| Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study. | |
| | |
MedLine Citation:
|
PMID: 10794295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECT: The gene therapy paradigm of intratumoral activation of ganciclovir (GCV) following transduction of tumor cells by retroviral vectors bearing the thymidine kinase (tk) gene has produced dramatic remissions of malignant gliomas in animal models. In human trials, although the technique has been deemed safe, little antitumor effect has been demonstrated. To evaluate the basis of this inefficacy in human gliomas, the authors conducted a gene-marking trial involving neuropathological and biochemical studies of treated tumor specimens. METHODS: Five patients with malignant recurrent gliomas underwent stereotactic biopsy sampling and intratumoral implantation procedures with three aliquots of 10(6) vector-producing cells (VPCs) in columns. After 5 days, the tumor was resected and the tumor bed reimplanted with VPCs, and a course of GCV was given. Patients received clinical and radiological follow up for 6 months. Tumor specimens were analyzed neuropathologically and for tk gene expression by anti-TK immunohistochemistry and TK enzymatic activity. Four patients tolerated the treatment well but experienced tumor progression. The other developed an abscess after the second operation and died. Increased TK enzymatic activity was demonstrated in the one tumor specimen analyzed. Immunohistochemical evidence of tk gene expression was limited to VPCs. Transduction of tumor cells was not seen. Viable tumor cells were seen near VPCs containing TK. The lymphocytic immune response was mild. CONCLUSIONS: Except for the risk of infection inherent in reoperation, this tk-GCV paradigm was both feasible and safe. Pathological studies indicated that limited dissemination of VPCs and vector from the infusion site and failure to transduce tumor cells with the tk gene are major barriers to efficacy. |
| | |
Authors:
|
G R Harsh; T S Deisboeck; D N Louis; J Hilton; M Colvin; J S Silver; N H Qureshi; J Kracher; D Finkelstein; E A Chiocca; F H Hochberg |
Related Documents
:
|
7529885 - Genotoxicity of trans-anethole in vitro. 11156085 - Efficacy of repeated adenoviral suicide gene therapy in a localized murine tumor model. 2158945 - Drug-induced perturbations in the in vivo distribution of oncological radiotracers--ii.... 9396605 - Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-pro... 6281115 - Expression of herpes simplex virus common surface antigens and malignancy by clonal cel... 12949415 - An anaplastic astrocytoma (optic chiasmatic-hypothalamic glioma) in a dog. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Journal of neurosurgery Volume: 92 ISSN: 0022-3085 ISO Abbreviation: J. Neurosurg. Publication Date: 2000 May |
Date Detail:
|
Created Date: 2000-05-17 Completed Date: 2000-05-17 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0253357 Medline TA: J Neurosurg Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 804-11 Citation Subset: AIM; IM |
Affiliation:
|
Department of Neurology, Massachusetts General Hospital Brain Tumor Center, USA. gharsh@stanford.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Aged Animals Antineoplastic Agents / therapeutic use* Antiviral Agents / therapeutic use* Brain Abscess / etiology Brain Neoplasms / pathology, surgery, therapy* Disease Models, Animal Disease Progression Feasibility Studies Female Follow-Up Studies Ganciclovir / therapeutic use* Genetic Vectors Glioma / pathology, surgery, therapy* Humans Immunohistochemistry Injections, Intralesional Lymphocytes / immunology Male Middle Aged Neoplasm Recurrence, Local / pathology, surgery, therapy* Remission Induction Retroviridae / genetics Stereotaxic Techniques Thymidine Kinase / genetics* Transduction, Genetic |
| Grant Support | |
ID/Acronym/Agency:
|
5PO1CA69246/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Antiviral Agents; 82410-32-0/Ganciclovir; EC 2.7.1.21/Thymidine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Efficacy of the Ghajar Guide revisited: a prospective study.
Next Document: Telovelar approach to the fourth ventricle: microsurgical anatomy.