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Article: Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells

TitleGene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells
Authors
Keywordsp53: hepatocellular carcinoma
Receptor-mediated gene transfer system
Issue Date2001
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2001, v. 93 n. 3, p. 393-400 How to Cite?
AbstractFor gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-β-galactosidase (β-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-β-gal gene complex injected peritumorally, β-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells. © 2001 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/88748
ISSN
2021 Impact Factor: 7.316
2020 SCImago Journal Rankings: 2.475
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorHan, JSen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorLiang, ZDen_HK
dc.contributor.authorTian, PKen_HK
dc.contributor.authorGu, JRen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-06T09:47:27Z-
dc.date.available2010-09-06T09:47:27Z-
dc.date.issued2001en_HK
dc.identifier.citationInternational Journal Of Cancer, 2001, v. 93 n. 3, p. 393-400en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88748-
dc.description.abstractFor gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-β-galactosidase (β-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-β-gal gene complex injected peritumorally, β-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells. © 2001 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectp53: hepatocellular carcinomaen_HK
dc.subjectReceptor-mediated gene transfer systemen_HK
dc.subject.meshAntineoplastic Agents - therapeutic useen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCarcinoma, Hepatocellular - metabolism - therapyen_HK
dc.subject.meshDNA - chemistryen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGene Therapy - methodsen_HK
dc.subject.meshGenes, p53en_HK
dc.subject.meshHemagglutinins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLiver Neoplasms - metabolism - therapyen_HK
dc.subject.meshOligopeptides - metabolismen_HK
dc.subject.meshReceptor, Epidermal Growth Factor - genetics - metabolismen_HK
dc.subject.meshRetroviridae - geneticsen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshbeta-Galactosidase - metabolismen_HK
dc.titleGene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=93&spage=393&epage=400&date=2001&atitle=Gene+delivery+using+a+receptor-mediated+gene+transfer+system+targeted+to+hepatocellular+carcinoma+cellsen_HK
dc.identifier.emailLee, TKW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.1340en_HK
dc.identifier.pmid11433405-
dc.identifier.scopuseid_2-s2.0-0035426950en_HK
dc.identifier.hkuros59751en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035426950&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume93en_HK
dc.identifier.issue3en_HK
dc.identifier.spage393en_HK
dc.identifier.epage400en_HK
dc.identifier.isiWOS:000169597200013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, TKW=7501439435en_HK
dc.identifier.scopusauthoridHan, JS=7406442934en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridLiang, ZD=8703879300en_HK
dc.identifier.scopusauthoridTian, PK=7005010932en_HK
dc.identifier.scopusauthoridGu, JR=7403129786en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.issnl0020-7136-

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