Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A replication-defective retroviral vector carrying the v-src oncogene and the gene for neomycin resistance was used to infect neurone- and fibroblast-depleted embryonic mouse brain cells in vitro. Cells resistant to the antibiotic G418 were obtained and continually passaged. Several cell lines were isolated which express high levels of v-src mRNA and v-src tyrosine kinase activity. The antigenic marker profile of either the pooled cells from an individual infection or sublines isolated from individual foci showed the cells to be immature glia: most cells expressed vimentin, A2B5 antigen and/or J1/tenascin glycoproteins, but not fibronectin. Sublines expressed different antigen profiles suggesting that the immortalised cells were derived from glial cells of different phenotypes. The cell lines expressed the 120 and 140 but not the 180 kd components of N-CAM as well as voltage-activated potassium channels, typical for glial cells. 01 antigen-positive oligodendrocytes were never observed in the lines or sublines after long term passage (over 1 year), but some cells expressed glial fibrillary acidic protein, a marker for mature astrocytes. Thus, expression of v-src in murine glial cells appears to arrest their development and prevent their differentiation.
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PMID:Expression of v-src arrests murine glial cell differentiation. 249 22

The murine anti-tenascin monoclonal antibody 81C6, following iodination, has been shown to be an efficient localizing and therapeutic agent in both subcutaneous and intracranial human glioma xenograft models in athymic mice and rats. Similarly, effective monoclonal antibody 81C6 localization has been demonstrated in glioma patients, and Phase I trials with the intact murine IgG2b kappa molecule are currently in progress. In order to maximize the potential for repeated administration by minimizing murine Fc-mediated immunogenicity and reducing Fc-mediated immune effects, we created murine 81C6 variable region/human IgG2 chimeric monoclonal antibodies by the molecular cloning of the variable region genes of mouse 81C6 and their genetic linkage to human constant region exons. The resulting chimeric constructs were introduced into SP2/0 cells, and stable transfectomas were selected by G418 and mycophenolic acid resistance. The resistant clones were screened for anti-tenascin activity on tenascin-coated plates by enzyme-linked immunosorbent assay. The N-terminal amino acid sequence of both heavy and light chains of the purified chimeric 81C6 antibody matched exactly with that of the native mouse 81C6 as well as with that deduced from the nucleotide sequence. The production level of chimeric 81C6 (13.9 mg/ml) from ascites in the highest expressing transfectoma was much higher than that of native mouse 81C6 (2.5 mg/ml). The chimeric antibody showed the same specificity and equivalent affinity for human intact tenascin or tenascin-expressing cells as the native mouse 81C6 antibody. Direct comparison of radioiodinated chimeric and radioiodinated mouse 81C6 biodistribution in subcutaneous and intracranial xenograft-bearing mice showed higher tumor-to-normal tissue ratios for chimeric 81C6 as compared with native mouse 81C6. The improved localizing and clearance characteristics of chimeric 81C6 in xenograft model systems suggests that chimeric 81C6 would be an improved reagent for intracompartmental therapy of tenascin-expressing tumors in the human central nervous system.
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PMID:Generation and characterization of a mouse/human chimeric antibody directed against extracellular matrix protein tenascin. 751 71