title: Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene.
abstract: Recombinant adenovirus-mediated transfer of the wild-type p53 gene into monolayer cultures or multicellular tumor spheroids of human non-small cell lung cancer cell line H358, which has a homozygous deletion of p53, markedly increased the cellular sensitivity of these cells to the chemotherapeutic drug cisplatin. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into H358 tumors s.c. implanted into nu/nu mice, followed by i.p. administration of cisplatin, induced massive apoptotic destruction of the tumors. These results support the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: E A
authors.initials: EA
authors.lastname: Grimm
authors.forename: T
authors.initials: T
authors.lastname: Mukhopadhyay
authors.forename: W W
authors.initials: WW
authors.lastname: Zhang
authors.forename: L B
authors.initials: LB
authors.lastname: Owen-Schaub
authors.forename: J A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D002945:Cisplatin