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逆转录病毒介导的基因治疗用于移植到无胸腺小鼠体内的人类肝细胞癌

Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.

作者信息

Ueki T, Nakata K, Mawatari F, Tsuruta S, Ido A, Ishikawa H, Nakao K, Kato Y, Ishii N, Eguchi K

机构信息

The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852, Japan.

出版信息

Int J Mol Med. 1998 Apr;1(4):671-5. doi: 10.3892/ijmm.1.4.671.

DOI:10.3892/ijmm.1.4.671
PMID:9852281
Abstract

Gene therapy using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of the 0.3-kb human alpha-fetoprotein (AFP) gene promoter (LNAF0.3TK virus) in combination with ganciclovir (GCV) treatment was performed in athymic mice harboring AFP-producing HuH-7 human hepatoma cells. GCV treatment resulted in pronounced growth inhibition of the virus-infected HuH-7 xenograft in mice, but did not affect growth of the parental xenograft. These results indicate that the AFP gene promoter sequence allows enough therapeutic gene expression to induce the GCV-mediated cytotoxicity in vivo in AFP-producing human hepatoma cells.

摘要

在携带产生甲胎蛋白的HuH-7人肝癌细胞的无胸腺小鼠中,进行了基因治疗,该治疗使用一种逆转录病毒载体,该载体携带在0.3 kb人甲胎蛋白(AFP)基因启动子控制下的单纯疱疹病毒胸苷激酶基因(LNAF0.3TK病毒),并联合更昔洛韦(GCV)治疗。GCV治疗导致小鼠中病毒感染的HuH-7异种移植瘤明显生长抑制,但不影响亲代异种移植瘤的生长。这些结果表明,AFP基因启动子序列允许足够的治疗性基因表达,以在产生AFP的人肝癌细胞中在体内诱导GCV介导的细胞毒性。

相似文献

1
Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.逆转录病毒介导的基因治疗用于移植到无胸腺小鼠体内的人类肝细胞癌
Int J Mol Med. 1998 Apr;1(4):671-5. doi: 10.3892/ijmm.1.4.671.
2
Retrovirus-mediated gene therapy for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by human alpha-fetoprotein enhancer directly linked to its promoter.逆转录病毒介导的肝细胞癌基因治疗:由直接与其启动子相连的人甲胎蛋白增强子调控的选择性和增强的自杀基因表达
Cancer Gene Ther. 1998 Sep-Oct;5(5):301-6.
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Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter.利用携带在人甲胎蛋白基因启动子控制下的单纯疱疹病毒胸苷激酶基因的逆转录病毒载体对肝癌细胞进行基因治疗。
Cancer Res. 1995 Jul 15;55(14):3105-9.
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Utilization of variant-type of human alpha-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma.人甲胎蛋白启动子变异型在肝细胞癌基因治疗中的应用。
Gene Ther. 1999 Apr;6(4):465-70. doi: 10.1038/sj.gt.3300870.
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Gene therapy targeting for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by a hypoxia-inducible enhancer linked to a human alpha-fetoprotein promoter.针对肝细胞癌的基因治疗:由与人类甲胎蛋白启动子相连的缺氧诱导增强子调控的选择性和增强的自杀基因表达。
Cancer Res. 2001 Apr 1;61(7):3016-21.
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Retrovirus-mediated gene therapy for hepatocellular carcinoma with reversely oriented therapeutic gene expression regulated by alpha-fetoprotein enhancer/promoter.利用甲胎蛋白增强子/启动子调控反向治疗基因表达的逆转录病毒介导的肝细胞癌基因治疗
Biochem Biophys Res Commun. 2001 Oct 5;287(4):1034-40. doi: 10.1006/bbrc.2001.5684.
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Gene therapy for alpha-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene.通过腺病毒介导单纯疱疹病毒胸苷激酶基因转移对产生甲胎蛋白的人肝癌细胞进行基因治疗。
Hepatology. 1996 Jun;23(6):1359-68. doi: 10.1002/hep.510230611.
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Assessment of α-fetoprotein targeted HSV1-tk expression in hepatocellular carcinoma with in vivo imaging.利用体内成像技术评估α-甲胎蛋白靶向的单纯疱疹病毒1型胸苷激酶在肝细胞癌中的表达
Cancer Biother Radiopharm. 2015 Feb;30(1):8-15. doi: 10.1089/cbr.2014.1716. Epub 2014 Dec 29.
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Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene.通过腺相关病毒转导单纯疱疹病毒胸苷激酶基因选择性杀伤甲胎蛋白阳性的肝癌细胞
Hum Gene Ther. 1996 Mar 1;7(4):463-70. doi: 10.1089/hum.1996.7.4-463.
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Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter.基于使用甲胎蛋白(AFP)增强子和管家基因启动子的肿瘤选择性自杀基因表达的肝细胞癌基因治疗。
Eur J Cancer. 2001 Jan;37(1):140-7. doi: 10.1016/s0959-8049(00)00344-0.

引用本文的文献

1
Suicide gene therapy in liver tumors.肝癌的自杀基因治疗
Methods Mol Med. 2004;90:433-50. doi: 10.1385/1-59259-429-8:433.
2
Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma.一种靶向肝细胞癌的可调控基因治疗载体的构建。
World J Gastroenterol. 2003 Apr;9(4):688-91. doi: 10.3748/wjg.v9.i4.688.
3
Hepatocellular carcinoma--cause, treatment and metastasis.肝细胞癌——病因、治疗与转移
World J Gastroenterol. 2001 Aug;7(4):445-54. doi: 10.3748/wjg.v7.i4.445.