1  3671 192 INFLAMMATION AND CANCER. INFECTION AND INFLAMMATION ACCOUNT FOR APPROXIMATELY 25% OF CANCER-CAUSING FACTORS. INFLAMMATION-RELATED CANCERS ARE CHARACTERIZED BY MUTAGENIC DNA LESIONS, SUCH AS 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE (8-OXODG) AND 8-NITROGUANINE. OUR PREVIOUS STUDIES DEMONSTRATED THE FORMATION OF 8-OXODG AND 8-NITROGUANINE IN THE TISSUES OF CANCER AND PRECANCEROUS LESIONS DUE TO INFECTION (E.G., OPISTHORCHIS VIVERRINI-RELATED CHOLANGIOCARCINOMA, SCHISTOSOMA HAEMATOBIUM-ASSOCIATED BLADDER CANCER, HELICOBACTER PYLORI-INFECTED GASTRIC CANCER, HUMAN PAPILLOMAVIRUS-RELATED CERVICAL CANCER, EPSTEIN-BARR VIRUS-INFECTED NASOPHARYNGEAL CARCINOMA) AND PRO-INFLAMMATORY FACTORS (E.G., ASBESTOS, NANOMATERIALS, AND INFLAMMATORY DISEASES SUCH AS BARRETT'S ESOPHAGUS AND ORAL LEUKOPLAKIA). INTERESTINGLY, SEVERAL OF OUR STUDIES SUGGESTED THAT INFLAMMATION-ASSOCIATED DNA DAMAGE IN CANCER STEM-LIKE CELLS LEADS TO CANCER DEVELOPMENT WITH AGGRESSIVE CLINICAL FEATURES. REACTIVE OXYGEN/NITROGEN SPECIES FROM INFLAMMATION DAMAGE NOT ONLY DNA BUT ALSO OTHER BIOMACROMOLECULES, SUCH AS PROTEINS AND LIPIDS, RESULTING IN THEIR DYSFUNCTION. WE IDENTIFIED OXIDATIVELY DAMAGED PROTEINS IN CANCER TISSUES BY 2D OXYBLOT FOLLOWED BY MALDI-TOF/TOF. AS AN EXAMPLE, OXIDATIVELY DAMAGED TRANSFERRIN RELEASED IRON ION, WHICH MAY MEDIATE FENTON REACTIONS AND GENERATE ADDITIONAL REACTIVE OXYGEN SPECIES. DYSFUNCTION OF ANTI-OXIDATIVE PROTEINS DUE TO THIS DAMAGE MIGHT INCREASE OXIDATIVE STRESS. SUCH DAMAGE IN BIOMACROMOLECULES MAY FORM A VICIOUS CYCLE OF OXIDATIVE STRESS, LEADING TO CANCER DEVELOPMENT. EPIGENETIC ALTERATIONS SUCH AS DNA METHYLATION AND MICRORNA DYSREGULATION PLAY VITAL ROLES IN CARCINOGENESIS, ESPECIALLY IN INFLAMMATION-RELATED CANCERS. WE EXAMINED EPIGENETIC ALTERATIONS, DNA METHYLATION AND MICRORNA DYSREGULATION, IN EPSTEIN-BARR VIRUS-RELATED NASOPHARYNGEAL CARCINOMA IN THE ENDEMIC AREA OF SOUTHERN CHINA AND FOUND SEVERAL DIFFERENTIALLY METHYLATED TUMOR SUPPRESSOR GENE CANDIDATES BY USING A NEXT-GENERATION SEQUENCER. AMONG THESE CANDIDATES, WE REVEALED HIGHER METHYLATION RATES OF RAS-LIKE ESTROGEN-REGULATED GROWTH INHIBITOR (RERG) IN BIOPSY SPECIMENS OF NASOPHARYNGEAL CARCINOMA MORE CONVENIENTLY BY USING RESTRICTION ENZYME-BASED REAL-TIME PCR. THIS RESULT MAY HELP TO IMPROVE CANCER SCREENING STRATEGIES. WE PROFILED MICRORNAS OF NASOPHARYNGEAL CARCINOMA TISSUES USING MICROARRAYS. QUANTITATIVE RT-PCR ANALYSIS CONFIRMED THE CONCORDANT DOWNREGULATION OF MIR-497 IN CANCER TISSUES AND PLASMA, SUGGESTING THAT PLASMA MIR-497 COULD BE USED AS A DIAGNOSTIC BIOMARKER FOR NASOPHARYNGEAL CARCINOMA. CHRONIC INFLAMMATION PROMOTES GENETIC AND EPIGENETIC ABERRATIONS, WITH VARIOUS PATHOGENESES. THESE CHANGES MAY BE USEFUL BIOMARKERS IN LIQUID BIOPSY FOR EARLY DETECTION AND PREVENTION OF CANCER.	2018	
                                                                                                                                                                    
2  5582  54 ROLE OF NITRATIVE AND OXIDATIVE DNA DAMAGE IN INFLAMMATION-RELATED CARCINOGENESIS. CHRONIC INFLAMMATION INDUCED BY BIOLOGICAL, CHEMICAL, AND PHYSICAL FACTORS HAS BEEN FOUND TO BE ASSOCIATED WITH THE INCREASED RISK OF CANCER IN VARIOUS ORGANS. WE REVEALED THAT INFECTIOUS AGENTS INCLUDING LIVER FLUKE, HELICOBACTER PYLORI, AND HUMAN PAPILLOMA VIRUS AND NONINFECTIOUS AGENTS SUCH AS ASBESTOS FIBER INDUCED INOS-DEPENDENT FORMATION OF 8-NITROGUANINE AND 8-OXO-7, 8-DIHYDRO-2'-DEOXYGUANOSINE (8-OXODG) IN CANCER TISSUES AND PRECANCEROUS REGIONS. OUR RESULTS WITH THE COLOCALIZATION OF PHOSPHORYLATED ATM AND GAMMA-H2AX WITH 8-OXODG AND 8-NITROGUANINE IN INFLAMMATION-RELATED CANCER TISSUES SUGGEST THAT DNA BASE DAMAGE LEADS TO DOUBLE-STRANDED BREAKS. IT IS INTERESTING FROM THE ASPECT OF GENETIC INSTABILITY. WE ALSO DEMONSTRATED IL-6-MODULATED INOS EXPRESSION VIA STAT3 AND EGFR IN EPSTEIN-BARR-VIRUS-ASSOCIATED NASOPHARYNGEAL CARCINOMA AND FOUND PROMOTER HYPERMETHYLATION IN SEVERAL TUMOR SUPPRESSOR GENES. SUCH EPIGENETIC ALTERATION MAY OCCUR BY CONTROLLING THE DNA METHYLATION THROUGH IL-6-MEDIATED JAK/STAT3 PATHWAYS. COLLECTIVELY, 8-NITROGUANINE WOULD BE A USEFUL BIOMARKER FOR PREDICTING THE RISK OF INFLAMMATION-RELATED CANCERS.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
3  6759  27 WNT SIGNALLING PATHWAY IN ORAL LESIONS. WINGLESS-INTEGRATED/BETA-CATENIN (WNT/?-CATENIN) SIGNALLING PATHWAY IS ONE OF THE PRINCIPAL INTERCELLULAR SIGNALLING PATHWAYS IN HUMANS. IT PLAYS AN INTRINSIC ROLE IN THE CELLULAR PROLIFERATION, DIFFERENTIATION AND REGENERATION ALONG WITH MANY OTHER CELLULAR FUNCTIONS. EPIGENETIC DEOXYRIBONUCLEIC ACID METHYLATIONS AND SILENCING OF WNT SIGNALLING PATHWAY GENES HAVE A SIGNIFICANT ROLE IN MALIGNANT TRANSFORMATION OF ORAL LESIONS SUCH AS ORAL SUBMUCOUS FIBROSIS, ORAL LEUKOPLAKIA, ORAL LICHEN PLANUS AND ERYTHROPLAKIA. THE INCREASE IN WNT INHIBITORY PROTEINS ALONG WITH INFLAMMATORY FACTORS CAUSE BONE LOSS IN PERIAPICAL LESIONS, SUCH AS CHRONIC APICAL PERIODONTITIS. THIS REVIEW DISCUSSES THE MOLECULAR GENETICS OF POTENTIALLY MALIGNANT ORAL LESIONS, SHEDS LIGHT ON OUR UNDERSTANDING OF WNT/?-CATENIN SIGNALLING IN BONE LOSS PERTAINING TO PERIAPICAL LESIONS, AND ALTERATION OF THIS PATHWAY FOR THERAPEUTIC BENEFITS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4  3030  38 GENETICS OF OPISTHORCHIS VIVERRINI-RELATED CHOLANGIOCARCINOMA. PURPOSE OF REVIEW: WE REVIEW THE GENETIC, EPIGENETIC AND TRANSCRIPTIONAL LANDSCAPE OF LIVER FLUKE (OPISTHORCHIS VIVERRINI, OV)-RELATED CHOLANGIOCARCINOMA (CCA). ITS DISTINCT ALTERATIONS, AS COMPARED WITH NON-OV-RELATED CCA MAY HELP SHED LIGHT ON ITS UNDERLYING MOLECULAR MECHANISMS. RECENT FINDINGS: RECENT WHOLE-EXOME AND TARGETED SEQUENCING NOT ONLY CONFIRMED FREQUENT MUTATIONS IN KNOWN CCA-RELATED GENES INCLUDING TP53 (44%), KRAS (16.7%) AND SMAD4 (16.7%), BUT ALSO REVEALED MUTATIONS IN NOVEL CCA-RELATED GENES ASSOCIATED WITH CHROMATIN REMODELING [BAP1 (2.8%), ARID1A (17.6%), MLL3 (13%) AND IDH1/2 (2.8%)], WNT SIGNALING [RNF43 (9.3%) AND PEG3 (5.6%)] AND KRAS/G PROTEIN SIGNALING [GNAS (9.3%) AND ROBO2 (9.3%)]. INTERESTINGLY, THERE IS A SIGNIFICANT DIFFERENCE IN THE FREQUENCY OF MUTATED GENES BETWEEN OV-RELATED CCA AND NON-OV-RELATED CCA, SUCH AS P53 AND IDH1/2, REFLECTING THE IMPACT OF CAUSE ON PATHOGENESIS. ALTERED DNA METHYLATION AND TRANSCRIPTIONAL PROFILES ASSOCIATED WITH XENOBIOTIC METABOLISM AND PRO-INFLAMMATORY RESPONSES WERE ALSO FOUND IN OV-RELATED CCA. SUMMARY: LIVER FLUKE-INDUCED CHRONIC INFLAMMATION PLAYS A CRUCIAL ROLE IN CHOLANGIOCARCINOGENESIS, RESULTING IN DISTINCT SIGNATURES OF GENETIC, EPIGENETIC AND TRANSCRIPTIONAL ALTERATIONS. THESE ALTERATIONS, WHEN CONTRASTED WITH NON-OV-RELATED CCA, INDICATE A UNIQUE PATHOGENIC PROCESS IN OV-RELATED CCA AND MAY HAVE POTENTIAL CLINICAL IMPLICATIONS ON DIAGNOSTICS, THERAPEUTICS AND PREVENTION.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
5  2938  26 GENETIC AND EPIGENETIC ALTERATIONS IN BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA. ESOPHAGEAL ADENOCARCINOMA (EAC) DEVELOPS FROM BARRETT'S ESOPHAGUS (BE), WHEREIN NORMAL SQUAMOUS EPITHELIA IS REPLACED BY SPECIALIZED INTESTINAL METAPLASIA IN RESPONSE TO CHRONIC GASTROESOPHAGEAL ACID REFLUX. BE CAN PROGRESS TO LOW- AND HIGH-GRADE DYSPLASIA, INTRAMUCOSAL, AND INVASIVE CARCINOMA. BOTH BE AND EAC ARE CHARACTERIZED BY LOSS OF HETEROZYGOSITY, ANEUPLOIDY, SPECIFIC GENETIC MUTATIONS, AND CLONAL DIVERSITY. GIVEN THE LIMITATIONS OF HISTOPATHOLOGY, GENOMIC AND EPIGENOMIC ANALYSES MAY IMPROVE THE PRECISION OF RISK STRATIFICATION. ASSAYS TO DETECT MOLECULAR ALTERATIONS ASSOCIATED WITH NEOPLASTIC PROGRESSION COULD BE USED TO IMPROVE THE PATHOLOGIC ASSESSMENT OF BE/EAC AND TO SELECT HIGH-RISK PATIENTS FOR MORE INTENSIVE SURVEILLANCE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
6   563  34 BARRETT'S ESOPHAGUS: CAN BIOMARKERS PREDICT PROGRESSION TO MALIGNANCY? BARRETT'S ESOPHAGUS (BE) IS ONE OF THE MOST COMMON PREMALIGNANT LESIONS AND CAN PROGRESS TO ESOPHAGEAL ADENOCARCINOMA. IT IS CHARACTERIZED HISTOLOGICALLY BY A SPECIALIZED INTESTINAL METAPLASIA THAT REPLACES THE SQUAMOUS EPITHELIUM OF THE DISTAL ESOPHAGUS, AND IS ASSOCIATED WITH CHRONIC GASTROESOPHAGEAL REFLUX DISEASE AND OBESITY. SIMILAR TO THE ADENOMA-CARCINOMA SEQUENCE OF COLORECTAL CARCINOMAS, ESOPHAGEAL ADENOCARCINOMA DEVELOPS THROUGH PROGRESSION FROM BE TO LOW- AND HIGH-GRADE DYSPLASIA, THEN TO ADENOCARCINOMA WITH ACCUMULATION OF GENETIC AND EPIGENETIC ABNORMALITIES. THE EXACT MALIGNANCY POTENTIAL OF BE IS UNCERTAIN. DYSPLASIA IS THE MOST PREDICTIVE MARKER FOR RISK OF ESOPHAGEAL ADENOCARCINOMA, WHEREAS ENDOSCOPIC AND HISTOLOGICAL DIAGNOSES ARE STILL THE GOLD STANDARD FOR SURVEILLANCE OF PATIENTS WITH BE. HOWEVER, BOTH ARE LIMITED, EITHER BY SAMPLING ERRORS IN BIOPSIES OR BY DIFFERENCES IN HISTOLOGICAL INTERPRETATION. SEVERAL STUDIES HAVE IDENTIFIED CANDIDATE BIOMARKERS THAT MAY HAVE PREDICTIVE VALUE AND MAY SERVE AS ADDITIONAL FACTORS FOR THE RISK ASSESSMENT OF ESOPHAGEAL ADENOCARCINOMA. THIS REVIEW DISCUSSES THE ROLE OF BIOMARKERS IN THE PROGRESSION FROM BE TO ADENOCARCINOMA, FOCUSING ON CLINICAL AND MOLECULAR MARKERS.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
7  1975  33 EPIGENETIC ALTERATIONS FROM BARRETT'S ESOPHAGUS TO ESOPHAGEAL ADENOCARCINOMA. BARRETT'S ESOPHAGUS (BE) IS A DISEASE ENTITY THAT IS A SEQUELA OF CHRONIC GASTROESOPHAGEAL REFLUX DISEASE THAT MAY RESULT IN ESOPHAGEAL ADENOCARCINOMA (EAC) DUE TO COLUMNAR EPITHELIAL DYSPLASIA. THE HISTOLOGICAL DEGREE OF DYSPLASIA IS THE SOLE BIOMARKER FREQUENTLY UTILIZED BY CLINICIANS. HOWEVER, THE COST OF ENDOSCOPY AND THE FACT THAT THE DEGREE OF DYSPLASIA DOES NOT PROGRESS IN MANY PATIENTS WITH BE DIMINISH THE EFFECTIVENESS OF HISTOLOGICAL GRADING AS A PERFECT BIOMARKER. MULTIPLE OR MORE QUANTITATIVE BIOMARKERS ARE REQUIRED BY CLINICIANS SINCE EARLY DIAGNOSIS IS CRUCIAL IN ESOPHAGEAL ADENOCANCERS, WHICH HAVE A HIGH MORTALITY RATE. THE PRESENCE OF EPIGENETIC FACTORS IN THE EARLY STAGES OF THIS NEOPLASTIC TRANSFORMATION HOLDS PROMISE AS A PREDICTIVE BIOMARKER. IN THIS REVIEW, CURRENT STUDIES ON DNA METHYLATIONS, HISTONE MODIFICATIONS, AND NONCODING RNAS (MIRNAS) THAT HAVE BEEN DISCOVERED DURING THE PROGRESSION FROM BE DYSPLASIA TO EAC WERE COLLATED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
8  1575  35 DNA METHYLATION PATTERNS OF GENES RELATED TO IMMUNE RESPONSE IN THE DIFFERENT CLINICAL FORMS OF ORAL LICHEN PLANUS. BACKGROUND: THE ORAL LICHEN PLANUS IS A CHRONIC INFLAMMATORY DISEASE. ALTHOUGH ITS AETIOLOGY IS NOT WELL UNDERSTOOD, THE ROLE OF T LYMPHOCYTES IN ITS INFLAMMATORY EVENTS IS RECOGNISED. IDENTIFYING THE EPIGENETIC MECHANISMS INVOLVED IN THE PATHOGENESIS OF THIS IMMUNE-MEDIATED CONDITION IS FUNDAMENTAL FOR UNDERSTANDING THE INFLAMMATORY REACTION THAT OCCURS IN THE DISEASE. THE PURPOSE OF THIS WORK WAS TO EVALUATE THE METHYLATION PATTERN OF 21 IMMUNE RESPONSE-RELATED GENES IN THE DIFFERENT CLINICAL FORMS OF ORAL LICHEN PLANUS. METHODS: A CROSS-SECTIONAL STUDY WAS PERFORMED TO ANALYSE THE DNA METHYLATION PATTERNS IN THREE DISTINCT GROUPS OF ORAL LICHEN PLANUS: (I) RETICULAR/PLAQUE LESIONS; (II) EROSIVE LESIONS; (III) NORMAL ORAL MUCOSA (CONTROL GROUP). AFTER DNA EXTRACTION FROM BIOPSIES, THE SAMPLES WERE SUBMITTED TO DIGESTIONS BY METHYLATION-SENSITIVE AND METHYLATION-DEPENDENT ENZYMES AND DOUBLE DIGESTION. THE RELATIVE PERCENTAGE OF METHYLATED DNA FOR EACH GENE WAS PROVIDED USING REAL-TIME POLYMERASE CHAIN REACTION ARRAYS. RESULTS: HYPERMETHYLATION OF THE STAT5A GENE WAS OBSERVED ONLY IN THE CONTROL GROUP (59.0%). A HIGHER HYPERMETHYLATION OF THE ELANE GENE WAS FOUND IN RETICULAR/PLAQUE LESIONS (72.1%) COMPARED TO THE EROSIVE LESIONS (50.0%). CONCLUSION: OUR RESULTS SHOW VARIATIONS IN THE METHYLATION PROFILE OF IMMUNE RESPONSE-RELATED GENES, ACCORDING TO THE CLINICAL TYPE OF ORAL LICHEN PLANUS AFTER COMPARING WITH THE NORMAL ORAL MUCOSA. FURTHER STUDIES ARE NECESSARY TO VALIDATE THESE FINDINGS USING GENE EXPRESSION ANALYSIS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9  5010  39 PEROXIDATION OF LINOLEIC, ARACHIDONIC AND OLEIC ACID IN RELATION TO THE INDUCTION OF OXIDATIVE DNA DAMAGE AND CYTOGENETIC EFFECTS. IN THE PRESENT STUDY, THE POSSIBLE ROLE OF THE POLYUNSATURATED FATTY ACIDS LINOLEIC AND ARACHIDONIC ACID IN THE CHEMICAL INDUCTION OF CARCINOGENESIS HAS BEEN INVESTIGATED. ANALYSIS OF 7,8-DIHYDRO-8-OXO-2'-DEOXYGUANOSINE (8-OXODG) LEVELS IN 2'-DEOXYGUANOSINE (DG) AND ISOLATED DNA HAS DEMONSTRATED THAT LINOLEIC AND ARACHIDONIC ACID ARE CAPABLE OF INDUCING THIS SPECIFIC GENOTOXIC DAMAGE. THIS EFFECT APPEARS TO BE RELATED TO THE DEGREE OF FATTY ACID UNSATURATION, SINCE IT WAS NOT INDUCED BY MONOUNSATURATED OLEIC ACID. ENZYMATIC PEROXIDATION OF LINOLEIC AND ARACHIDONIC ACID RESULTED IN A SIGNIFICANT INCREASE IN OXIDATIVE DNA DAMAGE. STUDIES ON THE INTERFERENCE OF RADICAL SCAVENGERS WITH THE INDUCTION OF 8-OXODG IN COMBINATION WITH ELECTRON SPIN RESONANCE SPECTROSCOPY DEMONSTRATED THAT THE SUPEROXIDE ANION WAS GENERATED DURING PEROXIDATION OF THESE FATTY ACIDS AND THAT SINGLET OXYGEN IS MOST LIKELY INVOLVED IN THE FORMATION OF OXIDATIVE DNA DAMAGE. THE LEVEL OF OXIDATIVE DAMAGE IN DG AND SINGLE-STRANDED DNA WAS HIGHER AS COMPARED TO THAT IN NATIVE DNA AFTER EQUIMOLAR TREATMENT. EXPOSURE OF HUMAN LYMPHOCYTES TO LINOLEIC OR ARACHIDONIC ACID DID NOT RESULT IN A SIGNIFICANT INCREASE IN LEVELS OF 8-OXODG. THIS MAY INDICATE THAT THE RATE OF INTRACELLULAR PEROXIDATION IS RELATIVELY LOW AND/OR THAT NUCLEAR DNA IN INTACT CELLS IS EFFECTIVELY PROTECTED AGAINST GENETIC DAMAGE INDUCED BY REACTIVE OXYGEN SPECIES. IT IS THEREFORE CONCLUDED THAT RELATIVELY SHORT PERIODS OF LINOLEIC OR ARACHIDONIC ACID ADMINISTRATION ARE NOT LIKELY TO IMPOSE A DIRECT GENOTOXIC RISK. IT CAN, HOWEVER, NOT BE EXCLUDED THAT CHRONIC EXPOSURE TO POLYUNSATURATED FATTY ACIDS INDUCES OXIDATIVE DNA DAMAGE OR IS RELATED TO CANCER RISK BY EPIGENETIC MECHANISMS, AS IS ALSO INDICATED BY THE OBSERVED CYTOTOXIC EFFECTS OF LINOLEIC AND ARACHIDONIC ACID.	1994	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
10  6871  31 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
11  5667  34 SFRP TUMOUR SUPPRESSOR GENES ARE POTENTIAL PLASMA-BASED EPIGENETIC BIOMARKERS FOR MALIGNANT PLEURAL MESOTHELIOMA. MALIGNANT PLEURAL MESOTHELIOMA (MPM) IS ASSOCIATED WITH ASBESTOS EXPOSURE. ASBESTOS CAN INDUCE CHRONIC INFLAMMATION WHICH IN TURN CAN LEAD TO SILENCING OF TUMOUR SUPPRESSOR GENES. WNT SIGNALING PATHWAY CAN BE AFFECTED BY CHRONIC INFLAMMATION AND IS ABERRANTLY ACTIVATED IN MANY CANCERS INCLUDING COLON AND MPM. SFRP GENES ARE ANTAGONISTS OF WNT PATHWAY, AND SFRPS ARE POTENTIAL TUMOUR SUPPRESSORS IN COLON, GASTRIC, BREAST, OVARIAN, AND LUNG CANCERS AND MESOTHELIOMA. THIS STUDY INVESTIGATED THE EXPRESSION AND DNA METHYLATION OF SFRP GENES IN MPM CELLS LINES WITH AND WITHOUT DEMETHYLATION TREATMENT. SIXTY-SIX PATIENT FFPE SAMPLES WERE ANALYSED AND HAVE SHOWED METHYLATION OF SFRP2 (56%) AND SFRP5 (70%) IN MPM. SFRP2 AND SFRP5 TUMOUR-SUPPRESSIVE ACTIVITY IN ELEVEN MPM LINES WAS CONFIRMED, AND LONG-TERM ASBESTOS EXPOSURE LED TO REDUCED EXPRESSION OF THE SFRP1 AND SFRP2 GENES IN THE MESOTHELIUM (MET-5A) VIA EPIGENETIC ALTERATIONS. FINALLY, DNA METHYLATION OF SFRPS IS DETECTABLE IN MPM PATIENT PLASMA SAMPLES, WITH METHYLATED SFRP2 AND SFRP5 SHOWING A TENDENCY TOWARDS GREATER ABUNDANCE IN PATIENTS. THESE DATA SUGGESTED THAT SFRP GENES HAVE TUMOUR-SUPPRESIVE ACTIVITY IN MPM AND THAT METHYLATED DNA FROM SFRP GENE PROMOTERS HAS THE POTENTIAL TO SERVE AS A BIOMARKER FOR MPM PATIENT PLASMA.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
12  4984  31 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
13  4437  35 MOLECULAR EVOLUTION OF METAPLASIA TO ADENOCARCINOMA IN THE ESOPHAGUS. ESOPHAGEAL ADENOCARCINOMA (EAC) DEVELOPS FROM BARRETT'S ESOPHAGUS (BE), A CONDITION WHERE THE NORMAL SQUAMOUS EPITHELIA IS REPLACED BY SPECIALIZED INTESTINAL METAPLASIA IN RESPONSE TO CHRONIC GASTROESOPHAGEAL ACID REFLUX. IN A MINORITY OF INDIVIDUALS, BE CAN PROGRESS TO LOW- AND HIGH-GRADE DYSPLASIA AND EVENTUALLY TO INTRA-MUCOSAL AND THEN INVASIVE CARCINOMA. BE PROVIDES RESEARCHERS WITH A UNIQUE MODEL TO CHARACTERIZE THE PROCESS BY WHICH A CARCINOMA ARISES FROM ITS PRECURSOR LESION. MOLECULAR STUDIES OF BE HAVE DEMONSTRATED THAT IT IS NOT SIMPLY A METAPLASTIC TISSUE, BUT RATHER IT HARBORS FREQUENT ALTERATIONS THAT ARE ALSO PRESENT IN DYSPLASTIC BE AND IN EAC. BOTH BE AND EAC ARE CHARACTERIZED BY LOSS OF HETEROZYGOSITY, ANEUPLOIDY, SPECIFIC GENETIC MUTATIONS, AND CLONAL DIVERSITY. EPIGENETIC ABNORMALITIES, PRIMARY ALTERATIONS IN DNA METHYLATION, ARE ALSO FREQUENTLY SEEN IN BE AND EAC. CANDIDATE GENE AND ARRAY-BASED APPROACHES HAVE DEMONSTRATED THAT NUMEROUS TUMOR SUPPRESSOR GENES EXHIBIT ABERRANT PROMOTER METHYLATION, AND SOME OF THESE ALTERED GENES ARE ASSOCIATED WITH THE NEOPLASTIC PROGRESSION OF BE. IT HAS ALSO BEEN SHOWN THAT THE BE AND EAC EPIGENOMES ARE CHARACTERIZED BY HYPOMETHYLATION OF INTRAGENIC AND NON-CODING REGIONS RECENT STUDIES HAVE ALSO PROVIDED NEW INSIGHT INTO THE EVOLUTIONARY FORCES UNDERLYING THE MOLECULAR ALTERATIONS SEEN IN BE AND EAC AND INTO THE MOLECULAR PATHOGENESIS OF EAC.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
14  5181  31 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15  4430  49 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	

16  3666  42 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
17  3170  30 GUT INFLAMMATION AND TUMORIGENESIS: EVERY SITE HAS A DIFFERENT TALE TO TELL. GUT INFLAMMATION HAS BEEN CORRELATED WITH CANCEROGENESIS BY DISRUPTING GASTROINTESTINAL HOMEOSTASIS. NUMEROUS CHRONIC INFLAMMATORY DISORDERS OF THE TUBULAR GASTROINTESTINAL TRACT (E.G., GASTROESOPHAGEAL REFLUX DISEASE, HELICOBACTER PYLORI-INDUCED AND AUTOIMMUNE CHRONIC GASTRITIS, CELIAC DISEASE, AND INFLAMMATORY BOWEL DISEASES) HAVE BEEN VARIABLY ASSOCIATED WITH AN INCREASED NEOPLASTIC RISK. GASTROINTESTINAL INFLAMMATION-INDUCED NEOPLASMS INCLUDE EPITHELIAL TUMORS (ESOPHAGEAL SQUAMOUS CELL CARCINOMA AND ADENOCARCINOMA, GASTRIC ADENOCARCINOMA AND NEUROENDOCRINE TUMORS, SMALL BOWEL ADENOCARCINOMA AND NEUROENDOCRINE TUMORS, AND COLORECTAL CANCER) AND LYMPHOMAS (SUCH AS GASTRIC MARGINAL ZONE LYMPHOMAS AND ENTEROPATHY-ASSOCIATED T CELL LYMPHOMA). IN THE LAST DECADES, NUMEROUS STUDIES HAVE INVESTIGATED THE PATHOGENETIC MECHANISMS AND THE MICROENVIRONMENTAL/MICROBIOME CHANGES THAT TRIGGER GENETIC AND/OR EPIGENETIC ALTERATIONS EVENTUALLY LEADING TO TUMORIGENESIS, OFTEN THROUGH A HISTOLOGICALLY RECOGNIZABLE INFLAMMATION-DYSPLASIA-CARCINOMA CANCEROGENIC SEQUENCE. IN THE PRESENT REVIEW, AN OVERVIEW OF THE CURRENT KNOWLEDGE ON THE LINKS BETWEEN INFLAMMATORY DISEASES AND NEOPLASMS OF THE TUBULAR GI TRACT, APPLYING A SITE-BY-SITE APPROACH, IS PROVIDED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
18  3231  34 HELICOBACTER PYLORI-INDUCED MODULATION OF THE PROMOTER METHYLATION OF WNT ANTAGONIST GENES IN GASTRIC CARCINOGENESIS. BACKGROUND: THIS STUDY AIMED TO INVESTIGATE THE CHANGES IN THE PROMOTER METHYLATION AND GENE EXPRESSION OF MULTIPLE WNT ANTAGONISTS BETWEEN THE CHRONIC INFECTION AND ERADICATION OF HELICOBACTER PYLORI (H. PYLORI) IN GASTRIC CARCINOGENESIS. METHODS: THE LEVELS OF METHYLATION AND CORRESPONDING MRNA EXPRESSION OF SEVEN WNT ANTAGONIST GENES (SFRP1, -2, -5, DKK1, -2, -3, WIF1) WERE COMPARED AMONG THE PATIENTS WITH H. PYLORI-POSITIVE GASTRIC CANCERS (GCS), AND H. PYLORI-POSITIVE AND H. PYLORI-NEGATIVE CONTROLS, BY QUANTITATIVE METHYLIGHT ASSAY AND REAL-TIME REVERSE TRANSCRIPTION (RT)-POLYMERASE CHAIN REACTION (PCR), RESPECTIVELY. THE CHANGES OF THE METHYLATION AND EXPRESSION LEVELS OF THE GENES WERE ALSO COMPARED BETWEEN THE H. PYLORI ERADICATION AND H. PYLORI-PERSISTENT GROUPS 1 YEAR AFTER ENDOSCOPIC RESECTION OF GCS. RESULTS: THE METHYLATION LEVELS OF SFRP AND DKK FAMILY GENES WERE SIGNIFICANTLY INCREASED IN THE PATIENTS WITH H. PYLORI-POSITIVE GCS AND FOLLOWED BY H. PYLORI-POSITIVE CONTROLS COMPARED WITH H. PYLORI-NEGATIVE CONTROLS (P < 0.001). SFRP1, -2, AND DKK3 GENE EXPRESSION WAS STEPWISE DOWNREGULATED FROM H. PYLORI-NEGATIVE CONTROLS, H. PYLORI-POSITIVE CONTROLS, AND TO H. PYLORI-POSITIVE GCS (P < 0.05). AMONG THE WNT ANTAGONISTS, ONLY THE DEGREES OF METHYLATION AND DOWNREGULATION OF DKK3 WERE SIGNIFICANTLY REDUCED AFTER H. PYLORI ERADICATION (P < 0.05). CONCLUSION: EPIGENETIC SILENCING OF SFRP AND DKK FAMILY GENES MAY FACILITATE THE FORMATION OF AN EPIGENETIC FIELD DURING H. PYLORI-ASSOCIATED GASTRIC CARCINOGENESIS. THE EPIGENETIC FIELD MAY NOT BE REVERSED EVEN AFTER H. PYLORI ERADICATION EXCEPT BY DKK3 METHYLATION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19  2994  43 GENETIC PATHOGENESIS OF INFLAMMATION-ASSOCIATED CANCERS IN DIGESTIVE ORGANS. EPIDEMIOLOGICAL, CLINICAL, AND BIOLOGICAL STUDIES CONVINCINGLY DEMONSTRATE THAT CHRONIC INFLAMMATION PREDISPOSES TO THE DEVELOPMENT OF HUMAN CANCERS. IN DIGESTIVE ORGANS, INFLAMMATION-ASSOCIATED CANCERS INCLUDE COLITIS-ASSOCIATED COLORECTAL CANCERS, HELICOBACTER PYLORI-ASSOCIATED GASTRIC CANCER, AS WELL AS BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA ASSOCIATED WITH CHRONIC DUODENOGASTRIC-ESOPHAGEAL REFLUX. CANCER IS A GENOMIC DISEASE, AND STEPWISE ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS OF TUMOR-RELATED GENES LEADS TO THE DEVELOPMENT OF TUMOR CELLS. RECENT GENOME ANALYSES SHOW THAT GENETIC ALTERATIONS, WHICH ARE EVOKED BY INFLAMMATION, ARE LATENTLY ACCUMULATED IN INFLAMED EPITHELIAL CELLS OF DIGESTIVE ORGANS. PRODUCTION OF REACTIVE OXYGEN AND ABERRANT EXPRESSION OF ACTIVATION-INDUCED CYTIDINE DEAMINASE, A NUCLEOTIDE-EDITING ENZYME, COULD BE INDUCED IN INFLAMED GASTROINTESTINAL EPITHELIAL CELLS AND PLAY A ROLE AS A GENOMIC MODULATOR OF INFLAMMATION-ASSOCIATED CARCINOGENESIS. UNDERSTANDING THE MOLECULAR LINKAGE BETWEEN INFLAMMATION AND GENETIC ALTERATIONS WILL OPEN UP A NEW FIELD OF TUMOR BIOLOGY AND PROVIDE A NOVEL STRATEGY FOR THE PREVENTION OF INFLAMMATION-ASSOCIATED TUMORIGENESIS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
20   196  30 ACID REFLUX AND OESOPHAGEAL CANCER. BARRETT'S METAPLASIA IS ONE OF THE COMMONEST PREMALIGNANT LESIONS IN THE WESTERN WORLD FOLLOWING COLORECTAL ADENOMAS. ONE IN 50 OF THE ADULT POPULATION DEVELOPS BARRETT'S AS A CONSEQUENCE OF CHRONIC GASTRO-OESOPHAGEAL REFLUX. THE MUCOSAL INFLAMMATION SEEN WITHIN PATIENTS WITH GASTRO-OESOPHAGEAL REFLUX SEEMS LIKELY TO DRIVE THE GROWTH OF THE METAPLASTIC MUCOSA AND ALSO HELP DIRECT FURTHER ONCOLOGICAL CHANGE, YET THE MOLECULAR EVENTS THAT CHARACTERIZE THE PATHWAY FROM INFLAMMATION TO METAPLASIA TO DYSPLASIA AND ADENOCARCINOMA ARE POORLY UNDERSTOOD. THERE IS HOPE THAT UNDERSTANDING THE ROLE OF OESOPHAGEAL INFLAMMATION WILL PROVIDE IMPORTANT INSIGHT INTO THE DEVELOPMENT OF BARRETT'S METAPLASIA AND OESOPHAGEAL CANCER. THIS CHAPTER WILL DISCUSS THE INFLAMMATION SEEN WITHIN CONTEXT OF BARRETT'S OESOPHAGUS AND ALSO CLINICAL TRIALS WHICH HOPE TO ADDRESS THIS COMMON PREMALIGNANT DISEASE. THERE ARE SEVERAL ONGOING CLINICAL TRIALS WHICH ARE AIMING TO PROVIDE DATA USING ANTI-INFLAMMATORY THERAPIES TO TACKLE THIS IMPORTANT PREMALIGNANT CONDITION. THERE IS NEW DATA PRESENTED WHICH SUGGESTS THAT DATA FROM THE ASPIRIN ESOMEPRAZOLE CHEMOPREVENTION TRIAL (ASPECT) MAY HOLD THE CLUE TO DISEASE TREATMENT AND THAT THE CYTOKINE TNF-ALPHA SEEMS TO BE A KEY SIGNALLING MOLECULE IN THE METAPLASIA-DYSPLASIA-CARCINOMA SEQUENCE. SPECIFICALLY IT APPEARS THAT BOTH EPIGENETIC AND INHERITED GENETICS COOPERATE TO MODULATE THE PROGNOSIS.	2011