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
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
BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissect...BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissection(ESD)affects postoperative recovery and complications in such patients.AIM To evaluate the influence of ESD on postoperative recovery and complications in patients with EGC or PCL.METHODS The study population included patients with EGC and PCL admitted to The First People’s Hospital of Fuyang District between December 2022 and December 2024,who were divided into the research(n=65)and control(n=55)groups if they underwent ESD and laparoscopic radical gastrectomy,respectively.Therapeutic outcomes(en bloc and curative resection rates),surgical parameters(incision length,intraoperative bleeding,and operative duration),postoperative recovery indices(time to first ambulation/flatus/first oral intake,and hospital stay duration),complications(infection,outflow obstruction,bleeding,and perforation),and tumor markers[carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)125/19-9]were comparatively evaluated.RESULTS Compared with the control group,the research group achieved a significantly higher en bloc resection rate but a notably lower curative resection rate.Additionally,the research group demonstrated shorter incision lengths,reduced intraoperative bleeding,and shorter operative duration.Regarding postoperative recovery,the research group demonstrated earlier ambulation,faster bowel function restoration,quicker oral intake resumption,and shorter hospital stays.Furthermore,an evidently lower overall complication rate was recorded in the research group,as well as markedly reduced postoperative CEA,CA125,and CA19-9 concentrations.CONCLUSION When performed for EGC and PCLs,ESD demonstrates advantages such as higher en bloc resection(although lower curative resection rates),surgical trauma minimization,shortened operative duration,and faster recovery.Moreover,it is effective in reducing serum tumor marker levels while maintaining favorable safety.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
BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-dela...BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-delayed postoperative bleeding(DPOB)-can significantly hinder patient recovery.AIM To build and validate a predictive model for assessing post-ESD DPOB risk in ECRC and PCL patients,utilizing logistic regression methodology.METHODS A retrospective review was conducted on ECRC/PCL 302 patients who received ESD at our hospital between July 2021 and July 2024.The cohort was stratified based on the incidence of DPOB following ESD,forming DPOB and non-DPOB groups.Through allocation,they were further allocated into model and validation cohorts.Clinical variables from both cohorts were collated and subjected to univariate analysis to determine potential factors associated with post-ESD DPOB.Subsequently,we constructed a predictive model for DPOB risk employing logistic regression analysis.Model performance assessment used receiver operating characteristic curves in both the training and validation cohorts,with internal validation accomplished via 10-fold cross-validation.RESULTS The occurrence rate of DPOB was 9.93%.Univariate analysis revealed that the number of lesions,lesion size,lesion location,degree of submucosal fibrosis,and intraoperative bleeding were significantly associated with DPOB.Binary logistic regression analysis identified the number of lesions,lesion size,lesion location,and degree of submucosal fibrosis as independent DPOB determinants.A nomogram that was developed to quantify the DPOB risk exhibited that an increment in the total score corresponded to an increased risk.The model achieved area under the curve values of 0.831 and 0.821 in the model and validation groups,respectively,with P values of 0.853 and 0.203 in the Hosmer-Lemeshow test.The model demonstrated robust discriminative performance,with an average area under the curve of 0.795(95%confidence interval:0.702-0.887)in 10-fold cross-validation.CONCLUSION Collectively,the presence of multiple lesions,lesion size of≥3 cm,lesion localization in the rectum,and severe fibrosis are significant independent predictors of DPOB in patients undergoing surgery for ECRC or PCLs.The proposed risk prediction model,which integrates these factors,demonstrates excellent predictive accuracy and clinical utility,thereby providing a valuable tool for risk stratification and postoperative management in this patient population.展开更多
Serological screening,endoscopic imaging,morphological visual verification of precancerous gastric diseases and changes in the gastric mucosa are the main stages of early detection,accurate diagnosis and preventive tr...Serological screening,endoscopic imaging,morphological visual verification of precancerous gastric diseases and changes in the gastric mucosa are the main stages of early detection,accurate diagnosis and preventive treatment of gastric precancer.Laboratory-serological,endoscopic and histological diagnostics are carried out by medical laboratory technicians,endoscopists,and histologists.Human factors have a very large share of subjectivity.Endoscopists and histologists are guided by the descriptive principle when formulating imaging conclusions.Diagnostic reports from doctors often result in contradictory and mutually exclusive conclusions.Erroneous results of diagnosticians and clinicians have fatal consequences,such as late diagnosis of gastric cancer and high mortality of patients.Effective population serological screening is only possible with the use of machine processing of laboratory test results.Currently,it is possible to replace subjective imprecise description of endoscopic and histological images by a diagnostician with objective,highly sensitive and highly specific visual recognition using convolutional neural networks with deep machine learning.There are many machine learning models to use.All machine learning models have predictive capabilities.Based on predictive models,it is necessary to identify the risk levels of gastric cancer in patients with a very high probability.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
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
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
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 further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues. METHODS: Endoscopic mucosa biopsy and histopathological examinations were made on 37 subjects from a hi...AIM:To further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues. METHODS: Endoscopic mucosa biopsy and histopathological examinations were made on 37 subjects from a high incidence area for both esophageal and gastric cardia carcinomas in northern China. All the biopsy samples were fixed in 850 ml. (-1)L alcohol and embedded in paraffin. Each block contained one piece of tissue and was serially section at 5 microm. Immunohistochemistry (ABC) was carried out on these gastric cardia samples to determine the alterations of p16 and Rb. RESULTS: Based on the histopathlogical examination there were 11 cases of chronic superficial gastritis, 12 cases of chronic atrophic gastritis and 14 cases of dysplasia. The immunostaining demonstrated different levels of unclear immunostaining of p16 and Rb in normal gastric cardia tissue and the tissues with different severity of lesions. With the lesions progressing, the positive immunostaining rates for p16 protein had a decreasing tendency. In contrast, the positive immunostaining rate for Rb protein had an increasing tendency. There was a significant negative relationship between the two parameters. Changes of p16 was CSG 11(100%), CAG 7(58%), DYS 4(29%) and changes of Rb was CSG 2(18%), CAG 8(67%) and DYS 12(86%), (P【0.05). CONCLUSION: The alterations of p16 and Rb protein may play a role in the early stages of gastric cardia carcinogenesis.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
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
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 ...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.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.
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BACKGROUND Early gastric cancer(EGC)or precancerous lesions(PCLs)are generally small tumors and carry a diminished chance of nodal infiltration.Thus far,very few studies have examined how endoscopic submucosal dissection(ESD)affects postoperative recovery and complications in such patients.AIM To evaluate the influence of ESD on postoperative recovery and complications in patients with EGC or PCL.METHODS The study population included patients with EGC and PCL admitted to The First People’s Hospital of Fuyang District between December 2022 and December 2024,who were divided into the research(n=65)and control(n=55)groups if they underwent ESD and laparoscopic radical gastrectomy,respectively.Therapeutic outcomes(en bloc and curative resection rates),surgical parameters(incision length,intraoperative bleeding,and operative duration),postoperative recovery indices(time to first ambulation/flatus/first oral intake,and hospital stay duration),complications(infection,outflow obstruction,bleeding,and perforation),and tumor markers[carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)125/19-9]were comparatively evaluated.RESULTS Compared with the control group,the research group achieved a significantly higher en bloc resection rate but a notably lower curative resection rate.Additionally,the research group demonstrated shorter incision lengths,reduced intraoperative bleeding,and shorter operative duration.Regarding postoperative recovery,the research group demonstrated earlier ambulation,faster bowel function restoration,quicker oral intake resumption,and shorter hospital stays.Furthermore,an evidently lower overall complication rate was recorded in the research group,as well as markedly reduced postoperative CEA,CA125,and CA19-9 concentrations.CONCLUSION When performed for EGC and PCLs,ESD demonstrates advantages such as higher en bloc resection(although lower curative resection rates),surgical trauma minimization,shortened operative duration,and faster recovery.Moreover,it is effective in reducing serum tumor marker levels while maintaining favorable safety.
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.
文摘BACKGROUND As a minimally invasive technique,endoscopic submucosal dissection(ESD)is widely used in treating early colorectal cancer(ECRC)and precancerous lesions(PCLs).However,a common postoperative complication-delayed postoperative bleeding(DPOB)-can significantly hinder patient recovery.AIM To build and validate a predictive model for assessing post-ESD DPOB risk in ECRC and PCL patients,utilizing logistic regression methodology.METHODS A retrospective review was conducted on ECRC/PCL 302 patients who received ESD at our hospital between July 2021 and July 2024.The cohort was stratified based on the incidence of DPOB following ESD,forming DPOB and non-DPOB groups.Through allocation,they were further allocated into model and validation cohorts.Clinical variables from both cohorts were collated and subjected to univariate analysis to determine potential factors associated with post-ESD DPOB.Subsequently,we constructed a predictive model for DPOB risk employing logistic regression analysis.Model performance assessment used receiver operating characteristic curves in both the training and validation cohorts,with internal validation accomplished via 10-fold cross-validation.RESULTS The occurrence rate of DPOB was 9.93%.Univariate analysis revealed that the number of lesions,lesion size,lesion location,degree of submucosal fibrosis,and intraoperative bleeding were significantly associated with DPOB.Binary logistic regression analysis identified the number of lesions,lesion size,lesion location,and degree of submucosal fibrosis as independent DPOB determinants.A nomogram that was developed to quantify the DPOB risk exhibited that an increment in the total score corresponded to an increased risk.The model achieved area under the curve values of 0.831 and 0.821 in the model and validation groups,respectively,with P values of 0.853 and 0.203 in the Hosmer-Lemeshow test.The model demonstrated robust discriminative performance,with an average area under the curve of 0.795(95%confidence interval:0.702-0.887)in 10-fold cross-validation.CONCLUSION Collectively,the presence of multiple lesions,lesion size of≥3 cm,lesion localization in the rectum,and severe fibrosis are significant independent predictors of DPOB in patients undergoing surgery for ECRC or PCLs.The proposed risk prediction model,which integrates these factors,demonstrates excellent predictive accuracy and clinical utility,thereby providing a valuable tool for risk stratification and postoperative management in this patient population.
文摘Serological screening,endoscopic imaging,morphological visual verification of precancerous gastric diseases and changes in the gastric mucosa are the main stages of early detection,accurate diagnosis and preventive treatment of gastric precancer.Laboratory-serological,endoscopic and histological diagnostics are carried out by medical laboratory technicians,endoscopists,and histologists.Human factors have a very large share of subjectivity.Endoscopists and histologists are guided by the descriptive principle when formulating imaging conclusions.Diagnostic reports from doctors often result in contradictory and mutually exclusive conclusions.Erroneous results of diagnosticians and clinicians have fatal consequences,such as late diagnosis of gastric cancer and high mortality of patients.Effective population serological screening is only possible with the use of machine processing of laboratory test results.Currently,it is possible to replace subjective imprecise description of endoscopic and histological images by a diagnostician with objective,highly sensitive and highly specific visual recognition using convolutional neural networks with deep machine learning.There are many machine learning models to use.All machine learning models have predictive capabilities.Based on predictive models,it is necessary to identify the risk levels of gastric cancer in patients with a very high probability.
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.
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.
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.
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the National Natural Science Foundation of China,No,39770296
文摘AIM:To further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues. METHODS: Endoscopic mucosa biopsy and histopathological examinations were made on 37 subjects from a high incidence area for both esophageal and gastric cardia carcinomas in northern China. All the biopsy samples were fixed in 850 ml. (-1)L alcohol and embedded in paraffin. Each block contained one piece of tissue and was serially section at 5 microm. Immunohistochemistry (ABC) was carried out on these gastric cardia samples to determine the alterations of p16 and Rb. RESULTS: Based on the histopathlogical examination there were 11 cases of chronic superficial gastritis, 12 cases of chronic atrophic gastritis and 14 cases of dysplasia. The immunostaining demonstrated different levels of unclear immunostaining of p16 and Rb in normal gastric cardia tissue and the tissues with different severity of lesions. With the lesions progressing, the positive immunostaining rates for p16 protein had a decreasing tendency. In contrast, the positive immunostaining rate for Rb protein had an increasing tendency. There was a significant negative relationship between the two parameters. Changes of p16 was CSG 11(100%), CAG 7(58%), DYS 4(29%) and changes of Rb was CSG 2(18%), CAG 8(67%) and DYS 12(86%), (P【0.05). CONCLUSION: The alterations of p16 and Rb protein may play a role in the early stages of gastric cardia carcinogenesis.
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.
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.
基金Supported by Tianjin Education Committee Foundation, No.020334
文摘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.
