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Titolo:
TREATMENT OF EXPERIMENTAL HUMAN MESOTHELIOMA USING ADENOVIRUS TRANSFER OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE
Autore:
SMYTHE WR; HWANG HC; ELSHAMI AA; AMIN KM; ECK SL; DAVIDSON BL; WILSON JM; KAISER LR; ALBELDA SM;
Indirizzi:
HOSP UNIV PENN,THORAC ONCOL RES LAB,809 MALONEY BLDG,3600 SPRUCE ST PHILADELPHIA PA 19104 UNIV PENN,DEPT SURG,ONCOL RES LAB,THORAC SURG SECT PHILADELPHIA PA 19104 UNIV PENN,DEPT MED,ONCOL RES LAB,PULM CRIT CARE SECT PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DEPT MED,HEMATOL ONCOL SECT PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DEPT MOLEC & CELLULAR ENGN PHILADELPHIA PA 19104 UNIV PENN,MED CTR,INST HUMAN GENE THERAPY PHILADELPHIA PA 19104 UNIV MICHIGAN,MED CTR,DEPT MED,RHEUMATOL SECT ANN ARBOR MI 48109
Titolo Testata:
Annals of surgery
fascicolo: 1, volume: 222, anno: 1995,
pagine: 78 - 86
SICI:
0003-4932(1995)222:1<78:TOEHMU>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
MALIGNANT PLEURAL MESOTHELIOMA; EXTRAPLEURAL PNEUMONECTOMY; RETROVIRAL VECTORS; BRAIN-TUMORS; CELLS; CANCER; GANCICLOVIR; TRANSDUCTION; SENSITIVITY; REGRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
W.R. Smythe et al., "TREATMENT OF EXPERIMENTAL HUMAN MESOTHELIOMA USING ADENOVIRUS TRANSFER OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE", Annals of surgery, 222(1), 1995, pp. 78-86

Abstract

Objective The authors demonstrate the ability of an adenovirus vectorexpressing the herpes simplex thymidine kinase (HSVtk) gene to treat human malignant mesothelioma growing within the peritoneal cavity of severe combined immunodeficient (SCID) mice. Background Data Introduction of the HSVtk gene into tumor cells renders them sensitive to the antiviral drug ganciclovir (GCV). This approach has been used previouslyto treat experimental brain tumors. Although malignant mesothelioma is refractory to current therapies, its localized nature and the accessibility of the pleural space make it a potential target for a similar type of in vivo gene therapy using adenovirus. Methods An adenovirus containing the HSVtk gene (Ad.RSVtk) was used to transduce mesotheliomacells in vitro. These cells were then injected into the flanks of SCID mice. Ad.RSVtk was also injected directly into the peritoneal cavityof SCID mice with established human mesothelioma tumors. Mice were subsequently treated for 7 days with GCV at a dose of 5 mg/kg. Results Mesothelioma cells transduced in vitro with Ad.RSVtk formed nodules when injected in the subcutaneous tissue. These tumors could be eliminated by the administration of GCV, even when as few as 10% of cells were transduced to express HSVtk (bystander effect). Administration of Ad.RSVtk into the peritoneal space of animals with established multifocal human mesothelioma followed by GCV therapy resulted in the eradicationof macroscopic tumor in 90% of animals and microscopic tumor in 80% of animals when evaluated after 30 days. The median survival of animalstreated with Ad.RSVtk/GCV was significantly longer than that of control animals treated with similar protocols. Conclusion These results indicate that an adenoviral vector containing the HSVtk gene is effective in treating established malignant mesothelioma in an in vivo settingand raise the possibility of using adenovirus transfer of HSVtk for clinical trials in mesothelioma and other localized tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 06:31:32