Molecular biological analysis of angiogenetic process of hepatocellular carcinoma, from the view point of standardization of diagnosis and treatment

从诊疗规范化角度对肝细胞癌血管生成过程进行分子生物学分析

• 批准号: 14570530
• 负责人: IKEDA Kenji
• 金额: $ 1.73万
• 依托单位: Okinaka Memorial Institute for Medical Research (OMIMR)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570530/
• 关键词: Hepatocellular carcinoma; alpha-smooth muscle actin; angiogenesis; VEGF; immunohistochemistry; non-triadal vessel; 血管新生; 早期肝細胞癌; 新生血管; non-triadal vessel; alpha-smooth muscle actin

To elucidate the relationship between angiographic features and histological findings, an immunohistological study of alpha-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography, and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich, and slender-shaped vessels (Type II), 8 (11.0%) had thin-walled, nuclei-poor, and oval-shaped vessels. (Type I), and the remaining 8 had a mixed type of II and Type I. Conversely among 33 patients without hypervascularity, 5 (15.2%) had a Type II, 21 (63.6%) had a Type I, 5 had a mixed type, and 2 had no positive vessel. Tumor size, histological classification, and amount of non-triadal vessels were also associated with the angiographic appearance of the … More tumors. Among varied aspects of the cancer including tumor size, tumor multiplicity, microscopic portal invasion, histological classification, amount of alpha-smooth muscle actin-positive vessels, and shape of alpha-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of alpha-smooth muscle actin positive vessels was solely associated with angiographic hypervascularity independently. Although the existence of non-triadal vessel characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the Type II vessel. A morphological change of non-triadal vessel from Type I to Type II was considered to occur in an early stage of hepatocellular carcinoma.Eleven surgically resected specimens of well-differentiated hepatocellular carcinoma were analyzed for neovascular structure using monoclonal alpha-smooth muscle actin antibody. Each paraffin specimen was serially sliced with a thickness of 3 micrometers for immunohistochemistry. All of the eleven liver cancers had thin-walled, round-or oval-shaped non-triadal vessels in their well-differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non-triadal vessels were connected to portal veins in portal triads in well-differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well-differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All eleven tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed "negative enhancement" on intra-arterial carbon dioxide-enhanced ultrasonography or computerized tomographic hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules. Less

为了阐明血管造影特征与组织学发现之间的关系，对106例小肝癌患者进行了α-平滑肌肌动蛋白的免疫组织学研究。数字减影血管造影显示73例（68.9%）为动脉优势型或门脉血供不足型，88例（83.0%）为CT动脉门脉造影显示，87例（82.1%）为二氧化碳增强超声显示。在73例血管造影显示血管丰富的患者中，57例（78.1%）为厚壁、富核、细长血管（II型），8例（11.0%）为薄壁、贫核、椭圆形血管。(Type其余8例为II型和I型混合型。相反，在33例无血管过多的患者中，5例（15.2%）为II型，21例（63.6%）为I型，5例为混合型，2例无阳性血管。肿瘤大小、组织学分类和非三叉血管的数量也与血管造影表现有关。 ...更多信息 肿瘤的在肿瘤大小、肿瘤多样性、显微镜下门脉侵犯、组织学分类、α-平滑肌肌动蛋白阳性血管数量和α-平滑肌肌动蛋白阳性血管形状等不同方面，多变量Logistic回归分析表明，α-平滑肌肌动蛋白阳性血管的形状仅与血管造影血管丰富独立相关。虽然非三轴血管的存在是肝细胞癌的特征，但血管造影的血管过多与II型血管密切相关。作者应用单克隆抗体α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）对11例高分化肝癌手术切除标本进行了血管结构分析。每个石蜡标本连续切片，厚度为3微米，用于免疫组织化学。所有11例肝癌的分化好的部位都有薄壁、圆形或椭圆形的非三叉血管。免疫组化连续薄切片的肝癌显示，这些非三联血管连接到门静脉三联体中的门静脉在分化良好的癌症，共9例（81.8%）。在分化良好的癌中发现的这种类型的新生血管结构似乎是在减少和消失的动脉和胆管中幸存的门静脉。所有11个肿瘤在普通数字减影血管造影上显示等血管染色，其中4个肿瘤在动脉内二氧化碳增强超声或计算机断层肝动脉造影上显示“阴性增强”，表明肿瘤结节内动脉血相对稀少。少

项目成果

Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of hepatocellular carcinogenesis with precore mutant virus and serum hepatitis B virus DNA concentration --- A longitudinal analysis of patients with cirrhosis"Hepatology Research. 10. 142-155 (1998)

Ikeda K、Saitoh S、Suzuki Y等：“肝细胞癌变与precore突变病毒和血清乙型肝炎病毒DNA浓度的关系——肝硬化患者的纵向分析”肝病学研究。

Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of hepatocellular carcinogenesis with precore mutant virus and ser um hepatitis B virus DNA concentration --------A longitudinal analysis of patients with cirrhosis."Hepatology Research. 10. 142-155 (1998

Ikeda K，Saitoh S，Suzuki Y，等：“肝细胞癌发生与前核突变病毒和血清乙型肝炎病毒DNA浓度的关系--------肝硬化患者的纵向分析。”肝病学研究。

Ikeda K, Arase Y, Saitoh S, et al.: "Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C --- A long-term observation study of 1643 patients using statistical bias correction with proportional hazard anal

Ikeda K、Arase Y、Saitoh S 等人：“干扰素治疗对慢性丙型肝炎患者肝细胞癌发生的影响——一项对 1643 名患者进行的长期观察研究，采用比例风险分析的统计偏差校正

Ikeda K, Kobayashi M, Saitoh S, et al.: "Recurrence rate and prognosis of patients with hepatocellular carcinoma that developed after elimination of hepatitis C virus-RNA by interferon therapy. ---- A closed cohort study using matched control patients."On

Ikeda K、Kobayashi M、Saitoh S等人：“通过干扰素治疗消除丙型肝炎病毒-RNA后发生的肝细胞癌患者的复发率和预后。----一项使用匹配对照患者的封闭队列研究。

Ikeda K, Saitoh S, Suzuki Y, et al.: "Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular carcinoma."J Gastroenterol Hepatol. 13. 1264-1271 (1998)

Ikeda K、Saitoh S、Suzuki Y 等人：“小肝细胞癌中血管造影结果与通过 α-平滑肌肌动蛋白免疫组织化学染色检测到的新生血管结构的关系。”J Gastroenterol Hepatol。