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Eukarytotic cells have developed a highly conserved network of processes to ensure that the damaged genome is repaired before replication or mitotic segregation. This protective mechanism is essential for maintaining genomic integrity and stability, cell viability, and prevention of mutations. The drugs used in the treatment of human malignancies are invariably genotoxic, and their effectiveness is...
Chronic HCV infection induces insulin resistance (IR). We studied this in a persistently infected cell line with defects in glucose homeostasis resulting from the phosphorylation of glycogen synthase (GS Ser641) and GS kinase isoform 3β (GSK 3βSer9). Reversal of these effects in cells cured of HCV with interferon supports viral specificity. Insulin signaling was disrupted by IRS-1 Ser312 phosphorylation...
Modulation of DNA repair represents a strategy to overcome acquired drug resistance of cells to genotoxic chemotherapeutic agents, including nitrogen mustards (NM). These agents induce DNA inter-strand cross-links, which in turn produce double strand breaks (dsbs). These breaks are primarily repaired via the nonhomologous end-joining (NHEJ) pathway. A DNA-dependent protein kinase (DNA-PK) complex...
The effective dose, schedule, molecular basis of the cytotoxicity of taxol and their dependence on the genetic background in tumor cells are still not well understood. Here, we examined how the dose-response relationship for taxol varies in lung cancer cells with different p53 status and under isogenic conditions. DNA content analyses in A 549 (p53, +/+) and H 1299 (p53, -/-) cells, showed that taxol...
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