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The incidence of digestive system tumors has been increasing in recent years. Gastric cancer (GC) is one of leading causes of cancer-related mortality. Although a lot of research has been conducted, the effect of GC treatment is still not good. Pterostilbene (PT) has pro-apoptosis and anti-proliferation effects on solid tumors but the effect of PT on GC is unclear. Our study analyzed the effect of PT on GC and miR-126-3p, and provided a reliable reference for future clinical treatment of GC. Through Real time PCR, we first determined that miR-126-3p was down-regulated in GC, which is not related to general characteristics of patients, including gender and age, but is related to differentiation, metastasis, and tumor TNM pathological staging, suggesting that miR-126-3 could be used for predicting the occurrence and prognosis of cancer. In vitro experiments confirmed that further down-regulation of miR-126-3p can increase tumor cell proliferation, decrease apoptosis, promote invasion, and inhibit EMT. On the other hand, overexpression of miR-126-3p inhibited cancer cell-related activities, but promoted EMT. Administration of PT suppressed GC cell activity, inhibited EMT, and increased the expression of miR-126-3p, indicating that PT may affect GC cells by regulating miR-126-3p, which may be one of options for new treatments of GC in the future.

BACKGROUND Gastric cancer is the second most common malignant tumor in China, ranking third among all malignant tumor mortality rates. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase significantly the effectiveness of intraperitoneal chemotherapeutic drugs, prolong the action time of these drugs on intraperitoneal tumor cells, and enhance their diffusion in tumor tissues. HIPEC may be one of the best choices for the eradication of residual cancer cells in the abdominal cavity. AIM The aim of this study was to study the role of preventive HIPEC after radical gastrectomy. METHODS A prospective analysis was performed with patients with cT4N0-3M0 gastric cancer to compare the effects of postoperative prophylactic HIPEC plus intravenous chemotherapy with those of routine adjuvant chemotherapy. Patients’ medical records were analyzed, and differences in the peritoneal recurrence rate, disease-free survival time, and total survival time between groups were examined. RESULTS The first site of tumor recurrence was the peritoneum in 11 cases in the conventional adjuvant chemotherapy group and in 2 cases in the HIPEC group (P = 0.020). The 1-year and 3-year disease-free survival rates were 91.9% and 60.4%, respectively, in the conventional adjuvant chemotherapy group and 92.1% and 63.0%, respectively, in the HIPEC group. The 1-year and 3-year overall survival rates were 95.2% and 66.3%, respectively, in the conventional adjuvant chemotherapy group and 96.1% and 68.6%, respectively, in the HIPEC group. No significant difference in postoperative or chemotherapy complications was observed between groups. CONCLUSION In patients with cT4N0-3M0 gastric cancer, prophylactic HIPEC after radical tumor surgery is beneficial to reduce peritoneal tumor recurrence and prolong survival.

Introduction Long non-coding RNA (lncRNA) DSCAM-AS1 was reported to be aberrantly expressed and play pivotal roles in various human cancers. The aim of the present study was to investigate the expression and roles of DSCAM-AS1 in colon cancer (CC). Methods Quantitative real-time PCR (qRT-PCR) was used to detect the expression of DSCAM-AS1, miR-204 and the mRNA level of SOX4. Cell proliferation and cell cycle were analyzed by MTT assay and flow cytometry, respectively. Transwell assay was used for migration capacity detection. Luciferase activity assay was conducted to verify the direct binding of DSCAM-AS1 and miR-204 or miR-204 and SOX4. The protein expression of SOX4 was determined by Western blot. Kaplan-Meier curves were calculated and the Log rank test was performed for the survival data analysis. Results DSCAM-AS1 was significantly upregulated in CC and high expression of DSCAM-AS1 was associated with poor prognosis in patients with colon cancer. Knockdown of DSCAM-AS1 significantly suppressed CC cells proliferation and migration. In addition, DSCAM-AS acted as a molecular sponge for miR-204 and SOX4 was identified as a direct target of miR-204 in CC. Moreover, the rescue assay revealed that miR-204 inhibition partly abolished the effects of DSCAM-AS1 knockdown on CC cells proliferation, migration and SOX4 expression. Discussion The present study demonstrated that DSCAM-AS1 acted as an oncogenic lncRNA in CC progression by regulating miR-204/SOX4 axis and DSCAM-AS1 may serve as a novel therapeutic target in the treatment of colon cancer.

Background The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis. Methods Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests. Results MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582. Conclusion MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.

Background To date, Siewert type II adenocarcinoma of the esophagogastric junction (ST-II AEG) can be removed radically utilizing either the abdominal-transhiatal (TH) or the right thoracoabdominal (RTA) approaches. Because of a paucity of high-quality direct evidence, the appropriate surgical approach for ST-II AEG remains debatable. In the present, only several retrospective studies are available, representing ambiguous results. Thus, prospective randomized clinical trials are demanded to compare the survival, oncological outcomes, safety and efficiency and life quality between the TH and RTA approach in patients with resectable AEG of Siewert type II. Methods A prospective, multicenter, open, randomized, and parallel controlled study named S2AEG will be conducted. Three hundred and twelve patients who match the inclusion criteria but not the exclusion criteria will be participating in the trial and randomly divided into the TH (156) and RTA (156) cohorts. The primary efficacy endpoint is the 3-year disease-free survival (DFS) following the operation. The rate of R0-resection, the number and site of lymph nodes infiltrated and dissected, postoperative complications, hospital days and life quality are the second endpoints. Discussion This study is the first prospectively randomized controlled trial aiming to compare the surgical outcomes between TH and RTA approaches in patients with resectable ST-II AEG. It is hypothesized that patients in the TH cohort would harvest equivalent oncological results and survival while maintaining acceptable life quality when compared to patients in the RTA cohort. Our findings will provide high-level clinical evidence for clinical decision-making on the appropriate surgical approach for patients with ST-II AEG. Embarked in November 2019, this research will be completed 3 years after the final participant’s enrolment date. Trial registration Clinical Trial.gov ID: NCT04910789 May 29, 2021. Name: S2AEG.

Background The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis. Methods Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests. Results MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582. Conclusion MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.

Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induced expression of inflammatory mediators (iNOS, COX-2, PGE2 and NO) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in RAW264.7 macrophages. Exendin-4 pretreatment mitigates LPS induced cellular ROS production. Mechanistically, Exendin-4 suppresses the LPS-induced activation of the JNK and AP-1 pathway. Furthermore, exendin-4 suppresses both nuclear p65 accumulation and transfected NF-κB promoter activity, indicating it inhibits the activation of the NF-κB pathway. Our study demonstrates that the GLP-1 agonist exendin-4 has a potent anti-inflammatory effect independent on its glucose reducing ability, and exendin-4 has the potential implication to treat inflammatory associated diseases.