Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.

Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in primary gastric adenocarcinomas

AIM: To investigate the genomic copy number alterations that may harbor key driver genes in gastric tumorigenesis. METHODS: Using high-resolution array comparative genomic hybridization (CGH), we investigated the genomic alterations of 20 advanced primary gastric adenocarcinomas (seventeen tubular and three mucinous) of Chinese patients from the Jilin province. Ten matching adjacent normal regions from the same patients were also studied. RESULTS: The most frequent imbalances detected in these cancer samples were gains of 3q26.31-q27.2, 5p, 8q, 11p, 18p, 19q and 20q and losses of 3p, 4p,18q and 21q. The use of high-resolution array CGH increased the resolution and sensitivity of the observed genomic changes and identified focal genetic imbalances, which included 54 gains and 16 losses that were smaller than 1 Mb in size. The most interesting focal imbalances were the intergenic loss/homozygous deletion of the fragile histidine triad gene and the amplicons 11q13, 18q11.2 and 19q12, as well as the novel amplicons 1p36.22 and 11p15.5. CONCLUSION: These regions, especially the focal amplicons, may harbor key driver genes that will serve as biomarkers for either the diagnosis or the prognosis of gastric cancer, and therefore, a large-scale investigation is recommended.

Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis:A case report

BACKGROUND Brain metastases(BM)are very rare in gastric adenocarcinoma(GaC),and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unclear.Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor(MET)amplification.Therefore,treatment with savolitinib,a small molecule inhibitor of c-Met,was selected.CASE SUMMARY A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain.Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy.The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department.Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification.After discussing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intracranial lesions shrank considerably.CONCLUSION BM is very rare in advanced GaC,especially in meningeal cancer,that is characterized by rapid disease deterioration.There are very few effective treatment options available;however,technological breakthroughs in genomics have provided a basis for personalized treatment.Furthermore,MET amplification may be a key driver of BM in gastric cancer;however,this conclusion requires further investigation.

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma

BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma.AIM To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma.METHODS This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma.We investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric adenocarcinoma.RESULTS CLDN18.2 expression was positive in 73.8%(48)of the patients.During the median 17.7-mo follow-up period,89.2%(58)of the patients died.Median progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients.In univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS.CONCLUSION CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be efficacious.There is no statistically significant correlation with clinicopathological characteristics and OS.CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma:A retrospective case series analysis

BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.

Effects of JAG-1 on the Proliferation and Migration of Gastric Adenocarcinoma Cells after TRAIP Knockout

[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.

Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy:A case report

BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Study on the Correlation between the Expression of Angiogenic Factor VEGF and Microsatellite Instability in Gastric Adenocarcinoma

Objective: To investigate the correlation between the microsatellite instability (MSI) and the expression of vascular endothelial growth factor (VEGF) in gastric adenocarcinoma. Methods: PCR SSCP method was used to detect MSI of thirty cases with gastric adenocarcinoma at five loci in each patient. Expression of VEGF was examined by the method of immunohistochemistry. Results: The positive of MSI was in 13 patients out of 30 patients (43.4%) in our study. Positive VEGF Immunostaining was detected in 18 patients (60.0%). VEGF was decreased in microsatellite instability high (MSI H) gastric adenocarcinoma. Conclusion: MSI H and microsatellite stable (MSS) gastric adenocarcinoma may follow a different pathway of angiogenesis. The low frequency of VEGF expression among MSI H cancer may partially explain why these cancers are less aggressive.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was performed in 13 nonneoplastic gastric adenocarcinorna, 30 intestinal-type gastric adenocarcinorna and 35 diffuse-type gastric adenocarcinorna samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher＇s exact test to assess associations between rnethylation status and clinico-pathological characteristics.RESULTS： Hypermethylation frequencies of CDH1, FHIT, MTAPand PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hyperrnethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hyperrnethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION： Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.

Study of Sonic hedgehog signaling pathway related molecules in gastric carcinoma

AIM： To study the expression of Sonic hedgehog pathway-related molecules, Sonic hedgehog （Shh） and Glil in gastric carcinoma. METHODS： Expression of Shh in 56 gastric specimens including non-cancerous gastric tissues, gastric adenocarcinoma, gastric squamous cell carcinoma was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Glil was observed by in situ hybridization. RESULTS： The positive rate of Shh and Glil expression was 0.0%, 0.0% in non-cancerous gastric tissues while it was 66.7%, 57.8% respectively in gastric adenocarcinoma, and 100%, 100% respectively in gastric squamous cell carcinoma. There was a significant difference between the non-cancerous gastric tissues and gastric carcinoma （P 〈 0.05）. Elevated expression of Shh and Glil in gastric tubular adenocarcinoma was associated with poorly differentiated tumors while the expression was absent in gastric mucinous adenocarcinoma. CONCLUSION： The elevated expression of Shh and Glil in gastric adenocarcinoma and gastric squamous cell carcinoma shows the involvement of activated Shh signaling in the cellular proliferation of gastric carcinogenesis. It suggests Shh signaling gene may be a new and good target gene for gastric tumor diagnosis and therapy.

Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China

AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China.METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203ESCC and 152 GCA) and 443 healthy controls.RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively).Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10,95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%,39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6%and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P＞0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95%CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46)in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes.CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.

Effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823

AIM： To investigate the effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. METHODS： Effects of tachyplesin and n-sodium butyrate on proliferation of BGC-823 cells were determined with trypan blue dye exclusion test and HE staining. Effects of tachyplesin and n-sodium butyrate on cell cycle were detected by flow cytometry. Protein levels of c-erbB-2, c-myc, p53 and p16 were examined by immunocytochemistry. RESULTS： The inhibiting effects were similar after 2.0 mg/L tachyplesin and 2.0 mmol/L n-sodium butyrate treatment, the inhibitory rate of cellular growth was 62.66% and 60.19% respectively, and the respective maximum mitotic index was decreased by 49.35% and 51.69% respectively. Tachyplesin and n-sodium buD/rate treatment could markedly increase the proportion of cells at G0/G1 phase and decrease the proportion at S phase. The expression levels of oncogene c-erbB-2, c-myc, and mtp53 proteins were down-regulated while the expression level of tumor suppressor gene p16 protein was up-regulated after the treatment with tachyplesin or n-sodium buD/rate. The effects of 1.0 mg/L tachyplesin in combination with 1.0 mmol/L n-sodium butyrate were obviously superior to their individual treatment in changing cell cycle distribution and expression of c-erbB-2, c-myc, mtp53 and p16 protein. The inhibitory rate of cellular growth of BGC-823 cells after combination treatment was 62.29% and the maximum mitotic index wasdecreased by 51.95%. CONCLUSION： Tachyplesin as a differentiation inducer of tumor cells has similar effects as n-sodium butyrate on proliferation of tumor cells, expression of correlative oncogene and tumor suppressor gene. It also has a synergistic effect on differentiation of tumor cells.

Relationship between expression and distribution of cyclooxygenase-2 and bcl-2 in human gastric adenocarcinoma

AIM: To explore expression and distribution features of COX-2 and bcl-2 in human gastric adenocarcinoma tissues and to study its biological significance.METHODS: Totally 36 human gastric carcinoma samples were enrolled in this study (cardiac adenocarcinoma 16 cases, distal gastric adenocarcinoma 20 cases). The expressions of COX-2 and bcl-2 in cancerous tissues and corresponding para-cancerous tissues were investigated by immunohistochemistry using COX-2 polyclonal antibody and bcl-2 monoclonal antibody. The normal gastric mucosa tissues were used as control.RESULTS: The expressions of COX-2 and bcl-2 in gastric carcinoma were significantly higher than that in the paracancerous tissues (77.8% vs 47.2%, P＜0.01, 80.56% vs 58.33%, P＜0.05). The expression of COX-2 in cardiac adenocarcinoma was remarkably higher than that in the distal gastric carcinoma (93.8% vs 65.0%, P＜0.01). The expression of COX-2 was mainly localized in the cytoplasm of tumor cells and partly in the nucleus. There is a transition of the COX-2 cytoplasmic positivity to nucleic in tumor cells with the increase of gastric carcinoma pathological grade. Interstitial macrophages, fibroblasts and vascular endothelial cells also expressed COX-2. The tissues with higher expression of COX-2 also expressed high level of bcl-2 protein.CONCLUSION: Abnormal expression pattern of COX-2within the tissues of human gastric cancer is correlated with tumor location and lymph node metastasis. COX-2may regulate expression of apoptosis suppressor gene (bcl-2) through interaction of tumor cells and stromal cells and play an important role in the generation and development of tumors, which will be of great help in developing new methods for antitumor therapy.