Drug Des Dev Ther
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Triweekly capecitabine plus irinotecan (XELIRI) is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV) as second-line chemotherapy for mCRC. ⋯ In mCRC patients with wild-type or heterozygous UGT1A1*6 or *28 genotype, biweekly XELIRI + BV is effective and feasible as second-line chemotherapy. Biweekly XELIRI + BV is considered a valid substitute for FOLFIRI + BV in mCRC.
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Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. ⋯ ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer.
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The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. ⋯ Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.
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The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. ⋯ The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.
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Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone; PLB), a naturally occurring naphthoquinone isolated from the roots of Plumbaginaceae plants, has been reported to possess anticancer activities in both in vitro and in vivo studies, but the effect of PLB on tongue squamous cell carcinoma (TSCC) is not fully understood. This study aimed to investigate the effects of PLB on cell cycle distribution, apoptosis, and autophagy, and the underlying mechanisms in the human TSCC cell line SCC25. The results have revealed that PLB exerted potent inducing effects on cell cycle arrest, apoptosis, and autophagy in SCC25 cells. ⋯ In addition, we found that wortmannin (a PI3K inhibitor) and SB202190 (a selective inhibitor of p38 MAPK) strikingly enhanced PLB-induced autophagy in SCC25 cells, suggesting the involvement of PI3K- and p38 MAPK-mediated signaling pathways. Moreover, PLB induced intracellular reactive oxygen species (ROS) generation and this effect was attenuated by l-glutathione (GSH) and n-acetyl-l-cysteine (NAC). Taken together, these results indicate that PLB promotes cellular apoptosis and autophagy in TSCC cells involving p38 MAPK- and PI3K/Akt/mTOR-mediated pathways with contribution from the GSK3β and ROS-mediated pathways.