Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.

Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

Treatment of gastric precancerous lesions with Weiansan

AIM： To observe the curative effect of Weiansan （WAS） on gastric precancerous lesions （GPL） and H pylori elimination. METHODS： Seventy-six patients with GPL were randomly divided into two groups： WAS group （n = 42） and Weifuchun （WFC） group （n = 34）. The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC （4 tablets） 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy （GA）, intestinal metaplasia （IM） and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley （SD） rats were used in animal experiments. Of these, 10 served as the control group （n = 10）, 40 were given ranitidine combined with N-methyl- N^1-nitro-N-nitrosoguanidine （MNNG） for 12 wk and divided into 4 groups randomly： model group （n = 10）, high-dose WAS group （n = 10）, low-close WAS group （n = 10） and WFC group （n = 10）. Twelve weeks later, all rats were killed and a 2 cm ×1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method. RESULTS： The curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of Hpylori infection in the model group （positive/negative： 9/1） was significantly higher than that in the control group （positive/negative： 1/9） （P 〈 0.01）. H pylori elimination in the high-dose WAS group （positive/negative： 4/6） and low-dose WAS group （positive/negative： 6/4） was similar to that in the WFC group （positive/negative： 4/6） （P 〉 0.05）.CONCLUSION： WAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.

Effect of Helicobacterpyloriinfection on Bax protein expression in patients with gastric precancerous lesions

AIM： To investigate the effect of Helicobacter pylori （H pylon） infection on Bax protein expression, and explore the role of Hpyloriin gastric carcinogenesis. METHODS： Hpyloriwas assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions. RESULTS： Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in Hpylori-positive gastric precancerous lesions （72.3%） was significantly higher than that in H pylori-negative gastric precancerous lesions （48.0%, x^2= 4.191, P〈0.05）. Hpyloriinfection was well correlated with the expression of Bax protein in gastric precancerous lesions （r= 0.978, P〈0.01）. After eradication of H pylori, the positivity of Bax protein expression significantly decreased in Hpylori-positive gastric precancerous lesions （x^2 = 5.506, P〈0.05）. In the persisting H pylori-infected patients, the positivity of Bax protein expression was not changed. CONCLUSION： H pyloriinfection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of Hpyloriinfection-induced gastric epithelial cell apoptosis. Hpylorimight act as a tumor promoter in the genesis of gastric carcinoma and eradication of Hpylori could inhibit gastric carcinogenesis.

Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population

BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.

A network pharmacology approach to investigate the mechanisms of Si-Jun-Zi decoction in the treatment of gastric precancerous lesions

Objective:To find out the potential mechanisms of Si-Jun-Zi(SJZ)decoction in the treatment of gastric precancerous lesions(GPL).Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of SJZ decoction in treating GPL.The compounds and predicted targets of SJZ decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the SJZ decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway enrichment analyses.Results:The results show that 111 compounds and 90 targets were obtained in this work.These targets were further mapped to 654 GO biological process terms and 21 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network,a target-pathways network,and an integrated GPL pathway.These results indicated that SJZ decoction may treat the dysfunctions of GPL mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusions:This work provided a novel approach to understand the pathogenesis of GPL and revealed the therapeutic mechanisms of SJZ decoction,which facilitate the modernization of herbal medicine for complex diseases in the future.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Review on the progress of treating gastric precancerous lesions with traditional Chinese medicine based on regulatory genes

In recent years,the incidence of Precancerous lesions of gastric cancer(PLGC)has gradually increased,and it is difficult to be cured and easy to recur.Traditional Chinese Medicine(TCM)emphasizes the prevention before the disease.The regulation of PLGC related tumor genes by Chinese medicine has become a research hotspot.This paper summarized PLGC related proto-oncogenes,tumor suppressor genes and apoptosis related genes,and discussed the mechanism of Chinese Medicine Therapy PLGC from the perspective of gene expression,providing new ideas and methods for clinical treatment of PLGC.

Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer

The microbiota is strongly association with cancer.Studies have shown significant differences in the gastric microbiota between patients with gastric cancer(GC)patients and noncancer patients,suggesting that the microbiota may play a role in the development of GC.Although Helicobacter pylori(H.pylori)infection is widely recognized as a primary risk factor for GC,recent studies based on microbiota sequencing technology have revealed that non-H.pylori microbes also have a significant impact on GC.A recent study discovered that Streptococcus anginosus(S.anginosus)is more prevalent in the gastric mucosa of patients with GC than in that of those without GC.S.anginosus infection can spontaneously induce chronic gastritis,mural cell atrophy,mucoid chemotaxis,and heterotrophic hyperplasia,which promote the development of precancerous lesions of GC(PLGC).S.anginosus also disrupts the gastric barrier function,promotes the proliferation of GC cells,and inhibits apoptosis.However,S.anginosus is underrepresented in the literature.Recent reports suggest that it may cause precancerous lesions,indicating its emerging pathogenicity.Modern novel molecular diagnostic techniques,such as polymerase chain reaction,genetic testing,and Ultrasensitive Chromosomal Aneuploidy Detection,can be used to gastric precancerous lesions via microbial markers.Therefore,we present a concise summary of the relationship between S.anginosus and PLGC.Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S.anginosus on PLGC.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Effects of Weipixiao(胃痞消)on Wnt Pathway-Associated Proteins in Gastric Mucosal Epithelial Cells from Rats with Gastric Precancerous Lesions*

Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.

Effect of Jinguo Weikang Capsule(金果胃康胶囊) on Proto-oncogene Expression of Gastric Mucosa in Rats with Gastric Precancerous Lesions

Objective： To study the effect of Jinguo Weikang Capsule （金果暖康胶囊, JWC） on the gene expression of H-ras, epidermal growth factor receptor （EGFR）, P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. Methods： A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using ^60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. Results： The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high- and medium-dose JWC treatment groups were significantly lower （P〈0.05） as compared with those of the model group. Conclusion： JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis.

A clinical study of Weining Granules in the treatment of gastric precancerous lesions

OBJECTIVE:To investigate the clinical effects of Weining Granules on gastric precancerous lesions(GPLs).METHODS:120 patients with GPLs were randomly assigned in a 1:1 ratio to receive Weining Granules(trial group) or the comparator Weifuchun tablets(control group) for 6 months.Outcomes were compared between the two groups including:overall response;gastroscopically-determined response;pathologically-confirmed response;eradication of Helicobacter pylori(HP);microvessel density(MVD) in the gastric mucosa;expression of vascular endothelial growth factor(VEGF);interleukin 2(IL-2);interleukin 6(IL-6);T lymphocyte subsets;immunoglobulins;symptom scores;quality of life(QOL);and adverse reactions.RESULTS:Patients in the trial group had a significantly higher(P<0.05) overall response rate(81.7%) as compared with those in the control group(63.3%).Relative to treatment with Weifuchun tablets treatment with Weining Granules resulted in a significant improvement(P<0.05) in the scores for gastric pain,distension and stuffiness in the hypochondrium,and anorexia.As compared with the tablets the Granules were associated with a significantly higher overall gastroscopically-determined response rate(78.3%;P<0.05).Pathological examination of tissue samples indicated that 61.7% of patients receiving the granules were cured with an overall response rate of 75.5%;these rates were significantly higher than in the control group(P<0.05).In comparison with patients receiving the tablets,those given the granules were significantly more likely to have their HP eradicated(75.0% vs.51.4%;P<0.05).Improvements in MVD,VEGF,CD4+,CD4+/CD8+,IL-2,IL-6 and IgG were significantly greater with the Weining Granules than with the Weifuchun tablets(P<0.05 or P<0.01).After follow-up of 1 year,17.5% of patients in the trial group relapsed as compared with 39.5% in the control group(P<0.05).Relative to the control group,the trial group showed significantly greater improvements in physical,psychological and social relationships,and in environmental domains(P<0.05 or P<0.01).No significant adverse reactions were observed during treatment.CONCLUSION:The Weining Granules appear to be effective in improving the gastric precancerous state and the main symptoms,in inhibiting angiogenesis,enhancing immune function and QOL,and in reducing 1-year relapses.In addition,this preparation seems to be associated with a low risk of adverse events,making it a safe and efficacious option for the treatment of GPLs.

ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type III intestinal metaplasia of gastric mucosa had significant difference, compared with that in type I an II intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type III intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15th, 25th and 40th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Risk Factors of Precancerous Gastric Lesions in A Population at High Risk of Gastric Cancer

Objective： In cancer prevention, the targeting of precancerous lesions has been recognized as the most promising method. However, little attention has been paid to the risk factors of precancerous gastric lesions, especially in rural China where there is high prevalence of precancerous gastric lesions. We therefore conducted a cross-sectional study in Liaoning province, China, to investigate the potential risk and protective factors of these precancerous gastric lesions. Methods： A total of 1,179 subjects with high risk of gastric cancer from Zhuanghe County were included in this study. Standard questionnaires were used in collecting epidemiological factors and the data were then analyzed by the unconditional logistic regression model. Results： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects, and the association of smoking or drinking and the precancerous gastric lesions increased in strength with the daily consumption and duration. As the factors such as age, gender, smoking, alcohol were controlled, a multivariable analysis revealed that there was a significant correlation between the deep-fry food intake and the gastric epithelial dysplasia with the odds ratio （OR） of 1.78 [95% confidence interval （CI）： 1.01-3.12]. Garlic eating was shown to confer protection against the development of gastric ulcer （OR=0.55, 95% CI： 0.33-0.92）. Conclusion： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects. Deep-fry food intake might be one of the risk factors for the precancerous gastric lesions and garlic eating was shown to confer protection against the development of gastric ulcer among rural Chinese population.

Regulative Effect of Traditional Chinese Medicine on Gene-expression Related to Precancerous Lesion of Gastric Cancer

The gene-expression changes related with precancerous lesion of gastric cancer (PLGC) are surveyed. Not only the regulative effect of traditional Chinese medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related with PLGC is analyzed, but also current research state is presented. It's showed that TCM has effects of therapy and inversion on PLGC. These effects are related with the inhibition to related oncogene expression, the regulation and activation to the deletion of antioncogene, the inhibition to the high-expression of mutant gene-protein about antioncogene, and the regulative function to anti-apoptosis gene.

Genetic Polymorphism of PSCA and Risk of Advanced Precancerous Gastric Lesions in a Chinese Population

Objective： To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen （PSCA） and the risk of advanced precancerous gastric lesions including intestinal metaplasia（IM） and dysplasia（Dys）, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer （GC） in China. Methods： The prevalence of gastric lesions including superficial gastritis（SG）, chronic atrophic gastritis（CAG）, IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression. Results： Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM （OR=1.38, 95% CI=1.11-1.71） and Dys （OR=1.75, 95% CI=1.36-2.26）, especially for subjects with H.pylori infection （IM： OR=1.34, 95% CI=1.05-1.71; Dys： OR=1.82, 95% CI=1.37-2.42）. Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of IM （OR=3.32, 95% CI=2.33-4.71） and Dys （OR=4.58, 95% CI=2.99-7.04）. Conclusion： This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.

AGE AND SITES-SPECIFIC PREVALENCE RATES OF PRECANCEROUS GASTRIC LESIONS AT A HIGH-RISK POPULATION OF STOMACH CANCER

A population-based screening for stomach cancer (SC) and its precancerous lesions was conducted in Linqu County, Shandong, China, one of the highest SC rates found in China and the world. An analysis of precancerous stomach lesions revealed that chronic atrophic gastritis (CAG) was a universal common among people aged 35-64 (96-98%). For 52% and 20% of the residents in this age group had Intestinal metaplasia (IM) or dysplssia (DYS). These more advanced lesions were more pronounced in the antrum for both males and females. Age-specific prevalence rates in different anatomic locations sshowed that CAG, developed in the antrum, particularly along the lesser curvature earter than other sites and spread to fundus. IM and DYS accrued under the background of CAG with a leading time in the antrum than the other part of the stomach. Although CAG, IM and DYS prevalence rates were higher in the antrum than In the fundus, the prevalence rates showed a similar smoothly slope, a result of accumulated somatic geneticdamage, suggesting a similar biological response to the stimulation of initiator of carcinogenesis, promoter leading to progression to SC.