Trial of Gene Therapy for Hepatocellular Carcinoma

肝细胞癌基因治疗试验

• 批准号: 07670607
• 负责人: IWAI Masaki
• 金额: $ 1.28万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670607/
• 关键词: Hepatocellular carcinoma; alpha-Fetoprotein; Albumin; Cell differentiation; Gap junction; Gene therapy; ギャプ結合; ギャップジャンクション

We investigated formation of gap junction (GJ), which has a function of cell to cell communication and differential expression of alpha-fetoprotein (AFP) and albumin (ALB) in ontogenesis of the liver to clarify a role for differentiation of hepatocytes.Connexin (Cx) 32 which is a subunit protein of GJ was expressed before birth by northern blot, and expression of Cx32 and Cx26 were increased after birth. Immunofluorescent study in gestational period showed large plaques of Cx32, and Cx32-and Cx26-positive plaques were scatteredly seen on some hepatocytes. AFP expression by in situ hybridization and immunocytochemistry was seen in all hepatocytes and ALB was already expressed in some hepatocytes. Just after birth Cx32-and Cx26-positive plaques were increased and GJ was ultrastructurally seen. AFP expression was decreased and ALB was expressed in all hepatocytes. A week after birth Cx32-positive small plaques were diffusely distributed in all hepatocytes and Cx26-positive plaques were localized in periporta tract, and structure of GJ was increased in number. AFP expression was remained in a few hepatocytes of central area and ALB expression was accentuated in portal tract.These findings suggest that formation of GJ in ontogenesis of the liver is closely related with differential expression of AFP and ALB,and compulsory expression of Cx may induce well differentiation in hepatoma cells and lead to one of gene therapy for hepatoma.

为探讨间隙连接（GJ）在肝细胞分化过程中的作用，北方印迹法检测了GJ亚基Cx32在出生前表达，Cx32和Cx26在出生后表达增强。妊娠期免疫荧光检查可见大面积Cx32阳性斑块，部分肝细胞可见散在Cx32和Cx26阳性斑块。原位杂交和免疫细胞化学法显示所有肝细胞均表达AFP，部分肝细胞已表达ALB。出生后Cx32和Cx26阳性斑块增加，超微结构可见GJ。所有肝细胞AFP表达降低，ALB表达。生后1周，Cx32阳性小斑块弥漫分布于肝细胞，Cx26阳性斑块局限于门周束，GJ结构增多。结果表明，肝细胞发育过程中GJ的形成与AFP和ALB的差异表达密切相关，Cx的强制性表达可诱导肝癌细胞分化，为肝癌的基因治疗提供了可能。

项目成果

岩井眞樹,他: "肝個体発生時のGap junction形成について-Cx26とCx32の発現からみて-" 薬理と治療. 24. 129-132 (1996)

Maki Iwai 等人：“肝脏个体发育过程中间隙连接的形成 - 来自 Cx26 和 Cx32 的表达 -”药理学和治疗 24. 129-132 (1996)。

M Iwai,et al.: "A role of gap junction for differentiation of hepatooytes in onto-genesis." Proceedings of 10th International Congress of Histochem Cytochem. 741-742 (1996)

M Iwai 等人：“间隙连接在个体发生中肝细胞分化中的作用。”

岩井眞樹,他: "癌胎児蛋白AFPの発現制御について-細胞接着装置形成の面から-" 日本臨床代謝学会記録. 32. 132-133 (1995)

Maki Iwai 等人：“癌胚蛋白 AFP 的表达调节 - 从细胞粘附装置形成的角度 -”日本临床代谢学会记录 32. 132-133 (1995)。

M Iwai,et al.: "Synthesis of secretory protein in regurating liver of rat after pautial hepatecfomy." J Gastroenteral Hepatol. 11. 1137-1142 (1996)

M Iwai 等人：“短暂肝切除术后调节大鼠肝脏分泌蛋白的合成”。

岩井眞樹,他: "Gap結合形成の細胞分化への影響について" 薬理と治療. 24. 145-148 (1996)

Maki Iwai 等人：“间隙键形成对细胞分化的影响”药理学和治疗 24. 145-148 (1996)。