Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ADENOVIRUS-MEDIATED HERPES-SIMPLEX VIRUS THYMIDINE KINASE GANCICLOVIRGENE-THERAPY IN PATIENTS WITH LOCALIZED MALIGNANCY - RESULTS OF A PHASE-I CLINICAL-TRIAL IN MALIGNANT MESOTHELIOMA/
Autore:
STERMAN DH; TREAT J; LITZKY LA; AMIN KM; COONROD L; MOLNARKIMBER K; RECIO A; KNOX L; WILSON JM; ALBELDA SM; KAISER LR;
Indirizzi:
HOSP UNIV PENN,DEPT SURG,6 SILVERSTEIN BLDG,3400 SPRUCE ST PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DIV PULM & CRIT CARE MED PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DIV HEMATOL ONCOL PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DEPT PATHOL PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DEPT SURG PHILADELPHIA PA 19104 UNIV PENN,MED CTR,NIH,GEN CLIN RES CTR PHILADELPHIA PA 19104 UNIV PENN,MED CTR,DEPT MOL & CELLULAR ENGN PHILADELPHIA PA 19104 UNIV PENN,MED CTR,INST HUMAN GENE THERAPY PHILADELPHIA PA 19104
Titolo Testata:
Human gene therapy
fascicolo: 7, volume: 9, anno: 1998,
pagine: 1083 - 1092
SICI:
1043-0342(1998)9:7<1083:AHVTKG>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CFTR CDNA; CYSTIC-FIBROSIS; PLEURAL MESOTHELIOMA; BRAIN-TUMORS; KINASE GENE; LUNG-CANCER; RECOMBINANT ADENOVIRUS; EXPERIMENTAL GLIOMAS; NASAL EPITHELIUM; VECTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
D.H. Sterman et al., "ADENOVIRUS-MEDIATED HERPES-SIMPLEX VIRUS THYMIDINE KINASE GANCICLOVIRGENE-THERAPY IN PATIENTS WITH LOCALIZED MALIGNANCY - RESULTS OF A PHASE-I CLINICAL-TRIAL IN MALIGNANT MESOTHELIOMA/", Human gene therapy, 9(7), 1998, pp. 1083-1092

Abstract

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 X 10(9) plaque-forming units (pfu) to 1 X 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene iswell tolerated and results in detectable gene transfer when deliveredat high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 11:39:51