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Impaired interleukinhyphen;12 production is associated with a defective antihyphen;tumor response in colorectal cancer

机译:白细胞介素连字符;12 生成受损与结直肠癌中抗连字符肿瘤反应缺陷有关

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INTRODUCTIONcolon;Despite development of many chemotherapeutic regimens, colorectal cancer continues to have a high mortality. One of the major new potential therapies is interleukinhyphen;12, a heterodimeric cytokine produced by antigen presenting cells.In vitroandin vivostudies have demonstrated the role of interleukinhyphen;12 in stimulating a cellhyphen;mediated antihyphen;tumor response against a number of colon adenocarcinoma tumor models. However, it is unknown whether patients with colorectal cancer have impaired interleukinhyphen;12 production. A study was performed to investigate production of interleukinhyphen;12 preoperatively and the relationship between these levels and disease stage at surgery.METHODScolon;Preoperative peripheral blood mononuclear cells from colorectal cancer patients and agematched controls were stimulated byStaphylococcus aureusCowan's Strain 1 lpar;0.0075 percent wtsol;volrpar;in vitrofor 24 hours. Expression of interleukinhyphen;12 was then assessed by enzymehyphen;linked immunosorbent assay. A single pathologist assessed the tumors for stage according to TNM and Dukes classifications.RESULTScolon;Twentyhyphen;eight patients with colorectal cancer and 14 controls were recruited for the study. Interleukinhyphen;12 production was significantly impaired in patients with colorectal cancer compared with controls lpar;Pequals;0.014rpar;, especially those with advanced diseasecolon; Dukes C,Pequals;0.001 and T4,P0.05.CONCLUSIONcolon;Interleukinhyphen;12 production is impaired in patients with colorectal cancer, especially those with advanced disease, suggesting a defective Th1hyphen;mediated antihyphen;tumor response. These patients may well benefit from exogenous interleukinhyphen;12 treatment.
机译:尽管开发了许多化疗方案,但结直肠癌的死亡率仍然很高。主要的新潜在疗法之一是白细胞介素&连字符&连字符;12,一种由抗原呈递细胞产生的异二聚体细胞因子。体外研究表明,白细胞介素&连字符;12 在刺激细胞&连字符介导的抗&连字符;肿瘤反应中对许多结肠腺癌肿瘤模型的作用。然而,目前尚不清楚结直肠癌患者是否存在白细胞介素&连字符&12 生成受损。进行了一项研究,以调查术前白细胞介素&连字符&连字符 12 的产生以及这些水平与手术时疾病分期之间的关系。方法&结肠;结直肠癌患者和年龄匹配的对照组的术前外周血单核细胞在体外用金黄色葡萄球菌Cowan菌株1(0.0075%wt/vol)体外刺激24小时。然后通过酶&连字符联免疫吸附测定评估白细胞介素&连字符&12的表达。一位病理学家根据 TNM 和 Dukes 分类评估了肿瘤的分期。结果&结肠;20&连字符;8名结直肠癌患者和14名对照组被招募参加该研究。与对照组(P=0.014)相比,结直肠癌患者的白细胞介素&连字符;12的产生显着受损,尤其是晚期结肠癌&dukes C,P=0.001和T4,P<0.05。结论&结肠;白细胞介素&连字符&12在结直肠癌患者中受损,尤其是晚期患者,提示Th1&连字符介导的抗&连字符;肿瘤反应缺陷。这些患者很可能受益于外源性白细胞介素&连字符;12 治疗。

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