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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): 589-598
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.
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.
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.urlhttp://direct.bl.uk/bld/PlaceOrder.do?UIN=101037666&ETOC=RN&from=searchenginehttp://www.nature.com/cgt/journal/v8/n8/abs/7700348a.html
dc.subject.meshAdenoviridae
dc.subject.meshAntineoplastic Agents, Alkylating
dc.subject.meshApoptosis
dc.subject.meshBrain Neoplasms
dc.subject.meshCombined Modality Therapy
dc.subject.meshDNA, Recombinant
dc.subject.meshDrug Resistance, Neoplasm
dc.subject.meshFas Ligand Protein
dc.subject.meshGalactosides
dc.subject.meshGanciclovir
dc.subject.meshGene Expression
dc.subject.meshGene Therapy
dc.subject.meshGenetic Vectors
dc.subject.meshGlioblastoma
dc.subject.meshHerpesvirus 1, Human
dc.subject.meshHumans
dc.subject.meshIndoles
dc.subject.meshLomustine
dc.subject.meshMembrane Glycoproteins
dc.subject.meshThymidine Kinase
dc.subject.meshTumor Cells, Cultured
dc.subject.meshbeta-Galactosidase
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.
dc.typeJournal article
html.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.


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