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A Novel Approach Using Transcomplementing Adenoviral Vectors for Gene Therapy of Adrenocortical Cancer

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dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: BSEL - Laboratorio de Ciencia e Ingeniería Biomédicaes
dc.contributor.authorWolkersdörfer, G. W.
dc.contributor.authorBornstein, S. R,
dc.contributor.authorHigginbotham, J. N.
dc.contributor.authorHiroi, N.
dc.contributor.authorVaquero López, Juan José
dc.contributor.authorGreen, M. V.
dc.contributor.authorBlaese, R. M.
dc.contributor.authorAguilera, G.
dc.contributor.authorChrousos, G. P.
dc.contributor.authorRamsey, W. J.
dc.date.accessioned2012-07-26T08:02:31Z
dc.date.available2012-07-26T08:02:31Z
dc.date.issued2002-06
dc.description.abstractCurrent therapies for adrenocortical carcinomas do not improve the life expectancy of patients. I n this study, we tested whether a gene-transfer therapy based upon a suicide gene/prodrug system would be effective in an animal model of the disease. We employed E4- and ElA/B-depleted. herpes simplex virus-thymidine kinase-expressing adenoviral mutants that transcomplement each other within tumor cells, hereby improving transgene delivery and efficacy by viral replication in situ. Transcomplementation of vectors increased the fraction of transduced of tumor cells. This increase was accompanied by greater tumor volume reduction compared to non-transcomplementing approaches. Survival time improved with non-replicating vectors plus GCV compared to controls. However, transcomplementation/replication of vectors led to a further significant increment in anti-tumor activity and survival time (p <0.02). In treated animals, we observed a high number of apoptotic nuclei both adjacent to and distant from injection sites and sites of viral oncolysis. Ultrastructural analyses exhibited nuclear inclusion bodies characteristic of virus production in situ, and provided further evidence that this therapy induced apoptotic cell death within tumor cells. We conclude that the efficacy of suicide gene therapy is significantly amplified by viral replication and, in combination with GCV, significantly reduces tumor burden and increases survival time.
dc.description.statusPublicado
dc.format.mimetypeapplication/pdf
dc.identifier.bibliographicCitationHormone and Metabolic Research, vol. 34, n. 6, june 2002. Pp. 279-287
dc.identifier.doi10.1055/s-2002-33255
dc.identifier.issn0018-5043 (print version)
dc.identifier.issn1439-4286 (online version)
dc.identifier.publicationfirstpage279
dc.identifier.publicationissuen. 6
dc.identifier.publicationlastpage287
dc.identifier.publicationtitleHormone and Metabolic Research
dc.identifier.publicationvolumevol. 34
dc.identifier.urihttps://hdl.handle.net/10016/14994
dc.language.isoeng
dc.publisherThieme Publishing
dc.relation.publisherversionhttp://dx.doi.org/10.1055/s-2002-33255
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subject.ecienciaBiología y Biomedicina
dc.subject.otherAdrenal Gland
dc.subject.otherCancer
dc.subject.otherGene Therapy
dc.subject.otherAdenovirus -Transcomplementing
dc.subject.otherBicistronic
dc.titleA Novel Approach Using Transcomplementing Adenoviral Vectors for Gene Therapy of Adrenocortical Cancer
dc.typeresearch article*
dc.type.hasVersionAM*
dspace.entity.typePublication
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