Study on the mechanism of tumor recurrence after liver transplantation using LEC rats.

LEC大鼠肝移植术后肿瘤复发机制的研究

• 批准号: 06454356
• 负责人: UNE Yoshie
• 金额: $ 2.11万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454356/
• 关键词: LEC rats; Liver transplatation; Hepatitis; Copper metabolism; Hepatic tumor; LECラット化学療法; 免疫抑制剤; 癌増殖機構

Aim : liver transplantation (OLTX) is one of the effective therapies on the chronic liver failure with hepatocellular carcinoma. LEC develop spontaneously hepatitis and hepatic tumor, while LEA rats do not. We conducted OLTX on LEA and LEC rats with various modalities of combination.Results were as follows,1. LEC rats transplanted LEA livers survived more than 300 days, which indicates the suppression of hepatitis.2. Transient elevation of serum transaminase levels were observed in LEA rats which were transplanted the LEC rat liver. The transaminase returned to normal levels 4 months after transplantation, and survived.3. The serum copper levels were lowered l month after OLTX in LEC rats which transplanted LEA liver. And serum ceruloplasmin concentrations elevated to the normal levels.4. On the microscopical of staining the LEA liver tissue in LEC rats had negative copper staining, while LEC liver tissue in LEA rats showed positive staining.Long term survived LEA rats which transplanted LEC liver developed liver cancer, while reverse combination of OLTX appeared no liver tumor.Further observation is needed to investigate occurrence of hepatic tumor in those OLTX models. Effects of immunosuppressive agents and anticancer drugs should be studied.

目的：肝移植是治疗肝癌合并慢性肝功能衰竭的有效方法之一。LEC可自发发生肝炎和肝癌，而莱亚大鼠则不发生。本实验采用不同的联合治疗方式对莱亚和LEC大鼠进行OLTX治疗。LEC大鼠移植莱亚肝存活300天以上，表明对肝炎有抑制作用.在莱亚大鼠中观察到LEC大鼠肝移植后血清转氨酶水平的一过性升高。移植后4个月转氨酶恢复正常，并存活.莱亚肝移植的LEC大鼠OLTX后1个月血清铜水平降低。血清铜蓝蛋白浓度升高至正常水平.染色镜下LEC大鼠莱亚肝组织铜染色呈阴性，而莱亚大鼠LEC肝组织铜染色呈阳性，长期存活的莱亚大鼠移植LEC肝后发生肝癌，而反向联合OLTX未出现肝癌，这些OLTX模型中肝肿瘤的发生情况有待进一步观察。应研究免疫抑制剂和抗癌药物的作用。

项目成果

Tsuchimoto,S.Une,Y.et al: "Liver transplantation in the LEC rats which sponta-neously develop hepatic injuries and hepatocellular carcinoma." (発表予定).

Tsuchimoto, S.Une, Y. 等人：“自发发生肝损伤和肝细胞癌的 LEC 大鼠的肝移植。”

槌本真也、宇根良衛、他: "肝炎肝癌自然発症LECラットにおける肝移植" (発表予定).

Shinya Tsuchimoto、Yoshie Une 等人：“患有自发性肝癌的 LEC 大鼠的肝移植”（待提交）。

Tsuchimoto, S., Une, Y., et al.: "Liver Transplantation in the LEC rats which spontaneously develop hepatic injuries and hepatocellular carcinoma." (in submit).

Tsuchimoto, S.、Une, Y. 等人：“LEC 大鼠的肝移植可自发发生肝损伤和肝细胞癌。”