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和组织学发现之间的关系，对106例小肝细胞癌患者进行了α-光滑肌肉肌动蛋白的免疫组织学研究。在数字减法血管造影（68.9％）中发现了动脉优势或门静脉血液缺乏，在计算机断层扫描的计算机层析造影术对88例（83.0％）中发现了动脉优势，在计算机断层扫描的患者中发现了88例（83.0％），在二氧化碳增强的超声检查中发现了87例（82.1％）。在73例血管造影高血管性的患者中，有57例（78.1％）的壁，核富含核和细长形的血管（II型），8（11.0％）的壁壁，核贫困和椭圆形容器。 （I型），其余8种具有混合类型的II和I型。相反，在33例没有血管过高的患者中，有5（15.2％）的II型，21（63.6％）具有I型，5种混合型，而2种没有正船。肿瘤大小，组织学分类和非三级视频的数量也与…更多肿瘤的血管造影外观有关。癌症的各个方面包括肿瘤大小，肿瘤多样性，微观门户入侵，组织学分类，α-光滑的肌肉肌肉肌动蛋白阳性视频的数量以及α-光滑肌肉肌动蛋白阳性视频的形状，多变量逻辑回归分析表明，alpha-smoscrose的形状与alpha-smosce susply syply syply syply syply syply syperlysimenty canti syperlysimenty sypertimenty sypertimenty canti是孤独的vissels ys sylysy是独立的。尽管非三级血管的存在表征了肝细胞癌，但血管造影高血管性与II型血管密切相关。非三体血管从I型变为II型的形态变化被认为发生在肝细胞癌的早期阶段。使用单与单与金色的alpha-Smotha-Smooth-Smooth肌肉肌动蛋白抗体，分析了通过手术切除的良好分化肝细胞癌的手术切除的标本。每个石蜡试样串行切成薄片，厚度为3微米，用于免疫组织化学。所有11种肝癌都在其分化明显的部位中都薄壁，圆形或椭圆形的非三级血管。 HCC系列薄切片的免疫组织化学表明，这些非三级血管在良好分化的癌症中与门户三合会的门静脉相连，总共九名患者（81.8％）。在良好的癌症中发现的这种新血管结构似乎是减少和消失的动脉和胆管中的生存门户静脉。所有十一次肿瘤均在普通数字减法血管造影上均表现出血管染色，其中四个肿瘤在动脉内二氧化碳增强的超声检查或计算机断层扫描动脉造影上显示出“阴性增强”，这表明肿瘤结节中相对动脉稀缺。较少的

项目成果

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, 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, 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, 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, Arase Y, Kobayashi M, et al.: "Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis"Intervirology. 46. 96-104 (2003)

Ikeda K、Arase Y、Kobayashi M 等人：“乙型肝炎病毒 DNA 持续低水平可避免 HBV 相关肝硬化患者发生肝细胞癌”Intervirology。