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)

Although transforming ras oncogenes have been implicated as causative factors in liver cell transformation, the exact function and phenotypic alterations generated by the expression of such transforming genes in liver epithelial cells has yet to be defined. We have utilized a retroviral vector system to deliver an inducible transforming ras gene into normal, anchorage dependent rat liver epithelial cells. The Moloney murine sarcoma virus based vector is composed of a dominant selectable marker, Neo, which is transcriptionally driven from the 5' proviral long terminal repeat (LTR) and a transforming Ha-ras gene under the transcriptional control of a glucocorticoid inducible LTR of the mouse mammary tumor virus. Subsequent to infection, G418 resistant, tumorigenic cell lines were isolated and one particular cell line, designated REL-Ras3, was extensively characterized. Single copies of a full length as well as a truncated provirus were integrated into REL-Ras3 cells. The integrated ras gene was transcribed into poly(A+) RNA with dexamethasone treatment increasing both the steady state level of ras mRNA as well as transcription initiated from the MMTV LTR. Western blot analysis confirmed the presence of P21 containing a transforming mutation in position 12. Phenotypic alterations associated with ras expression in REL-Ras3 cells include: gross morphological alterations; loss of contact inhibition of growth; becoming lethally tumorigenic and anchorage independent; alterations in growth kinetics involving a diminished lag phase of the growth curve; and increases in glucose transport. Differences in growth kinetics and glucose transport could be directly correlated with the levels of ras expression.
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PMID:Expression and phenotypic alterations caused by an inducible transforming ras oncogene introduced into rat liver epithelial cells. 306 Jul 90

To explore the effect of a tyrosine-kinase inhibitor STI571 and P21(WAF) gene clone on the proliferation, cycle, apoptosis of leukemia cell line K562, P21(WAF) gene was obtained by RT-PCR, and its sequence was approved to be correct, then P21-pcDNA3.1 vector was constructed and transfected into K562 cell line. After selected with G418, P21-pcDNA3.1-K562 cell clone that stably expression P21(WAF) was isolated. P21(WAF) protein was identified by Western blot. The survival rate were tested by MTT. Cell cycle and apoptosis were tested by flow cytometry. The results showed that the expression of P21(WAF) protein could be detected by Western blot in P21-pcDNa3.1-K562 cells. A strong inhibition of cell proliferation was observed in P21-pcDNA3.1-K562 cells as compared with that of the control. The cells cycle were arrested in G(0)/G(1) phase. The percentage of apoptosis was declined slightly after P21-pcDNA3.1-K562 cells were combined with STI571, meanwhile its survival rate declined more slowly than that of K562 cell with STI571. In conclusion, P21(WAF) inhibits the proliferation of K562 cell, meanwhile slightly inhibits its apoptosis induced by STI571and decrease its sensitivity to STI571.
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PMID:[Experimental research on tyrosine-kinase inhibitor STI571 and P21WAF gene clone to treat chronic myeloid leukemia]. 1563 51

To investigate the role of human Na(+)/dicarboxylate cotransporter 3 (hNaDC3) in the replicative senescence of normal human embryonic lung diploid fibroblasts (WI-38), a retroviral vector containing hNaDC3 was constructed. hNaDC3 was introduced into normal WI-38 cells through infection with the retroviral virus. Monoclones were selected with G418. The integration and expression of exotic genes were confirmed by Northern blot and Western blot. When compared with the control cells, WI-38 cells transfected with hNaDC3 cDNA showed significant suppression of growth rate (by 40%), increase of positive rate of SA-beta-gal staining, decrease of mitochondrial membrane potential, shortening of telomere length, and increase of P16 and P21 expression. The morphology characteristics of senescent fibroblasts appeared earlier. Our results have, for the first time, demonstrated that high expression of hNaDC3 may be able to, at least partly, promote the cellular senescence of human diploid fibroblasts.
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PMID:Effects of human Na(+)/dicarboxylate cotransporter 3 on the replicative senescence of human embryonic lung diploid fibroblasts. 1598 72

Nonsense mutations constitute ~10% of TP53 mutations in cancer. They introduce a premature termination codon that gives rise to truncated p53 protein with impaired function. The aminoglycoside G418 can induce TP53 premature termination codon readthrough and thus increase cellular levels of full-length protein. Small molecule phthalimide derivatives that can enhance the readthrough activity of G418 have also been described. To determine whether readthrough enhancers exist among drugs that are already approved for use in humans, we tested seven antimalarial drugs for readthrough of the common R213X TP53 nonsense mutation in HDQ-P1 breast cancer cells. Mefloquine induced no TP53 readthrough activity as a single agent but it strongly potentiated readthrough by G418. The two enantiomers composing pharmaceutical mefloquine potentiated readthrough to similar levels in HDQ-P1 cells and also in SW900, NCI-H1688 and HCC1937 cancer cells with different TP53 nonsense mutations. Exposure to G418 and mefloquine increased p53 phosphorylation at Ser15 and P21 transcript levels following DNA damage, indicating p53 produced via readthrough was functional. Mefloquine does not appear to enhance readthrough via lysosomotropic effects as it did not significantly affect lysosomal pH, the cellular levels of G418 or its distribution in organellar or cytosolic fractions. The availability of a readthrough enhancer that is already approved for use in humans should facilitate study of the therapeutic potential of TP53 readthrough in preclinical cancer models.
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PMID:The antimalarial drug mefloquine enhances TP53 premature termination codon readthrough by aminoglycoside G418. 3112 Sep 2