct-10-0049
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发表时间：
2010-05
影响因子：
5.7
通讯作者：
Knapp DW
中科院分区：
文献类型：
--
作者：
Dhawan D;Craig BA;Cheng L;Snyder PW;Mohammed SI;Stewart JC;Zheng R;Loman RA;Foster RS;Knapp DW
在美国，高级别浸润性移行细胞癌（InvTCC）每年导致> 14，000人死亡，需要更好的治疗。环氧合酶-2（考克斯-2）在膀胱癌中过度表达。在动物研究中，考克斯抑制剂已经引起InvTCC的缓解，并且癌症消退与肿瘤中凋亡指数加倍相关。本研究的目的是确定塞来昔布（一种考克斯-2抑制剂）在人体InvTCC中的诱导凋亡作用。入选了选择接受化疗的InvTCC患者（至少10例配对肿瘤样本）。主要研究终点为诱导肿瘤组织凋亡。患者在诊断时间（TURBT;经尿道切除术）和膀胱切除术时间（InvTCC的标准一线治疗）之间接受塞来昔布（400 mg，每日两次，口服，至少14天）。对TURBT和cysteine标本进行TUNEL检测和免疫组化。在13例接受塞来昔布治疗的病例中，3例患者在化疗时（塞来昔布治疗后）未发现残留浸润性癌。在10例残留癌患者中，7例在其肿瘤中诱导了凋亡。在未接受考克斯抑制剂的对照组患者中，诱导细胞凋亡的频率较低[3/13例，p < 0.04]。与未治疗的对照病例相比，在治疗的患者中肿瘤细胞中VEGF的表达更频繁地降低[p < 0.026]。塞来昔布治疗的生物学效应（细胞凋亡增加）证明了进一步研究考克斯-2抑制剂在InvTCC中的抗肿瘤作用的合理性。
High grade invasive transitional cell carcinoma (InvTCC) kills >14,000 people yearly in the United States, and better therapy is needed. Cyclooxygenase-2 (Cox-2) is over-expressed in bladder cancer. Cox inhibitors have caused remission of InvTCC in animal studies, and cancer regression was associated with doubling of the apoptotic index in the tumor. The purpose of this study was to determine the apoptosis-inducing effects of celecoxib (a Cox-2 inhibitor) in InvTCC in humans. Patients (minimum of 10 with paired tumor samples) with InvTCC who had elected to undergo cystectomy were enrolled. The main study end point was induction of apoptosis in tumor tissues. Patients received celecoxib (400mg twice daily po for a minimum of 14 days) between the time of diagnosis (TURBT; transurethral resection) and the time of cystectomy (standard frontline treatment for InvTCC). TUNEL assay and immunohistochemistry were performed on TURBT and cystectomy samples. Of 13 cases treated with celecoxib, no residual invasive cancer was identified in 3 patients at the time of cystectomy (post celecoxib). Of the 10 patients with residual cancer, 7 had induction of apoptosis in their tumor. Induction of apoptosis was less frequent [3 of 13 cases, p < 0.04] in control patients not receiving a Cox inhibitor. Expression of VEGF in the tumor cells decreased more frequently [p < 0.026] in the treated patients as compared to non-treated control cases. The biological effects of celecoxib treatment (increased apoptosis) justify further study of the antitumor effects of Cox-2 inhibitors in InvTCC.