Vincristine (VCR), vinblastine (VBL) and vinorelbine (VRL) are anticancer agents from the Vinca alkaloid family that have the potential to induce genotoxic effect. The aim of the present study was to compare the genotoxic effect of VCR, VBL and VRL. Levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and sister chromatid exchanges (SCEs) were measured in cultured human blood lymphocytes treated with VCR, VBL and VRL at concentrations of 0.01 and 0.1 μg/mL. Results showed that VCR, VBL and VRL significantly increased the 8-OHdG levels (p <0.05), whereas it did not cause a significant increase in the frequencies of SCEs in human blood lymphocytes as compared to controls. On the other hand, all three agents significantly increased cells mitotic index (p <0.05). At both tested concentrations, the magnitude of the increase in 8-OHdG was VBL>VCR>VRL. In conclusion, VCR, VBL and VRL induce DNA damage as indicated by the increase in the 8-OHdG biomarker but with different magnitude.
A 1 -A 3 0 7 tions (2010-present) was employed using key search terms: "meta-analysis" OR "mixed treatment comparison" OR "multiple treatments comparison" AND "multiple sclerosis" AND ("relapsing remitting" OR "relapsing"). Key aspects of each identified NMA were assessed (inclusion/exclusion criteria, model endpoints, model approach, covariates, inconsistency tests, and sensitivity analyses) and extracted for analysis. Results: 25 NMAs were identified (PubMed/Cochrane: 9; scientific congresses: 6; HTA appraisals: 10). Randomized controlled trial and relapsing-remitting MS were the most frequently cited inclusion criteria in the systematic literature reviews. Annualized relapse rate was the most frequently reported endpoint, closely followed by proportion of patients with disease progression. Most NMAs investigated self-injectable therapies as comparator strategies. A frequentist random-effects approach was most commonly used, although Bayesian methodology has become more common in recent NMAs. Patient and study characteristics were used as covariates in meta-regression; baseline disease characteristics and publication year significantly impacted results. Consistency approaches were not commonly reported; however, when reported, the Bucher method was the most common approach used to analyze inconsistency. The majority of NMAs did not report sensitivity analyses; however, sensitivity analyses should be performed across model methodologies to ensure the robustness of results. ConClusions: NMAs provide a valuable means for assessing indirect evidence; however, a critical assessment of methodologic approaches is needed when evaluating results.
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