Significance of immunological tolerance on development and progress of hepatocellular carcinoma and proposal for a novel therapeutic approach Experimental study on murine liver tumor using MH-134 hepatoma cells mouse liver transplantation model
免疫耐受对肝细胞癌发生发展的意义及治疗新途径的提出 MH-134肝癌细胞小鼠肝移植模型对小鼠肝脏肿瘤的实验研究
基本信息
- 批准号:10671226
- 负责人:
- 金额:$ 1.79万
- 依托单位:
- 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 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
It was hypothesized that immunological tolerance plays an essential role in development and progression of hepatocellular carcinoma(HCC) to which the carrier state of hepatitis viruses generally predisposed. Therefore, the experiments using orthotopic mouse live transplantation model (OMLT: C3H/He->DBA/2) are expected to the optimal in evaluation the significance of immunological tolerance because immunological tolerance is achieved as a rule. First, the number of HCC nodules developed in the recipient's liver was estimated after the injection of MH-134 heptoma cells via portal vein at various timing after liver transplantation, i.e. Day14, Day28, Day42, and Day100. The result showed that the degree of immunological tolerance in recipients have a significant influence on the number of HCC nodules. Second, the effect of anti IL_4 monoclonal antibody(11B11) was evaluated. IL-4 is regarded as an essential mediator of immunological tolerance. Our previous data showed that neutralization of IL-4 with 11B11 on Day28 or Day42 prevented induction of tolerance but not on Day100 when immunological tolerance is established. In this study, recipients were divided into two groups, i e. the control group : recipients were simultaneously injected 4mg of Rat IgG intraperitoneally and MH-134 hepatoma cells (1×10ィイD18ィエD1cells) via portal vein on Day14, Day28, Day42, and Day100, and the experimental group : recipients were injected 4mg of 11B11 and MH-134 hepatoma cells similarly. The experimental group developed significantly larger number of HCC nodules when 11B11 and MH-134 heptoma cells were injected on Day28 and Day42 but not on Day100. These data also suggested that immunological tolerance or IL-4 is essential for development and progression of HCC. In conclusion, host immunological tolerance could be a new target in the treatment of HCC.
据推测,免疫耐受在肝细胞癌(HCC)的发生和发展中起着至关重要的作用,肝炎病毒的携带状态通常易患HCC。因此,利用小鼠原位肝移植模型(OMLT:C_3H/He->DBA/2)进行的实验有望成为评价免疫耐受意义的最佳实验,因为免疫耐受通常是可以实现的。首先,在肝移植后的不同时间,即第14天、第28天、第42天和第100天,通过门静脉注射MH-134肝癌细胞后,估计受体肝脏中发展的HCC结节的数量。结果表明,受者免疫耐受程度对肝癌结节数有显著影响。第二,评价抗IL_4单克隆抗体(11B 11)的作用。IL-4被认为是免疫耐受的重要介质。我们以前的数据表明,在第28天或第42天用11B 11中和IL-4可防止诱导耐受,但在建立免疫耐受的第100天不能。在这项研究中,受体被分为两组,即。对照组:实验组:11B 11和MH-134肝癌细胞各4 mg。对照组:11B 11和MH-134肝癌细胞各4 mg。当在第28天和第42天注射11B 11和MH-134肝瘤细胞时,实验组出现了明显更多数量的肝癌结节,但在第100天则没有。这些数据还表明,免疫耐受或IL-4是必要的HCC的发展和进展。因此,宿主免疫耐受可能成为肝癌治疗的新靶点。
项目成果
期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
杉岡 篤: "転移性肝腫瘍に対する外科的切除の適応と限界" 臨床外科. 54・2. 181-189 (1999)
Atsushi Sugioka:“转移性肝脏肿瘤手术切除的适应症和局限性”《临床外科》54・2(1999)。
- DOI:
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- 影响因子:0
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- 通讯作者:
森田美和: "マウス同所性肝移植(カフ法)"臓器移植実験マニュアル. 細胞工学(別冊). 104-108 (1999)
Miwa Morita:“小鼠原位肝移植(袖带法)”器官移植实验手册(分册)104-108(1999)。
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- 影响因子:0
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Sugioka, A: "Kinetics and significance of graft tissue nitric oxide after rat and mouse liver transplantation"Transplantation Proceedings. 31. 860-862 (1999)
Sugioka, A:“大鼠和小鼠肝移植后移植组织一氧化氮的动力学和意义”移植论文集。
- DOI:
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- 影响因子:0
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- 通讯作者:
A.Sugioka: "Kinetics and Significance of Graft Tissue Nitric Oxide After Rat and Mouse Liver Transplantation" Transplantation Proceedings. 31. 860-862 (1999)
A.Sugioka:“大鼠和小鼠肝脏移植后移植组织一氧化氮的动力学和意义”移植论文集。
- DOI:
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- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sugioka, A: "Indications and contraindecations of hepatic resection for liver metastases"Journal of clinical surgery. 54(2). 181-189 (1999)
Sugioka,A:“肝转移瘤肝切除术的适应症和禁忌症”临床外科杂志。
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{{ truncateString('UYAMA Ichiro', 18)}}的其他基金
Experimental study for the immunological tolerance using orthotopic liver transplantation using mice
小鼠原位肝移植免疫耐受的实验研究
- 批准号:
12671183 - 财政年份:2000
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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