Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to realize a novel vaccination treatment for malignant gliomas using tumor cells genetically modified to express certain cytokines, it is essential to achieve an efficient gene transduction into primary cultured cells. We investigated the feasibility of preparing a glioma vaccine through retrovirus-mediated gene transduction. Glioma cells were cultured primarily from surgically resected tumor tissues of six patients. We obtained more than 1000-fold proliferation of cultures within eight weeks in all six cases. In vitro infection with a recombinant retrovirus GKlacZ carrying an Escherichia coli beta-galactosidase marker gene resulted in over 65% gene transfer to the primary cultured glioma cells. Further enrichment (approximately 90%) of transduced cells was possible by employing repeated infections or using vectors with neo' marker gene. Two cytokine genes, granulocyte-macrophage colony-stimulating factor and interleukin-4, were introduced into glioma cells by sequential transduction with two single-expression GK vectors. The transduced glioma cells produced high levels of both cytokines. We also evaluated simultaneous introduction of two genes with double-expression GK vectors containing internal ribosomal entry site (IRES) or internal promoter (PGK). Although the cells transduced with double-expression vectors secreted both cytokines, the level of the gene product following IRES or PGK was 10 times lower than that of the upstream gene product. The transduced cells retained cytokine secretion in vitro for 14 days after 100 Gy irradiation. Our data indicate the feasibility of retrovirus-mediated preparation of gene-modified tumor vaccines from clinical glioma materials, which could be useful for potentiating antitumor immunity in glioma patients.
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PMID:Efficient retrovirus-mediated cytokine-gene transduction of primary-cultured human glioma cells for tumor vaccination therapy. 914 Jan 15

The paper reports the construction of retroviral vector pLNTK carrying HSV-tk gene driven by PGK promoter and the successful transfer into human glioma cell SHG44. The in vitro study confirmed that ayclovir (ACV) sensitive level of the gene-transferred glioma cell (SHGLNTK) was 1,000 times that of SHG44. 3H-TdR incorporation confirmed that the DNA replication in SHGLNTK was considerably suppressed when treated with ACV. The in vivo study confirmed that ACV could suppress tumor formation of the SHGLNTK cells. In situ gene transfer treatment of nude mice carrying SHG44 tumor showed good therapeutic results. Such treatment may be used as an innovative method for brain tumor therapy.
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PMID:[Experimental study on human glioma SHG44 treated by HSV-tk gene therapy]. 938 14