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[环氧化酶-2在膀胱癌中的表达:肿瘤生物学及临床意义]

[Cyclooxygenase-2-expression in bladder cancer: tumor-biological and clinical implications].

作者信息

Wülfing C, Eltze E, Von Struensee D, Wülfing P, Bode M E, Bettendorf O, Piechota Hj, Hertle L

机构信息

Klinik und Poliklinik für Urologie, Universitätsklinikum Münster.

出版信息

Aktuelle Urol. 2004 Aug;35(4):331-8. doi: 10.1055/s-2004-818537.

Abstract

PURPOSE

Cyclooxygenase-2 (Cox-2) contributes to the carcinogenesis of human tumors by various mechanisms. As Cox-2-expression has been found in most human neoplasms, selective Cox-2-inhibitors could be used as a molecular targeted therapy, and first clinical trials have already been initiated. Moreover, Cox-2-inhibitors have been shown to add to the activity of conventional cytotoxic therapies in experimental and clinical studies. We analyzed Cox-2-expression in bladder cancer and its implications on clinical parameters.

MATERIALS AND METHODS

Cox-2-expression was evaluated immunohistochemically in 157 patients undergoing radical cystectomy. Sixty-two patients had received cisplatin-based treatment during follow-up, either as adjuvant therapy or for metastatic disease. Cox-2-expression was correlated with clinical and pathological parameters, survival data and outcome of chemotherapy.

RESULTS

Cox-2 was expressed in 83.4 % of tumors. No association was found with TNM-staging and histological grading, but a significant relation to the histologic subtype (transitional vs. squamous cell carcinoma, p = 0.038) was present. Survival analysis showed no impact of Cox-2-expression on overall or disease-free survival. However, a subgroup of chemotherapy patients demonstrated a significant correlation of strong Cox-2-expression with worse overall survival time (p = 0.01).

CONCLUSIONS

Cox-2-expression was found in the majority of invasive bladder tumors. For patients who underwent chemotherapy, a significant relation of Cox-2-expression and worse overall survival was demonstrated. Cox-2 seems to be an interesting molecular target for the diagnosis and therapy of bladder cancer. Further experimental and clinical studies are warranted to elucidate whether Cox-2-inhibition can serve as an additive therapy to chemotherapy of bladder cancer.

摘要

目的

环氧合酶-2(Cox-2)通过多种机制促进人类肿瘤的发生。由于在大多数人类肿瘤中都发现了Cox-2表达,选择性Cox-2抑制剂可作为一种分子靶向治疗药物,且已启动了首批临床试验。此外,在实验和临床研究中,Cox-2抑制剂已被证明可增强传统细胞毒性疗法的活性。我们分析了膀胱癌中Cox-2的表达及其对临床参数的影响。

材料与方法

对157例行根治性膀胱切除术的患者进行免疫组织化学评估Cox-2表达。62例患者在随访期间接受了以顺铂为基础的治疗,作为辅助治疗或用于转移性疾病。Cox-2表达与临床和病理参数、生存数据及化疗结果相关。

结果

83.4%的肿瘤表达Cox-2。未发现与TNM分期和组织学分级相关,但与组织学亚型(移行细胞癌与鳞状细胞癌,p = 0.038)存在显著相关性。生存分析显示Cox-2表达对总生存期或无病生存期无影响。然而,化疗患者亚组中,Cox-2强表达与较差的总生存时间显著相关(p = 0.01)。

结论

在大多数浸润性膀胱肿瘤中发现了Cox-2表达。对于接受化疗的患者,Cox-2表达与较差的总生存期存在显著相关性。Cox-2似乎是膀胱癌诊断和治疗中一个有趣的分子靶点。有必要进行进一步的实验和临床研究,以阐明Cox-2抑制是否可作为膀胱癌化疗的辅助治疗。

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