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)

In the experiments reported here, I was unable to detect any fusion between host cells and transplanted tumor cells; however, spontaneous hybridization between tumor cells appears to occur in the B16 melanoma. This hybridization was demonstrated by mixing together B16-F10RR cells (universal fusers) and B16-F10 cells, allowing them to grow in close juxtaposition, and recovering putative hybrids in the appropriate selection media. The tumor cell-tumor cell composition of the resultant hybrids is inferred from the relative frequency of fusions, compared with the infrequency of tumor cell-host cell fusion when single populations of B16-F10RR cells were used, and by the chromosomal content of the hybrids. Definitive proof that hybridization occurs between both types of tumor cell rather than between a tumor cell and some other type of cell would require the use of a third biochemical marker on the unmarked tumor cells. I am now repeating these experiments using B16-F10 cells that exhibit resistance to the neomycinlike antibiotic G418. Nonetheless, it is not surprising to find that such closely related tumor cells fuse with one another. The efficiency of in vitro hybridization mediated by polyethylene glycol is increased when the hybridizing cells are histologically or developmentally related, so that B16 melanoma cells fuse more readily with one another than they do with unrelated cells such as UV-2237 cells (I. Hart, unpublished observations). Moreover, early hybridization protocols did not call for the use of fusogens, but merely the cocultivation of participating cells in the two-dimensional constraints of a tissue culture dish (e.g., Barski et al. 1961, Silagi 1967). Presumably, the increased contact between cells within a growing tumor mass would increase the likelihood of such spontaneous fusion. In vivo hybridization could play a significant role in neoplastic progression and variation in metastatic efficiency by at least two separate, but not necessarily mutually exclusive, mechanisms. First, fusion of two contiguous tumor cells would increase the chromosome content of the resultant single cell; this increase in ploidy could facilitate and heighten the apparent inherent genetic instability of neoplastic cells (Nowell 1976). Although segregation and chromosome loss may or may not be random or preferential in nature (Campbell and Worton 1981), the mere occurrence of such a phenomenon could also cause chromosomal disjunction and the possible extinction and reexpression of specific genes, which would lead to the independent variation and progression of different tumor cell characteristics in the manner cited by Foulds (1969).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tumor cell hybridization and neoplastic progression. 638 3

Since there is much indirect evidence for dominant suppressor genes for melanoma, we sought to isolate such a gene. Metastatic B16-F10 murine melanoma cells were lipofected with a normal human genomic library in a cosmid vector that also confers resistance to the drug G418. A few of the G418-resistant colonies acquired combinations of properties resembling those of normal melanocytes, including differentiated features (pigmentation, dendricity), slower growth, flat shape, monolayered colony form, stimulation of proliferation by a phorbol ester, and anchorage dependence. Four out of eight also showed reduced tumorigenicity in mice. Southern blotting indicated the presence of numerous cosmids in the melanocyte-like transfectants. DNA from one such line was used for secondary transfection. One secondary G418-resistant line showed pronounced melanocytic properties and marked tumour suppression in syngeneic and nude mice. A human repetitive sequence detected in this line was used in the polymerase chain reaction (PCR) to isolate intervening unique DNA sequences. One unique human sequence was attenuated in all tumors arising from both primary and secondary transfectants, suggesting close linkage with the sequence responsible for tumour suppression.
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PMID:Detection of a human DNA sequence correlated with melanocyte-like differentiation and tumour suppression after transfection into murine melanoma cells. 773 53

TNF has certain radioprotective effect on host tissues and can enhance the antitumor effect of radiotherapy. In addition, the promoter region of Egr-1 gene can be activated by radiation. So a radiation-inducible, double copy retroviral vector expressing TNF named pETDC was constructed by fusing of Egr-1 promoter to hTNF-alpha gene. After packaged with Psi-2 and Crip cells, the virus titer in the supermatant was 4 x 10(5) CFU/ml. By infection with the virus supermatant and by G418 resistant selection, positive clones from murine fibroblast cells NIH3T3 and murine melanoma cells B16.F10 were obtained and found to secrete 2.1 ng/ml and 1.1 ng/ml TNF respectively. After 20 Gy radiation of the cells, the TNF levels secreted by the two positive clones were elevated to 13.8 ng/ml (6.6-fold) and 5.7 ng/ml (5.2-fold). Furthermore, hTNF-alpha expression was confirmed with RT-PCR. These in vitro data provide an experimental basis for the in vivo use of combination TNF gene therapy with local radiotherapy in cancer patients.
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PMID:[An in vitro study on radiation-induced TNF gene therapy of cancer]. 938 44