Monden T, Morimoto H, Murotani M, Yagyu T, Nagaoka H, Shimano T, Mori T
Second Department of Surgery, Osaka University Medical School, Japan.
Nihon Geka Gakkai Zasshi. 1991 Jan;92(1):31-6.
We found that antitumor effect of OK-432, a lyophylized preparation of an attenuated strain of streptococcus pyogenes, on colorectal carcinoma was greatly augmented when it was injected intratumorally in conjunction with fibrinogen. Twenty cases of colorectal cancer received intratumoral injection of 5 KE of OK-432 mixed with 80mg of fibrinogen including factor-XIII and 1ml of aprotinin at the time of endoscopic examination. Changes in the shape of the tumors were observed endoscopically within a few days after injection, and in most cases, decrease in the height of tumor margin was noted. Histopathological findings on surgically resected specimens revealed that the fine meshwork of fibrin was formed at the injected site soon after the injection, and a marked infiltration of inflammatory cells including neutrophils, plasma cells, macrophages, eosinophils and lymphocytes. Such granulomatous changes developed over 7 days after injection, and the degradation of tumors were observed. By 14 days after the injection, tumor tissues were largely replaced with granulomas, and shrinkage of tissues were observed. These findings indicated that fibrinogen including factor-XIII and aprotinin has a potential ability to augment the immunoreaction induced by biological response modifiers, and intratumoral injection of OK-432 in conjunction with fibrinogen solution was superior to intratumoral injection of OK-432 alone as the local immunotherapy of colorectal cancer.
我们发现，将化脓性链球菌减毒株的冻干制剂OK-432与纤维蛋白原联合瘤内注射时，其对结直肠癌的抗肿瘤作用大大增强。20例结直肠癌患者在内镜检查时接受瘤内注射5KE的OK-432，其与80mg含因子XIII的纤维蛋白原及1ml抑肽酶混合。注射后数天内通过内镜观察肿瘤形状的变化，大多数情况下，可见肿瘤边缘高度降低。手术切除标本的组织病理学检查结果显示，注射后不久在注射部位形成了纤维蛋白的精细网状结构，并有包括中性粒细胞、浆细胞、巨噬细胞、嗜酸性粒细胞和淋巴细胞在内的炎性细胞明显浸润。这种肉芽肿性变化在注射后7天以上出现，并观察到肿瘤降解。注射后14天，肿瘤组织大部分被肉芽肿取代，并观察到组织萎缩。这些结果表明，含因子XIII的纤维蛋白原和抑肽酶具有增强生物反应调节剂诱导的免疫反应的潜在能力，并且将OK-432与纤维蛋白原溶液联合瘤内注射作为结直肠癌的局部免疫治疗优于单独瘤内注射OK-432。
