1  3773 121 INTERACTION OF CERVICAL MICROBIOME WITH EPIGENOME OF EPITHELIAL CELLS: SIGNIFICANCE OF INFLAMMATION TO PRIMARY HEALTHCARE. ONE PILLAR OF THE PREDICTIVE, PREVENTIVE, AND PERSONALIZED MEDICINE FRAMEWORK STRATEGIES IS THE FEMALE HEALTH. THE EVALUATION OF WOMEN'S LIFESTYLE AND DIETARY HABITS IN CONTEXT WITH GENETIC AND MODIFIABLE RISK FACTORS MAY REFLECT THE PREVENTION OF CERVICAL CANCER BEFORE THE OCCURRENCE OF CLINICAL SYMPTOMS AND PREDICTION OF CERVICAL LESION BEHAVIOR. THE MAIN AIM OF THIS REVIEW IS TO ANALYZE PUBLICATIONS IN THE FIELD OF PRECISION MEDICINE THAT ALLOW THE USE OF RESEARCH KNOWLEDGE OF CERVICAL MICROBIOME, EPIGENETIC MODIFICATIONS, AND INFLAMMATION IN POTENTIAL APPLICATION IN CLINICAL PRACTICE. PERSONALIZED APPROACH IN EVALUATING PATIENT'S RISK OF FUTURE DEVELOPMENT OF CERVICAL ABNORMALITY SHOULD CONSIDER THE BIOMARKERS OF THE LOCAL MICROENVIRONMENT CHARACTERIZED BY THE MICROBIAL COMPOSITION, EPIGENETIC PATTERN OF CERVICAL EPITHELIUM, AND PRESENCE OF CHRONIC INFLAMMATION. NOVEL SEQUENCING TECHNIQUES ENABLE A MORE DETAILED CHARACTERIZATION OF ACTUAL STATE IN CERVICAL EPITHELIUM. BETTER UNDERSTANDING OF ALL CHANGES IN MULTIOMICS LEVEL ENABLES A BETTER ASSESSMENT OF DISEASE PROGNOSIS AND SELECTS THE ELIGIBLE TARGETED THERAPY IN PERSONALIZED MEDICINE. RESTORING OF HEALTHY VAGINAL MICROFLORA AND REVERSING THE OUTBREAK OF CERVICAL ABNORMALITY CAN BE ALSO ACHIEVED BY DIETARY HABITS AS WELL AS UPTAKE OF PREBIOTICS, PROBIOTICS, SYNBIOTICS, MICROBIAL TRANSPLANTATION, AND OTHERS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
2  3671  31 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	
                                                                                                                                                                                                                                                                              
3  5127  23 POSTMENOPAUSAL UTERINE LEIOMYOMAS AND CHRONIC LYMPHADENOPATHY: EXPLORING EPIGENETIC CHANGES AND PATHOPHYSIOLOGY. UTERINE LEIOMYOMAS (LM) ARE TUMORS ARISING FROM THE NON-NEOPLASTIC PROLIFERATION OF SMOOTH MUSCLE CELLS WITHIN THE MYOMETRIUM. LIKE BENIGN TUMORS, LM ARE NOT GENERALLY SPREAD THROUGH THE LYMPHATIC SYSTEM, AND THEREFORE SHOULD NOT BE ASSOCIATED WITH LYMPHADENOPATHY. HEREIN, WE PRESENT A CASE OF A 60-YEAR-OLD FEMALE WHO PRESENTED TO THE CLINIC WITH POSTMENOPAUSAL BLEEDING IN THE SETTING OF SONOGRAPHICALLY EVIDENT UTERINE LM AND ABDOMINAL LYMPHADENOPATHY. A LYMPH NODE BIOPSY REVEALED PLASMA CELLS AND AN EOSINOPHILIC MATERIAL PRESUMPTIVELY DIAGNOSED AS AMYLOID. SHE THEN UNDERWENT AN ABDOMINAL HYSTERECTOMY FOR DEFINITIVE TREATMENT OF LM. SURGICAL PATHOLOGY CONFIRMED THE CLINICAL DIAGNOSIS OF UTERINE AND CERVICAL LEIOMYOMA. CURRENT LITERATURE SUGGESTS THAT GENETIC AND EPIGENETIC ABNORMALITIES CONTRIBUTE TO THE PATHOGENESIS OF LM IN ADDITION TO HORMONAL SIGNALS SUCH AS ESTROGEN AND PROGESTERONE. IT IS UNUSUAL FOR LM TO OCCUR IN POST-MENOPAUSAL WOMEN DUE TO REDUCED HORMONAL INFLUENCE. THEREFORE, THIS CASE EXPLORED AN ALTERNATIVE MECHANISM OF TUMOR PROLIFERATION. THIS CASE HYPOTHESIZES THAT GENETIC MUTATIONS AND EPIGENETIC CHANGES RESULTING FROM CHRONIC INFLAMMATORY OFFENSES CONTRIBUTED TO LM GROWTH AND LYMPHADENOPATHY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
4  3850  23 IS GENDER A FACTOR AFFECTING LONG-TERM HETEROTOPIC OSSIFICATION INCIDENCE AFTER SINGLE-LEVEL CERVICAL DISC ARTHROPLASTY? BACKGROUND: CERVICAL DISC DISEASES HAVE BEEN TREATED BY CERVICAL DISC ARTHROPLASTY (CDA). NEVERTHELESS, SOME PATIENTS WILL EXPERIENCE A MOBILITY FAILURE IN THEIR CERVICAL PROSTHESES OVER TIME BECAUSE OF HETEROTOPIC OSSIFICATION. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE ROLE OF GENDER IN LONG-TERM OUTCOMES AFTER CDA. METHODS: A RETROSPECTIVE, SINGLE-CENTER STUDY OF PATIENTS WHO UNDERWENT SINGLE-LEVEL CDA WITH A BRYAN CERVICAL DISC PROSTHESIS WAS PERFORMED, INCLUDING A NARRATIVE REVIEW ABOUT GENDER DIFFERENCES IN BOTH STRUCTURAL AND BIOMECHANICAL FEATURES OF THE CERVICAL SPINE. RESULTS: STUDY PATIENTS (14 MEN, 30 WOMEN) HAD AN AVERAGE FOLLOW-UP OF 9.8 +/- 3.2 YEARS. SIGNIFICANT DIFFERENCES EMERGED BETWEEN GENDERS FOR SPECIFIC ITEMS IN NECK DISABILITY INDEX PREOPERATIVE EVALUATION, WITH WOMEN REPORTING WORSE PAIN SCORES (P = 0.05). AFTER STRATIFICATION BY AGE, WE FOUND A HIGHER PREOPERATIVE OVERALL NECK DISABILITY INDEX SCORE FOR FEMALE PATIENTS <36 YEARS OF AGE (P = 0.03). IN AN INTERGENDER, BODY MASS INDEX-SPECIFIC COMPARISON, WE ALSO FOUND A SIGNIFICANT DIFFERENCE IN NECK DISABILITY INDEX PREOPERATIVE SCORE WITH NORMAL-WEIGHT MALE PATIENTS FARING WORSE THAN OVERWEIGHT MALE PATIENTS (P = 0.05). AT A RADIOLOGICAL LEVEL, WE FOUND A TENDENCY TOWARD A HIGHER HETEROTOPIC OSSIFICATION INCIDENCE IN MALE PATIENTS (62% IN MEN, 17% IN WOMEN, P = 0.06). THE FEMALE CERVICAL SPINE HAS DISTINCTIVE FEATURES, INCLUDING BONE STRUCTURE, MUSCULAR ACTION, SOFT TISSUE RESPONSE, AND GENETIC AND EPIGENETIC RESPONSE TO OSTEOARTHRITIS. CONCLUSIONS: THE INCIDENCE OF MOBILITY FAILURE IN OUR SERIES OF SINGLE-LEVEL CDA WAS LOWER IN FEMALE PATIENTS. SEVERAL GENDER-SPECIFIC FACTORS BOTH IN STATIC AND IN DYNAMIC FEATURES MAY PLAY A SIGNIFICANT ROLE IN SPINAL PATHOLOGY AND CDA LONG-TERM RADIOLOGICAL OUTCOME.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
5  3597  33 IMPLICATIONS OF VIRAL INFECTIONS AND ONCOGENESIS IN UTERINE CERVICAL CARCINOMA ETIOLOGY AND PATHOGENESIS. BACKGROUND: UTERINE CERVICAL CARCINOMA (UCC) IS THE MOST PREVALENT GYNECOLOGICAL MALIGNANCY GLOBALLY, WITH A RISING INCIDENCE IN RECENT YEARS. ACCUMULATING EVIDENCE INDICATES THAT SPECIFIC VIRAL INFECTIONS, INCLUDING HUMAN PAPILLOMAVIRUS (HPV), EPSTEIN-BARR VIRUS (EBV), HEPATITIS B AND C VIRUSES (HBV AND HCV), AND HUMAN HERPESVIRUS (HHV), MAY CONTRIBUTE TO UCC DEVELOPMENT AND PROGRESSION. UNDERSTANDING THE COMPLEX INTERPLAY BETWEEN VIRAL INFECTIONS AND UCC RISK IS CRUCIAL FOR DEVELOPING NOVEL PREVENTATIVE AND THERAPEUTIC INTERVENTIONS. METHODS: THIS COMPREHENSIVE REVIEW INVESTIGATES THE ASSOCIATION BETWEEN VIRAL INFECTIONS AND UCC RISK BY EXAMINING THE ROLES OF VARIOUS VIRAL PATHOGENS IN UCC ETIOLOGY AND PATHOGENESIS, AND POSSIBLE MOLECULAR MECHANISMS. ADDITIONALLY, WE EVALUATE CURRENT DIAGNOSTIC METHODS AND POTENTIAL THERAPEUTIC STRATEGIES TARGETING VIRAL INFECTIONS FOR UCC PREVENTION OR TREATMENT. RESULTS: THE PREVENTION OF UCC HAS BEEN SIGNIFICANTLY ADVANCED BY THE EMERGENCE OF SELF-SAMPLING FOR HPV TESTING AS A CRUCIAL TOOL, ALLOWING FOR EARLY DETECTION AND INTERVENTION. HOWEVER, AN ESSENTIAL CHALLENGE IN UCC PREVENTION LIES IN UNDERSTANDING HOW HPV AND OTHER VIRAL COINFECTIONS, INCLUDING EBV, HBV, HCV, HHV, HIV, OR THEIR CONCURRENT PRESENCE, MAY POTENTIALLY CONTRIBUTE TO UCC DEVELOPMENT. THE MOLECULAR MECHANISMS IMPLICATED IN THE ASSOCIATION BETWEEN VIRAL INFECTIONS AND CERVICAL CANCER DEVELOPMENT INCLUDE: (1) INTERFERENCE OF VIRAL ONCOGENES WITH CELLULAR REGULATORY PROTEINS, RESULTING IN UNCONTROLLED CELL PROLIFERATION AND MALIGNANT TRANSFORMATION; (2) INACTIVATION OF TUMOR SUPPRESSOR GENES BY VIRAL PROTEINS; (3) EVASION OF HOST IMMUNE RESPONSES BY VIRUSES; (4) INDUCTION OF A PERSISTENT INFLAMMATORY RESPONSE, CONTRIBUTING TO A TUMOR-PROMOTING MICROENVIRONMENT; (5) EPIGENETIC MODIFICATIONS THAT LEAD TO ABERRANT GENE EXPRESSION; (6) STIMULATION OF ANGIOGENESIS BY VIRUSES; AND (7) ACTIVATION OF TELOMERASE BY VIRAL PROTEINS, LEADING TO CELLULAR IMMORTALIZATION. ADDITIONALLY, VIRAL COINFECTIONS CAN ALSO ENHANCE ONCOGENIC POTENTIAL THROUGH SYNERGISTIC INTERACTIONS BETWEEN VIRAL ONCOPROTEINS, EMPLOY IMMUNE EVASION STRATEGIES, CONTRIBUTE TO CHRONIC INFLAMMATION, MODULATE HOST CELLULAR SIGNALING PATHWAYS, AND INDUCE EPIGENETIC ALTERATIONS, ULTIMATELY LEADING TO CERVICAL CARCINOGENESIS. CONCLUSION: RECOGNIZING THE IMPLICATIONS OF VIRAL ONCOGENES IN UCC ETIOLOGY AND PATHOGENESIS IS VITAL FOR ADDRESSING THE ESCALATING BURDEN OF UCC. DEVELOPING INNOVATIVE PREVENTATIVE AND THERAPEUTIC INTERVENTIONS REQUIRES A THOROUGH UNDERSTANDING OF THE INTRICATE RELATIONSHIP BETWEEN VIRAL INFECTIONS AND UCC RISK.	2023	
                                                                                                                                                                                                                                                                                                                                           
6   563  33 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  6711  35 VIRTUES AND WEAKNESSES OF DNA METHYLATION AS A TEST FOR CERVICAL CANCER PREVENTION. EPIGENETICS IS THE STUDY OF HERITABLE AND NON-HERITABLE GENETIC CODING THAT IS ADDITIVE TO INFORMATION CONTAINED WITHIN CLASSICAL DNA BASE PAIR SEQUENCES. DIFFERENTIAL METHYLATION HAS A FUNDAMENTAL ROLE IN THE DEVELOPMENT AND OUTCOME OF MALIGNANCIES, CHRONIC AND DEGENERATIVE DISEASES AND AGING. DNA METHYLATION CAN BE MEASURED ACCURATELY AND EASILY VIA VARIOUS MOLECULAR METHODS AND HAS BECOME A KEY TECHNOLOGY FOR RESEARCH AND HEALTHCARE DELIVERY, WITH IMMEDIATE ROLES IN THE ELUCIDATION OF DISEASE NATURAL HISTORY, DIAGNOSTICS AND DRUG DISCOVERY. THIS REVIEW FOCUSES ON CANCERS OF THE LOWER GENITAL TRACT, FOR WHICH THE MOST EPIGENETIC INFORMATION EXISTS. DNA METHYLATION HAS BEEN PROPOSED AS A TRIAGE FOR WOMEN INFECTED WITH HUMAN PAPILLOMAVIRUS (HPV) AND MAY EVENTUALLY DIRECTLY COMPLEMENT OR REPLACE HPV SCREENING AS A ONE-STEP MOLECULAR DIAGNOSTIC AND PROGNOSTIC TEST. METHYLATION OF HUMAN GENES IS STRONGLY ASSOCIATED WITH CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) AND CANCER. OF THE MORE THAN 100 HUMAN METHYLATION BIOMARKER GENES TESTED SO FAR IN CERVICAL TISSUE, CLOSE TO 20 HAVE BEEN REPORTED IN DIFFERENT STUDIES, AND APPROXIMATELY 10 HAVE BEEN REPEATEDLY SHOWN TO HAVE ELEVATED METHYLATION IN CERVICAL CANCERS AND HIGH-GRADE CIN (CIN2 AND CIN3), MOST PROMINENTLY CADM1, EPB41L3, FAM19A4, MAL, MIR-124, PAX1 AND SOX1. OBTAINING CONSISTENT PERFORMANCE DATA FROM THE LITERATURE IS QUITE DIFFICULT BECAUSE MOST METHYLATION STUDIES USED A VARIETY OF DIFFERENT ASSAY METHODOLOGIES AND HAD INCOMPLETE AND/OR BIASED CLINICAL SPECIMEN SETS, VARYING ASSAY THRESHOLDS AND DISPARATE TARGET GENE REGIONS. THERE HAVE BEEN RELATIVELY FEW VALIDATION STUDIES OF DNA METHYLATION BIOMARKERS IN LARGE POPULATION-BASED SCREENING STUDIES, BUT AN ENCOURAGING DEVELOPMENT MORE RECENTLY IS THE EXECUTION OF WELL-DESIGNED STUDIES TO TEST THE TRUE PERFORMANCE OF THE MARKERS IN REAL-WORLD SETTINGS. METHYLATION OF HPV GENES, ESPECIALLY HPV16, HPV18, HPV31, HPV33 AND HPV45, IN DISEASE PROGRESSION HAS BEEN A MAJOR FOCUS OF RESEARCH. ELEVATED METHYLATION OF THE HPV16 L1 AND L2 OPEN READING FRAMES, IN PARTICULAR, IS ASSOCIATED WITH CIN2, CIN3 AND INVASIVE CANCER. ESSENTIALLY ALL CANCERS HAVE HIGH LEVELS OF METHYLATION FOR HUMAN GENES AND FOR DRIVER HPV TYPES, WHICH SUGGESTS THAT QUANTITATIVE METHYLATION TESTS MAY HAVE UTILITY IN PREDICTING CIN2 AND CIN3 THAT ARE LIKELY TO PROGRESS. IT IS STILL EARLY IN THE PROCESS OF DEVELOPMENT OF METHYLATION BIOMARKERS, BUT ALREADY THEY ARE SHOWING STRONG PROMISE AS A UNIVERSAL AND SYSTEMATIC APPROACH TO MOLECULAR TRIAGE, APPLICABLE TO ALL CANCERS, NOT JUST CANCER OF THE CERVIX. DNA METHYLATION TESTING IS BETTER THAN HPV GENOTYPING TRIAGE AND IS COMPETITIVE WITH OR COMPLEMENTARY TO OTHER APPROACHES SUCH AS CYTOLOGY AND P16 STAINING. GENOME-WIDE STUDIES ARE UNDERWAY TO SYSTEMATICALLY EXPAND METHYLATION CLASSIFIER PANELS AND FIND THE BEST COMBINATIONS OF BIOMARKERS. METHYLATION TESTING IS LIKELY TO SHOW BIG IMPROVEMENTS IN PERFORMANCE IN THE NEXT 5 YEARS.	2016	

8  2842  27 FREQUENT CONCOMITANT EPIGENETIC SILENCING OF SOX1 AND SECRETED FRIZZLED-RELATED PROTEINS (SFRPS) IN HUMAN HEPATOCELLULAR CARCINOMA. BACKGROUND AND AIM: EXCEPT FOR GENETIC MUTATIONS, EPIGENETIC CHANGES ARE ALSO INVOLVED IN THE DEVELOPMENT OF HUMAN CANCERS. RECENTLY, WE HAVE IDENTIFIED SOX1, SRY (SEX DETERMINING REGION Y)-BOX 1, IS HYPERMETHYLATED IN CERVICAL CANCER AND OVARIAN CANCER. THEREFORE, WE INVESTIGATED WHETHER PROMOTER HYPERMETHYLATION OF SOX1 IS COMMON IN HEPATOCELLULAR CARCINOMA (HCC). METHODS: WE USED METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION (MS-PCR) AND BISULFITE SEQUENCING TO ANALYZE THE METHYALTION LEVEL OF THE SOX1 PROMOTER IN SEVEN HCC CELL LINES, 54 CLINICAL HCCS, 42 CIRRHOTIC LIVERS, 21 LIVERS WITH CHRONIC HEPATITIS, AND 15 CONTROL LIVERS. THEN, WE EMPLOYED QUANTITATIVE MS-PCR (QMSP) TO VALIDATE IN AN INDEPENDENT SET OF SAMPLES (60 PAIRED HCCS AND 30 CONTROL LIVERS). FINALLY, WE USED LUCIFERASE REPORTER AND COLONY FORMATION ASSAY TO CHECK THE EFFECT OF SOX1 IN HCC. RESULTS: PROMOTER METHYLATION OF SOX1 WAS SIGNIFICANTLY FREQUENT IN HCC CELL LINES AND CLINICAL HCCS, CIRRHOTIC LIVERS, BUT NOT IN CONTROL LIVERS (P < 0.0001). THERE IS A SIGNIFICANT CORRELATION BETWEEN DOWNREGULATION OF SOX1 EXPRESSION AND PROMOTER METHYLATION. QMSP RESULTS CONFIRMED THAT PROMOTER HYPERMETHYLATION OF SOX1 IS SIGNIFICANTLY MORE FREQUENT IN HCCS THAN CONTROL LIVERS (P < 0.0001). THE FREQUENCY OF SOX1 METHYLATION IN PATIENTS WITH SECRETED FRIZZLED-RELATED PROTEINS (SFRPS) METHYLATION IS SIGNIFICANTLY HIGHER THAN IN PATIENTS WITHOUT SFRPS METHYLATION (P < 0.0001). FURTHERMORE, ECTOPIC EXPRESSION OF SOX1 COULD SUPPRESS T-CELL FACTOR-DEPENDENT TRANSCRIPTIONAL ACTIVITY AND COLONY FORMATION NUMBER IN HCCS. CONCLUSIONS: CONCOMITANT EPIGENETIC SILENCING OF SOX1 AND SFRPS THROUGH PROMOTER HYPERMETHYLATION IS FREQUENT IN HCCS, AND THIS MIGHT CONTRIBUTE TO ABNORMAL ACTIVATION OF CANONICAL WNT SIGNAL PATHWAY.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
9  5181  27 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
10   734  36 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
11  3683  32 INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. CONTEXT: CHRONIC INFLAMMATION OF THE PROSTATE HAS BEEN ASSOCIATED WITH PRENEOPLASTIC LESIONS AND CANCER DEVELOPMENT. MULTIPLE CAUSES HAVE BEEN CONSIDERED FOR CHRONIC INFLAMMATION OF THE PROSTATE. INFLAMMATORY CYTOKINES SUCH AS INTERLEUKINS ARE IMPLICATED IN PROSTATE CARCINOGENESIS AND DEVELOPMENT. OBJECTIVE: TO EVALUATE LITERATURE PUBLISHED ON ETIOLOGICAL FACTORS, URINARY MICROBIOTA, MORPHOLOGICAL FEATURES OF PROLIFERATIVE INFLAMMATORY ATROPHY AND HIGH-GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA, GENETIC POLYMORPHISMS, INFLAMMATORY STRESS, AND CYTOKINE SIGNALING. EVIDENCE ACQUISITION: WE SEARCHED LITERATURE FROM PUBMED FROM 2010 AND ALSO INCLUDED THE MOST IMPORTANT PUBLICATIONS FROM THE PREVIOUS PERIOD. EVIDENCE SYNTHESIS: PROSTATE CANCER INFLAMMATION AND PREMALIGNANT LESIONS HAVE BEEN FREQUENTLY DISCUSSED IN SCIENTIFIC LITERATURE. A LIMITED NUMBER OF MODELS ARE AVAILABLE FOR STUDYING INFLAMMATION AND PREMALIGNANT LESIONS. HOWEVER, MORPHOLOGICAL PATHOLOGY COULD BE COMPLEMENTED BY ANALYSIS OF GENE POLYMORPHISMS IN THESE PATIENTS AND APPROPRIATE FUNCTIONAL STUDIES. CONCLUSIONS: PROSTATITIS COULD BE CAUSED BY BACTERIAL OR VIRAL INFECTIONS, DIETARY COMPOUNDS, AND CHANGES IN TESTOSTERONE:ESTRADIOL RATIO. IN SOME CASES, THE MICROBIOTA CAN EXERT DIRECT EFFECTS ON CANCER DEVELOPMENT. PROSTATE INFLAMMATORY ATROPHY OR HIGH GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA HAVE BEEN ASSOCIATED WITH RESPONSE TO CELLULAR STRESS AND HAVE BEEN DISCUSSED IN CONNECTION TO EARLY CANCER DEVELOPMENT. A LARGE NUMBER OF GENETIC POLYMORPHISMS HAVE BEEN IDENTIFIED IN INFLAMMATORY PROSTATE. GENETIC AND EPIGENETIC ALTERATIONS MAY BE A CONSEQUENCE OF THE PROINFLAMMATORY STRESS IN THE PROSTATE. PROINFLAMMATORY CYTOKINES INTERLEUKIN-6 AND -8 CONTRIBUTE TO PROSTATE MALIGNANCY; HOWEVER, THEIR FUNCTION WAS MORE FREQUENTLY INVESTIGATED IN CANCER TISSUE RATHER THAN IN INFLAMMATION. PATIENT SUMMARY: WE PERFORMED A REVIEW OF RECENT LITERATURE RELATED TO PROSTATE INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. NEW FUNCTIONAL APPROACHES ARE REQUIRED FOR A BETTER UNDERSTANDING OF THE ROLE OF INFLAMMATION AND CANCER DEVELOPMENT.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
12  3232  21 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
13  1031  38 CIRCULATING TUMOR DNA DETECTION AND ITS APPLICATION STATUS IN GASTRIC CANCER: A NARRATIVE REVIEW. CIRCULATING TUMOR DNA (CTDNA) IS THE SMALL GENOMIC FRAGMENT RELEASED BY TUMOR CELLS INTO THE CIRCULATING SYSTEM, WHICH CARRIES THE GENE VARIATION FEATURES, SUCH AS MUTATION, INSERTION, DELETION, REARRANGEMENT, COPY NUMBER VARIATION (CNV) AND METHYLATION, RENDERING IT AN IMPORTANT BIOMARKER. IT CAN BE USED NOT ONLY TO DIAGNOSE CERTAIN TYPES OF SOLID TUMORS, BUT ALSO TO MONITOR THE THERAPEUTIC RESPONSE AND EXPLORE THE MINIMAL RESIDUAL DISEASE (MRD) AND RESISTANT MUTATION OF TARGETED THERAPY. THEREFORE, CTDNA DETECTION MAY BECOME THE PREFERRED NON-INVASIVE TUMOR SCREENING METHOD. FOR PATIENTS WHO CANNOT RECEIVE FURTHER GENE DETECTION DUE TO INSUFFICIENT OR RESTRICTED SAMPLE COLLECTION WITH THE DEFINED PATHOLOGICAL DIAGNOSIS, CTDNA DETECTION CAN BE CARRIED OUT TO DETERMINE THE GENE MUTATION TYPE, WITH NO NEED FOR REPEATED SAMPLING. GASTRIC CANCER (GC) IS A MALIGNANCY WITH EXTREMELY HIGH MORBIDITY AND MORTALITY, AND ITS GENESIS AND DEVELOPMENT ARE THE CONSEQUENCE OF INTERACTIONS OF MULTIPLE FACTORS, INCLUDING ENVIRONMENT, DIET, HEREDITY, HELICOBACTER PYLORI INFECTION, CHRONIC INFLAMMATORY INFILTRATION, AND PRECANCEROUS LESION. AS THE RESEARCH ON GC MOVES FORWARD, THE EXISTING RESEARCH MAINLY FOCUSES ON GENETIC AND EPIGENETIC CHANGES, INCLUDING DNA METHYLATION, HISTONE MODIFICATION, NON-CODING RNA CHANGES, GENE MUTATION, GENE HETEROZYGOSITY LOSS AND MICROSATELLITE INSTABILITY. THIS PAPER AIMED TO SUMMARIZE THE CONTENTS OF CTDNA DETECTION, ITS APPLICATION STATUS IN GC AND CLINICAL SIGNIFICANCE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
14  2656  22 EPIMUTATION AND CANCER: A NEW CARCINOGENIC MECHANISM OF LYNCH SYNDROME (REVIEW). EPIMUTATION IS DEFINED AS ABNORMAL TRANSCRIPTIONAL REPRESSION OF ACTIVE GENES AND/OR ABNORMAL ACTIVATION OF USUALLY REPRESSED GENES CAUSED BY ERRORS IN EPIGENETIC GENE REPRESSION. EPIMUTATION ARISES IN SOMATIC CELLS AND THE GERMLINE, AND CONSTITUTIONAL EPIMUTATION MAY ALSO OCCUR. EPIMUTATION IS THE FIRST STEP OF TUMORIGENESIS AND CAN BE A DIRECT CAUSE OF CARCINOGENESIS. CANCERS ASSOCIATED WITH EPIMUTATION INCLUDE LYNCH SYNDROME (HEREDITARY NON-POLYPOSIS COLORECTAL CANCER, HNPCC), CHRONIC LYMPHOCYTIC LEUKEMIA, BREAST CANCER AND OVARIAN CANCER. EPIMUTATION HAS BEEN SHOWN FOR MANY TUMOR SUPPRESSOR GENES, INCLUDING RB, VHL, HMLH1, APC AND BRCA1, IN SPORADIC CANCERS. METHYLATION HAS RECENTLY BEEN SHOWN IN DNA FROM NORMAL TISSUES AND PERIPHERAL BLOOD IN CASES OF SPORADIC COLORECTAL CANCER AND MANY STUDIES SHOW CONSTITUTIVE EPIMUTATION IN CANCERS. EPIMUTATION OF DNA MISMATCH REPAIR (MMR) GENES (BRCA1, HMLH1 AND HMSH2) INVOLVED IN DEVELOPMENT FAMILIAL CANCERS HAS ALSO BEEN FOUND. THESE RESULTS HAVE LED TO A FOCUS ON EPIMUTATION AS A NOVEL ONCOGENIC MECHANISM.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15  4960  22 PATHOGENESIS OF PRE-NEOPLASTIC LESIONS OF THE STOMACH: TARGETS FOR PREVENTION. GASTRIC ATROPHY AND INTESTINAL METAPLASIA ARE GENERALLY CONSIDERED TO BE PRECANCEROUS LESIONS OF THE STOMACH. CHRONIC HELICOBACTER PYLORI INFECTION IS ONE THE MOST IMPORTANT FACTORS IN THE DEVELOPMENT OF THESE PRE-MALIGNANT GASTRIC LESIONS. IN ADDITION TO BACTERIAL FACTORS, POLYMORPHISMS IN THE CYTOKINE GENES OF THE HOST THAT MODULATE INFLAMMATORY RESPONSES ARE FOUND TO HAVE A SYNERGISTIC EFFECT IN THE DEVELOPMENT OF GASTRIC CANCER AS WELL AS PRE-NEOPLASTIC LESIONS. RECENTLY, INAPPROPRIATE ACTIVATION OF THE INTESTINE-SPECIFIC TRANSCRIPTION FACTOR LIKE THE HOMEOBOX GENE COMPLEX CDX1 AND CDX2 ARE FOUND TO BE AN IMPORTANT CONTRIBUTING FACTOR IN THE INDUCTION OF INTESTINAL METAPLASIA IN THE STOMACH. ABERRANT EXPRESSION OF CYCLOOXYGENASE-2 AND EPIGENETIC CHANGES ARE ALSO FREQUENTLY DETECTED IN PRE-NEOPLASTIC GASTRIC LESIONS. ONE OF THE MOST IMPORTANT QUESTIONS RELATING TO THESE PRE-NEOPLASTIC GASTRIC LESIONS IS THAT WHETHER H. PYLORI ERADICATION COULD REVERSE THESE CHANGES. HOWEVER, MOST CONTROLLED STUDIES SHOWED NO OR JUST MODEST IMPROVEMENT IN INTESTINAL METAPLASIA AFTER H. PYLORI ERADICATION. FURTHER STUDIES SHOULD EVALUATE THE ROLE OF OTHER CHEMOPREVENTIVE AGENTS, PARTICULARLY CYCLOOXYGENASE-2 INHIBITOR, ON REGRESSION OF PRE-NEOPLASTIC LESIONS.	2004	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
16  3222  27 HELICOBACTER PYLORI ASSOCIATED CHRONIC GASTRITIS, CLINICAL SYNDROMES, PRECANCEROUS LESIONS, AND PATHOGENESIS OF GASTRIC CANCER DEVELOPMENT. HELICOBACTER PYLORI (H. PYLORI) INFECTION IS WELL KNOWN TO BE ASSOCIATED WITH THE DEVELOPMENT OF PRECANCEROUS LESIONS SUCH AS CHRONIC ATROPHIC GASTRITIS (AG), OR GASTRIC INTESTINAL METAPLASIA (GIM), AND CANCER. VARIOUS MOLECULAR ALTERATIONS ARE IDENTIFIED NOT ONLY IN GASTRIC CANCER (GC) BUT ALSO IN PRECANCEROUS LESIONS. H. PYLORI TREATMENT SEEMS TO IMPROVE AG AND GIM, BUT STILL REMAINS CONTROVERSIAL. IN CONTRAST, MANY STUDIES, INCLUDING META-ANALYSIS, SHOW THAT H. PYLORI ERADICATION REDUCES GC. MOLECULAR MARKERS DETECTED BY GENETIC AND EPIGENETIC ALTERATIONS RELATED TO CARCINOGENESIS REVERSE FOLLOWING H. PYLORI ERADICATION. THIS INDICATES THAT THESE CHANGES MAY BE AN IMPORTANT FACTOR IN THE IDENTIFICATION OF HIGH RISK PATIENTS FOR CANCER DEVELOPMENT. PATIENTS WHO UNDERWENT ENDOSCOPIC TREATMENT OF GC ARE AT HIGH RISK FOR DEVELOPMENT OF METACHRONOUS GC. A RANDOMIZED CONTROLLED TRIAL FROM JAPAN CONCLUDED THAT PROPHYLACTIC ERADICATION OF H. PYLORI AFTER ENDOSCOPIC RESECTION SHOULD BE USED TO PREVENT THE DEVELOPMENT OF METACHRONOUS GC, BUT RECENT RETROSPECTIVE STUDIES DID NOT SHOW THE TENDENCY. PATIENTS WITH PRECANCEROUS LESIONS (MOLECULAR ALTERATIONS) THAT DO NOT REVERSE AFTER H. PYLORI TREATMENT, REPRESENT THE "POINT OF NO RETURN" AND MAY BE AT HIGH RISK FOR THE DEVELOPMENT OF GC. THEREFORE, EARLIER H. PYLORI ERADICATION SHOULD BE CONSIDERED FOR PREVENTING GC DEVELOPMENT PRIOR TO THE APPEARANCE OF PRECANCEROUS LESIONS.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
17  5180  22 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
18  5582  23 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
19  6201  22 THE INFLAMMATORY MICROENVIRONMENT AND MICROBIOME IN PROSTATE CANCER DEVELOPMENT. CHRONIC INFLAMMATION PROMOTES THE DEVELOPMENT OF SEVERAL TYPES OF SOLID CANCERS AND MIGHT CONTRIBUTE TO PROSTATE CARCINOGENESIS. THIS HYPOTHESIS PARTLY ORIGINATES IN THE FREQUENT OBSERVATION OF INFLAMMATORY CELLS IN THE PROSTATE MICROENVIRONMENT OF ADULT MEN. INFLAMMATION IS ASSOCIATED WITH PUTATIVE PROSTATE CANCER PRECURSOR LESIONS, TERMED PROLIFERATIVE INFLAMMATORY ATROPHY. INFLAMMATION MIGHT DRIVE PROSTATE CARCINOGENESIS VIA OXIDATIVE STRESS AND GENERATION OF REACTIVE OXYGEN SPECIES THAT INDUCE MUTAGENESIS. ADDITIONALLY, INFLAMMATORY STRESS MIGHT CAUSE EPIGENETIC ALTERATIONS THAT PROMOTE NEOPLASTIC TRANSFORMATION. PROLIFERATIVE INFLAMMATORY ATROPHY IS ENRICHED FOR PROLIFERATIVE LUMINAL EPITHELIAL CELLS OF INTERMEDIATE PHENOTYPE THAT MIGHT BE PRONE TO GENOMIC ALTERATIONS LEADING TO PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATE CANCER. STUDIES IN ANIMALS SUGGEST THAT INFLAMMATORY CHANGES IN THE PROSTATE MICROENVIRONMENT CONTRIBUTE TO REPROGRAMMING OF PROSTATE EPITHELIAL CELLS, A POSSIBLE STEP IN TUMOUR INITIATION. PROSTATIC INFECTION, CONCURRENT WITH EPITHELIAL BARRIER DISRUPTION, MIGHT BE A KEY DRIVER OF AN INFLAMMATORY MICROENVIRONMENT; THE DISCOVERY OF A URINARY MICROBIOME INDICATES A POTENTIAL SOURCE OF FREQUENT EXPOSURE OF THE PROSTATE TO A DIVERSE NUMBER OF MICROORGANISMS. HENCE, CURRENT EVIDENCE SUGGESTS THAT INFLAMMATION AND ATROPHY ARE INVOLVED IN PROSTATE CARCINOGENESIS AND SUGGESTS A ROLE FOR THE MICROBIOME IN ESTABLISHING AN INFLAMMATORY PROSTATE MICROENVIRONMENT THAT MIGHT PROMOTE PROSTATE CANCER DEVELOPMENT AND PROGRESSION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
20  3803  27 INTESTINAL METAPLASIA OF THE STOMACH. A STATUS REPORT. INTESTINAL METAPLASIA IN THE STOMACH INCREASES THE RISK OF GASTRIC CANCER, AND THE INCREASED RISK IS PROPORTIONAL TO THE EXTENT OF THE METAPLASIA. THIS RISK COULD BE GENERATED BY ONE OR MORE MECHANISMS: (1) THE METAPLASTIC TISSUE IS AN EARLY STEP IN A MULTISTEP INDUCTION PROCESS; (2) THE METAPLASTIC TISSUE IS AN EPIGENETIC CHANGE THAT RAISES THE PH OF GASTRIC JUICE BY REPLACING OXYNTIC MUCOSA, FAVORING THE GROWTH OF A BACTERIA CAPABLE OF GENERATING ENDOGENOUS MUTAGENS; AND/OR (3) THE METAPLASIA IS ONLY A MARKER FOR CHRONIC GASTRITIS DUE TO H. PYLORI INFECTION OR PERNICIOUS ANEMIA. WITH THE LAST MECHANISM, THE INFLAMMATORY RESPONSE FAVORS INTRAMURAL MUTAGENESIS THAT MIGHT RESULT IN METAPLASIA OR NEOPLASIA AS INDEPENDENT EVENTS. FINDING GENE REARRANGEMENTS COMMON TO BOTH METAPLASTIC AND NEOPLASTIC TISSUE MAY ESTABLISH A DIRECT LINK BETWEEN THEM, BUT TOO FEW HAVE BEEN IDENTIFIED TO ACCOUNT FOR THE LARGE NUMBER OF STOMACH CANCERS THAT DEVELOP IN HIGH RISK POPULATIONS. HISTOCHEMICAL AND IMMUNOCHEMICAL STAINS THAT IDENTIFY ENZYMES OR MUCOSUBSTANCES MAY SUGGEST THAT METAPLASTIC EPITHELIAL CELLS RESEMBLE SMALL OR LARGE INTESTINAL CELLS, BUT THEY ARE DISTINCTLY DIFFERENT FROM BOTH. MOREOVER, THESE STAINS DO NOT INDICATE WHETHER A GIVEN CYTOLOGIC CHANGE IS GENETIC OR EPIGENETIC; THEREFORE, THEY CANNOT BE USED TO DEFINE THE RELATIONSHIP BETWEEN METAPLASIA AND NEOPLASIA. IT IS UNNECESSARY FOR PRACTICING PHYSICIANS TO AWAIT RESOLUTION OF THIS QUESTION. IT CAN BE ASSUMED THAT ANY PERSON WITH EXTENSIVE METAPLASIA IS AT HIGH RISK FOR GASTRIC CANCER AND SHOULD BE SUBJECT TO PERIODIC SCREENING. THE EXTENT OF THE METAPLASTIC PROCESS IS PROBABLY MORE IMPORTANT THAN THE METAPLASTIC SUBTYPE.	1994