Pathophysiological role of IL-6 and IL-8 in the progression of prostate cancer and cachexia

IL-6 和 IL-8 在前列腺癌和恶病质进展中的病理生理作用

• 批准号: 10671494
• 负责人: NAKASHIMA Jun
• 金额: $ 2.18万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671494/
• 关键词: crostate cancer; interleukin 6; prognosis; TNF; IL-6; 骨転移; 細胞増殖; インターロイキン6

In in vitro experiments, prostate cancer cell lines, PC3, DU145, JCA1 produced IL-6. The growth of PCS cells was enhanced by IL-6. The growth of JCA1 cells was inhibited in the presence of anti IL-6 antibody. These results suggest that IL-6 is produced by prostate cancer cells and regulate the growth of prosate cancer cells. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. There was no significant association between tumor histology and serum IL-6. The serum PSA, LDH and ALP levels in the patients with serum IL-6 levels 【greater than or equal】 7 pg/ml were significantly higher than those in patients with serum IL-6 levels < 7 pg/ml. A significant association was found between EOD and serum IL-6. Patients with serum IL-6 【greater than or equal】 7 pg/ml had a significantly lower survival rate than those with serum IL-6 < 7 pg/ml. Multivariate Cox's proportional hazards model analysis showed that the significant prognostic factors were EOD and IL-6. These results indicate that the serum IL-6 level is asoociate with disease aggressiveness and a significant prognostic factor for prostate cancer. Serum TNF activity was elevated in patients with relapsed disease, when compared with the untreated patients and patients in remission. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower than those in patients with undetectable serum TNF levels. The serum TNF levels of patients with serum albumin levels of < 3.5 g/dl, hemoglobin levels of < 11.0 g/dl and a body mass index of < 21 kg/m2 were significantly higher than the values in their respective counterparts. Patients with elevated serum TNF levels had a significantly higher mortality rate than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer.

在体外实验中，前列腺癌细胞系PC 3、DU 145、JCA 1产生IL-6。IL-6可促进PCS细胞的生长。抗IL-6抗体可抑制JCA 1细胞的生长。这些结果表明，IL-6是由前列腺癌细胞产生的，并调节前列腺癌细胞的生长。血清IL-6水平与前列腺癌临床分期显著相关。肿瘤组织学与血清IL-6之间无显著相关性。血清IL-6水平≥ 7 pg/ml者血清PSA、LDH、ALP水平均显著高于血清IL-6水平< 7 pg/ml者。发现EOD与血清IL-6之间存在显著相关性。血清IL-6 [大于或等于] 7 pg/ml的患者生存率显著低于血清IL-6 < 7 pg/ml的患者。多因素考克斯比例风险模型分析显示EOD和IL-6是影响预后的重要因素。提示血清IL-6水平与前列腺癌的侵袭性有关，是前列腺癌的一个重要预后因素。与未治疗患者和缓解患者相比，复发性疾病患者血清TNF活性升高。血清TNF水平升高的患者的血清总蛋白和白蛋白水平、血红蛋白水平和体重指数显著低于血清TNF水平检测不到的患者。血清白蛋白水平< 3.5 g/dl、血红蛋白水平< 11.0 g/dl和体重指数< 21 kg/m2的患者的血清TNF水平显著高于其相应对应者的值。血清TNF水平升高的患者的死亡率明显高于血清TNF水平检测不到的患者。这些结果表明，TNF可能是导致前列腺癌患者恶病质综合征的因素之一。

项目成果

Jun Nakashima et al.: "The value of γ-seminoprotein in combination with prostate specific antigen in detecting prostate cancer"Int J Urol. 6. 298-304 (1999)

Jun Nakashima 等人：“γ-精蛋白与前列腺特异性抗原结合在检测前列腺癌中的价值”Int J Urol. 6. 298-304 (1999)

Jun Nakashima, et al.: "Serum interleukin 6 as a prognostic factor in patients with prostate cancer."Clinical Cancer Research. 6. 2702-2706 (2000)

Jun Nakashima 等人：“血清白细胞介素 6 作为前列腺癌患者的预后因素。”临床癌症研究。