Expression-targeted gene therapy for the treatment of transitional cell carcinoma

X. Zhang, A. Atala, W. T. Godbey, Paul H. Flower, Donna D. Flower

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Targeted gene delivery for induced apoptosis of transitional cell carcinomas was carried out in vivo in mice via utilization of the murine cyclooxygenase type 2 (Cox-2) promoter (Tis10). MB49 cells, which constitutively overexpress Cox-2 like numerous other carcinomas, selectively expressed delivered genes that utilized this transcriptional control element. The products of the delivered genes were artificially inducible forms of caspases 3 and 9, which remained inactive until a chemical inducer of dimerization was later injected intraperitoneally. The genes were delivered intravesically as plasmids complexed with poly(ethylenimine). Significant improvements, in the form of reduced bladder mass, reduced tumor volume, anti-angiogenesis and inhibition of tumor growth were seen versus untreated or unactivated controls. In some instances, tumors were seen to go into complete remission. There were no apparent bystander effects associated with the treatments. This targeted gene therapy regimen could have wide applicability to numerous cancers due to constitutive overexpression of Cox-2.

Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalCancer Gene Therapy
Volume15
Issue number8
DOIs
StatePublished - Aug 18 2008
Externally publishedYes

Fingerprint

Transitional Cell Carcinoma
Genetic Therapy
Cyclooxygenase 2
Genes
Bystander Effect
Neoplasms
Caspase 9
Dimerization
Therapeutics
Tumor Burden
Caspase 3
Urinary Bladder
Plasmids
Apoptosis
Carcinoma
Growth

Keywords

  • Bladder
  • Cancer
  • Caspase
  • Cox-2
  • Expression-targeting
  • Gene delivery

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Zhang, X., Atala, A., Godbey, W. T., Flower, P. H., & Flower, D. D. (2008). Expression-targeted gene therapy for the treatment of transitional cell carcinoma. Cancer Gene Therapy, 15(8), 543-552. https://doi.org/10.1038/cgt.2008.7

Expression-targeted gene therapy for the treatment of transitional cell carcinoma. / Zhang, X.; Atala, A.; Godbey, W. T.; Flower, Paul H.; Flower, Donna D.

In: Cancer Gene Therapy, Vol. 15, No. 8, 18.08.2008, p. 543-552.

Research output: Contribution to journalArticle

Zhang, X, Atala, A, Godbey, WT, Flower, PH & Flower, DD 2008, 'Expression-targeted gene therapy for the treatment of transitional cell carcinoma', Cancer Gene Therapy, vol. 15, no. 8, pp. 543-552. https://doi.org/10.1038/cgt.2008.7
Zhang, X. ; Atala, A. ; Godbey, W. T. ; Flower, Paul H. ; Flower, Donna D. / Expression-targeted gene therapy for the treatment of transitional cell carcinoma. In: Cancer Gene Therapy. 2008 ; Vol. 15, No. 8. pp. 543-552.
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