Gene Transfer of Endostatin cDNA to Bone Marrow Cells of Mice with Hepatocellular Carcinoma
Gene Transfer of Endostatin cDNA to Bone Marrow Cells of Mice with Hepatocellular Carcinoma
批准号:
15590700
负责人:
TORIMURA Takuji
金额:
$2.24万
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:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2005
中文摘要
肝细胞癌是一种富血供的肿瘤。在本研究中,我们研究了抗血管生成因子cDNA的基因治疗对肝癌是否有效,内皮抑素和Kringle 1 -5,这两种有效的抗血管生成因子,在体外抑制内皮祖细胞的增殖。用逆转录病毒转染系统将内皮抑素和kringle 1 -5基因转染骨髓细胞。Kringle 1 -5 cDNA成功转染。然而,内皮抑制素未被转染。然后,我们静脉注射脂质体kringle 1 -5 cDNA复合物在裸鼠体内植入肝癌细胞系,以研究肿瘤的生长,肝内转移和生存。kringle 1 -5基因转染抑制三种肝癌细胞系的肿瘤生长。kringle 1 -5基因转染可延长生存期,减少肝内转移灶数目。接下来,我们用kringle 1 -5 cDNA转染的骨髓细胞对裸鼠进行骨髓转染。然后,裸鼠接受肝癌细胞肝内移植。骨髓转染4周后,处死小鼠。在肿瘤组织中,约10%的血管内皮细胞由骨髓来源的内皮祖细胞组成。约20%的内皮祖细胞来源的血管内皮细胞产生Kringle 1-5蛋白。而骨髓转染Kringle 1 -5 cDNA后,肿瘤体积和肿瘤组织血管密度均未受到抑制,这可能是由于逆转录病毒系统的转染效率较低,导致Kringle 1 -5蛋白在肿瘤组织中的表达较弱,无法抑制肿瘤的发生发展。
英文摘要
Hepatocellular carcinoma is a hypervascular tumor. In the present study, we investigated whether gene therapy with anti-angiogenic factor cDNA could be effective or not for hepatocellular carcinoma.Endostatin and Kringle1-5, which were potent anti-angiogenic factors, suppressed proliferation of endothelial progenitor cells in vitro. We transfected endostatin and kringle1-5 cDNAs to bone marrow cells with retrovirus fransfection system. Kringle1-5 cDNA was successfully transfected. However, endostatin was not transfected. Then we injected intravenously liposome-kringle1-5 cDNA complexes in nude mice implanted into the liver with hepatoma cell lines to study tumor growth, intrahepatic metastasis and survival. Gene transfer of kringle1-5 suppressed tumor growth of the three hepatoma cell lines. kringle1-5 gene transfer prolonged the survival period, reduced the number of intrahepatic metastases. Next, we performed bone marrow transfection to nude mice with kringle1-5 cDNA transfected bone marrow cells. Then, the nude mice were received hepatoma cell transplantation in the liver. After 4 weeks of the bone marrow transfection, the mice were sacrificed. In tumor tissues, about 10% of vascular endothelial cells were consisted with bone marrow derived endothelial progenitor cells. About 20% of vascular endothelial cells derived from endothelial progenitor cells produced kringle 1-5 protein. However, tumor volume and vascular density in tumor tissues were not suppressed by bone marrow transfection with kringle1-5 cDNA at all.These results seems that the expression of kringle1-5 protein in tumor tissues was too weak to suppress the tumor development due to low transfection efficacy of retrovirus system.
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肝癌の発生進展と血管新生
肝癌的发育进展和血管生成
DOI:
--
发表时间:
2004
期刊:
肝胆膵 48(4)
影响因子:
--
作者:
[鳥村拓司, 上野隆登, 佐田通夫]
通讯作者:
佐田通夫
Gene Transfer of Kringle 1-5 Suppresses Tumor Development and Improves Probnosis of Mice with Hepatoccellular Carcinoma
Kringle 1-5 的基因转移抑制肿瘤发展并改善肝细胞癌小鼠的预后
DOI:
--
发表时间:
2006
期刊:
Gastroenterology 130(4)
影响因子:
--
作者:
[Takuji Torimura, et al.]
通讯作者:
et al.
Loposome-Mediated Gene Transfer of Kringle 1-5 Supress Tumor Development and Improves the Prognosis of Hepatocellular Carcinoma
脂质体介导的 Kringle 1-5 基因转移抑制肿瘤发展并改善肝细胞癌的预后
DOI:
--
发表时间:
期刊:
MEDICAL MOLECULAR MORPHOLOGY In prss
影响因子:
--
作者:
[Takuji Torimura, et al.]
通讯作者:
et al.
DOI:
10.1053/j.gastro.2006.02.020
发表时间:
2006-04-01
期刊:
GASTROENTEROLOGY
影响因子:
29.4
作者:
[Torimura, T, Ueno, T, Cao, YH]
通讯作者:
Cao, YH
Development of iPS cells-derived vector cells for antiangiogenic gene therapy for hepatocellular carcinoma.
-
批准号:22590752
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2010
-
负责人:TORIMURA Takuji
-
依托单位:
Antiangiogenic gene therapy for hepatocellular carcinoma with bone marrow-derived progenitor cells
-
批准号:19590796
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2007
-
负责人:TORIMURA Takuji
-
依托单位:
Gene transfer of Endostatin and K1-5 suppresses the growth of hepatocellular carcinoma
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批准号:11670550
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.37万
-
财政年份:1999
-
负责人:TORIMURA Takuji
-
依托单位:
Inhibitory effect of the angiogenesis inhibitor TNP-470 on hepatocellular carcinomas
-
批准号:07670634
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$1.22万
-
财政年份:1995
-
负责人:TORIMURA Takuji
-
依托单位:
海外基金