BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,n...BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,negative biopsy results often increase patients’risks,economic burdens,and lead to additional healthcare costs.Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.AIM To explore the relationships between the endoscopist biopsy rate(EBR),qualifications of endoscopists and endoscopic assistants,and detection rate of GPLs.METHODS EBR,endoscopists,and endoscopic assistants were divided into four groups:Low,moderate,high,and very high levels.Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions.Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR,endoscopist or endoscopic assistant qualifications,and the detection rate of positive lesions.RESULTS Compared with those in the low EBR group,the odds ratio(OR)values for detecting positive lesions in the moderate,high,and very high EBR groups were 1.12[95%confidence interval(CI):1.06-1.19,P<0.001],1.22(95%CI:1.14-1.31,P<0.001),and 1.38(95%CI:1.29-1.47,P<0.001),respectively.EBR was positively correlated with the detection rate of gastric precancerous conditions(atrophic gastritis/intestinal metaplasia)(ρ=0.465,P=0.004).In contrast,the qualifications of the endoscopists were positively correlated with GPLs detection(ρ=0.448,P=0.005).Compared to endoscopists with low qualification levels,those with moderate,high,and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13%(OR=1.13,95%CI:0.98-1.31),20%(OR=1.20,95%CI:1.03-1.39),and 32%(OR=1.32,95%CI:1.15-1.52),respectively.Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia(ρ=0.350,P=0.034),angularis(ρ=0.396,P=0.015)and gastric body(ρ=0.453,P=0.005)but not in the antrum(ρ=0.292,P=0.079).Moreover,the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications(ρ=0.427,P=0.015).CONCLUSION Endoscopists and endoscopic assistants with high/very high qualifications,but not EBR,can improve the detection rate of GPLs.These results provide reliable evidence for the development of gastroscopic quality control indicators.展开更多
BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric...BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.展开更多
The problem of gastric cancer(GC)prevention remains relevant for a long time.Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created a...The problem of gastric cancer(GC)prevention remains relevant for a long time.Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created at present.Modern endoscopic and morphological methods of verification of the diagnosis of precancerous diseases and changes in the gastric mucosa have been introduced into the practice of gastroenterologists and oncologists.GC risk stratification systems allow the formation of risk groups that require population screening.Practical hints for population serological screening of atrophic gastritis,endoscopic and morphological verification of precancerous changes and diseases of the stomach recommend using it:When developing state programs for the prevention of stomach cancer;when implementing preventive measures for stomach cancer by doctors of all specialties;the authors also offer the possibility of use by anyone over the age of 40,provided that they seek methodological help from their doctor;in the work of health schools in any medical and preventive institutions.The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.展开更多
Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality wor...Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.展开更多
BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly im...BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals.AIM To determine the effect of endoscopic submucosal dissection(ESD)on efficacy,serum tumor markers(STMs),and 6-month postoperative recurrence rate in patients with either EPL or EEC.METHODS This study initially enrolled 120 patients with EPL or EEC,who were admitted from April 2021 to April 2024.Participants were divided into the control group(60 cases),which underwent thoracotomy,and the research group(60 cases)which received ESD treatment.The comparative analysis involved information regarding the efficacy(dissection area and resection rate per unit time),complications(delayed bleeding,wound infection,esophageal reflux,and postoperative esophageal stenosis),surgery-related parameters(bleeding volume,operation duration,and hospital length of stay),STMs[carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724),and tumor-specific growth factor(TSGF)],and the 6-month postoperative recurrence rate of the two groups.RESULTS Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group.Meanwhile,the research group demonstrated a notably lower overall incidence rate of complications,bleeding volume,operation duration,and hospital length of stay.Further,the CEA,CA724,and TSGF were markedly reduced in the research group after treatment,which were statistically lower compared to the baseline and those of the control group.Finally,during the follow-up,a comparable 6-month postoperative recurrence rate was determined in the two groups.CONCLUSION ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.展开更多
Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the mole...Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.展开更多
This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump ...This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.展开更多
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 micro...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.展开更多
BACKGROUND The 5-year survival rate of patients with advanced gastric cancer remains extremely low(<15%),whereas the 5-year survival rate of patients with early gastric cancer(EGC)is>90%.Consequently,strengtheni...BACKGROUND The 5-year survival rate of patients with advanced gastric cancer remains extremely low(<15%),whereas the 5-year survival rate of patients with early gastric cancer(EGC)is>90%.Consequently,strengthening the screening of patients with EGC and precancerous lesions(PCLs)is essential.AIM To identify the value of serum pepsinogen ratio(PGR)screening for EGC and PCLs in the Shengli Oilfield Central Hospital.METHODS We first selected 385 patients with gastric lesions in the Youcheng area,deter-mining benign lesions,PCLs,and EGC in 135,123,and 127 cases,respec-tively,based on endoscopy and case diagnosis.The positive rates of pepsinogen I,pep-sinogen II and Helicobacter pylori(H.pylori)in the three groups were detected,and the PGR was calculated.Subsequently,we plotted receiver operating charac-teristic curves to analyze the screening value of PGR and H.pylori-positive rates for PCLs and EGC.RESULTS PGR expression demonstrated a decreasing trend in patients with benign lesions,PCLs,and EGC successively according to the detection results,whereas the H.pylori-positive rate was notably increased in patients with PCLs and EGC compared to those with benign lesions.The area under the curves(AUCs)of PGR,H.pylori,and their combination in differentiating patients with benign lesions from those with PCLs were 0.611,0.582,and 0.689,respectively;PGR,H.pylori,and their combination had an AUC of 0.618,0.502,and 0.618 in distinguishing PCL patients from EGC patients,respectively;the AUCs of PGR,H.pylori,and their combination in discriminating patients with benign lesions from those with EGC were 0.708,0.581,and 0.750,respectively.CONCLUSION PGR has great screening potential for patients with EGC and PCLs in the Youcheng area,and the screening efficiency is further improved by combining the H.pylori-positive rate.展开更多
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 ...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.展开更多
Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triag...Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.展开更多
OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the bre...OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.展开更多
INTRODUCTION Helicobacter pylori(Hp)infection has beenconsidered to play significant roles in pathogenesisof peptic ulcer.Additionally Hp is associated withthe development of gastric epithelial hyperplasiaand lymphoid...INTRODUCTION Helicobacter pylori(Hp)infection has beenconsidered to play significant roles in pathogenesisof peptic ulcer.Additionally Hp is associated withthe development of gastric epithelial hyperplasiaand lymphoid malignancies.The InternationalAgency for Research on Cancer has classified lip asa class Ⅰ carcinogen and a definite cause of gastriccancer in humans.Hp infection first causes chronicactive gastritis and may slowly lead to infection ofwhole stomach.In the late stages of infection,mucosal atrophy and intestinal metaplasia(IM),展开更多
INTRODUCTIONThe esophageal carcinoma is a common malignanttumor in Linzhou City (Linxian) of Henan Provincein northern China.Although the etiology andnatural history of csophageal carcinoma are notclear,a substantial ...INTRODUCTIONThe esophageal carcinoma is a common malignanttumor in Linzhou City (Linxian) of Henan Provincein northern China.Although the etiology andnatural history of csophageal carcinoma are notclear,a substantial amount of evidence has beenprovided to suggest that the development of humanesophageal squamous cell carcinomas (SCC) is amultistage progressive process.An展开更多
AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were ...AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.展开更多
AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical ...AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.展开更多
AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gast...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
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 pylo...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.展开更多
Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and t...Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.展开更多
BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate de...BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.展开更多
基金Supported by Jiangsu Science and Technology Project,No.BK20211039the Top Talent Support Program for Young and Middle-Aged People of the Wuxi Health Committee,No.BJ2023008+3 种基金the Major Program of Wuxi Medical Center,Nanjing Medical University,No.WMCM202305the Cohort and Clinical Research Program of Wuxi Medical Center,Nanjing Medical University,No.WMCC202302the Scientific Research Program of Wuxi Health Commission,No.Z202208Wuxi Municipal Health and Health Commission Precision Medicine Project,No.J202104.
文摘BACKGROUND Detecting gastric precancerous lesions(GPLs)is critical for the early diagnosis and treatment of gastric cancer.Endoscopy combined with tissue examination is an important method for detecting GPLs.However,negative biopsy results often increase patients’risks,economic burdens,and lead to additional healthcare costs.Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.AIM To explore the relationships between the endoscopist biopsy rate(EBR),qualifications of endoscopists and endoscopic assistants,and detection rate of GPLs.METHODS EBR,endoscopists,and endoscopic assistants were divided into four groups:Low,moderate,high,and very high levels.Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions.Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR,endoscopist or endoscopic assistant qualifications,and the detection rate of positive lesions.RESULTS Compared with those in the low EBR group,the odds ratio(OR)values for detecting positive lesions in the moderate,high,and very high EBR groups were 1.12[95%confidence interval(CI):1.06-1.19,P<0.001],1.22(95%CI:1.14-1.31,P<0.001),and 1.38(95%CI:1.29-1.47,P<0.001),respectively.EBR was positively correlated with the detection rate of gastric precancerous conditions(atrophic gastritis/intestinal metaplasia)(ρ=0.465,P=0.004).In contrast,the qualifications of the endoscopists were positively correlated with GPLs detection(ρ=0.448,P=0.005).Compared to endoscopists with low qualification levels,those with moderate,high,and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13%(OR=1.13,95%CI:0.98-1.31),20%(OR=1.20,95%CI:1.03-1.39),and 32%(OR=1.32,95%CI:1.15-1.52),respectively.Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia(ρ=0.350,P=0.034),angularis(ρ=0.396,P=0.015)and gastric body(ρ=0.453,P=0.005)but not in the antrum(ρ=0.292,P=0.079).Moreover,the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications(ρ=0.427,P=0.015).CONCLUSION Endoscopists and endoscopic assistants with high/very high qualifications,but not EBR,can improve the detection rate of GPLs.These results provide reliable evidence for the development of gastroscopic quality control indicators.
基金the National Natural Science Foundation of China,No.82374292,82205095,and 82305179the Horizontal Development Foundation of Beijing University of Chinese Medicine,No.BUCM-2021-JS-KF-065the China Postdoctoral Science Foundation Grant,No.2022M720520.
文摘BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.
文摘The problem of gastric cancer(GC)prevention remains relevant for a long time.Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created at present.Modern endoscopic and morphological methods of verification of the diagnosis of precancerous diseases and changes in the gastric mucosa have been introduced into the practice of gastroenterologists and oncologists.GC risk stratification systems allow the formation of risk groups that require population screening.Practical hints for population serological screening of atrophic gastritis,endoscopic and morphological verification of precancerous changes and diseases of the stomach recommend using it:When developing state programs for the prevention of stomach cancer;when implementing preventive measures for stomach cancer by doctors of all specialties;the authors also offer the possibility of use by anyone over the age of 40,provided that they seek methodological help from their doctor;in the work of health schools in any medical and preventive institutions.The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.
文摘Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.
文摘BACKGROUND Tumor progression in patients with esophageal precancerous lesions(EPLs)or early esophageal carcinoma(EEC)is typically confined in both extent and location.Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals.AIM To determine the effect of endoscopic submucosal dissection(ESD)on efficacy,serum tumor markers(STMs),and 6-month postoperative recurrence rate in patients with either EPL or EEC.METHODS This study initially enrolled 120 patients with EPL or EEC,who were admitted from April 2021 to April 2024.Participants were divided into the control group(60 cases),which underwent thoracotomy,and the research group(60 cases)which received ESD treatment.The comparative analysis involved information regarding the efficacy(dissection area and resection rate per unit time),complications(delayed bleeding,wound infection,esophageal reflux,and postoperative esophageal stenosis),surgery-related parameters(bleeding volume,operation duration,and hospital length of stay),STMs[carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724),and tumor-specific growth factor(TSGF)],and the 6-month postoperative recurrence rate of the two groups.RESULTS Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group.Meanwhile,the research group demonstrated a notably lower overall incidence rate of complications,bleeding volume,operation duration,and hospital length of stay.Further,the CEA,CA724,and TSGF were markedly reduced in the research group after treatment,which were statistically lower compared to the baseline and those of the control group.Finally,during the follow-up,a comparable 6-month postoperative recurrence rate was determined in the two groups.CONCLUSION ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.
基金Supported by the National Administration of Traditional Chinese Medicine National Superior Specialty Project of Traditional Chinese Medicine,No.[2024]90Shanghai Municipal Administrator of Traditional Chinese Medicine Policy Letter[2024],No.20+1 种基金Science and Technology Development Fund of Shanghai University of Traditional Chinese Medicine,No.23KFL102Shuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304。
文摘Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.
文摘This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.
文摘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.
文摘BACKGROUND The 5-year survival rate of patients with advanced gastric cancer remains extremely low(<15%),whereas the 5-year survival rate of patients with early gastric cancer(EGC)is>90%.Consequently,strengthening the screening of patients with EGC and precancerous lesions(PCLs)is essential.AIM To identify the value of serum pepsinogen ratio(PGR)screening for EGC and PCLs in the Shengli Oilfield Central Hospital.METHODS We first selected 385 patients with gastric lesions in the Youcheng area,deter-mining benign lesions,PCLs,and EGC in 135,123,and 127 cases,respec-tively,based on endoscopy and case diagnosis.The positive rates of pepsinogen I,pep-sinogen II and Helicobacter pylori(H.pylori)in the three groups were detected,and the PGR was calculated.Subsequently,we plotted receiver operating charac-teristic curves to analyze the screening value of PGR and H.pylori-positive rates for PCLs and EGC.RESULTS PGR expression demonstrated a decreasing trend in patients with benign lesions,PCLs,and EGC successively according to the detection results,whereas the H.pylori-positive rate was notably increased in patients with PCLs and EGC compared to those with benign lesions.The area under the curves(AUCs)of PGR,H.pylori,and their combination in differentiating patients with benign lesions from those with PCLs were 0.611,0.582,and 0.689,respectively;PGR,H.pylori,and their combination had an AUC of 0.618,0.502,and 0.618 in distinguishing PCL patients from EGC patients,respectively;the AUCs of PGR,H.pylori,and their combination in discriminating patients with benign lesions from those with EGC were 0.708,0.581,and 0.750,respectively.CONCLUSION PGR has great screening potential for patients with EGC and PCLs in the Youcheng area,and the screening efficiency is further improved by combining the H.pylori-positive rate.
文摘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.
文摘Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.
文摘OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.
文摘INTRODUCTION Helicobacter pylori(Hp)infection has beenconsidered to play significant roles in pathogenesisof peptic ulcer.Additionally Hp is associated withthe development of gastric epithelial hyperplasiaand lymphoid malignancies.The InternationalAgency for Research on Cancer has classified lip asa class Ⅰ carcinogen and a definite cause of gastriccancer in humans.Hp infection first causes chronicactive gastritis and may slowly lead to infection ofwhole stomach.In the late stages of infection,mucosal atrophy and intestinal metaplasia(IM),
基金the National Natural Science Foundation of China,No.39840012
文摘INTRODUCTIONThe esophageal carcinoma is a common malignanttumor in Linzhou City (Linxian) of Henan Provincein northern China.Although the etiology andnatural history of csophageal carcinoma are notclear,a substantial amount of evidence has beenprovided to suggest that the development of humanesophageal squamous cell carcinomas (SCC) is amultistage progressive process.An
基金Supported by Jinan Science and Technology Bureau for Independent Innovation Projects of Universities and Research Institutes in Jinan city,China,No.201102060
文摘AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.
基金Supported by National Natural Science Foundation of China, No.30973503Special Fund for Climbing Scholars of Universities in Liaoning Province, China, 2009-2010
文摘AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.
基金Supported by the National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
基金Support by The National Natural Science Foundation of China, No. 30370637
文摘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.
文摘Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.
基金Supported by the National Natural Science Foundation of China,No.81070319the Beijing Natural Science Foundation of China,No.7102013the Beijing Municipal Education Commission Research Program,China,No.KM201610025004
文摘BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.
