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

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

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions

BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

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

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

Early-Stage Cervical Cancerous Cell Detection from Cervix Images Using YOLOv5

Cervical Cancer(CC)is a rapidly growing disease among women throughout the world,especially in developed and developing countries.For this many women have died.Fortunately,it is curable if it can be diagnosed and detected at an early stage and taken proper treatment.But the high cost,awareness,highly equipped diagnosis environment,and availability of screening tests is a major barrier to participating in screening or clinical test diagnoses to detect CC at an early stage.To solve this issue,the study focuses on building a deep learning-based automated system to diagnose CC in the early stage using cervix cell images.The system is designed using the YOLOv5(You Only Look Once Version 5)model,which is a deep learning method.To build the model,cervical cancer pap-smear test image datasets were collected from an open-source repository and these were labeled and preprocessed.Then the YOLOv5 models were applied to the labeled dataset to train the model.Four versions of the YOLOv5 model were applied in this study to find the best fit model for building the automated system to diagnose CC at an early stage.All of the model’s variations performed admirably.The model can effectively detect cervical cancerous cell,according to the findings of the experiments.In the medical field,our study will be quite useful.It can be a good option for radiologists and help them make the best selections possible.

Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin

BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso

Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV) infection, remains a global public health problem. The cellular transformation and maintenance of the malignant phenotype of these HPVs are attributed to the viral oncoproteins E6 and E7. Objective: This study aims to detect the presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous lesions, histologically confirmed in Burkina Faso. Methods: This descriptive cross-sectional study focused on cases of cervical cancer and high-grade intraepithelial neoplasia (CIN) and was conducted from June to December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues were collected from the pathological anatomy and cytology laboratories of hospitals in the capital of Burkina Faso. High-risk human papillomavirus (HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was 50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and high-grade CIN were positive for at least one high-risk human papillomavirus (HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18, 31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%;95% CI: [94.58 - 99.94]) were also positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16, 18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6 and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool for improved assessment of the progression to cervical cancer.

Uncoupling protein 2 deficiency of non-cancerous tissues inhibits the progression of pancreatic cancer in mice

Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.

Retraction: Toxic chemotherapeutic nutrition of cancer cells by alkaline glucosodiene molecules via targeting metabolic of cancerous tumors: a promising theory for cancer treatment. Cancer Adv. 2023;6:e23010. doi:10.53388/2023623010

Cancer Advance has retracted this article at the request of the corresponding author because there are significant errors in the structure of the compound,which forms the basis of the research.Cancer Advance received this manuscript on 15 April 2023.After the plagiarism check on 19 April 2023,the overall similarity rate of this manuscript was 20%,which was qualified.Then the manuscript was started to be sent to peer review at 9:17 on 19 April 2023.This manuscript was sent to fourteen reviewers and two of them sent back the comments.These two reviewers are invited to review on 19 April 2023.Due to the journal's single-blind peer review policy,we do not give the names of the two reviewers here.One reviewer gave the decision“Accept with major revision”and the other reviewer gave the decision“Accept with minor revision”.

Toxic chemotherapeutic nutrition of cancer cells by alkaline glucosodiene molecules via targeting metabolic of cancerous tumors: a promising theory for cancer treatment

Cancer is a genetic disease characterized by heritable defects in cellular regulatory mechanisms.Tumor cells must adapt their metabolism to survive and proliferate in the challenging conditions of the tumor microenvironment.To maintain uncontrolled cellular growth and survival,cancer cells alter their metabolism,which makes them dependent on a steady supply of nutrients and energy.Almost a century ago,the Warburg theory suggested that cancer cells consume glucose even in the presence of oxygen.Recent studies have confirmed that cancer cells indeed consume significantly more glucose than normal cells.Cancerous tumors require an acidic microenvironment with low oxygen levels for growth and spread.However,recent advances in pH measurement have shown that the intracellular pH of cancer cells is neutral or slightly alkaline compared to normal tissue cells.This finding indicates that not all tumors are highly acidic.Taking advantage of cancer cells’high glucose consumption,a strategy to lyse cancer cells is tested by means of glucose modifications that exploit the characteristics of their uncontrolled growth process.From the study of the molecular structure to give him alkaline properties that enable him to make defects in the tumor structure and possibly achieve cell killing,this situation will have a killing effect on cancer cells if small molecules of toxic atoms(alkaline atoms)can be continuously supplied to them through food,due to the uncontrolled consumption of glucose molecules by cancer cells.This theory attempts to investigate by changing the atomic structure of glucose molecules to make them alkaline glucosodiene molecules as one of the methods to kill cancer cells.By preparing alkaline glucosodiene molecules and performing animal experiments and histological observations,it was shown that tumors without alkaline treatment showed a tendency to infiltrate and grow,while tumors treated with glucosodiene molecules showed complete disappearance of cell structure and nucleolysis,supporting the validity of the theory.

Expression and significance of Musashi-1 in gastric cancer and precancerous lesions

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.

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

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.

Protein expression trends of DNMT1 in gastrointestinal diseases:From benign to precancerous lesions to cancer

BACKGROUND In recent years,the incidence of gastrointestinal(GI)cancer in China has increased annually.Early detection and appropriate therapy are considered to be the key to treat GI cancer.DNMT1 takes an active part in the advancement of GI cancer,which will change as the disease progresses.But its expression characteristics in the dynamic variations of GI carcinogenesis are still unclear.AIM To investigate the expression characteristics of DNMT1 in different GI diseases.METHODS We detected the expression of DNMT1 in 650 cases of different GI diseases by immunohistochemistry,including 90 cases of chronic superficial gastritis(CSG),72 cases of atrophic gastritis with intestinal metaplasia(AG/GIM),54 cases of low-grade intraepithelial neoplasia(GLIN),66 cases of high-grade intraepithelial neoplasia(GHIN),71 cases of early gastric cancer(EGC),90 cases of normal intestinal mucosa(NIM),54 cases of intestinal low-grade intraepithelial neoplasia(ILIN),71 cases of intestinal high-grade intraepithelial neoplasia(IHIN),and 82 cases of early colorectal cancer(ECRC).RESULTS In the CSG group,all cases showed weakly positive or negative expression of DNMT1.However,in other four groups(AG/GIM,GLIN,GHIN,and EGC),the positive expression rate gradually increased with the severity of the diseases;the negative or weakly positive cases accounted for 55.56%(40/72),38.89%(21/54),1.52%(1/66),and 1.41%(1/71),respectively.Besides,the moderately positive cases were 44.44%(32/72),57.41%(31/54),80.30%(53/66),and 43.66%(31/71),respectively.The strongly positive cases only existed in the GLIN(3.70%,2/54),GHIN(18.18%,12/66),and EGC(54.93%,39/71)groups.The differences between any two groups were statistically significant(P<0.05).Similarly,in the NIM group,cases with weakly positive expression of DNMT1 were predominant(91.11%,82/90),and the rest were moderately positive cases(8.89%,8/90).In the ILIN,IHIN,and ECRC groups,the rates of cases with weak or negative expression of DNMT1 were 46.30%(25/54),12.68%(9/71),and 4.88%(4/82),respectively;with moderately positive expression were 53.70%(29/54),71.83%(51/71),and 34.15%(28/82),respectively;and with strongly positive expression were 0.00%(0/54),15.49%(11/71),and 60.98%(50/82),respectively.The differences between any two groups were also statistically significant(P<0.05).CONCLUSION The overexpression of DNMT1 protein could effectively predict early GI cancers and severe precancerous lesions,which may have potential clinical application value.

Gastric epithelial histology and precancerous conditions

The most common histological type of gastric cancer(GC)is gastric adenocarcinoma arising from the gastric epithelium.Less common variants include mesenchymal,lymphoproliferative and neuroendocrine neoplasms.The Lauren scheme classifies GC into intestinal type,diffuse type and mixed type.The WHO classification includes papillary,tubular,mucinous,poorly cohesive and mixed GC.Chronic atrophic gastritis(CAG)and intestinal metaplasia are recommended as common precancerous conditions.No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended.Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus.Presently,the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis,treatment and surveillance.Management of precancerous conditions promotes the early detection and treatment of early GC,and even prevent the occurrence of GC.In the review,precancerous conditions including CAG,metaplasia,foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded,based on the overview of gastric epithelial histological organization and its renewal.

Abnormal Change of p53 Gene in Gastric and PrecancerousLesions and APC Gene Deletion in Gastric Carcinoma and Near Tissues

p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric

Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions

Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.

Gastric mucosal precancerous lesions in Helicobacter pyloriinfected pediatric patients in central China:A single-center,retrospective investigation

BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

The Role of Ras Gene Mutation in Gastric Cancer and Precancerous Lesions

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia,atypical hyperplasia, early-stage cancer and advanced cancer was 16. 7%, 31. 2 %, 50. 0%, and 32. 2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of Hras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G→T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P<0.05, P<0.01, P<0.01,respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.