1  3804 81 INTESTINAL MICROBIOTA, CHRONIC INFLAMMATION, AND COLORECTAL CANCER. IN ADDITION TO GENETIC AND EPIGENETIC FACTORS, VARIOUS ENVIRONMENTAL FACTORS, INCLUDING DIET, PLAY IMPORTANT ROLES IN THE DEVELOPMENT OF COLORECTAL CANCER (CRC). RECENTLY, THERE IS INCREASING INTEREST IN THE INTESTINAL MICROBIOTA AS AN ENVIRONMENTAL RISK FACTOR FOR CRC, BECAUSE DIET ALSO INFLUENCES THE COMPOSITION OF THE INTESTINAL MICROBIOTA. THE HUMAN INTESTINAL MICROBIOTA COMPRISES ABOUT 100 TRILLION MICROBES. THIS MICROBIOME THRIVES ON UNDIGESTED DIETARY RESIDUES IN THE INTESTINAL LUMEN AND PRODUCES VARIOUS METABOLITES. IT IS WELL KNOWN THAT THE DIETARY RISK FACTORS FOR CRC ARE MEDIATED BY DYSBIOSIS OF THE INTESTINAL MICROBIOTA AND THEIR METABOLITES. IN THIS REVIEW, WE DESCRIBE THE BACTERIAL TAXA ASSOCIATED WITH CRC, INCLUDING FUSOBACTERIUM NUCLEATUM, ENTEROTOXIGENIC BACTEROIDES FRAGILIS, ESCHERICHIA COLI, AND BUTYRATE-PRODUCING BACTERIA. WE ALSO DISCUSS THE HOST-DIET INTERACTION IN COLORECTAL CARCINOGENESIS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
2  4271 35 MICROBIAL DYSBIOSIS-INDUCED OBESITY: ROLE OF GUT MICROBIOTA IN HOMOEOSTASIS OF ENERGY METABOLISM. THE GLOBAL OBESITY EPIDEMIC HAS NECESSITATED THE SEARCH FOR BETTER INTERVENTION STRATEGIES INCLUDING THE EXPLOITATION OF THE HEALTH BENEFITS OF SOME GUT MICROBIOTA AND THEIR METABOLIC PRODUCTS. THEREFORE, WE EXAMINED THE GUT MICROBIAL COMPOSITION AND MECHANISMS OF INTERACTION WITH THE HOST IN RELATION TO HOMOEOSTATIC ENERGY METABOLISM AND PATHOPHYSIOLOGY OF DYSBIOSIS-INDUCED METABOLIC INFLAMMATION AND OBESITY. WE ALSO DISCUSSED THE EUBIOTIC, HEALTH-PROMOTING EFFECTS OF PROBIOTICS AND PREBIOTICS AS WELL AS EPIGENETIC MODIFICATIONS ASSOCIATED WITH GUT MICROBIAL DYSBIOSIS AND RISK OF OBESITY. HIGH-FAT/CARBOHYDRATE DIET PROGRAMMES THE GUT MICROBIOTA TO ONE PREDOMINATED BY FIRMICUTES (CLOSTRIDIUM), PREVOTELLA AND METHANOBREVIBACTER BUT DEFICIENT IN BENEFICIAL GENERA/SPECIES SUCH AS BACTEROIDES, BIFIDOBACTERIUM, LACTOBACILLUS AND AKKERMANSIA. ALTERED GUT MICROBIOTA IS ASSOCIATED WITH DECREASED EXPRESSION OF SCFA THAT MAINTAIN INTESTINAL EPITHELIAL BARRIER INTEGRITY, REDUCE BACTERIAL TRANSLOCATION AND INFLAMMATION AND INCREASE EXPRESSION OF HUNGER-SUPPRESSING HORMONES. REDUCED AMOUNTS OF BENEFICIAL MICRO-ORGANISMS ALSO INHIBIT FASTING-INDUCED ADIPOCYTE FACTOR EXPRESSION LEADING TO DYSLIPIDAEMIA. A LOW-GRADE CHRONIC INFLAMMATION (METABOLIC ENDOTOXAEMIA) ENSUES WHICH CULMINATES IN OBESITY AND ITS CO-MORBIDITIES. THE SYNERGY OF HIGH-FAT DIET AND DYSBIOTIC GUT MICROBIOTA INITIATES A RECIPE THAT EPIGENETICALLY PROGRAMMES THE HOST FOR INCREASED ADIPOSITY AND POOR GLYCAEMIC CONTROL. INTERESTINGLY, THESE OBESOGENIC MECHANISTIC PATHWAYS THAT ARE TRANSMITTABLE FROM ONE GENERATION TO ANOTHER CAN BE MODULATED THROUGH THE ADMINISTRATION OF PROBIOTICS, PREBIOTICS AND SYNBIOTICS. THOUGH THE INFLUENCE OF GUT MICROBIOTA ON THE RISK OF OBESITY AND SEVERAL INTERVENTION STRATEGIES HAVE BEEN EXTENSIVELY DEMONSTRATED IN ANIMAL MODELS, APPLICATION IN HUMANS STILL REQUIRES FURTHER ROBUST INVESTIGATION.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
3  4430 27 MOLECULAR BIOLOGY OF ONCOGENIC INFLAMMATORY PROCESSES. I. NON-ONCOGENIC AND ONCOGENIC PATHOGENS, INTRINSIC INFLAMMATORY REACTIONS WITHOUT PATHOGENS, AND MICRORNA/DNA INTERACTIONS (REVIEW). IN SOME INFLAMMASOMES TUMOR CELLS ARE GENERATED. THE INTERNAL ENVIRONMENT OF THE INFLAMMASOME IS CONDUCIVE TO THE INDUCTION OF MALIGNANT TRANSFORMATION. EPIGENETIC CHANGES INITIATE THIS PROCESS. THE SUBVERTED STROMAL CONNECTIVE TISSUE CELLS ACT TO PROMOTE AND SUSTAIN THE PROCESS OF MALIGNANT TRANS-FORMATION. IN ITS EARLY STAGES, THE PREMALIGNANT CELLS DEPEND ON PARACRINE CIRCUITRIES FOR THE RECEPTION OF GROWTH FACTORS. THE LIGANDS ARE DERIVED FROM THE CONNECTIVE TISSUE, AND THE RECEPTORS ARE EXPRESSED ON THE RECIPIENT PREMALIGNANT CELLS. THE INITIAL EVENTS ARE NOT A DIRECT ATTACK ON THE PROTO-ONCOGENES, AND THUS IT MAY BE ENTIRELY REVERSIBLE. EPIGENETIC PROCESSES OF HYPERMETHYLATION OF THE GENES AT THE PROMOTERS OF TUMOR SUPPRESSOR GENES (TO SILENCE THEM), AND DEACETYLATION OF THE HISTONES AIMED AT THE PROMOTERS OF PROTO-ONCOGENES (TO ACTIVATE THEM) ARE ON-GOING. A LARGE NUMBER OF SHORT RNA SEQUENCES (INTERFERING, MICRO-, SHORT HAIRPIN, NON-CODING RNAS) SILENCE TUMOR SUPPRESSOR GENES, BY NEUTRALIZING THEIR MRNAS. IN A SERIAL SEQUENCE ONCOGENES UNDERGO AMPLIFICATIONS, POINT-MUTATIONS, TRANSLOCATIONS AND FUSIONS. IN ITS EARLIEST STAGE, THE PROCESS IS REVERSIBLE BY DEMETHYLATION OF THE SILENCED SUPPRESSOR GENE PROMOTERS (TO REACTIVATE THEM), OR RE-ACETYLATION OF THE HISTONES OF THE ONCOGENE PROMOTERS, THUS DE-ACTIVATING THEM. THE EXTERNAL ADMINISTRATION OF HISTONE DEACETYLASE INHIBITORS USUALLY LEADS TO THE RESTORATION OF HISTONE ACETYLATION. IN TIME, THE UNCORRECTED PROCESSES SOLIDIFY INTO CONSTITUTIVE AND IRREVERSIBLE GENE MUTATIONS. SOME OF THE PATHOGENS INDUCING INFLAMMATIONS WITH CONSQUENTIAL MALIGNANT TRANSFORMATION CONTAIN ONCOGENIC GENE SEQUENCES (PAPILLOMA VIRUSES, EPSTEIN-BARR VIRUS, KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS, HEPATITIS B AND C VIRUSES, MERKEL CELL POLYOMA VIRUS, HELICOBACTER PYLORI, ENTEROTOXIGENIC BACTEROIDES FRAGILIS). THESE INDUCED MALIGNANCIES MAY BE MULTIFOCAL. OTHER PATHOGENS ARE DEVOID OF ANY KNOWN ONCOGENIC GENOMIC SEQUENCES (MYCOPLASMA VAV-CARCINOGENESIS, CHLAMYDIA MALT-LYMPHOMA GENESIS). IN THESE CASES THE HOST'S INFLAMMATORY REACTIONS INDUCE THE MALIGNANT TRANSFORMATION IN SERIAL SEQUENCES OF GENE ALTERATIONS INITIATED BY HYPOXIA AND REACTIVE OXYGEN AND NITROGEN SPECIES GENERATION. CARCINOGENIC INTRINSIC INFLAMMATORY PROCESSES ENDOGENOUSLY INITIATED WITHOUT A PATHOGEN ARE RECOGNIZED. CHRONIC INFLAMMATORY PROCESSES SIGNAL THE RNA/DNA COMPLEX. IN RESPONSE, THE DNA MAY REVERT INTO ITS ANCIENT PRIMORDIAL 'IMMORTAL' FORMAT, WHICH THE CLINICS RECOGNIZE AS 'ONCOGENESIS'. THE DNA REMAINS THE ULTIMATE MASTER OF BIOENGINEERING IN ORDER TO SUSTAIN LIFE. A DISCUSSION ON THE MOST VERSATILE AND RESISTANT PRIMORDIAL RNA/DNA COMPLEX AND THE PRE-, PROTO-, AND UNICELLULAR WORLD IN WHICH THEY CO-EXISTED IS INCLUDED.	2012	

4  4270 24 MICROBIAL DYSBIOSIS AND THE HOST AIRWAY EPITHELIAL RESPONSE: INSIGHTS INTO HIV-ASSOCIATED COPD USING MULTI'OMICS PROFILING. BACKGROUND: PEOPLE LIVING WITH HIV (PLWH) ARE AT INCREASED RISK OF DEVELOPING CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INDEPENDENT OF CIGARETTE SMOKING. WE HYPOTHESIZED THAT DYSBIOSIS IN PLWH IS ASSOCIATED WITH EPIGENETIC AND TRANSCRIPTOMIC DISRUPTIONS IN THE AIRWAY EPITHELIUM. METHODS: AIRWAY EPITHELIAL BRUSHINGS WERE COLLECTED FROM 18 COPD + HIV + , 16 COPD - HIV + , 22 COPD + HIV - AND 20 COPD - HIV - SUBJECTS. THE MICROBIOME, METHYLOME, AND TRANSCRIPTOME WERE PROFILED USING 16S SEQUENCING, ILLUMINA INFINIUM METHYLATION EPIC CHIP, AND RNA SEQUENCING, RESPECTIVELY. MULTI 'OMIC INTEGRATION WAS PERFORMED USING DATA INTEGRATION ANALYSIS FOR BIOMARKER DISCOVERY USING LATENT COMPONENTS. A CORRELATION > 0.7 WAS USED TO IDENTIFY KEY INTERACTIONS BETWEEN THE 'OMES. RESULTS: THE COPD + HIV -, COPD -HIV + , AND COPD + HIV + GROUPS HAD REDUCED SHANNON DIVERSITY (P = 0.004, P = 0.023, AND P = 5.5E-06, RESPECTIVELY) COMPARED TO INDIVIDUALS WITH NEITHER COPD NOR HIV, WITH THE COPD + HIV + GROUP DEMONSTRATING THE MOST REDUCED DIVERSITY. MICROBIAL COMMUNITIES WERE SIGNIFICANTLY DIFFERENT BETWEEN THE FOUR GROUPS (P = 0.001). MULTI 'OMIC INTEGRATION IDENTIFIED CORRELATIONS BETWEEN BACTEROIDETES PREVOTELLA, GENES FUZ, FASTKD3, AND ACVR1B, AND EPIGENETIC FEATURES CPG-FUZ AND CPG-PHLDB3. CONCLUSION: PLWH WITH COPD MANIFEST DECREASED DIVERSITY AND ALTERED MICROBIAL COMMUNITIES IN THEIR AIRWAY EPITHELIAL MICROBIOME. THE REDUCTION IN PREVOTELLA IN THIS GROUP WAS LINKED WITH EPIGENETIC AND TRANSCRIPTOMIC DISRUPTIONS IN HOST GENES INCLUDING FUZ, FASTKD3, AND ACVR1B.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
5  6871 23 [PATHOGENETIC IMPORTANCE OF HELICOBACTER PYLORI INFECTION]. H. PYLORI ARE ETIOLOGICAL FACTOR OF HUMAN ACUTE AND CHRONIC GASTRITIS. DEPENDING ON PATHOGENIC FACTORS OF MICROORGANISM AND POLYMORPHISM OF HUMAN GENES, CHRONIC GASTRITIS CAN BE A CAUSE FOR ULCERATIVE ENTERITIS OF THE DUODENUM OR STOMACH, GASTRIC ADENOCARCINOMA AND MALT-LYMPHOMA DEVELOPMENT. WE REVEALED GENETIC FEATURES OF BACTERIA, DETERMINED THE INTENSITY OF INFLAMMATION, SUCH AS PATHOGENIC FACTORS--CAG, PLASTIC REGION OF THE GENOME AND ADHESIN CODING GENES. EPIGENETIC CHANGES, FOR EXAMPLE THE METHYLATION OF E-CADHERIN GENE ASSOCIATED WITH H PYLORI, ARE CRUCIAL FOR CARCINOGENESIS. THEREBY, PREDISPOSITION OF CHRONIC GASTRITIS ASSOCIATED WITH H. PYLORI TO ULCERATIVE ENTERITIS OF THE DUODENUM, ULCERATIVE STOMACH DISEASE OR GASTRIC ADENOCARCINOMA DEPENDS ON TOPOGRAPHY, THE INTENSITY OF INFLAMMATION AND CHANGES OF ACID PRODUCTION IN THE STOMACH.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
6  4984 28 PATHWAYS OF GASTRIC CARCINOGENESIS, HELICOBACTER PYLORI VIRULENCE AND INTERACTIONS WITH ANTIOXIDANT SYSTEMS, VITAMIN C AND PHYTOCHEMICALS. HELICOBACTER PYLORI IS A CLASS ONE CARCINOGEN WHICH CAUSES CHRONIC ATROPHIC GASTRITIS, GASTRIC INTESTINAL METAPLASIA, DYSPLASIA AND ADENOCARCINOMA. THE MECHANISMS BY WHICH H. PYLORI INTERACTS WITH OTHER RISK AND PROTECTIVE FACTORS, PARTICULARLY VITAMIN C IN GASTRIC CARCINOGENESIS ARE COMPLEX. GASTRIC CARCINOGENESIS INCLUDES METABOLIC, ENVIRONMENTAL, EPIGENETIC, GENOMIC, INFECTIVE, INFLAMMATORY AND ONCOGENIC PATHWAYS. THE MOLECULAR CLASSIFICATION OF GASTRIC CANCER SUBTYPES HAS REVOLUTIONIZED THE UNDERSTANDING OF GASTRIC CARCINOGENESIS. THIS INCLUDES THE TUMOUR MICROENVIRONMENT, GERMLINE MUTATIONS, AND THE ROLE OF HELICOBACTER PYLORI BACTERIA, EPSTEIN BARR VIRUS AND EPIGENETICS IN SOMATIC MUTATIONS. THERE IS EVIDENCE THAT ASCORBIC ACID, PHYTOCHEMICALS AND ENDOGENOUS ANTIOXIDANT SYSTEMS CAN MODIFY THE RISK OF GASTRIC CANCER. GASTRIC JUICE ASCORBATE LEVELS DEPEND ON DIETARY INTAKE OF ASCORBIC ACID BUT CAN ALSO BE DECREASED BY H. PYLORI INFECTION, H. PYLORI CAGA SECRETION, TOBACCO SMOKING, ACHLORHYDRIA AND CHRONIC ATROPHIC GASTRITIS. ASCORBIC ACID MAY BE PROTECTIVE AGAINST GASTRIC CANCER BY ITS ANTIOXIDANT EFFECT IN GASTRIC CYTOPROTECTION, REGENERATING ACTIVE VITAMIN E AND GLUTATHIONE, INHIBITING ENDOGENOUS N-NITROSATION, REDUCING TOXIC EFFECTS OF INGESTED NITROSODIMETHYLAMINES AND HETEROCYCLIC AMINES, AND PREVENTING H. PYLORI INFECTION. THE EFFECTIVENESS OF SUCH CYTOPROTECTION IS RELATED TO H. PYLORI STRAIN VIRULENCE, PARTICULARLY CAGA EXPRESSION. THE ROLE OF VITAMIN C IN EPIGENETIC REPROGRAMMING IN GASTRIC CANCER IS STILL EVOLVING. OTHER FACTORS IN CONJUNCTION WITH VITAMIN C ALSO PLAY A ROLE IN GASTRIC CARCINOGENESIS. ERADICATION OF H. PYLORI MAY LEAD TO RECOVERY OF VITAMIN C SECRETION BY GASTRIC EPITHELIUM AND ENABLE REGRESSION OF PREMALIGNANT GASTRIC LESIONS, THEREBY INTERRUPTING THE CORREA CASCADE OF GASTRIC CARCINOGENESIS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
7  3232 20 HELICOBACTER PYLORI-INDUCED SIGNALING PATHWAYS CONTRIBUTE TO INTESTINAL METAPLASIA AND GASTRIC CARCINOGENESIS. HELICOBACTER PYLORI (H. PYLORI) INDUCES CHRONIC GASTRIC INFLAMMATION, ATROPHIC GASTRITIS, INTESTINAL METAPLASIA, AND CANCER. ALTHOUGH THE RISK OF GASTRIC CANCER INCREASES EXPONENTIALLY WITH THE EXTENT OF ATROPHIC GASTRITIS, THE PRECISE MECHANISMS OF GASTRIC CARCINOGENESIS HAVE NOT BEEN FULLY ELUCIDATED. H. PYLORI INDUCES GENETIC AND EPIGENETIC CHANGES IN GASTRIC EPITHELIAL CELLS THROUGH ACTIVATING INTRACELLULAR SIGNALING PATHWAYS IN A CAGPAI-DEPENDENT MANNER. H. PYLORI EVENTUALLY INDUCES GASTRIC CANCER WITH CHROMOSOMAL INSTABILITY (CIN) OR MICROSATELLITE INSTABILITY (MSI), WHICH ARE CLASSIFIED AS TWO MAJOR SUBTYPES OF GASTRIC CANCER. ELUCIDATION OF THE PRECISE MECHANISMS OF GASTRIC CARCINOGENESIS WILL ALSO BE IMPORTANT FOR CANCER THERAPY.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
8  5793 13 STAPHYLOCOCCAL ENTEROTOXIN B INFLUENCES THE DNA METHYLATION PATTERN IN NASAL POLYP TISSUE: A PRELIMINARY STUDY. STAPHYLOCOCCAL ENTEROTOXINS MAY INFLUENCE THE PRO-INFLAMMATORY PATTERN OF CHRONIC SINUS DISEASES VIA EPIGENETIC EVENTS. THIS WORK INTENDED TO INVESTIGATE THE POTENTIAL OF STAPHYLOCOCCAL ENTEROTOXIN B (SEB) TO INDUCE CHANGES IN THE DNA METHYLATION PATTERN. NASAL POLYP TISSUE EXPLANTS WERE CULTURED IN THE PRESENCE AND ABSENCE OF SEB; GENOMIC DNA WAS THEN ISOLATED AND USED FOR WHOLE GENOME METHYLATION ANALYSIS. RESULTS SHOWED THAT SEB STIMULATION ALTERED THE METHYLATION PATTERN OF GENE REGIONS WHEN COMPARED WITH NON STIMULATED TISSUE. DATA ENRICHMENT ANALYSIS HIGHLIGHTED TWO GENES: THE IKBKB AND STAT-5B, BOTH PLAYING A CRUCIAL ROLE IN T- CELL MATURATION/ACTIVATION AND IMMUNE RESPONSE.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
9  3666 20 INFECTION, STEM CELLS AND CANCER SIGNALS. THE ASSOCIATION OF CANCER WITH PRECEDING PARASITIC INFECTIONS HAS BEEN OBSERVED FOR OVER 200 YEARS. SOME SUCH CANCERS ARISE FROM INFECTION OF TISSUE STEM CELLS BY VIRUSES WITH INSERTION OF VIRAL ONCOGENES INTO THE HOST DNA (MOUSE POLYOMA VIRUS, MOUSE MAMMARY TUMOR VIRUS). IN OTHER CASES THE VIRUS DOES NOT INSERT ITS DNA INTO THE HOST CELLS, BUT RATHER COMMANDEERS THE METABOLISM OF THE INFECTED CELLS, SO THAT THE CELLS CONTINUE TO PROLIFERATE AND DO NOT DIFFERENTIATE (HUMAN PAPILLOMA VIRUS AND CERVICAL CANCER). CYTOPLASMIC EPSTEIN BARR VIRUS INFECTION IS ASSOCIATED WITH A SPECIFIC GENE TRANSLOCATION (IG/C-MYC) THAT ACTIVATES PROLIFERATION OF AFFECTED CELLS (BURKITT LYMPHOMA). IN CHRONIC OSTEOMYELITIS AN INFLAMMATORY REACTION TO THE INFECTION APPEARS TO ACT THROUGH PRODUCTION OF INFLAMMATORY CYTOKINES AND OXYGEN RADICAL FORMATION TO INDUCE EPITHELIAL CANCERS. INFECTION WITH HELICOBACTER PYLORI LEADS TO EPIGENETIC CHANGES IN METHYLATION AND INFECTION BY A PARASITE. CLONORCHIS SINENSIS ALSO ACTS AS A PROMOTER OF CANCER OF THE BILE DUCTS OF THE LIVER (CHOLANIOCARCINOMA). THE COMMON THREAD AMONG THESE DIVERSE PATHWAYS IS THAT THE INFECTIONS ACT TO ALTER TISSUE STEM CELL SIGNALING WITH CONTINUED PROLIFERATION OF TUMOR TRANSIT AMPLIFYING CELLS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
10  5180 21 PREMALIGNANT CONDITIONS OF GASTRIC CANCER. PREMALIGNANT LESIONS OF GASTRIC CANCER ENCOMPASS A VARIETY OF CONDITIONS SUCH AS CHRONIC GASTRITIS, INTESTINAL METAPLASIA AND DYSPLASIA, IN WHICH ELEVATED RISK OF DEVELOPING GASTRIC CANCER HAVE BEEN DOCUMENTED. AMONG THEM, INTESTINAL METAPLASIA IS FREQUENTLY ENCOUNTERED IN OUR DAILY ENDOSCOPIC EXAMINATION, YET ITS CLINICAL SIGNIFICANCE IS OFTEN UNDERESTIMATED DESPITE OF A NUMBER OF REPORTS DEMONSTRATING GENETIC AND EPIGENETIC ALTERATIONS IN THE INTESTINAL METAPLASTIC MUCOSA. IN THIS REVIEW, I WILL DESCRIBE THE MOLECULAR MECHANISMS OF PHENOTYPIC CHANGES FROM GASTRIC MUCOSA TO INTESTINAL METAPLASIA BASED ON OUR ANALYSIS OF MOUSE MODEL OF INTESTINAL METAPLASIA GENERATED BY ECTOPIC EXPRESSION OF CDX2 IN CONJUNCTION WITH THE STUDIES WITH HUMAN INTESTINAL METAPLASIA.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
11  5181 29 PREMALIGNANT LESIONS IN GASTRIC CANCER. DESPITE A PLATEAU IN INCIDENCE, GASTRIC CANCER IS ONE OF THE MOST COMMON CANCERS WORLDWIDE AND CAUSES CONSIDERABLE MORBIDITY AND MORTALITY. PREMALIGNANT GASTRIC LESIONS ARE WELL KNOWN RISK FACTORS FOR THE DEVELOPMENT OF INTESTINAL-TYPE GASTRIC ADENOCARCINOMAS. IN THIS MULTISTEP MODEL OF GASTRIC CARCINOGENESIS, HELICOBACTER PYLORI CAUSES CHRONIC ACTIVE INFLAMMATION OF THE GASTRIC MUCOSA, WHICH SLOWLY PROGRESSES THROUGH THE PREMALIGNANT STAGES OF ATROPHIC GASTRITIS, INTESTINAL METAPLASIA, AND ADENOMA/DYSPLASIA TO GASTRIC CARCINOMA. THIS PROGRESSION IS PARALLELED BY A STEPWISE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC ABNORMALITIES. DETECTION, TREATMENT, AND MOLECULAR ANALYSES OF PREMALIGNANT LESIONS MAY THUS PROVIDE A BASIS FOR GASTRIC CANCER PREVENTION. THIS REVIEW DESCRIBES AN OVERVIEW OF CURRENT KNOWLEDGE ON PREMALIGNANT GASTRIC LESIONS. IT ALSO REVIEWS THE ISSUE OF SURVEILLANCE OF PATIENTS WITH PREMALIGNANT LESIONS IN ORDER TO IMPROVE THE SURVIVAL OF PATIENTS WITH GASTRIC CANCER.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
12  3226 27 HELICOBACTER PYLORI INFECTION, ONCOGENIC PATHWAYS AND EPIGENETIC MECHANISMS IN GASTRIC CARCINOGENESIS. CHRONIC COLONIZATION OF THE HUMAN STOMACH BY HELICOBACTER PYLORI, A GRAM-NEGATIVE BACTERIUM, IS THE MAJOR CAUSE OF CHRONIC GASTRITIS, PEPTIC ULCERS AND GASTRIC CANCER. RECENT PROGRESS HAS ELUCIDATED IMPORTANT BACTERIAL AND HOST FACTORS THAT ARE RESPONSIBLE FOR H. PYLORI-INDUCED GASTRIC INFLAMMATION AND GASTRIC MALIGNANCY. H. PYLORI CYTOTOXIN-ASSOCIATED ANTIGEN A IS THE MAJOR ONCOGENIC FACTOR INJECTED INTO HOST CELLS FROM BACTERIA AND IT DISRUPTS EPITHELIAL CELL FUNCTIONS. TOGETHER WITH H. PYLORI CAG PATHOGENICITY ISLAND, IT CAUSES GENERAL INFLAMMATORY STRESS WITHIN GASTRIC MUCOSA AND ACTIVATES MULTIPLE ONCOGENIC PATHWAYS IN EPITHELIAL CELLS. A GROWING LIST OF THESE PATHWAYS INCLUDES NF-KAPPAB, ACTIVATOR PROTEIN-1, PI3K, SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION 3, WNT/BETA-CATENIN AND CYCLOOXYGENASE 2. H. PYLORI INDUCES EPIGENETIC ALTERATIONS, SUCH AS DNA METHYLATION AND HISTONE MODIFICATION, WHICH PLAY CRITICAL ROLES IN ONCOGENIC TRANSFORMATION. IN ADDITION, INVESTIGATIONS INTO GASTRIC STEM CELL OR PROGENITOR CELL BIOLOGY HAVE SHED LIGHT ON THE MECHANISMS THROUGH WHICH GASTRIC CANCER MAY ORIGINATE. CONTINUED INVESTIGATION IN THESE AREAS WILL YIELD NOVEL INSIGHTS AND HELP TO ELUCIDATE THE MECHANISMS OF BACTERIA-INDUCED CARCINOGENESIS.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
13  3413 22 HSA-MIR-29C AND HSA-MIR-135B DIFFERENTIAL EXPRESSION AS POTENTIAL BIOMARKER OF GASTRIC CARCINOGENESIS. AIM: TO INVESTIGATE THE EXPRESSION PROFILES OF HSA-MIR-29C AND HSA-MIR-135B IN GASTRIC MUCOSAL SAMPLES AND THEIR VALUES AS GASTRIC CARCINOGENESIS BIOMARKERS. METHODS: THE EXPRESSION LEVELS OF HSA-MIR-29C AND HSA-MIR-135B IN NORMAL GASTRIC MUCOSA, NON-ATROPHIC CHRONIC GASTRITIS, INTESTINAL METAPLASIA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA WERE ANALYSED USING QUANTITATIVE REAL-TIME PCR. THE DIFFERENCE BETWEEN HSA-MIR-29C AND HSA-MIR-135B EXPRESSION PROFILES IN THE GROUPED SAMPLES WAS EVALUATED BY ANOVA AND STUDENT'S T-TEST TESTS. THE RESULTS WERE ADJUSTED FOR MULTIPLE TESTING BY USING BONFERRONI'S CORRECTION. P VALUES </= 0.05 WERE CONSIDERED STATISTICALLY SIGNIFICANT. TO EVALUATE HSA-MIR-29C AND HSA-MIR-135B EXPRESSIONS AS POTENTIAL BIOMARKERS OF GASTRIC CARCINOGENESIS, WE PERFORMED A RECEIVER OPERATING CHARACTERISTIC CURVE ANALYSIS AND THE DERIVED AREA UNDER THE CURVE, AND A CATEGORICAL PRINCIPAL COMPONENTS ANALYSIS. IN SILICO IDENTIFICATION OF THE GENETIC TARGETS OF HSA-MIR-29C AND HSA-MIR-135B WAS PERFORMED USING DIFFERENT PREDICTION TOOLS, IN ORDER TO IDENTIFY POSSIBLE GENES INVOLVED IN GASTRIC CARCINOGENESIS. RESULTS: THE EXPRESSION LEVELS OF HSA-MIR-29C WERE HIGHER IN NORMAL GASTRIC MUCOSAL SAMPLES, AND DECREASED PROGRESSIVELY IN NON-ATROPHIC CHRONIC GASTRITIS SAMPLES, INTESTINAL METAPLASIA SAMPLES AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA SAMPLES. THE EXPRESSION OF HSA-MIR-29C IN THE GASTRIC LESIONS SHOWED THAT NON-ATROPHIC GASTRITIS HAVE AN INTERMEDIATE PROFILE TO GASTRIC NORMAL MUCOSA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA, AND THAT INTESTINAL METAPLASIA SAMPLES PRESENTED AN EXPRESSION PATTERN SIMILAR TO THAT IN INTESTINAL-TYPE GASTRIC ADENOCARCINOMA. THIS MICRORNA (MIRNA) HAS A GOOD DISCRIMINATORY ACCURACY BETWEEN NORMAL GASTRIC SAMPLES AND (1) INTESTINAL-TYPE GASTRIC ADENOCARCINOMA; AND (2) INTESTINAL METAPLASIA, AND REGULATES THE DMNT3A ONCOGENE. HSA-MIR-135B IS UP-REGULATED IN NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA SAMPLES AND DOWN-REGULATED IN NORMAL GASTRIC MUCOSA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA SAMPLES. NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA ARE SIGNIFICANTLY DIFFERENT FROM NORMAL GASTRIC MUCOSA SAMPLES. HSA-MIR-135B EXPRESSION PRESENTED A GREATER DISCRIMINATORY ACCURACY BETWEEN NORMAL SAMPLES AND GASTRIC LESIONS. THIS MIRNA WAS ASSOCIATED WITH HELICOBACTER PYLORI PRESENCE IN NON-ATROPHIC CHRONIC GASTRITIS SAMPLES AND REGULATES THE APC AND KLF4 TUMOUR SUPPRESSOR GENES. CONCLUSION: OUR RESULTS PROVIDE EVIDENCE OF EPIGENETIC ALTERATIONS IN NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA AND SUGGEST THAT HSA-MIR-29C AND HSA-MIR-135B ARE PROMISING BIOMARKERS OF GASTRIC CARCINOGENESIS.	2016	
                                                                                                                                                             
14  2853 21 FROM HELICOBACTER PYLORI INFECTION TO GASTRIC CANCER: CURRENT EVIDENCE ON THE IMMUNE RESPONSE. GASTRIC CANCER (GC) IS THE RESULT OF A MULTIFACTORIAL PROCESS WHOSE MAIN COMPONENTS ARE INFECTION BY HELICOBACTER PYLORI (H. PYLORI), BACTERIAL VIRULENCE FACTORS, HOST IMMUNE RESPONSE AND ENVIRONMENTAL FACTORS. THE DEVELOPMENT OF THE NEOPLASTIC MICROENVIRONMENT ALSO DEPENDS ON GENETIC AND EPIGENETIC CHANGES IN ONCOGENES AND TUMOR SUPPRESSOR GENES, WHICH RESULTS IN DEREGULATION OF CELL SIGNALING PATHWAYS AND APOPTOSIS PROCESS. THIS REVIEW SUMMARIZES THE MAIN ASPECTS OF THE PATHOGENESIS OF GC AND THE IMMUNE RESPONSE INVOLVED IN CHRONIC INFLAMMATION GENERATED BY H. PYLORI.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
15  4409 23 MOLECULAR ANATOMY AND PATHOGENIC ACTIONS OF HELICOBACTER PYLORI CAGA THAT UNDERPIN GASTRIC CARCINOGENESIS. CHRONIC INFECTION WITH HELICOBACTER PYLORI CAGA-POSITIVE STRAINS IS THE STRONGEST RISK FACTOR FOR GASTRIC CANCER. THE CAGA GENE PRODUCT, CAGA, IS DELIVERED INTO GASTRIC EPITHELIAL CELLS VIA THE BACTERIAL TYPE IV SECRETION SYSTEM. DELIVERED CAGA THEN UNDERGOES TYROSINE PHOSPHORYLATION AT THE GLU-PRO-ILE-TYR-ALA (EPIYA) MOTIFS IN ITS C-TERMINAL REGION AND ACTS AS AN ONCOGENIC SCAFFOLD PROTEIN THAT PHYSICALLY INTERACTS WITH MULTIPLE HOST SIGNALING PROTEINS IN BOTH TYROSINE PHOSPHORYLATION-DEPENDENT AND -INDEPENDENT MANNERS. ANALYSIS OF CAGA USING IN VITRO CULTURED GASTRIC EPITHELIAL CELLS HAS INDICATED THAT THE NONPHYSIOLOGICAL SCAFFOLDING ACTIONS OF CAGA CELL-AUTONOMOUSLY PROMOTE THE MALIGNANT TRANSFORMATION OF THE CELLS BY ENDOWING THE CELLS WITH MULTIPLE PHENOTYPIC CANCER HALLMARKS: SUSTAINED PROLIFERATION, EVASION OF GROWTH SUPPRESSORS, INVASIVENESS, RESISTANCE TO CELL DEATH, AND GENOMIC INSTABILITY. TRANSGENIC EXPRESSION OF CAGA IN MICE LEADS TO IN VIVO ONCOGENIC ACTION OF CAGA WITHOUT ANY OVERT INFLAMMATION. THE IN VIVO ONCOGENIC ACTIVITY OF CAGA IS FURTHER POTENTIATED IN THE PRESENCE OF CHRONIC INFLAMMATION. SINCE HELICOBACTER PYLORI INFECTION TRIGGERS A PROINFLAMMATORY RESPONSE IN HOST CELLS, A FEEDFORWARD STIMULATION LOOP THAT AUGMENTS THE ONCOGENIC ACTIONS OF CAGA AND INFLAMMATION IS CREATED IN CAGA-INJECTED GASTRIC MUCOSA. GIVEN THAT HELICOBACTER PYLORI IS NO LONGER COLONIZED IN ESTABLISHED GASTRIC CANCER LESIONS, THE MULTISTEP NATURE OF GASTRIC CANCER DEVELOPMENT SHOULD INCLUDE A "HIT-AND-RUN" PROCESS OF CAGA ACTION. THUS, ACQUISITION OF GENETIC AND EPIGENETIC ALTERATIONS THAT COMPENSATE FOR CAGA-DIRECTED CANCER HALLMARKS MAY BE REQUIRED FOR COMPLETION OF THE "HIT-AND-RUN" PROCESS OF GASTRIC CARCINOGENESIS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
16  1799 30 EFFECT OF HELICOBACTER PYLORI INFECTION ON THE COMPOSITION OF GASTRIC MICROBIOTA IN THE DEVELOPMENT OF GASTRIC CANCER. BACKGROUND: GASTRIC CANCER IS ONE OF THE MOST COMMON CANCER TYPES WORLDWIDE. IN CHINA, GASTRIC CANCER HAS BECOME ONE OF THE MAJOR THREATS FOR PUBLIC HEALTH, RANKING SECOND ON INCIDENCE AND THIRD ON CAUSE OF CANCER DEATH. DESPITE THE COMMON RISK FACTORS THAT PROMOTE THE DEVELOPMENT OF GASTRIC CANCER, THE HUGE QUANTITY OF MICROORGANISM COLONIES WITHIN THE GASTROINTESTINAL TRACT, PARTICULARLY HELICOBACTER PYLORI INFECTION, DEMONSTRATES A CORRELATION WITH CHRONIC INFLAMMATION AND GASTRIC CARCINOGENESIS, AS EPIDEMIOLOGICAL STUDIES HAVE DETERMINED THAT H. PYLORI INFECTION CONFERS APPROXIMATELY 75% OF THE ATTRIBUTABLE RISK FOR GASTRIC CANCER. SUMMARY: THE CURRENT ARTICLE DRAWS AN OVERVIEW ON THE CORRELATION BETWEEN THE MICROBIOTA, INFLAMMATION AND GASTRIC TUMORIGENESIS. H. PYLORI INFECTION HAS BEEN IDENTIFIED AS THE MAIN RISK FACTOR AS IT TRIGGERS EPITHELIAL BARRIER DISRUPTION, SURVIVAL SIGNALING AS WELL AS GENETIC/EPIGENETIC MODULATION. APART FROM H. PYLORI, THE EXISTENCE OF A DIVERSE AND COMPLEX COMPOSITION OF MICROBIOTA IN THE STOMACH HAS BEEN IDENTIFIED, WHICH SUPPORTS A ROLE OF MICROBIOTA IN THE DEVELOPMENT OF GASTRIC CANCER. MOREOVER, METAGENOMICS STUDIES FOCUSED ON THE COMPOSITION AND FUNCTION OF THE MICROBIOTA HAVE ASSOCIATED MICROBIOTA WITH GASTRIC METABOLIC DISEASES AND EVEN TUMORIGENESIS. APART FROM THE GASTRIC MICROBIOTA, INFLAMMATION IS ANOTHER IDENTIFIED CONTRIBUTOR TO CANCER DEVELOPMENT AS WELL. KEY MESSAGE: THOUGH H. PYLORI INFECTION AND THE NON-H. PYLORI MICROBIOTA PLAY A ROLE IN GASTRIC CANCER, THE PROPERTIES OF GASTRIC MICROBIOTA AND MECHANISMS BY WHICH THEY PARTICIPATE IN THE GENESIS OF GASTRIC CANCER ARE STILL NOT CLEARLY DEPICTED. MOREOVER, IT REMAINS TO BE UNDERSTOOD HOW THE PRESENCE OF MICROBIOTA ALONG WITH H. PYLORI INFECTION AFFECTS THE PROGRESS FROM GASTRIC DISEASE TO CANCER. PRACTICAL IMPLICATIONS: THIS ARTICLE SUMMARIZED A CLUE OF THE CURRENT STUDIES ON MICROBIOTA, H. PYLORI INFECTION AND THE PROGRESSION FROM GASTRIC DISEASE TO CANCER.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
17  3230 28 HELICOBACTER PYLORI-INDUCED INFLAMMATION AND EPIGENETIC CHANGES DURING GASTRIC CARCINOGENESIS. THE SEQUENCE OF EVENTS ASSOCIATED WITH THE DEVELOPMENT OF GASTRIC CANCER HAS BEEN DESCRIBED AS "THE GASTRIC PRECANCEROUS CASCADE". THIS CASCADE IS A DYNAMIC PROCESS THAT INCLUDES LESIONS, SUCH AS ATROPHIC GASTRITIS, INTESTINAL METAPLASIA AND DYSPLASIA. ACCORDING TO THIS MODEL, HELICOBACTER PYLORI (H. PYLORI) INFECTION TARGETS THE NORMAL GASTRIC MUCOSA CAUSING NON-ATROPHIC GASTRITIS, AN INITIATING LESION THAT CAN BE CURED BY CLEARING H. PYLORI WITH ANTIBIOTICS OR THAT MAY THEN LINGER IN THE CASE OF CHRONIC INFECTION AND PROGRESS TO ATROPHIC GASTRITIS. THE PRESENCE OF VIRULENCE FACTORS IN THE INFECTING H. PYLORI DRIVES THE CARCINOGENESIS PROCESS. INDEPENDENT EPIDEMIOLOGICAL AND ANIMAL STUDIES HAVE CONFIRMED THE SEQUENTIAL PROGRESSION OF THESE PRECANCEROUS LESIONS. PARTICULARLY LONG-TERM FOLLOW-UP STUDIES ESTIMATED A RISK OF 0.1% FOR ATROPHIC GASTRITIS/INTESTINAL METAPLASIA AND 6% IN CASE OF DYSPLASIA FOR THE LONG-TERM DEVELOPMENT OF GASTRIC CANCER. WITH THIS IN MIND, A BETTER UNDERSTANDING OF THE GENETIC AND EPIGENETIC CHANGES ASSOCIATED WITH PROGRESSION OF THE CASCADE IS CRITICAL IN DETERMINING THE RISK OF GASTRIC CANCER ASSOCIATED WITH H. PYLORI INFECTION. IN THIS REVIEW, WE WILL SUMMARIZE SOME OF THE MOST RELEVANT MECHANISMS AND FOCUS PREDOMINANTLY BUT NOT EXCLUSIVELY ON THE DISCUSSION OF GENE PROMOTER METHYLATION AND MIRNAS IN THIS CONTEXT.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
18  6369 32 THE ROLE OF MICRORNAS IN HELICOBACTER PYLORI PATHOGENESIS AND GASTRIC CARCINOGENESIS. GASTRIC CARCINOGENESIS IS A MULTISTEP PROCESS ORCHESTRATED BY ABERRANCIES IN THE GENETIC AND EPIGENETIC REGULATION OF ONCOGENES AND TUMOR SUPPRESSOR GENES. CHRONIC INFECTION WITH HELICOBACTER PYLORI IS THE STRONGEST KNOWN RISK FACTOR FOR THE DEVELOPMENT OF GASTRIC CANCER. H. PYLORI EXPRESSES A SPECTRUM OF VIRULENCE FACTORS THAT DYSREGULATE HOST INTRACELLULAR SIGNALING PATHWAYS THAT LOWER THE THRESHOLD FOR NEOPLASTIC TRANSFORMATION. IN ADDITION TO BACTERIAL DETERMINANTS, NUMEROUS HOST AND ENVIRONMENTAL FACTORS INCREASE THE RISK OF GASTRIC CARCINOGENESIS. RECENT DISCOVERIES HAVE SHED NEW LIGHT ON THE INVOLVEMENT OF MICRORNAS (MIRNAS) IN GASTRIC CARCINOGENESIS. MIRNAS REPRESENT AN ABUNDANT CLASS OF SMALL, NON-CODING RNAS INVOLVED IN GLOBAL POST-TRANSCRIPTIONAL REGULATION AND, CONSEQUENTLY, PLAY AN INTEGRAL ROLE AT MULTIPLE STEPS IN CARCINOGENESIS, INCLUDING CELL CYCLE PROGRESSION, PROLIFERATION, APOPTOSIS, INVASION, AND METASTASIS. EXPRESSION LEVELS OF MIRNAS ARE FREQUENTLY ALTERED IN MALIGNANCIES, WHERE THEY FUNCTION AS EITHER ONCOGENIC MIRNAS OR TUMOR SUPPRESSOR MIRNAS. THIS REVIEW FOCUSES ON MIRNAS DYSREGULATED BY H. PYLORI AND POTENTIAL ETIOLOGIC ROLES THEY PLAY IN H. PYLORI-MEDIATED GASTRIC CARCINOGENESIS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
19  1321 24 DEMONSTRATION AND CHARACTERIZATION OF MUTATIONS INDUCED BY HELICOBACTER PYLORI ORGANISMS IN GASTRIC EPITHELIAL CELLS. BACKGROUND: HELICOBACTER PYLORI GASTRITIS INCREASES GASTRIC CANCER RISK. MICROSATELLITE INSTABILITY-TYPE MUTATIONS ARE SECONDARY TO DEFICIENT DNA MISMATCH REPAIR. H. PYLORI GASTRITIS IS MORE FREQUENT IN PATIENTS WITH MICROSATELLITE INSTABILITY-POSITIVE GASTRIC CANCERS, AND H. PYLORI ORGANISMS INDEPENDENTLY OF INFLAMMATION CAN REDUCE DNA MISMATCH REPAIR PROTEIN LEVELS, RAISING THE HYPOTHESIS THAT H. PYLORI ORGANISMS MIGHT LEAD TO MUTAGENESIS DURING INFECTION. MATERIALS AND METHODS: MUTATIONS WERE DETECTED USING A GREEN FLUORESCENT PROTEIN REPORTER VECTOR (PEGFP-CA13). GASTRIC CANCER AGS CELLS TRANSFECTED WITH PEGFP-CA13 WERE COCULTURED WITH H. PYLORI OR ESCHERICHIA COLI. THE NUMBERS OF GREEN FLUORESCENT PROTEIN (GFP)-POSITIVE CELLS WERE DETERMINED, AND GFP, HMSH2, AND HMLH1 PROTEIN LEVELS WERE MEASURED BY WESTERN BLOT. THE EFFECT OF H. PYLORI ON CPG METHYLATION STATUS OF HMLH1 WAS DETERMINED BY METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION. RESULTS: GFP LEVELS AND GFP-POSITIVE CELL NUMBERS IN AGS CELLS COCULTURED WITH H. PYLORI SIGNIFICANTLY INCREASED, AS THE LEVELS OF HMLH1 AND HMSH2 DROPPED. H. PYLORI COCULTURES INDUCED LOW-LEVEL CPG METHYLATION OF THE HMLH1 PROMOTER. SEQUENCE ANALYSIS OF CELLS COCULTURED WITH H. PYLORI SHOWED AN INCREASED NUMBER OF FRAMESHIFT MUTATIONS AND POINT MUTATIONS AS COMPARED TO CELLS NOT COCULTURED WITH H. PYLORI (P = .03 AND P = .001, RESPECTIVELY). CONCLUSIONS: THIS IS THE FIRST REPORT SHOWING THAT H. PYLORI BACTERIA MAY LEAD TO ACCUMULATION OF GENOMIC MUTATIONS, INDEPENDENTLY OF UNDERLYING INFLAMMATION. THIS IS ASSOCIATED WITH REDUCED DNA MISMATCH REPAIR, AND IS AT LEAST IN PART ASSOCIATED WITH CPG METHYLATION OF THE HMLH1 PROMOTER. THESE DATA SUPPORT THE NOTION THAT H. PYLORI-INDUCED MUTATIONS AND EPIGENETIC ALTERATIONS IN GASTRIC EPITHELIAL CELLS DURING CHRONIC GASTRITIS MAY CONTRIBUTE TO AN INCREASED RISK OF GASTRIC CANCER ASSOCIATED WITH H. PYLORI INFECTION.	2006	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
20  3229 26 HELICOBACTER PYLORI-INDUCED GASTRIC INFLAMMATION AND GASTRIC CANCER. HELICOBACTER PYLORI (H. PYLORI) INFECT OVER HALF OF THE WORLD'S POPULATION. THE PREVALENCE OF H. PYLORI INFECTION AND THE PREDOMINANT GENOTYPE OF H. PYLORI VIRULENCE FACTORS VARY CONSIDERABLY ACROSS DIFFERENT GEOGRAPHICAL REGIONS. H. PYLORI COULD UNIQUELY PERSIST FOR DECADES IN THE HARSH STOMACH ENVIRONMENT, WHERE IT DAMAGES THE GASTRIC MUCOSA AND CHANGES THE PATTERN OF GASTRIC HORMONE RELEASE, THEREBY AFFECTS GASTRIC PHYSIOLOGY. BY UTILIZING VARIOUS VIRULENCE FACTORS, H. PYLORI TARGETS DIFFERENT CELLULAR PROTEINS TO MODULATE THE HOST INFLAMMATORY RESPONSE AND INITIATE MULTIPLE "HITS" ON THE GASTRIC MUCOSA, RESULTING IN CHRONIC GASTRITIS AND PEPTIC ULCERATION. AMONG THE LONG-TERM CONSEQUENCES OF H. PYLORI INFECTION IS GASTRIC MALIGNANCIES, PARTICULARLY GASTRIC CANCER (GC) AND GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA. AS SUCH, H. PYLORI HAS BEEN RECOGNIZED AS A CLASS I CARCINOGEN BY THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. DESPITE A CLOSE CAUSAL LINK BETWEEN H. PYLORI INFECTION AND THE DEVELOPMENT OF GASTRIC MALIGNANCIES, THE PRECISE MECHANISMS INVOLVED IN THIS PROCESS ARE STILL OBSCURE. STUDIES OVER THE PAST TWO DECADES HAVE REVEALED THAT H. PYLORI EXERT ONCOGENIC EFFECTS ON GASTRIC MUCOSA THROUGH A COMPLEX INTERACTION BETWEEN BACTERIAL FACTORS, HOST FACTORS, AND ENVIRONMENTAL FACTORS. NUMEROUS SIGNALING PATHWAYS CAN BE ACTIVATED BY H. PYLORI. IN THIS REVIEW, WE AIM TO ELABORATE ON THE RECENT DEVELOPMENTS IN THE PATHOPHYSIOLOGICAL MECHANISMS OF H. PYLORI-INDUCED GASTRIC INFLAMMATION AND GASTRIC CANCER.	2014