Background Cisplatin (CDDP) plays a vital role in the treatment of advanced gastric adenocarcinoma (GAC); however, the development of chemoresistance depletes the overall benefit of CDDP. This study harbored the aim to investigate the role of a novel circular RNA (circRNA), circ_0000260, in DDP-resistant GAC and provide a potential mechanism to explain its function. Methods The morphology of tumor tissues and normal tissues was observed by hematoxylin-eosin (HE) staining. The isolated exosomes were observed and examined using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The expression of circ_0000260, miR-129-5p and matrix metalloproteinase 11 (MMP11) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CD63, CD81, fibronectin, vitronectin and MMP11 were detected by Western blot. Cell viability, colony formation, cell apoptosis, migration, invasion and cell adhesion were monitored by cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, scratch assay, transwell assay and cell adhesion assay, respectively. The interaction between miR-129-5p and circ_0000260 or MMP11 predicted by bioinformatics analysis was verified by dual-luciferase reporter assay. Animal experiments were performed in nude mice to explore the role of circ_0000260 in vivo. Results The expression of circ_0000260 was promoted in tumor tissues and serum-derived exosomes of GAC patients, and circ_0000260 expression in CDDP-resistant tumor tissues was higher than that in CDDP-sensitive tumor tissues. Circ_0000260 knockdown lessened CDDP chemoresistance, suppressed cell proliferation, migration, invasion and adhesion, and induced apoptosis. In mechanism, circ_0000260 regulated the expression of MMP11 by targeting miR-129-5p. MiR-129-5p inhibition could reverse the functions of circ_0000260 knockdown, and MMP11 knockdown could also reverse the effects of miR-129-5p inhibition. Besides, circ_0000260 knockdown attenuated CDDP resistance during tumor growth in vivo by regulating the expression of miR-129-5p and MMP11. Conclusion Circ_0000260 regulated CDDP chemoresistance of GAC by promoting MMP11 expression via targeting miR-129-5p.
Background The retropancreatic fusion fascia is recognized as the anatomical landmark during retropancreatic mobilization. However, its role in D2 total gastrectomy for proximal advanced gastric cancer (PAGC) remains unexplored. This study aimed to develop the retropancreatic fusion fascia-oriented ex vivo approach for splenic hilar lymphadenectomy (RP-SL) to avoid difficulty in using the total laparoscopic approach (TL-SL). Material/Methods The data for patients with PAGC who underwent D2 total gastrectomy were retrieved from our clinical database and electronic medical records (December 2016 to December 2018), with a 1:1 match ratio for balance of the 2 groups. Results In sum, 84 matched patients were included in the study. There were 2360 retrieved lymph nodes (LNs), with an average of 28.10. Sixteen patients were confirmed with positive splenic hilar lymphadenectomy, and the mean harvested lymph nodes (LNs) were significantly increased in the RP-SL group compared to the TL-SL group (3.07 vs. 2.29, P<0.001), decreased operative time (193.21 min vs. 247.74 min, P<0.001), and less blood loss (96.90 mL vs. 185.24 mL, P=0.001) in the RP-SL group. Postoperative hospital stay (6.55 days vs. 7.26 days), rate of morbidity (9.50% vs. 11.91%), and overall costs (¥65255.64 vs. ¥64419.91) were comparable between the groups (P>0.05). Conclusions The landmark at the conjunction between the superior mesenteric vessels and the inferior pancreatic margin made it feasible to identify the retropancreatic areolar. The RP-SL approach was safe and efficient for splenic hilar lymphadenectomy.
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