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诱导型和组成型一氧化氮合酶在人膀胱癌中的免疫定位

Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer.

作者信息

Klotz T, Bloch W, Jacobs G, Niggemann S, Engelmann U, Addicks K

机构信息

Department of Urology and Institute I of Anatomy, University of Cologne, Germany.

出版信息

Urology. 1999 Sep;54(3):416-9. doi: 10.1016/s0090-4295(99)00212-5.

DOI:10.1016/s0090-4295(99)00212-5
PMID:10475345
Abstract

OBJECTIVES

Nitric oxide (NO) is synthesized by the enzyme family of NO synthases (NOS) and plays an important role in tumor growth and angiogenesis. NO generation by inducible NOS (iNOS) also influences the cytotoxicity of macrophages and tumor-induced immunosuppression. Before now, the expression of iNOS and constitutive NOS in bladder carcinoma tissue had not been determined.

METHODS

Bladder carcinoma tissue specimens were procured from 18 patients (mean age 69.7 years) undergoing transurethral resection. In every patient, tumor biopsies were compared with biopsies of benign bladder regions. Histochemical NADPH-diaphorase staining and NOS immunohistochemistry were performed on all tissue specimens.

RESULTS

Positive NADPH-diaphorase staining was detected in all sections from bladder carcinoma tissue. NOS immunohistochemistry showed a different pattern. The malignant epithelial cells were highly iNOS positive. Specimens of bladder mucosa outside of the malignant regions showed only a weak positive iNOS immunostaining. The endothelial cells of abundant precapillary vessels in the stroma of bladder tumors showed a highly positive endothelial NOS (eNOS) immunostaining compared with the stroma of nonmalignant bladder tissue. Neuronal NOS immunoreactivity was only found in nitrinergic fibers in the fibromuscular stroma.

CONCLUSIONS

Bladder carcinoma tissue had a high iNOS content; benign tissue did not. NO generation from iNOS in the malignant epithelium and from eNOS in tumor stroma may play different roles in tumor angiogenesis and tumor-induced immunosuppression.

摘要

目的

一氧化氮(NO)由一氧化氮合酶(NOS)家族合成,在肿瘤生长和血管生成中起重要作用。诱导型NOS(iNOS)产生的NO也影响巨噬细胞的细胞毒性和肿瘤诱导的免疫抑制。此前,尚未确定膀胱癌组织中iNOS和组成型NOS的表达情况。

方法

从18例接受经尿道切除术的患者(平均年龄69.7岁)获取膀胱癌组织标本。对每位患者,将肿瘤活检组织与良性膀胱区域的活检组织进行比较。对所有组织标本进行组织化学NADPH - 黄递酶染色和NOS免疫组织化学检测。

结果

在膀胱癌组织的所有切片中均检测到阳性NADPH - 黄递酶染色。NOS免疫组织化学显示出不同的模式。恶性上皮细胞iNOS高度阳性。恶性区域外的膀胱黏膜标本iNOS免疫染色仅呈弱阳性。与非恶性膀胱组织的基质相比,膀胱肿瘤基质中丰富的毛细血管前血管内皮细胞内皮型NOS(eNOS)免疫染色呈高度阳性。神经元型NOS免疫反应性仅在纤维肌性基质中的硝酸能纤维中发现。

结论

膀胱癌组织iNOS含量高;良性组织则不然。恶性上皮细胞中的iNOS和肿瘤基质中的eNOS产生的NO可能在肿瘤血管生成和肿瘤诱导的免疫抑制中发挥不同作用。

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