Role of epithelial-mesenchymal transition in gastric cancer initiation and progression

Gastric cancer is one of the most common malignant tumors worldwide.Due to its intricate initiation and progression mechanisms,early detection and effective treatment of gastric cancer are difficult to achieve.The epithelial-mesenchymal transition(EMT)is characterized as a fundamental process that is critical for embryonic development,wound healing and fibrotic disease.Recent evidence has established that aberrant EMT activation in the human stomach is closely associated with gastric carcinogenesis and tumor progression.EMT activation endows gastric epithelial cells with increased characteristics of mesenchymal cells and reduces their epithelial features.Moreover,mesenchymal cells tend to dedifferentiate and acquire stem cell or tumorigenic phenotypes such as invasion,metastasis and apoptosis resistance as well as drug resistance during EMT progression.There are a number of molecules that indicate the stage of EMT(e.g.,E-cadherin,an epithelial cell biomarker);therefore,certain transcriptional proteins,especially E-cadherin transcriptional repressors,may participate in the regulation of EMT.In addition,EMT regulation may be associated with certain epigenetic mechanisms.The aforementioned molecules can be used as early diagnostic markers for gastric cancer,and EMT regulation can provide potential targets for gastric cancer therapy.Here,we review the role of these aspects of EMT in gastric cancer initiation and development.

Clinicopathological Characteristics and Prognosis of Hepatoid Adenocarcinoma of the Stomach:Evaluation of a Pooled Case Series

Hepatoid adenocarcinoma of the stomach (HAS)is an extremely rare and unique gastric malignancy.The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis.We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016,as well as 294 cases reported prior to 2017 in research databases.Among these patients,45.6%(115/252)had lesions in the gastric antrum and 77.0%(235/305)were male.Elevated levels of serum alpha-fetoprotein (AFP)were detected in most patients(75/93,80.6%).Vascular invasion(199/286,69.6%),lymph node metastasis (222/283,78.4%),and preoperative distant metastasis (121/328,36.9%)were commonly observed.The 5-year disease-free survival (DFS)and disease-specific survival (DSS) were 20.7%and 29.2%,respectively.DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS:P<0.001, hazard ratio (HR)=-1.831,95%confidence interval (CI):0.060-0.429;DSS:P<0.001,HR=-2.185, 95%CI:0.032-0.401].In conclusion,HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer.Complete surgery,early pTNM stage,and adjuvant therapy may predict a more favorable prognosis.Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

AIM: To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS: Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS: SMYD3 over-expression in HCC was associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de- methylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% ± 7.97%, Pgenesil-1-s2 72.14% ± 9.68% vs Pgenesil-1-hk 6.89% ± 4.12%, P < 0.01) and migration (Pgenesil-1-s1 4.24% ± 1.58%, Pgenesil- 1-s1 4.87% ± 0.73% vs Pgenesil-1 19.03% ± 4.63%, Pgenesil-1-hk 19.95% ± 5.21%, P < 0.01) and induced apoptosis (FCM subG1 phase Pgenesil-1-s1 19.07% ± 1.78%, Pgenesil-1-s2 17.68% ± 2.36% vs Pgenesil-1 0.47% ± 0.12%, Pgenesil-1-hk 1.46% ± 0.28%, P < 0.01. TUNEL-positive cells: Pgenesil-1-s1 40.24% ± 5.18%, Pgenesil-1-s2 38.48% ± 4.65% vs Pgenesil-1 2.18% ± 1.34%, Pgenesil-1-hk 2.84% ± 1.22%, P < 0.01) in HepG2 cells. CONCLUSION: These results demonstrate that SMYD3 plays a critical role in the carcinogenesis and progression of HCC. The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZ1 CpG promoter hypermethylation.

Enhanced Chemotherapy Sensitivity of Human Colon Cancer Cells to 5-Fluorouracil by siRNA Recombinant Expression Vector Targeting Survivin Gene

Objective To investigate the effects of small interfering RNA(siRNA) recombinant expression vector targeting survivin gene on chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil.Methods siRNA recombinant expression vector targeting survivin gene was constructed and transfected into human colon cancer cell lines LOVO.After 48 hours of transfection,cells were harvested for analysis of survivin mRNA and protein expressions using RT-PCR and Western blot.In addition,after human colon cancer cell lines were treated with Survivin siRNA and/or 5-fluorouracil,MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis.Results Restriction endonuclease analysis confirmed that siRNA recombinant expression vector targeting survivin gene was successfully constructed.Inhibitory ratios of survivin mRNA and protein expressions by Survivin siRNA were 36.33% and 44.65%,respectively.Survivin siRNA combined with 5-fluorouracil significantly increased the cell proliferation inhibitory ratio and apoptosis ratio compared with 5-fluorouracil treating alone(P<0.05).Conclusion The siRNA recombinant expression vector targeting survivin gene can inhibit the expression of survivin gene,and enhance chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil.

Clinical outcomes and ergonomics analysis of three laparoscopic techniques for Hirschsprung's disease

AIM: To report the clinical outcomes and ergonomics analysis of three laparoscopic approaches in the management of Hirschsprung's disease(HD).METHODS: There were 90 pediatric patients(63 boys, 27 girls; mean age: 3.6 ± 2.7 mo; range: 1.0-90.2 mo) who underwent laparoscopic endorectal pull-through Soave procedures for short- and long-segment HD in our hospital. Three laparoscopic approaches were used: conventional laparoscopic pull-through(CLP) in 30 patients between 2009 and 2013, single-incision laparoscopic pull-through(SILP) in 28 patients between 2010 and 2013, and hybrid single-incision laparoscopic pull-through(H-SILP) in 32 patients between 2011 and 2013. We applied the hybrid version of the single-incision approach in 2011 to preserve the cosmetic advantage of SILP and the ergonomic advantage of CLP. We retrospectively analyzed the clinical data, cosmetic results, and ergonomics of these three approaches to have a better understanding of the selection of one approach over another. RESULTS: The CLP, SILP, and H-SILP groups were similar in regard to age, sex, transition zone, blood loss, hospital stay, and intraoperative complications. Early and late postoperative results were not different, with equal daily defecation frequency and postoperative complications. No conversion to open technique was needed and none of the patients had recurrent constipation. With proper training, the ergonomics challenges were overcome and similar operative times were registered for the general operative time in the patients < 1 year of age and the short-segment HD patients. However, significantly shorter operative times were registered compared to SILP for patients > 1 year of age(CLP and H-SILP: 120 ± 15 min and 119 ± 12 min, respectively, vs 140 ± 7 min; P < 0.05) and for long-segment HD patients(152 ± 3.5 min and 154 ± 3.6 min, respectively, vs 176 ± 2.3 min; P < 0.05). The best cosmetic result was registered with the SILP(scarless), followed by the H-SILP(near scarless appearance) and the CLP(visible scars) procedures. CONCLUSION: Based on the results, we believed that the laparoscopic approach should be selected according to the age, transition zone, and desired cosmetic result.

Application of laparoscopic total mesorectal excision combined with sphincter-preserving surgery in low or ultralow rectal cancer

This study aimed to investigate the influence of laparoscopic total mesorectal excision combined with sphincter-preserving surgery on the postoperative defecation function,urinary function and sexual function in low or ultralow rectal cancer.A retrospective study was undertaken on 107 patients(65 laparoscopic resection and 42 laparoctomic resection)with rectal cancer undergoing laparoscopic or open laparoscopic total mesorectal excision combined with sph incter-preserving surgery from April 2009 to April 2013.The quality of life outcomes of all patients,including defection,urinary and sexual function,were assessed at 6,12 and 24 months after operation.Gastrointestinal quality of life index(GQOLI)was used to evaluate the fecal incont inence and bowel dysfunction.Urinary and sexual functions were studied by means of questionnaires on the basis of the international prostatic symptom score(IPSS)and international index of erectile function(IEF),respectively.In laparoscopic surgery group,there were two cases of anastomotic leakage,three cases of anast omotic strict ure,seven cases of local recurrence,ten cases of hepatic metastasis and five cases of lung metastasis.The satisfaction rates of patients about their defe-cation function reached 60.3%(35/58,84.5%(49/58)and 913%(53/58)at6,12,and 24 months follow-up,respectively.The assessment after one year showed that the overall incidence of uri-nary dysfunction was 10.7%(7/65);Among male patients,18.4%(7/36)sufered from erectile dysfunction and 27.8%(10/36)sufered from ejaculatory dysfunction;65.5%(19/29)female patients investigated were satisfied with their postoperative sexual life.In open surgery group,there were two cases of anastomotic leakage,two cases of anastomotic stricture,nine cases of local recurrence,ten cases of hepatic metastasis and seven cases of kung metastasis.The satisfaction rates of patients about their defecation function were 56.4%(22/39),82.1%(32/39)and 94.8%(37/39)at 6,12,and 24 months follow-up,respectively.The assessment after one year showed that the overall incidence of urinary dysfunction was 11.9%(5/42);25%(4/16)male patients suffered from erectile dysfunction and 313%(5/16)sufered from ejaculatory dysfunction;69.2%(19/26)female patients investigated were satisfied of their postoperative sexual life.There was no statistic difference in the two groups.Laparoscopic total mesorectal excision combined with sphincter-preserving surgery in low or ultralow rectal carcinoma is safe and pract icable.It can be helpful for enhancing the probability of anus reservation,and obtains satisfactory defecation,sexual and urinary functions.

Risk Factors of Anastomotic Leakage After Anterior Resection for Rectal Cancer Patients

Objective Anastomotic leakage(AL)is one of the serious complications after anterior resection for rectal cancer.Defunctioning stoma(DS)is one of the most widely used approaches to prevent it;however,the effect of DS on the occurrence of AL remains controversial.This study aimed to investigate risk factors of AL and assess the effect of DS after anterior resection for rectal cancer patients.Methods A retrospective analysis was conducted for the data of 1840 patients who underwent anterior resection for rectal cancer from January 2014 to December 2019.Results The results showed the overall AL incidence was 7.5%.Multivariate analyses revealed that males[odds ratio(OR)1.562]and T3–T4 stage(OR 1.729)were independent risk factors for all patients.After propensity score matching analysis,the AL incidence was 14.1%in the group with no DS and 6.4%in the DS group(P<0.001).The clinical AL(grade B+grade C)incidence was 12.4%in no DS group and 4.6%in the DS group(P<0.001).Conclusion The study suggested that males and T3–T4 stage were independent risk factors of AL.In addition,DS could reduce the rate of symptomatic AL.

Development of a magnetite-gene complex for gene transfection

The key to successful gene therapy is tofind a suitable method and carrier for transfection to allow a gene to be transferred into a cell and integrated into the target gene.The aim of this study was to determine whether biomagnetic material could be combined with the nucleic acid for gene transfection.Dextran-coated iron oxide nanoparticles(DCIONPs)were prepared and mixed with the plasmid pGenesil-1 containing the test gene,which expresses enhanced greenfluorescent protein(eGFP).PGenesil-1 empty vector was used as a control.The binding ability was assessed by electrophoresis of the DNA on agarose gels and quantification using BANDS-CAN software.Using different gene carriers,Lipofecta-mine 2000,Sofast,and DCIONPs,the large intestine cancer(Lovo)cell line was transfected in vitro with or without a magneticfield.The expression of eGFP was observed byfluorescence microscopy,and the transfection efficiency was compared.The results showed there was a rapid increase in combining rate when the quality ratio of DCIONPs and pGenesil-1 ascended from 1∶1 to 5∶1.However,the combining rate increased less rapidly as the quality ratio continued ascending.The expression of eGFP showed that the early transfection rate could be improved by applying a magneticfield.In conclusion,the DCIONPs we synthesized are able to carry plasmid DNA and enhance the early transfection efficiency when using a magneticfield.