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dc.contributor.authorMavria, Gen_US
dc.date.accessioned2018-06-05T11:09:54Z
dc.date.issued2001-06en_US
dc.identifierhttp://www.nature.com/gt/journal/v8/n12/full/3301483a.htmlen_US
dc.identifier.citationGENE THERAPY, 2001, 8 (12), pp. 913 - 920en_US
dc.identifier.issn0969-7128en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1711
dc.description.abstractReduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment. Using a recombinant retrovirus with ecotropic envelope we have achieved high efficiency of transduction of endothelial cells in the vasculature of subcutaneous xenografts arising from the co-injection of tumour cells and irradiated virus producers. We have used this experimental system to assess the efficacy of the herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) prodrug activation system in anti-vascular therapy. Treatment of KSY-1 xenografts with HSV-tk transduction in the vascular compartment with the S-phase-dependent drug GCV resulted in extensive haemorrhagic necrosis, indicative of vascular damage. Therapeutic potential in tumours with transduced endothelial cells comprising 5% or less of the total tumour mass was similar to that of tumours with HSV-tk expression in over 46% of tumour cells. GCV treatment of animals bearing MDA-MB-361 breast carcinoma, SW620 and CACO2 colon carcinomas with HSV-fk expression in the vascular compartment also resulted in reduced tumour growth. We conclude that HSV-fk/GCV prodrug activation is an effective strategy for eradicating tumour vasculature, and that direct targeting of proliferating endothelial cells in established vasculature results in reduced tumour growth. The therapeutic potential observed with the slow-growing CACO2 colon and MD-AMB-361 breast carcinomas supports the notion that anti-vascular therapy targeted at proliferating endothelium is likely to prove efficacious in human cancers that generally grow at a lower rate than experimental tumours.en_US
dc.format.extent913 - 920en_US
dc.subjectangiogenesis; tumor vasculature; gene therapy; endothelial; retroviral vector; HSV-tk/GCV ENDOTHELIAL-CELL-PROLIFERATION; TUMOR-GROWTH; GENE-THERAPY; COLORECTAL XENOGRAFTS; MICROVESSEL DENSITY; COMBRETASTATIN A-4; ANTITUMOR IMMUNITY; RETROVIRAL VECTOR; HUMAN BREAST; IN-VIVOen_US
dc.titleReduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartmenten_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2001-06en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfGENE THERAPYen_US
pubs.issue12en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
pubs.volume8en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneen_US
dc.contributor.icrauthorPorter, Colinen_US


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