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卡介苗膀胱内给药对浅表性膀胱癌患者肿瘤坏死因子的产生情况

Production of tumor necrosis factor by intravesical administration of bacillus Calmette Guérin in patients with superficial bladder cancer.

作者信息

Kim C I, Shin J S, Kim H I, Lee J M, Kim S J

机构信息

Department of Urology, Kyemyung University College of Medicine, Taegu, Korea.

出版信息

Yonsei Med J. 1993 Dec;34(4):356-64. doi: 10.3349/ymj.1993.34.4.356.

DOI:10.3349/ymj.1993.34.4.356
PMID:8128741
Abstract

Although an immune response to bacillus Calmette Guérin (BCG) has often been associated with antitumor activity, the action mechanism(s) of intravesical BCG therapy for prophylaxis and treatment of superficial bladder cancer is not clearly understood. In an attempt to evaluate the roles of tumor necrosis factor (TNF)-alpha and lymphotoxin (LT) in the antitumor activity, TNF-alpha productivities by peripheral blood monocytes, serum levels of TNF-alpha, and LT productivities by peripheral blood lymphocytes were studied in superficial bladder cancer patients after six intravesical administrations of BCG. TNF-alpha productivities by peritoneal macrophages of guinea pigs were also studied after six intravesical administrations of BCG. The maximum TNF-alpha productivities by peripheral blood monocytes of superficial bladder cancer patients were seen after the fourth week of administration of BCG, and the serum TNF-alpha levels were also slightly increased after intravesical BCG administration in the superficial bladder cancer patients. LT productivities by peripheral blood lymphocytes of superficial bladder cancer patients were significantly enhanced and the maximum LT productivity was also seen after the third or fifth BCG administration. TNF-alpha productivities by peritoneal macrophages of guinea pigs were significantly enhanced and the maximum TNF-alpha productivity was seen after the second or third BCG administration. Our data might suggest that six consecutive intravesical BCG administrations could induce the increased productions of TNF-alpha and LT, which might play an important role in the antitumor activity in superficial bladder cancer.

摘要

尽管对卡介苗(BCG)的免疫反应常与抗肿瘤活性相关,但膀胱内灌注BCG预防和治疗浅表性膀胱癌的作用机制尚不清楚。为了评估肿瘤坏死因子(TNF)-α和淋巴毒素(LT)在抗肿瘤活性中的作用,我们研究了浅表性膀胱癌患者在膀胱内灌注6次BCG后外周血单核细胞的TNF-α产生能力、血清TNF-α水平以及外周血淋巴细胞的LT产生能力。我们还研究了豚鼠在膀胱内灌注6次BCG后腹腔巨噬细胞的TNF-α产生能力。浅表性膀胱癌患者外周血单核细胞的最大TNF-α产生能力在灌注BCG后第4周出现,浅表性膀胱癌患者膀胱内灌注BCG后血清TNF-α水平也略有升高。浅表性膀胱癌患者外周血淋巴细胞的LT产生能力显著增强,最大LT产生能力在第3次或第5次灌注BCG后出现。豚鼠腹腔巨噬细胞的TNF-α产生能力显著增强,最大TNF-α产生能力在第2次或第3次灌注BCG后出现。我们的数据可能表明,连续6次膀胱内灌注BCG可诱导TNF-α和LT产生增加,这可能在浅表性膀胱癌的抗肿瘤活性中发挥重要作用。

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Yonsei Med J. 1993 Dec;34(4):356-64. doi: 10.3349/ymj.1993.34.4.356.
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Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.BCG 膀胱内灌注治疗非肌层浸润性膀胱癌可诱导获得性免疫,降低呼吸道感染风险。
J Immunother Cancer. 2023 Jan;11(1). doi: 10.1136/jitc-2022-005518.
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MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model.
MyD88 依赖性卡介苗免疫疗法可减少膀胱癌小鼠模型中的肿瘤并调节肿瘤微环境。
Sci Rep. 2021 Aug 2;11(1):15648. doi: 10.1038/s41598-021-95157-6.
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100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19.卡介苗免疫治疗 100 年:从牛到 COVID-19。
Nat Rev Urol. 2021 Oct;18(10):611-622. doi: 10.1038/s41585-021-00481-1. Epub 2021 Jun 15.
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Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer.训练免疫作为膀胱癌卡介苗免疫治疗的分子机制。
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