Abstract. Chemotherapy is one of the few effective choices for patients with advanced or recurrent gastric cancer (GC). However, the development of mutidrug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of advanced GC. Additionally, the mechanism of MDR remains to be determined. In the present study, we tested IC 50 of cisplating (DDP), vincristine (VCR) and 5-fluorouracil (5-FU) in SGC7901, SGC7901/DDP and SGC7901/VCR gastric cancer cells using an MTT assay. The expression of let-7b and c-Myc in these cells was detected by qPCR and western blot analysis. The relationship between let-7b and c-Myc was explored using a luciferase reporter assay. Transfection of let-7b mimic or inhibitor was used to confirm the effect of let-7b on drug sensitivity in chemotherapy via the regulation of c-Myc expression. We found that the expression of let-7b was lower in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells than that in chemotherapysensitive SGC7901 cells. By contrast, the expression of c-Myc was higher in SGC7901/DDP and SGC7901/VCR cells than that in SGC7901 cells. Furthermore, we confirmed that let-7b suppresses c-Myc gene expression at the mRNA and protein levels in a sequence-specific manner, while transfection of let-7b mimic increases drug sensitivity in chemotherapyresistant SGC7901/DDP and SGC7901/VCR cells by targeting downregulation of c-Myc. In SGC7901 drug-sensitive cells, however, the sensitivity of chemotherapy was significantly decreased following let-7b inhibitor transfection. The present study results demonstrated that let-7b increases drug sensitivity in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells by targeting the downregulation of c-Myc and that, let-7b mimic reverses MDR by promoting cancer stem cell differentiation controlled by double-negative autoregulatory loops (Lin28/let-7 and Myc/let-7) and a double-positive autoregulatory loop (Lin28/Lin28B/Myc) existing in GC cells, which remains to be confirmed.

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Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients' survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C-index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery.

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Background:Although the safety and the advantages of laparoscopic and robotic colorectal surgeries have been confirmed, the use of both modalities in patients with previous abdominal surgeries (PAS) history remains uncertain. Herein, we perform a meta-analysis to investigate the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries.Methods:We will search PUBMED, the Cochrane Library, the Chinese Biomedical database (CBM), WanFang data, China National Knowledge Infrastructure (CNKI) up to January 2018. Studies will be screened by title, abstract, and full text independently and in duplicate. Studies that report the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries will be eligible for inclusion. Outcome variables will be assessed included combined resection, conversion, operation time, blood loss, number of retrieved lymph nodes, days to soft diet intake, length of hospital stay, and postoperative complications. Assessment of risk of bias and data synthesis will be performed using STATA SE 12.0. Heterogeneity among studies will be assessed using the I2 statistic.Results:Randomized controlled trials, prospective cohort studies, and propensity-matched comparative studies will be used for the quantitative synthesis of the meta-analysis to evaluate the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries.Conclusions:We aim to draw an objective conclusion of the comparisons in aspects of perioperative outcomes and provide physicians level I evidences for clinical decision makings.