Oncotarget
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Review
The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets.
Cholangiocarcinoma (CCA) is a relatively rare malignancy that arises from the epithelial cells of the intrahepatic, perihilar and distal biliary tree. Intrahepatic CCA (ICC) represents the second most common primary liver cancer, after hepatocellular cancer. Two-thirds of the patients with ICC present with locally advanced or metastatic disease. ⋯ In this review, we will discuss the evolving genetic landscape of CCA, with an in depth focus on novel fusions (e.g. FGFR2 and ROS1) and somatic mutations (e.g. IDH1/2), which are promising actionable molecular targets.
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Review Meta Analysis
Safety and efficacy profile of lenvatinib in cancer therapy: a systematic review and meta-analysis.
To systematically review the safety and efficacy of lenvatinib in the treatment of patients, we retrieved all the relevant clinical trials on the adverse events (AEs) and survival outcomes of lenvatinib through PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trial. Fourteen eligible studies involving a total of 978 patients were included in our analysis. The most common all-grade AEs observed in patients treated with lenvatinib were hematuria (56.6%), fatigue (52.2%) and decreased appetite (50.5%). ⋯ Subgroup analyses showed that mean PFS for renal cell carcinoma was 10.933±1.828 months (95% CI 7.350-14.515, p < 0.001), and that for thyroid cancer was 18.344±0.083 months (95% CI 18.181-18.506, p < 0.001). In conclusion, lenvatinib is an effective agent in thyroid cancer. Early monitoring and effective management of side effects are crucial for the safe use of this drug.
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We previously demonstrated that the methylation of ring finger protein 180 (RNF180) DNA promoter was specific to gastric cancer tissues. We reported that four hypermethylated CpG islands, namely, CpG-116, CpG-80, CpG+97, and CpG+102, in RNF180 promoter were significantly associated with the postoperative overall survival of gastric cancer patients. Correlation analysis revealed that the methylated status of CpG islands was significantly associated with the lymph node metastasis of gastric cancer. ⋯ Conventional detections for the biological characteristics of cancer cells showed that 1) the methylation of CpG+102 island in RNF180 DNA promoter could remarkably influence the comprehensively malignant biological characteristics of gastric cancer cells, including their proliferation, invasion, cell cycle, anti-apoptosis, and tumorigenicity. 2) The CpG+97 island, in addition to the CpG+102 island, should be considered as the other key methylated locus in RNF180 DNA promoter to mediate the malignant biological characteristics of gastric cancer cells. The methylated status of the key CpG islands of RNF180 DNA promoter may be used to predict the variations of the malignant biological characteristics of gastric cancer cells. The proposed method is a promising molecular therapy for gastric cancer.
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Postoperative atrial fibrillation (POAF) is a serious, common complication after coronary artery bypass grafting (CABG) surgery. Recently, 5 novel loci were identified to be associated with atrial fibrillation susceptibility using a combination of genotyping, eQTL mapping, and functional validation. In current study, we aim to evaluated the positive findings for POAF susceptibility after CABG among Chinese population, using a population-based, two-stage, nested case-control study with 1,400 patients. ⋯ When pooled together, the ORs for each additional copy of minor allele was 1.29 (95% CI: 1.13-1.48, P = 1.7×10-4) for NEURL rs12415501, and 1.21 (95% CI: 1.08-1.36, P = 9.8×10-4) for CAND2 rs4642101. Functional validation experiments found the AF risk allele of NEURL rs6584555 and CAND2 rs4642101 correlated with an increased expression of its corresponding genes (P<0.001). In this independently collected cardiac surgery cohort, we replicated the previous findings, and 2 novel loci are independently associated with POAF risk in patients who undergo CABG surgery in Chinese population.