In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.
BackgroundIncreasing evidence suggests the involvement of enhancer of zeste homologue 2 (EZH2) in chemoresistance of cancer treatment. Nevertheless, its function and molecular mechanisms in gastric cancer (GC) chemoresistance are still not well elucidated.Materials and methodsIn the present study, we investigated the functional role of EZH2 in 5-fluorouracil (5-FU) resistance of GC cells and discovered the underlying molecular mechanism.ResultsResults revealed that EZH2 was upregulated in 5-FU-resistant GC tissues and cell lines. High ZEH2 expression was correlated with poor prognosis of GC patients. EZH2 knockdown enhanced 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Moreover, EZH2 could epigenetically suppress FBXO32 expression. FBXO32 overexpression could mimic the functional role of downregulated EZH2 in 5-FU resistance. FBXO32 knockdown counteracted the inductive effect of EZH2 inhibition on 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Furthermore, EZH2 knockdown facilitated 5-FU sensitivity of 5-FU-resistant GC cells in vivo.ConclusionIn summary, EZH2 depletion overcame 5-FU resistance in GC by epigenetically silencing FBXO32, providing a novel therapeutic target for GC chemoresistance.
Gastric cancer is one of the leading mortal causes. Targeted therapy is a new type of cancer treatment, which precisely identifies and attacks cancer cells and significantly reduces side effects. In this network meta-analysis, we focused on the efficacy and safety of 12 targeted agents on gastric cancer among a total of 8,405 patients from 24 trials. Hazard ratio (HR) with 95% credible interval (CrI) were calculated for primary outcomes, including overall survival (OS) and progression-free survival (PFS), while odds ratio (OR) with 95% CrI were calculated for secondary outcomes. Surface under the cumulative ranking curve (SUCRA) were calculated to illustrate the rank probability of various agents for different outcomes. Compared with other analyzed treatments, ramucirumab is outstanding in survival outcomes. However, higher risk of hematological events should be noted during its application. Lapatinib is also efficacious in progression reduction, while it is always combined with severe gastrointestinal events. Trastuzumab is proposed for its high efficacy in improving survival rate and safety, which is proper for most patients. In conclusion, trastuzumab was recommended as the optimal targeted agent combined with chemotherapy for gastric cancer patients.
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