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Abstract: Objective: To investigate whether the serum miR-221 expression correlates with clinicopathologic features and the prognosis of hepatocellular carcinoma (HCC) patients. Methods: Four miRNAs (miR-221, miR-222, miR-21 and miR-224) related to HCC were selected in the present study. Serum miRNA expression was investigated in 46 HCC patients and 20 healthy normal controls by using real-time PCR technique, and then correlations between miR-221 expression and the clinicopathological features and prognosis of HCC patients were evaluated. Results: The four miRNAs were found to be differentially overexpressed in HCC serum samples, and high level of miR-221 expression was correlated with tumor size (P <0.001), cirrhosis (P =0.003) and tumor stage (P =0.016). In addition, Kaplan–Meier survival analysis showed that the overall survival rate of the high miR-221 expression group (27.6%) was significantly lower than that of the low miR-221 expression group (62.3%, P <0.05). Conclusions: Serum miR-221, upregulated in HCC, can provide predictive significance for prognosis of HCC patients. [Copyright &y& Elsevier]

Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC. • PB suppresses the proliferation and induces the apoptosis of GC cells. • PB inhibits the transcriptional and post-transcriptional activity of STAT3. • PB and trametinib synergistically induce the apoptosis of GC cells. • The combination of PB and trametinib suppresses both ERK and STAT3 phosphorylation. [ABSTRACT FROM AUTHOR]