Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90130
Title:
Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.
Authors:
Djeha, A Hakim; Hulme, Alison N; Dexter, T Michael; Mountain, Andrew; Young, Lawrence S; Searle, Peter F; Kerr, David J; Wrighton, Christopher J
Abstract:
Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.
Affiliation:
Cobra Therapeutics Ltd., The Science Park, University of Keele, United Kingdom. hakimd@cancer.bham.ac.uk
Citation:
Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954. 2000, 7 (5):721-31 Cancer Gene Ther.
Journal:
Cancer Gene Therapy
Issue Date:
May-2000
URI:
http://hdl.handle.net/10541/90130
DOI:
10.1038/sj.cgt.7700171
PubMed ID:
10830719
Type:
Article
Language:
en
ISSN:
0929-1903
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDjeha, A Hakimen
dc.contributor.authorHulme, Alison Nen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorMountain, Andrewen
dc.contributor.authorYoung, Lawrence Sen
dc.contributor.authorSearle, Peter Fen
dc.contributor.authorKerr, David Jen
dc.contributor.authorWrighton, Christopher Jen
dc.date.accessioned2010-01-20T14:56:24Z-
dc.date.available2010-01-20T14:56:24Z-
dc.date.issued2000-05-
dc.identifier.citationExpression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954. 2000, 7 (5):721-31 Cancer Gene Ther.en
dc.identifier.issn0929-1903-
dc.identifier.pmid10830719-
dc.identifier.doi10.1038/sj.cgt.7700171-
dc.identifier.urihttp://hdl.handle.net/10541/90130-
dc.description.abstractExpression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.en
dc.language.isoenen
dc.subjectHead and Neck Canceren
dc.subjectLiver Canceren
dc.subjectCancer Transplantationen
dc.subjectExperimental Canceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshAziridines-
dc.subject.meshCarcinoma, Hepatocellular-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCross-Linking Reagents-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshEscherichia coli-
dc.subject.meshHead and Neck Neoplasms-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Nude-
dc.subject.meshNecrosis-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshNeoplasms, Experimental-
dc.subject.meshNitroreductases-
dc.subject.meshProdrugs-
dc.subject.meshRemission Induction-
dc.subject.meshTime Factors-
dc.subject.meshTumor Cells, Cultured-
dc.titleExpression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.en
dc.typeArticleen
dc.contributor.departmentCobra Therapeutics Ltd., The Science Park, University of Keele, United Kingdom. hakimd@cancer.bham.ac.uken
dc.identifier.journalCancer Gene Therapyen

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