Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.

2.50
Hdl Handle:
http://hdl.handle.net/2436/16696
Title:
Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.
Authors:
Maleniak, Tricia C.; Darling, John L.; Lowenstein, Pedro R.; Castro, Maria G.
Abstract:
Due to minimal treatment success with surgery, radiotherapy, and chemotherapy, the aim of this study was to test the therapeutic potential of gene therapy for the treatment of glioblastoma multiforme (GBM). We have quantitatively analyzed two gene therapy approaches using short-term human glioma cell cultures derived from surgical biopsies (designated IN859, IN1612, IN2045, IN1760, and IN1265) and compared the results of gene therapy with the chemosensitivity of the same cells. All of the glioma cell cultures tested were susceptible to recombinant adenovirus (RAd)-mediated infection. Expression of herpes simplex virus type 1-thymidine kinase (RAd128), followed by ganciclovir treatment, induced apoptosis in all of the glioma cell cultures studied, including three that are resistant to the chemotherapeutic drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Expression of murine Fas ligand (RAdhCMV-mFasL) also induced cell death in four of the five cell cultures studied. One cell culture that was resistant to CCNU was also resistant to apoptosis induced by mFasL expression. These results suggest that sensitivity to chemotherapeutic agents does not necessarily correlate with the sensitivity to gene therapy treatments. RAds expressing therapeutic gene products in human glioma cell cultures are able to induce apoptosis even in some cells that are resistant to a commonly used chemotherapeutic agent. Therefore, RAd-mediated gene transfer could be a good candidate to further develop gene therapy for the treatment of GBM.
Citation:
Cancer Gene Therapy, 8(8): 589-598
Publisher:
Nature Publishing Group
Issue Date:
2001
URI:
http://hdl.handle.net/2436/16696
DOI:
10.1038/sj.sgt.7700348
PubMed ID:
11571537
Additional Links:
http://www.nature.com/cgt/journal/v8/n8/abs/7700348a.html; http://direct.bl.uk/bld/PlaceOrder.do?UIN=101037666&ETOC=RN&from=searchengine
Type:
Article
Language:
en
Description:
Metadata only. Full text available at links above.
ISSN:
0929-1903
Appears in Collections:
Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorMaleniak, Tricia C.-
dc.contributor.authorDarling, John L.-
dc.contributor.authorLowenstein, Pedro R.-
dc.contributor.authorCastro, Maria G.-
dc.date.accessioned2008-01-23T15:12:27Z-
dc.date.available2008-01-23T15:12:27Z-
dc.date.issued2001-
dc.identifier.citationCancer Gene Therapy, 8(8): 589-598en
dc.identifier.issn0929-1903-
dc.identifier.pmid11571537-
dc.identifier.doi10.1038/sj.sgt.7700348-
dc.identifier.urihttp://hdl.handle.net/2436/16696-
dc.descriptionMetadata only. Full text available at links above.en
dc.description.abstractDue to minimal treatment success with surgery, radiotherapy, and chemotherapy, the aim of this study was to test the therapeutic potential of gene therapy for the treatment of glioblastoma multiforme (GBM). We have quantitatively analyzed two gene therapy approaches using short-term human glioma cell cultures derived from surgical biopsies (designated IN859, IN1612, IN2045, IN1760, and IN1265) and compared the results of gene therapy with the chemosensitivity of the same cells. All of the glioma cell cultures tested were susceptible to recombinant adenovirus (RAd)-mediated infection. Expression of herpes simplex virus type 1-thymidine kinase (RAd128), followed by ganciclovir treatment, induced apoptosis in all of the glioma cell cultures studied, including three that are resistant to the chemotherapeutic drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Expression of murine Fas ligand (RAdhCMV-mFasL) also induced cell death in four of the five cell cultures studied. One cell culture that was resistant to CCNU was also resistant to apoptosis induced by mFasL expression. These results suggest that sensitivity to chemotherapeutic agents does not necessarily correlate with the sensitivity to gene therapy treatments. RAds expressing therapeutic gene products in human glioma cell cultures are able to induce apoptosis even in some cells that are resistant to a commonly used chemotherapeutic agent. Therefore, RAd-mediated gene transfer could be a good candidate to further develop gene therapy for the treatment of GBM.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.nature.com/cgt/journal/v8/n8/abs/7700348a.htmlen
dc.relation.urlhttp://direct.bl.uk/bld/PlaceOrder.do?UIN=101037666&ETOC=RN&from=searchengine-
dc.subject.meshAdenoviridaeen
dc.subject.meshAntineoplastic Agents, Alkylatingen
dc.subject.meshApoptosisen
dc.subject.meshBrain Neoplasmsen
dc.subject.meshCombined Modality Therapyen
dc.subject.meshDNA, Recombinanten
dc.subject.meshDrug Resistance, Neoplasmen
dc.subject.meshFas Ligand Proteinen
dc.subject.meshGalactosidesen
dc.subject.meshGancicloviren
dc.subject.meshGene Expressionen
dc.subject.meshGene Therapyen
dc.subject.meshGenetic Vectorsen
dc.subject.meshGlioblastomaen
dc.subject.meshHerpesvirus 1, Humanen
dc.subject.meshHumansen
dc.subject.meshIndolesen
dc.subject.meshLomustineen
dc.subject.meshMembrane Glycoproteinsen
dc.subject.meshThymidine Kinaseen
dc.subject.meshTumor Cells, Cultureden
dc.subject.meshbeta-Galactosidaseen
dc.titleAdenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.en
dc.typeArticleen
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