New Immunotherapy for hepatocellular carcinoma after hepatectomy

实验研究：采用核分裂指数（MI）和溴脱氧尿苷（BrdU）标记指数（LI）检测IL-2对70%肝切除的东柳大鼠肝再生的影响。在肝切除术后立即使用输注泵通过门静脉连续给予IL-2（45，000 JRU/天）或盐水。在肝切除术后1、2或4天，在任何组中均未观察到肝重量、血清Alb、GPT或Bil的差异。肝切除术后缝隙连接开始消失，并在第2天达到最低值。肝切除术后4天，IL-2治疗组中重新出现的缝隙连接的密度明显低于接受生理盐水治疗的组。然而，在所有组中，肝切除术后6天，密度恢复到接近术前水平。持续门静脉输注LI-2可短暂干扰肝再生过程中间隙连接的重现。然而，没有其他肝再生或肝功能参数不同。的 ...更多信息 这些结果表明，肝切除术后肝内注射IL-2不会出现严重并发症。临床研究：我们对12例肝细胞癌（HCC）患者在肝切除术后14天进行了动脉内联合免疫治疗（ACIT）。ACIT由IL-2、OK-432、阿霉素、环磷酰胺和法莫替丁组成。治疗组3年生存率为100%，未治疗组38例3年生存率为60%。因此，肝切除术后动脉内联合免疫治疗显着提高了HCC患者的生存率。3例HCC患者接受ACIT治疗。切除标本的组织学分析显示，HCC病变周围有大量淋巴细胞浸润。免疫组化结果显示，浸润淋巴细胞主要为CD 8+和HLA-DR+淋巴细胞，在淋巴细胞浸润区，肿瘤细胞Fas抗原呈强阳性表达。结论：ACIT的抗肿瘤作用可能与激活肿瘤浸润淋巴细胞有关。这些淋巴细胞可以以凋亡的方式杀死肿瘤细胞。少

Experimental study : The influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. IL-2 (45,000 JRU/day) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. No difference in the weight of the liver, serum Alb, GPT,or Bil was observed in any groups at 1,2, or 4 days after hepatectomy. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of LI-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. The … More se results suggest that intrahepatic IL-2 administration can be performed without serious complications after hepatectomy.Clinical Study : We performed intraarterial combined immunotherapy (ACIT) for 12 paticnts with hepatocellular carcinoma (HCC) 14 days after hepatectomy. ACIT consists of IL-2, OK-432, adriamycin, cyclophosphamide, and famotidine. The 3-year survial rate of treated patients was 100%, while, that of 38 untreated patiens was 60%. Thus, intraarterial combined immunotherapy following hepatectomy significantly improved the survival rate in patients with HCC.Three patients with HCC were treated with ACIT.Histological analysis using the resected specimen revealed massive invasion of lymphocytes around HCC lesions. Immunohistochemical analysis demonstrated that the major invaded lymphocytes were the CD8 positive and HLA-DR positive lymphocytes.Furthermore, in the lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly expressed. In conclusion, the antitumor effect of ACIT may be related with the activation of tumor infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic fashion. Less