Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin

BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.

Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45

AIM:To clarify the role of activated Notch2 in the invasiveness of gastric cancer.METHODS:To investigate the invasiveness of silencing Notch2 gene expression,we established a Notch2small interfering RNA(siRNA) transfected cell line using the MKN-45 gastric cancer cell line.After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting,migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer.RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9(MMP9),Akt,p-Akt.To confirm the relationship between PI3KAkt and MMP9,the PI3K inhibitor LY294002 was used to treat MKN-45 cells.RESULTS:Notch2 expression was dramatically decreased after Notch2 siRNA transfection(100.00% ± 9.74% vs 11.61% ± 3.85%,P < 0.01 by qRT-PCR).There was also a marked reduction of Notch target gene Hes1(100.00% ± 4.74% vs 61.61% ± 3.58%,P < 0.05) at the mRNA,indicating an inhibition of Notch signaling.Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels(100.00% ± 9.74% vs 65.61% ± 7.58%,P < 0.05).Down-regulation of Notch2 by siRNA enhanced tumor cell invasion(100.00% ± 21.64% vs 162.22% ± 16.84%,P < 0.05) and expression of MMP9(1.56 fold,P < 0.05),and activated the pro-MMP9 protein to its active form(1.48 fold,P < 0.05).There was no significant difference in the protein levels of Akt between the two groups(100.00% ± 10.87% vs 96.61% ± 7.33%,P > 0.05),while down-regulation of Notch2 elevated p-Akt expression(100.00% ± 9.87% vs 154.61% ± 13.10%,P < 0.05).Furthermore,p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002(p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%,P < 0.05;MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%,P < 0.05).CONCLUSION:Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

Correction to"Liu LP,Sheng XP,Shuai TK,Zhao YX,Li B,Li YM.Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.World J Gastroenterol 2018;24:4565-4577[PMID:30386106 DOI:10.3748/wjg.v24.i40.4565]."In this article,we have identified some of the images in Figure 2A,C,E,G,and I are identical to the images in Figures 1B,2A,3B,3E,and 3G of another paper entitled"Liu L,Zhao Y,Fan G,Shuai T,Li B,Li Y.Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.",which was published by us in the Molecular Medicine Reports in December,2018[PMID:30320396 DOI:10.3892/mmr.2018.9558].The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology(WJG)and Molecular Medicine Reports,we uploaded the wrong pictures to the WJG,which were same as those submitted to the Molecular Medicine Reports.We apologize for this negligence and any inconvenience that this may cause.We would be grateful if you could replace the wrong pictures with the correct ones attached.

Synthesis and Photocatalytic Property of ZnO/TiO2 Inverse Opals Films with Controllable Composition and Topology

制作控制作文、控制拓扑学的 ZnO/TiO2 反的蛋白石(IO ) 的一个新奇方法拍摄使用一个积极牺牲的 ZnO IO 模板被开发了。这个方法包括一个二拍子的圆舞过程，由简单电气化学的免职用的 ZnO IO 的准备一自己组装由液体阶段免职(LPD ) 的 ZnO/TiO2 IO 的胶体的水晶模板和准备在房间温度处理的聚苯乙烯。ZnO/TiO2 IO 的作文和拓扑学能被改变 LPD 的持续时间容易控制。在 20 min LPD 过程以后，有非拥挤不堪的以脸为中心的立方的空气范围数组的 ZnO/TiO2 合成 IO 被获得。延长持续时间到 60 min，有显然变厚的墙的纯 TiO2 IO (TIO-LPD60 ) 被形成。为组合、拓扑的变化的形成机制被讨论。为甲又蓝色的降级的样品的紫外 photocatalytic 性质上的初步的研究表明作文和拓扑学显著地影响了 IO 电影的 photocatalytic 活动。ZnO/TiO2 合成 IO 比纯 ZnO 和纯 TiO2 IO 表明活动的更高的度，尽管他们让类似的 IO 围厚度。而且，与从 ~ 增加 IO 墙厚度 52 nm 到 ~ 90 nm， TIO-LPD60 展出 photocatalytic 性能的高水平。

Synchronous gastric cancer complicated with chronic myeloid leukemia (multiple primary cancers):A case report

BACKGROUND With the advancement of medical technology and improvement in living standards,the incidence of multiple primary cancers has gradually increased.In particular,tumors of the digestive system account for a large proportion of multiple primary cancers.The diagnosis and treatment of chronic myeloid leukemia,particularly with synchronous gastric cancer,at the first consultation is relatively rare.CASE SUMMARY Herein,we present the case of a middle-aged man who was referred to the Department of Hematology owing to an elevated white blood cell count.After the examination,he was diagnosed with chronic myeloid leukemia and was administered imatinib.Three months after the initial diagnosis,he visited our hospital again for abdominal pain,and further examination revealed gastric malignancy.After discussion with a multidisciplinary team,S-1(Tegafur,Gimeracil,and Oteracil Potassium Capsules) combined with oxaliplatin—SOX regimen—was initiated.Later,the patient’s condition rapidly progressed.He developed colonic obstruction and underwent an ostomy;however,he died less than 6 months after the initial diagnosis.CONCLUSION Multiple primary cancers are influenced by environmental and genetic factors;a standardized multidisciplinary discussion plays a key role in treatment.