1 1890 183 ENDOMETRIOSIS-ASSOCIATED OVARIAN CARCINOMAS: INSIGHTS INTO PATHOGENESIS, DIAGNOSTICS, AND THERAPEUTIC TARGETS-A NARRATIVE REVIEW. ENDOMETRIOSIS IS A BENIGN GYNECOLOGIC CONDITION AFFECTING UP TO ONE WOMAN OUT OF TEN OF REPRODUCTIVE AGE. IT IS DEFINED BY THE PRESENCE OF ENDOMETRIAL-LIKE TISSUE IN LOCALIZATIONS OUTSIDE OF THE UTERINE CAVITY. IT OFTEN CAUSES SYMPTOMS SUCH AS CHRONIC PAIN, MOST FREQUENTLY ASSOCIATED WITH THE MENSTRUAL CYCLE, AND INFERTILITY, BUT MAY ALSO BE OLIGO- OR ASYMPTOMATIC. THERE IS EVIDENCE THAT SOME OVARIAN CARCINOMA (OC) HISTOTYPES, MAINLY THE OVARIAN CLEAR CELL (OCCC) AND ENDOMETRIOID (ENOC) CARCINOMA, MAY ARISE FROM ENDOMETRIOSIS. THE MOST FREQUENT GENOMIC ALTERATIONS IN THESE CARCINOMAS ARE MUTATIONS IN THE AT-RICH INTERACTING DOMAIN CONTAINING PROTEIN 1A (ARID1A) GENE, A SUBUNIT OF THE SWI/SNF CHROMATIN REMODELING COMPLEX, AND ALTERATIONS IN THE PHOSPHATIDYLINOSITOL 3-KINASE (PI3K)/AKT/MTOR PATHWAY, WHICH FREQUENTLY CO-OCCUR. IN ARID1A DEFICIENT CANCERS PRECLINICAL EXPERIMENTAL DATA SUGGEST DIFFERENT TARGETABLE MECHANISMS INCLUDING EPIGENETIC REGULATION, CELL CYCLE, GENOMIC INSTABILITY, THE PI3K/AKT/MTOR PATHWAY, INFLAMMATORY PATHWAYS, IMMUNE MODULATION, OR METABOLIC ALTERATIONS AS POTENTIAL PRECISION ONCOLOGY APPROACHES. MOST OF THESE STRATEGIES ARE RELYING ON THE CONCEPT OF SYNTHETIC LETHALITY IN WHICH TUMORS DEFICIENT IN ARID1A ARE MORE SENSITIVE TO THE DIFFERENT COMPOUNDS. SOME OF THESE APPROACHES ARE CURRENTLY BEING OR HAVE RECENTLY BEEN INVESTIGATED IN EARLY CLINICAL TRIALS. THE REMARKABLY FREQUENT OCCURRENCE OF THESE MUTATIONS IN ENDOMETRIOSIS-ASSOCIATED OVARIAN CANCER, THE OCCURRENCE IN A RELATIVELY YOUNG POPULATION, AND THE HIGH PROPORTION OF PLATINUM-RESISTANT DISEASE CERTAINLY WARRANTS FURTHER INVESTIGATION OF PRECISION ONCOLOGY OPPORTUNITIES IN THIS POPULATION. FURTHERMORE, ADVANCED KNOWLEDGE ABOUT ONCOGENIC MUTATIONS INVOLVED IN ENDOMETRIOSIS-ASSOCIATED OVARIAN CARCINOMAS MAY BE POTENTIALLY USEFUL FOR EARLY CANCER DETECTION. HOWEVER, THIS APPROACH MAY BE COMPLICATED BY THE FREQUENT OCCURRENCE OF SOMATIC MUTATIONS IN BENIGN ENDOMETRIOTIC TISSUE AS RECENT STUDIES SUGGEST. IN THIS NARRATIVE REVIEW OF THE CURRENT LITERATURE, WE WILL DISCUSS THE DATA AVAILABLE ON ENDOMETRIOSIS-ASSOCIATED OVARIAN CARCINOMA, WITH SPECIAL EMPHASIS ON EPIDEMIOLOGY, DIAGNOSIS AND MOLECULAR CHANGES THAT COULD HAVE THERAPEUTIC IMPLICATIONS AND CLINICAL APPLICABILITY IN THE FUTURE. 2020 2 3005 53 GENETIC, EPIGENETIC, AND STEROIDOGENIC MODULATION MECHANISMS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE, AFFECTING UP TO 10% OF REPRODUCTIVE-AGE WOMEN. THE EXACT CAUSE OF THE DISEASE IS UNKNOWN; HOWEVER, IT IS A HERITABLE CONDITION AFFECTED BY MULTIPLE GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. PREVIOUS STUDIES REPORTED VARIATIONS IN THE EPIGENETIC PATTERNS OF NUMEROUS GENES KNOWN TO BE INVOLVED IN THE ABERRANT MODULATION OF CELL CYCLE STEROIDOGENESIS, ABNORMAL HORMONAL, IMMUNE AND INFLAMMATORY STATUS IN ENDOMETRIOSIS, APOPTOSIS, ADHESION, ANGIOGENESIS, PROLIFERATION, IMMUNE AND INFLAMMATORY PROCESSES, RESPONSE TO HYPOXIA, STEROIDOGENIC PATHWAY AND HORMONE SIGNALING ARE INVOLVED IN THE PATHOGENESIS OF ENDOMETRIOSIS. ACCUMULATING EVIDENCE SUGGEST THAT VARIOUS EPIGENETIC ABERRATIONS MAY CONTRIBUTE TO THE PATHOGENESIS OF ENDOMETRIOSIS. AMONG THEM, DNA METHYLTRANSFERASES, HISTONE DEACETYLATORS, AND NON-CODING MICRORNAS DEMONSTRATE DIFFERENTIAL EXPRESSION WITHIN ENDOMETRIOTIC LESIONS AND IN THE ENDOMETRIUM OF PATIENTS WITH ENDOMETRIOSIS. IT HAS BEEN INDICATED THAT THE IDENTIFICATION OF EPIGENETIC DIFFERENCES WITHIN THE DNA OR HISTONE PROTEINS MAY CONTRIBUTE TO THE DISCOVERY OF A USEFUL PROGNOSTIC BIOMARKER, WHICH COULD AID IN THE FUTURE EARLIER DETECTION, TIMELY DIAGNOSIS, AND INITIATION OF A NEW APPROACH TO THE TREATMENT OF ENDOMETRIOSIS, AS WELL AS INFORM US ABOUT THE EFFECTIVENESS OF TREATMENT AND THE STAGE OF THE DISEASE. AS THE ETIOLOGY OF ENDOMETRIOSIS IS HIGHLY COMPLEX AND STILL FAR FROM BEING FULLY ELUCIDATED, THE PRESENTED REVIEW FOCUSES ON DIFFERENT APPROACHES TO IDENTIFY THE GENETIC AND EPIGENETIC LINKS OF ENDOMETRIOSIS AND ITS PATHOGENESIS. 2020 3 3003 64 GENETIC, EPIGENETIC AND STEM CELL ALTERATIONS IN ENDOMETRIOSIS: NEW INSIGHTS AND POTENTIAL THERAPEUTIC PERSPECTIVES. HUMAN ENDOMETRIUM IS A HIGHLY DYNAMIC TISSUE, UNDERGOING PERIODIC GROWTH AND REGRESSION AT EACH MENSTRUAL CYCLE. ENDOMETRIOSIS IS A FREQUENT CHRONIC PATHOLOGICAL STATUS CHARACTERIZED BY ENDOMETRIAL TISSUE WITH AN ECTOPIC LOCALIZATION, CAUSING PELVIC PAIN AND INFERTILITY AND A VARIABLE CLINICAL PRESENTATION. IN ADDITION, THERE IS WELL-ESTABLISHED EVIDENCE THAT, ALTHOUGH ENDOMETRIOSIS IS CONSIDERED BENIGN, IT IS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT TRANSFORMATION IN APPROXIMATELY 1.0% OF AFFECTED WOMEN, WITH THE INVOLVEMENT OF MULTIPLE PATHWAYS OF DEVELOPMENT. INCREASING EVIDENCE SUPPORTS A KEY CONTRIBUTION OF DIFFERENT STEM/PROGENITOR CELL POPULATIONS NOT ONLY IN THE CYCLIC REGENERATION OF EUTOPIC ENDOMETRIUM, BUT ALSO IN THE PATHOGENESIS OF AT LEAST SOME TYPES OF ENDOMETRIOSIS. EVIDENCE HAS ARISEN FROM EXPERIMENTS IN ANIMAL MODELS OF DISEASE THROUGH DIFFERENT KINDS OF ASSAYS (INCLUDING CLONOGENICITY, THE LABEL-RETAINING CELL APPROACH, THE ANALYSIS OF UNDIFFERENTIATION MARKERS), AS WELL AS FROM DESCRIPTIVE STUDIES ON ECTOPIC AND EUTOPIC TISSUE SAMPLES HARVESTED FROM AFFECTED WOMEN. CHANGES IN STEM CELL POPULATIONS IN ENDOMETRIOTIC LESIONS ARE ASSOCIATED WITH GENETIC AND EPIGENETIC ALTERATIONS, INCLUDING IMBALANCE OF MIRNA EXPRESSION, HISTONE AND DNA MODIFICATIONS AND CHROMOSOMAL ABERRATIONS. THE PRESENT SHORT REVIEW MAINLY SUMMARIZES THE LATEST OBSERVATIONS CONTRIBUTING TO THE CURRENT KNOWLEDGE REGARDING THE PRESENCE AND THE POTENTIAL CONTRIBUTION OF STEM/PROGENITOR CELLS IN EUTOPIC ENDOMETRIUM AND THE AETIOLOGY OF ENDOMETRIOSIS, TOGETHER WITH A REPORT OF THE MOST RECENTLY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS IN ENDOMETRIOSIS. WE ALSO DESCRIBE THE POTENTIAL ADVANTAGES OF SINGLE CELL MOLECULAR PROFILING IN ENDOMETRIUM AND IN ENDOMETRIOTIC LESIONS. ALL THESE DATA CAN HAVE CLINICAL IMPLICATIONS AND PROVIDE A BASIS FOR NEW POTENTIAL THERAPEUTIC APPLICATIONS. 2014 4 1028 53 CIRCULATING MIRNAS RELATED TO EPITHELIAL-MESENCHYMAL TRANSITIONS (EMT) AS THE NEW MOLECULAR MARKERS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE DEFINED BY THE PRESENCE OF ENDOMETRIAL-LIKE TISSUE FOUND OUTSIDE THE UTERUS, MOST COMMONLY IN THE PERITONEAL CAVITY. ENDOMETRIOSIS LESIONS ARE HETEROGENOUS BUT USUALLY CONTAIN ENDOMETRIAL STROMAL CELLS AND EPITHELIAL GLANDS, IMMUNE CELL INFILTRATES AND ARE VASCULARIZED AND INNERVATED BY NERVES. THE COMPLEX ETIOPATHOGENESIS AND HETEROGENITY OF THE CLINICAL SYMPTOMS, AS WELL AS THE LACK OF A SPECIFIC NON-INVASIVE DIAGNOSTIC BIOMARKERS, UNDERLINE THE NEED FOR MORE ADVANCED DIAGNOSTIC TOOLS. UNFORTUNATELY, THE CONTRIBUTION OF ENVIRONMENTAL, HORMONAL AND IMMUNOLOGICAL FACTORS IN THE DISEASE ETIOLOGY IS INSUFFICIENT, AND THE CONTRIBUTION OF GENETIC/EPIGENETIC FACTORS IS STILL FRAGMENTARY. THEREFORE, THERE IS A NEED FOR MORE FOCUSED STUDY ON THE MOLECULAR MECHANISMS OF ENDOMETRIOSIS AND NON-INVASIVE DIAGNOSTIC MONITORING SYSTEMS. MICRORNAS (MIRNAS) DEMONSTRATE HIGH STABILITY AND TISSUE SPECIFICITY AND PLAY A SIGNIFICANT ROLE IN MODULATING A RANGE OF MOLECULAR PATHWAYS, AND HENCE MAY BE SUITABLE DIAGNOSTIC BIOMARKERS FOR THE ORIGIN AND DEVELOPMENT OF ENDOMETRIOSIS. OF THESE, THE MOST FREQUENTLY STUDIED ARE THOSE RELATED TO ENDOMETRIOSIS, INCLUDING THOSE INVOLVED IN EPITHELIAL-MESENCHYMAL TRANSITION (EMT), WHOSE EXPRESSION IS ALTERED IN PLASMA OR ENDOMETRIOTIC LESION BIOPSIES; HOWEVER, THE RESULTS ARE AMBIGUOUS. SPECIFIC MIRNAS EXPRESSED IN ENDOMETRIOSIS MAY SERVE AS DIAGNOSTICS MARKERS WITH PROGNOSTIC VALUE, AND THEY HAVE BEEN PROPOSED AS MOLECULAR TARGETS FOR TREATMENT. THE AIM OF THIS REVIEW IS TO PRESENT SELECTED MIRNAS ASSOCIATED WITH EMT KNOWN TO HAVE EXPERIMENTALLY CONFIRMED SIGNIFICANCE, AND DISCUSS THEIR UTILITY AS BIOMARKERS IN ENDOMETRIOSIS. 2021 5 5378 34 RECENT INSIGHTS ON THE GENETICS AND EPIGENETICS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A GYNECOLOGIC DISEASE AFFECTING UP TO 10% OF THE WOMEN AND A MAJOR CAUSE OF PAIN AND INFERTILITY. IT IS CHARACTERIZED BY THE IMPLANTATION OF FUNCTIONAL ENDOMETRIAL TISSUE AT ECTOPIC POSITIONS GENERALLY WITHIN THE PERITONEUM. THIS COMPLEX DISEASE HAS AN IMPORTANT GENETIC COMPONENT WITH A HERITABILITY ESTIMATED AT AROUND 50%. THIS REVIEW AIMS AT PROVIDING RECENT INSIGHTS INTO THE GENETIC BASES OF ENDOMETRIOSIS, AND PRESENTS A DETAILED OVERVIEW OF EVIDENCE OF EPIGENETIC ALTERATIONS SPECIFIC TO THIS DISEASE. IN THE FUTURE, THESE ALTERATIONS MAY CONSTITUTE THERAPEUTIC TARGETS FOR PHARMACOLOGICAL COMPOUNDS ABLE TO MODIFY THE EPIGENETIC CODE. 2017 6 5892 58 SYSTEMS GENETICS VIEW OF ENDOMETRIOSIS: A COMMON COMPLEX DISORDER. ENDOMETRIOSIS IS A CONDITION IN WHICH CELLS DERIVED FROM THE ENDOMETRIUM GROW OUTSIDE THE UTERUS, E.G. IN THE PERITONEUM (EXTERNAL GENITAL ENDOMETRIOSIS). AS THESE CELLS ARE UNDER THE INFLUENCE OF FEMALE HORMONES, MAJOR SYMPTOMS OF ENDOMETRIOSIS ARE PAIN, ESPECIALLY DURING THE CYCLE, AND INFERTILITY. NUMEROUS HYPOTHESES FOR THE FORMATION OF ENDOMETRIOSIS CAN BE FOUND IN THE LITERATURE, BUT THERE IS GROWING EVIDENCE OF SERIOUS GENETIC CONTRIBUTIONS TO ENDOMETRIOSIS SUSCEPTIBILITY. THE INVOLVEMENT OF GENES, STEROID HORMONE METABOLISM, IMMUNOLOGICAL REACTIONS, RECEPTOR FORMATION, INFLAMMATION, PROLIFERATION, APOPTOSIS, INTERCELLULAR ADHESION, CELL INVASION AND ANGIOGENESIS AS WELL AS GENES REGULATING THE ACTIVITY OF AFOREMENTIONED ENZYMES HAVE BEEN SUGGESTED. SOME MORE RECENTLY SUGGESTED CANDIDATE GENES PICKED UP IN GENOME-WIDE ASSOCIATION STUDIES ARE INVOLVED IN ONCOGENESIS, METAPLASIA OF ENDOMETRIUM CELLS AND PATHWAYS OF EMBRYONIC DEVELOPMENT OF THE FEMALE REPRODUCTIVE SYSTEM. HOWEVER, GENE MUTATIONS PROVEN TO BE CAUSATIVE FOR ENDOMETRIOSIS HAVE NOT BEEN IDENTIFIED SO FAR, EVEN THOUGH THE ABNORMAL EXPRESSION OF CANDIDATE GENES FOR ENDOMETRIOSIS COULD BE PROVOKED BY DIFFERENT EPIGENETIC MODIFICATIONS INCLUDING DNA METHYLATION, HETEROCHROMATIZATION OR INTRODUCTION OF REGULATORY MIRNA. WE HYPOTHESIZE THAT ENDOMETRIOSIS IS INDUCED BY A COMBINATION OF ABNORMAL GENETIC AND/OR EPIGENETIC MUTATIONS: THE LATTER PAVE THE WAY FOR PATHOLOGICAL CHANGES WHICH BECOME IRREVERSIBLE, AND ACCORDING TO THE "EPIGENETIC LANDSCAPE" THEORY, THIS PROCEEDS TO THE TYPICAL CLINICAL MANIFESTATIONS. TWO STAGES IN THE ENDOMETRIOSIS PATHWAY ARE SUGGESTED: (1) INDUCTION OF PRIMARY ENDOMETRIAL CELLS TOWARD ENDOMETRIOSIS, AND (2) IMPLANTATION AND PROGRESSION OF THESE CELLS INTO ENDOMETRIOSIS LESIONS. THE MODEL FAVORS ENDOMETRIOSIS AS AN OUTGROWTH OF PRIMARY CELLS DIFFERENT IN THEIR ORIGIN, CANALIZATION OF PATHOLOGICAL PROCESSES, MANIFESTATION DIVERSITY PROVOKED BY UNIQUE GENETIC BACKGROUND AND EPIGENETIC INFLUENCES, WHICH RESULT IN MANY DIFFERENT CLINICAL FORMS OF THE DISEASE. 2015 7 6116 34 THE EPIGENETIC CORRELATION AMONG OVARIAN CANCER, ENDOMETRIOSIS AND PCOS: A REVIEW. OVARIAN CANCER IS A FREQUENT MALIGNANCY THAT AFFECTS A LARGE PERCENTAGE OF WOMEN. ENDOMETRIOSIS IS A CHRONIC CONDITION, WHERE THERE IS A PRODUCTION OF BENIGN LESIONS WERE OBSERVED IN THE UTERINE ENVIRONMENT. PCOS IS A METABOLIC DISORDER CHARACTERIZED BY THE PRESENCE OF NUMEROUS CYSTS IN THE OVARIES. THE RELATION BETWEEN OVARIAN MALIGNANCIES AND PCOS, BY AN INCREASED RATIO OF OVARIAN STROMAL TISSUES IN PCOS PATIENTS. THE DIRECT CORRELATION IS NOT YET CONFIRMED AMONG THE THREE DISORDERS, BUT IT IS OFTEN NOTED THAT THEY SHARE RISK FACTORS, SUCH AS OBESITY, HORMONAL IMBALANCES. EPIGENETIC FACTORS HAVE SHOWN TO BE AN IMPORTANT REASON FOR CANCER PROGRESSION. OUR FINDINGS AT THE EPIGENETIC LEVEL INCLUDES A COMPARATIVE ANALYSIS, POINT MUTATIONS IN GENES, OVERACTIVATION OF SIGNALING PATHWAYS. THIS REVIEW PAPER, HIGHLIGHT THE POSSIBLE CORRELATION BETWEEN THE THREE DISORDERS IN TERMS OF GENETIC AND EPIGENETIC FACTORS AND HOW IT COULD TOGETHER TRIGGER THE CANCER PROGRESSION AND METASTASIS. 2022 8 2086 46 EPIGENETIC DYSREGULATION IN ENDOMETRIOSIS: IMPLICATIONS FOR PATHOPHYSIOLOGY AND THERAPEUTICS. ENDOMETRIOSIS IS A PREVALENT GYNECOLOGICAL CONDITION ASSOCIATED WITH PELVIC PAIN AND INFERTILITY. DESPITE MORE THAN A CENTURY OF RESEARCH, THE ETIOLOGY OF ENDOMETRIOSIS STILL ELUDES SCIENTIFIC CONSENSUS. THIS LACK OF CLARITY HAS RESULTED IN SUBOPTIMAL PREVENTION, DIAGNOSIS, AND TREATMENT OPTIONS. EVIDENCE OF GENETIC CONTRIBUTORS TO ENDOMETRIOSIS IS INTERESTING BUT LIMITED; HOWEVER, SIGNIFICANT PROGRESS HAS BEEN MADE IN RECENT YEARS IN IDENTIFYING EPIGENETIC ROLE IN THE PATHOGENESIS OF ENDOMETRIOSIS THROUGH CLINICAL STUDIES, IN VITRO CELL CULTURE EXPERIMENTS, AND IN VIVO ANIMAL MODELS. THE PREDOMINANT FINDINGS INCLUDE ENDOMETRIOSIS-RELATED DIFFERENTIAL EXPRESSION OF DNA METHYLTRANSFERASES AND DEMETHYLASES, HISTONE DEACETYLASES, METHYLTRANSFERASES, AND DEMETHYLASES, AND REGULATORS OF CHROMATIN ARCHITECTURE. THERE IS ALSO AN EMERGING ROLE FOR MIRNAS IN THE CONTROL OF EPIGENETIC REGULATORS IN THE ENDOMETRIUM AND ENDOMETRIOSIS. CHANGES IN THESE EPIGENETIC REGULATORS RESULT IN DIFFERENTIAL CHROMATIN ORGANIZATION AND DNA METHYLATION WITH CONSEQUENCES FOR GENE EXPRESSION INDEPENDENT OF A GENETIC SEQUENCE. EPIGENETICALLY ALTERED EXPRESSION OF GENES RELATED TO STEROID HORMONE PRODUCTION AND SIGNALING, IMMUNE REGULATION, AND ENDOMETRIAL CELL IDENTITY AND FUNCTION HAVE ALL BEEN IDENTIFIED AND APPEAR TO PLAY INTO THE PATHOPHYSIOLOGICAL MECHANISMS OF ENDOMETRIOSIS AS WELL AS RESULTING INFERTILITY. THIS REVIEW SUMMARIZES AND CRITICALLY DISCUSSES EARLY SEMINAL FINDINGS, THE EVER-GROWING RECENT EVIDENCE OF EPIGENETIC CONTRIBUTIONS TO THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS, AND IMPLICATIONS FOR PROPOSED EPIGENETICALLY TARGETED THERAPEUTICS. 2023 9 2676 43 ETIOPATHOGENESIS OF OVARIAN CANCER. AN INFLAMM-AGING ENTITY? OVARIAN CANCER IS ONE OF THE MOST COMMON GYNECOLOGIC CANCERS AND HAS THE HIGHEST MORTALITY RATE. THE RISK/PROTECTIVE FACTORS OF OVARIAN CANCER SUGGEST THAT ITS ETIOLOGY IS MULTIFACTORIAL. SEVERAL FACTORS ARE INVOLVED IN AGE-RELATED INCREASES IN CARCINOGENESIS, INCLUDING THE ACCUMULATION OF SENESCENT CELLS, INFLAMMAGING (A CHRONIC INFLAMMATORY STATE THAT PERSISTS IN THE ELDERLY), AND IMMUNOSENESCENCE (AGING OF THE IMMUNE SYSTEM) CHANGES ASSOCIATED WITH POOR IMMUNE SURVEILLANCE. AT SITES OF INFLAMMATION, EXPOSURE TO HIGH LEVELS OF INFLAMMATORY MEDIATORS, SUCH AS REACTIVE OXYGEN SPECIES, CYTOKINES, PROSTAGLANDINS, AND GROWTH FACTORS, CONTRIBUTES TO INCREASED CELL DIVISION AND GENETIC AND EPIGENETIC CHANGES. THESE EXPOSURE-INDUCED CHANGES PROMOTE EXCESSIVE CELL PROLIFERATION, INCREASED SURVIVAL, MALIGNANT TRANSFORMATION, AND CANCER DEVELOPMENT. FURTHERMORE, THE PROINFLAMMATORY TUMOR MICROENVIRONMENT CONTRIBUTES TO OVARIAN CANCER METASTASIS AND CHEMORESISTANCE. THIS NARRATIVE REVIEW OF THE LITERATURE WAS CARRIED OUT TO DELINEATE THE POSSIBLE ROLE OF INFLAMMAGING IN THE ETIOPATHOGENESIS OF OVARIAN CANCER DEVELOPMENT. WE DISCUSS THE CURRENT CARCINOGENIC HYPOTHESES, SITES OF ORIGIN, AND ETIOLOGICAL FACTORS OF OVARIAN CANCER. TREATMENT OF INFLAMMATION MAY REPRESENT AN ATTRACTIVE STRATEGY FOR BOTH THE PREVENTION AND THERAPY OF OVARIAN CANCER. 2022 10 4429 39 MOLECULAR BIOLOGY AS A TOOL FOR THE TREATMENT OF CANCER. CANCER IS A GENETIC DISEASE CHARACTERIZED BY UNCONTROLLED CELL GROWTH AND METASTASIS. CANCER CAN HAVE A NUMBER OF CAUSES, SUCH THE ACTIVATION OF ONCOGENES, THE INACTIVATION OF TUMOR-SUPPRESSING GENES, MUTAGENESIS PROVOKED BY EXTERNAL FACTORS, AND EPIGENETIC MODIFICATIONS. THE DEVELOPMENT OF DIAGNOSTIC TOOLS AND TREATMENTS USING A MOLECULAR BIOLOGICAL APPROACH PERMITS THE USE OF SENSITIVE, LOW-COST, NONINVASIVE TESTS FOR CANCER PATIENTS. BIOMARKERS CAN BE USED TO PROVIDE RAPID, PERSONALIZED ONCOLOGY, IN PARTICULAR THE MOLECULAR DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA, AND GASTRIC, COLON, AND BREAST CANCERS. MOLECULAR TESTS BASED ON DNA METHYLATION CAN ALSO BE USED TO DIRECT TREATMENTS OR EVALUATE THE TOXIC EFFECTS OF CHEMOTHERAPY. THE ADEQUATE DIAGNOSIS, PROGNOSIS, AND PREDICTION OF THE RESPONSE OF CANCER PATIENTS TO TREATMENT ARE ESSENTIAL TO ENSURE THE MOST EFFECTIVE THERAPY, REDUCE THE DAMAGING EFFECTS OF TREATMENT, AND DIRECT THE THERAPY TO SPECIFIC TARGETS, AND IN THIS CONTEXT, MOLECULAR BIOLOGY HAS BECOME INCREASINGLY IMPORTANT IN ONCOLOGY. IN THIS BRIEF REVIEW, WE WILL DEMONSTRATE THE FUNDAMENTAL IMPORTANCE OF MOLECULAR BIOLOGY FOR THE TREATMENT OF THREE TYPES OF CANCER-CHRONIC MYELOID LEUKEMIA, HEREDITARY DIFFUSE GASTRIC CANCER, AND ASTROCYTOMAS (SPORADIC TUMORS OF THE CENTRAL NERVOUS SYSTEM). IN EACH OF THESE THREE MODELS, DISTINCT BIOLOGICAL MECHANISMS ARE INVOLVED IN THE TRANSFORMATION OF THE CELLS, BUT IN ALL CASES, MOLECULAR BIOLOGY IS FUNDAMENTAL TO THE DEVELOPMENT OF PERSONALIZED ANALYSES FOR EACH PATIENT AND EACH TYPE OF NEOPLASIA, AND TO GUARANTEE THE SUCCESS OF THE TREATMENT. 2018 11 4435 47 MOLECULAR DYSREGULATIONS UNDERLYING THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A CRIPPLING DISEASE CHARACTERIZED BY THE PRESENCE OF ENDOMETRIUM-LIKE TISSUE OR SCAR OUTSIDE THE UTERINE CAVITY, COMMONLY CONFINED TO THE PERITONEAL AND SEROSAL SURFACES OF THE PELVIC ORGANS. 10-15% OF WOMEN IN REPRODUCTIVE AGE ARE ESTIMATED TO BE AFFECTED BY ENDOMETRIOSIS. MOST OF THESE PATIENTS PRESENT WITH INFERTILITY AND SUFFER FROM PELVIC PAIN. THE BENIGN DISEASE RARELY PROGRESSES TO MALIGNANCY. REGARDLESS OF ITS HIGH PREVALENCE, THE PATHOGENESIS OF THE DISEASE IS NOT FULLY UNDERSTOOD. TREATMENT OPTIONS FOR ENDOMETRIOSIS ARE LIMITED AND ARE OFTEN BASED ON A SYMPTOMATIC APPROACH. THE UNAVAILABILITY OF PROPER DIAGNOSTIC APPROACHES, FEWER THERAPEUTIC OPTIONS, AND SPARSE UNDERSTANDING OF MOLECULAR ALTERATIONS ARE RESPONSIBLE FOR THE CONTINUED DISEASE BURDEN. EXPLORING THE MOLECULAR ELEMENTS CAUSING THE PATHOGENESIS OF ENDOMETRIOSIS MAY LEAD TO A NUMBER OF BREAKTHROUGHS IN THE TREATMENT OF THE ILLNESS, SUCH AS THE DISCOVERY OF NEW BIOMARKERS FOR DIAGNOSIS AND THERAPEUTIC TARGETS THAT CAN BE A GUIDE TO BETTER PROGNOSIS AND REDUCED RECURRENCE. THE GOAL OF THIS REVIEW IS TO PROVIDE THE READER A CRITICAL UNDERSTANDING OF THE DISEASE BY SUMMARIZING THE GENETIC, IMMUNOLOGICAL, HORMONAL, AND EPIGENETIC DEREGULATIONS THAT SUPPORT THE MOLECULAR BASIS FOR DEVELOPMENT OF ENDOMETRIOTIC CYST, WITH A SPECIAL FOCUS ON THE STUDY MODELS NEEDED TO ANALYZE THESE CHANGES IN THE ENDOMETRIOTIC MICROENVIRONMENT. 2021 12 1889 44 ENDOMETRIOSIS MALIGNANT TRANSFORMATION: EPIGENETICS AS A PROBABLE MECHANISM IN OVARIAN TUMORIGENESIS. ENDOMETRIOSIS, DEFINED AS THE PRESENCE OF ECTOPIC ENDOMETRIAL GLANDS AND STROMA OUTSIDE THE UTERINE CAVITY, IS A CHRONIC, HORMONE-DEPENDENT GYNECOLOGIC DISEASE AFFECTING MILLIONS OF WOMEN ACROSS THE WORLD, WITH SYMPTOMS INCLUDING CHRONIC PELVIC PAIN, DYSMENORRHEA, DYSPAREUNIA, DYSURIA, AND SUBFERTILITY. IN ADDITION, THERE IS WELL-ESTABLISHED EVIDENCE THAT, ALTHOUGH ENDOMETRIOSIS IS CONSIDERED BENIGN, IT IS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT TRANSFORMATION, WITH THE INVOLVEMENT OF VARIOUS MECHANISMS OF DEVELOPMENT. MORE AND MORE EVIDENCE REVEALS AN IMPORTANT CONTRIBUTION OF EPIGENETIC MODIFICATION NOT ONLY IN ENDOMETRIOSIS BUT ALSO IN MECHANISMS OF ENDOMETRIOSIS MALIGNANT TRANSFORMATION, INCLUDING DNA METHYLATION AND DEMETHYLATION, HISTONE MODIFICATIONS, AND MIRNA ABERRANT EXPRESSIONS. IN THIS PRESENT REVIEW, WE MAINLY SUMMARIZE THE RESEARCH PROGRESS ABOUT THE CURRENT KNOWLEDGE REGARDING THE EPIGENETIC MODIFICATIONS OF THE RELATIONS BETWEEN ENDOMETRIOSIS MALIGNANT TRANSFORMATION AND OVARIAN CANCER IN AN EFFORT TO IDENTIFY SOME RISK FACTORS PROBABLY ASSOCIATED WITH ECTOPIC ENDOMETRIUM TRANSFORMATION. 2018 13 4957 40 PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY. OBJECTIVE: TO STUDY THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS. DESIGN: OVERVIEW OF OBSERVATIONS ON ENDOMETRIOSIS. SETTING: NOT APPLICABLE. PATIENT(S): NONE. INTERVENTIONS(S): NONE. MAIN OUTCOME MEASURE(S): THE HYPOTHESIS IS COMPATIBLE WITH ALL OBSERVATIONS. RESULT(S): ENDOMETRIOSIS, ENDOMETRIUM-LIKE TISSUE OUTSIDE THE UTERUS, HAS A VARIABLE MACROSCOPIC APPEARANCE AND A POORLY UNDERSTOOD NATURAL HISTORY. IT IS A HEREDITARY AND HETEROGENEOUS DISEASE WITH MANY BIOCHEMICAL CHANGES IN THE LESIONS, WHICH ARE CLONAL IN ORIGIN. IT IS ASSOCIATED WITH PAIN, INFERTILITY, ADENOMYOSIS, AND CHANGES IN THE JUNCTIONAL ZONE, PLACENTATION, IMMUNOLOGY, PLASMA, PERITONEAL FLUID, AND CHRONIC INFLAMMATION OF THE PERITONEAL CAVITY. THE SAMPSON HYPOTHESIS OF IMPLANTED ENDOMETRIAL CELLS FOLLOWING RETROGRADE MENSTRUATION, ANGIOGENIC SPREAD, LYMPHOGENIC SPREAD, OR THE METAPLASIA THEORY CANNOT EXPLAIN ALL OBSERVATIONS IF METAPLASIA IS DEFINED AS CELLS WITH REVERSIBLE CHANGES AND AN ABNORMAL BEHAVIOR/MORPHOLOGY DUE TO THE ABNORMAL ENVIRONMENT. WE PROPOSE A POLYGENETIC/POLYEPIGENETIC MECHANISM. THE SET OF GENETIC AND EPIGENETIC INCIDENTS TRANSMITTED AT BIRTH COULD EXPLAIN THE HEREDITARY ASPECTS, THE PREDISPOSITION, AND THE ENDOMETRIOSIS-ASSOCIATED CHANGES IN THE ENDOMETRIUM, IMMUNOLOGY, AND PLACENTATION. TO DEVELOP TYPICAL, CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS, A VARIABLE SERIES OF ADDITIONAL TRANSMISSIBLE GENETIC AND EPIGENETIC INCIDENTS ARE REQUIRED TO OCCUR IN A CELL WHICH MAY VARY FROM ENDOMETRIAL TO STEM CELLS. SUBTLE LESIONS ARE VIEWED AS ENDOMETRIUM IN A DIFFERENT ENVIRONMENT UNTIL ADDITIONAL INCIDENTS OCCUR. TYPICAL CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS ARE HETEROGENEOUS AND REPRESENT THREE DIFFERENT DISEASES. CONCLUSION(S): THE GENETIC EPIGENETIC THEORY IS COMPATIBLE WITH ALL OBSERVATIONS ON ENDOMETRIOSIS. IMPLICATIONS FOR TREATMENT AND PREVENTION ARE DISCUSSED. 2019 14 1893 58 ENDOMETRIOSIS: NEW PERSPECTIVE FOR THE DIAGNOSIS OF CERTAIN CYTOKINES IN WOMEN AND ADOLESCENT GIRLS, AS WELL AS THE PROGRESSION OF DISEASE OUTGROWTH: A SYSTEMATIC REVIEW. ENDOMETRIOSIS IS A COMMON CHRONIC GYNECOLOGICAL DISORDER THAT UNDOUBTEDLY IMPACTS ON QUALITY OF LIFE, AND IS ONE OF THE MORE COMPLEX AND MYSTERIOUS ILLNESSES OF OUR CENTURY, WHICH IS ASSOCIATED WITH THE IMPROPER GROWTH OF ENDOMETRIAL TISSUE OUTSIDE OF THE UTERINE CAVITY. THIS PATHOLOGICALLY IMPLANTED TISSUE CAN BE FOUND MOST FREQUENTLY IN THE MINOR PELVIS, BUT ALSO IN THE PERITONEAL CAVITY, AND CAN AFFECT MANY ORGANS, LEADING TO CHRONIC PELVIC PAIN SYNDROME, INFERTILITY, AND DYSMENORRHEA. ENDOMETRIAL TISSUE IS A PARTICULARLY DYNAMIC TISSUE THAT HAS A DIRECT IMPACT ON THE PROGRESSION OF THE DISEASE, WITH ALTERED IMMUNITY, AS WELL AS CYTOKINE STORMS WITHIN THE METAPLASTIC ENDOMETRIOTIC SITE, AS POSSIBLE KEY FACTORS. CURRENTLY, DIAGNOSIS OF THIS MYSTERIOUS CHRONIC ILLNESS RELIES ON PERFORMING A LAPAROSCOPIC PROCEDURE WITH TISSUE SAMPLING. ONE OF THE MOST TROUBLESOME OUTCOMES OF THIS UNINTENDED PROGRESSION IS THAT WE LACK ANY SPECIFIC, SENSITIVE, NON-INVASIVE DIAGNOSTIC TOOLS. CURRENTLY, THE VAST MAJORITY OF REGIME STEWARDSHIP OPTIONS RELY ON ANTI-CONTRACEPTIVE DRUGS, OR OTHER REMEDIES THAT SUPPRESS THE RELEASE OF ESTROGEN THROUGH THE GONADS-ALTHOUGH IN MOST CLINICAL TRIALS, ENDOMETRIOSIS IS A CHRONIC PROGRESSIVE DISORDER THAT DEPENDS MOSTLY ON THE HIGH CONCENTRATION OF ESTROGEN. MOREOVER, MANY SPECIFIC TRIALS HAVE DEMONSTRATED THAT THE EUTOPIC ENDOMETRIAL CELLS IN INDIVIDUALS WITH ENDOMETRIOSIS REMAIN MUCH MORE RESISTANT TO THE IMMUNOLOGICAL ANNIHILATION PROCESS CAUSED BY CERTAIN ELEMENTS OF THE IMMUNE SYSTEM. NEVERTHELESS, EUTOPIC ENDOMETRIAL CELLS HAVE THE POTENTIAL TO SIMILARLY ESCALATE THE EXPRESSION OF AROMATASE RECEPTORS ON THE SURFACE OF THE PATHOLOGICAL CELLS, WHICH IN THE FINAL CASCADE CAUSE AN INCREASE IN THE CONCENTRATION OF ESTROGEN, AS WELL AS OTHER INFLAMMATORY PROTEINS THAT CONTRIBUTE TO PATHOLOGICAL OUTGROWTH. DATA REVEAL OCCURRENCE AMONG FIRST-DEGREE RELATIVES, SUGGESTING THAT THE SPECIFIC CASCADE COULD BE RELATED TO INHERITED AS WELL AS EPIGENETIC (ACQUIRED) MECHANISMS. IN WOMEN WITH THE DISEASE, CONFIRMED BY LAPAROSCOPIC PROCEDURES, DIAGNOSIS OF ENDOMETRIOSIS CAN BE ESTABLISHED ALSO VIA DETECTION BY GENE POLYMORPHISM IN THE GENES WHICH ARE RESPONSIBLE FOR RESPONSIBLE FOR THE DETOXIFICATION PHASE OF ESTROGEN RECEPTORS AND OTHER IMMUNOMODULATOR COMPONENTS. A RECENT PUBLICATION AIMS TO REVEAL A NEW PROSPECT FOR THE NON-INVASIVE DIAGNOSIS, DETECTION, AND ESTIMATION OF CERTAIN BIOMARKERS FOR MUCH MORE SPECIFIC INVESTIGATION OF THE DISEASE'S PROGRESSION. 2021 15 3958 45 LONG NON-CODING RNAS IN BONE METASTASIS: PROGRESSES AND PERSPECTIVES AS POTENTIAL DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. IN A PRECISION MEDICINE PERSPECTIVE, AMONG THE BIOMARKERS POTENTIALLY USEFUL FOR EARLY DIAGNOSIS OF CANCERS, AS WELL AS TO DEFINE THEIR PROGNOSIS AND EVENTUALLY TO IDENTIFY NOVEL AND MORE EFFECTIVE THERAPEUTIC TARGETS, THERE ARE THE LONG NON-CODING RNAS (LNCRNAS). THE TERM LNCRNA IDENTIFIES A CLASS OF NON-CODING RNA MOLECULES INVOLVED IN THE REGULATION OF GENE EXPRESSION THAT INTERVENE AT THE TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND EPIGENETIC LEVEL. METASTASIS IS A NATURAL EVOLUTION OF SOME MALIGNANT TUMOURS, FREQUENTLY ENCOUNTERED IN PATIENTS WITH ADVANCED CANCERS. ONSET AND DEVELOPMENT OF METASTASIS REPRESENTS A DETRIMENTAL EVENT THAT WORSEN THE PATIENT'S PROGNOSIS BY PROFOUNDLY INFLUENCING THE QUALITY OF LIFE AND IS RESPONSIBLE FOR THE OMINOUS PROGRESSION OF THE DISEASE. DUE TO THE PECULIAR ENVIRONMENT AND THE BIOMECHANICAL PROPERTIES, BONE IS A PREFERENTIAL SITE FOR THE SECONDARY GROWTH OF BREAST, PROSTATE AND LUNG CANCERS. UNFORTUNATELY, ONLY PALLIATIVE AND PAIN THERAPIES ARE CURRENTLY AVAILABLE FOR PATIENTS WITH BONE METASTASES, WHILE NO EFFECTIVE AND DEFINITIVE TREATMENTS ARE AVAILABLE. THE UNDERSTANDING OF PATHOPHYSIOLOGICAL BASIS OF BONE METASTASIS FORMATION AND PROGRESSION, AS WELL AS THE IMPROVEMENT IN THE CLINICAL MANAGEMENT OF THE PATIENT, ARE CENTRAL BUT CHALLENGING TOPICS IN BASIC RESEARCH AND CLINICAL PRACTICE. THE IDENTIFICATION OF NEW MOLECULAR SPECIES THAT MAY HAVE A ROLE AS EARLY HALLMARKS OF THE METASTATIC PROCESS COULD OPEN THE DOOR TO THE DEFINITION OF NEW, AND MORE EFFECTIVE, THERAPEUTIC AND DIAGNOSTIC APPROACHES. NON-CODING RNAS SPECIES AND, PARTICULARLY, LNCRNAS ARE PROMISING COMPOUNDS IN THIS SETTING, AND THEIR STUDY MAY BRING TO THE IDENTIFICATION OF RELEVANT PROCESSES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF LNCRNAS AS EMERGING MOLECULES IN MEDIATING THE FORMATION AND DEVELOPMENT OF BONE METASTASES, AS POSSIBLE BIOMARKERS FOR CANCER DIAGNOSIS AND PROGNOSIS, AND AS THERAPEUTIC TARGETS TO COUNTERACT CANCER SPREAD. 2023 16 731 51 CANCER CHEMOPREVENTION: CLASSIC AND EPIGENETIC MECHANISMS INHIBITING TUMORIGENESIS. WHAT HAVE WE LEARNED SO FAR? CANCERS DERIVE FROM STEP BY STEP PROCESSES WHICH ARE DIFFERENTIATED BY THE PROGRESSIVELY ACCUMULATED MUTATIONS. FOR SOME TUMORS THERE IS A CLEAR PROGRESSIVE ADVANCEMENT FROM BENIGN LESIONS TO MALIGNANCY AND FOR THESE, PREVENTIVE SCREENING PROGRAMS EXIST. IN SUCH CASES HAVING THOSE BENIGN LESIONS ARE A CLEAR INDICATOR OF PREDISPOSITION WHILE FOR SOME OTHER CASES, FAMILIAL PATTERNS OF CANCER INCIDENCE AND THE IDENTIFICATION OF MUTATIONS ARE THE MAIN INDICATORS OF HIGHER RISK FOR HAVING THE DISEASE. FOR PATIENTS IDENTIFIED AS HAVING PREDISPOSITION, CHEMOPREVENTION IS A GOAL AND IN SOME CASES A POSSIBILITY. CHEMOPREVENTION IS THE USE OF ANY COMPOUND, EITHER NATURAL OR SYNTHETIC THAT ABROGATES CARCINOGENESIS OR TUMOR PROGRESSION, THROUGH DIFFERENT MECHANISMS, SOME OF WHICH HAVE ALREADY BEEN DESCRIBED. FOR EXAMPLE, THE CLASSIC MECHANISMS MAY INVOLVE ACTIVATION OF FREE RADICAL SCAVENGING ENZYMES, CONTROL OF CHRONIC INFLAMMATION, AND DOWNREGULATION OF SPECIFIC SIGNALING PATHWAYS. MORE RECENTLY, EPIGENETICS ALLOWED FURTHER UNDERSTANDING OF THE CHEMOPREVENTIVE POTENTIAL OF SEVERAL AGENTS, SUCH AS SULFORAPHANE, GREEN TEA DERIVED COMPOUNDS, RESVERATROL, ISOFLAVONES, AND OTHERS WHICH WE EXPLOIT IN THIS REVIEW ARTICLE. THROUGHOUT THE TEXT WE DISCUSS THE PROPERTIES COMPOUNDS SHOULD HAVE IN ORDER TO BE CLASSIFIED AS CHEMOPREVENTIVE ONES AND THE CHALLENGES IN TRANSLATIONAL RESEARCH IN THIS AREA, AS LOTS OF THE SUCCESS ACHIEVED IN VITRO CANNOT BE TRANSLATED INTO THE CLINICAL SETTINGS, DUE TO SEVERAL DIFFERENT DRAWBACKS, WHICH INCLUDE TOXICITY, COST, DOSE DEFINITION, PATIENT ADHERENCE, AND REGIMEN OF USE. 2018 17 1522 48 DNA METHYLATION CHANGE PROFILING OF COLORECTAL DISEASE: SCREENING TOWARDS CLINICAL USE. COLON CANCER REMAINS ONE OF THE LEADING CAUSES OF CANCER-RELATED DEATHS WORLDWIDE. TRANSFORMATION OF COLON EPITHELIAL CELLS INTO INVASIVE ADENOCARCINOMAS HAS BEEN WELL KNOWN TO BE DUE TO THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC CHANGES. IN THE PAST DECADE, THE ETIOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD) WHICH IS CHARACTERIZED BY CHRONIC INFLAMMATION OF THE INTESTINAL MUCOSA, WAS ONLY PARTIALLY EXPLAINED BY GENETIC STUDIES PROVIDING SUSCEPTIBILITY LOCI, BUT RECENTLY EPIGENETIC STUDIES HAVE PROVIDED CRITICAL EVIDENCES AFFECTING IBD PATHOGENESIS. OVER THE PAST DECADE, A DEEP UNDERSTANDING OF EPIGENETICS ALONG WITH TECHNOLOGICAL ADVANCES HAVE LED TO IDENTIFYING NUMEROUS GENES THAT ARE REGULATED BY PROMOTER DNA HYPERMETHYLATION IN COLORECTAL DISEASES. RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF DNA METHYLATION IN COLORECTAL DISEASES COULD IMPROVE A MULTITUDE OF POWERFUL DNA METHYLATION-BASED BIOMARKERS, PARTICULARLY FOR USE AS DIAGNOSIS, PROGNOSIS, AND PREDICTION FOR THERAPEUTIC APPROACHES. THIS REVIEW FOCUSES ON THE EMERGING POTENTIAL FOR TRANSLATIONAL RESEARCH OF EPIGENETIC ALTERATIONS INTO CLINICAL UTILITY AS MOLECULAR BIOMARKERS. MOREOVER, THIS REVIEW DISCUSSES RECENT PROGRESS REGARDING THE IDENTIFICATION OF UNKNOWN HYPERMETHYLATED GENES IN COLON CANCERS AND IBD, AS WELL AS THEIR POSSIBLE ROLE IN CLINICAL PRACTICE, WHICH WILL HAVE IMPORTANT CLINICAL SIGNIFICANCE, PARTICULARLY IN THE ERA OF THE PERSONALIZED MEDICINE. 2021 18 2275 53 EPIGENETIC REGULATION AND T-CELL RESPONSES IN ENDOMETRIOSIS - SOMETHING OTHER THAN AUTOIMMUNITY. ENDOMETRIOSIS IS DEFINED AS THE PRESENCE OF ENDOMETRIAL-LIKE GLANDS AND STROMA LOCATED OUTSIDE THE UTERINE CAVITY. THIS COMMON, ESTROGEN DEPENDENT, INFLAMMATORY CONDITION AFFECTS UP TO 15% OF REPRODUCTIVE-AGED WOMEN AND IS A WELL-RECOGNIZED CAUSE OF CHRONIC PELVIC PAIN AND INFERTILITY. DESPITE THE STILL UNKNOWN ETIOLOGY OF ENDOMETRIOSIS, MUCH EVIDENCE SUGGESTS THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DISEASE ETIOPATHOGENESIS. THE MAIN RATIONALE IS BASED ON THE FACT THAT HERITABLE PHENOTYPE CHANGES THAT DO NOT INVOLVE ALTERATIONS IN THE DNA SEQUENCE ARE COMMON TRIGGERS FOR HORMONAL, IMMUNOLOGICAL, AND INFLAMMATORY DISORDERS, WHICH PLAY A KEY ROLE IN THE FORMATION OF ENDOMETRIOTIC FOCI. EPIGENETIC MECHANISMS REGULATING T-CELL RESPONSES, INCLUDING DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS, DESERVE ATTENTION BECAUSE TISSUE-RESIDENT T LYMPHOCYTES WORK IN CONCERT WITH ORGAN STRUCTURAL CELLS TO GENERATE APPROPRIATE IMMUNE RESPONSES AND ARE FUNCTIONALLY SHAPED BY ORGAN-SPECIFIC ENVIRONMENTAL CONDITIONS. THUS, A FAILURE TO PRECISELY REGULATE IMMUNE CELL TRANSCRIPTION MAY RESULT IN COMPROMISED IMMUNOLOGICAL INTEGRITY OF THE ORGAN WITH AN INCREASED RISK OF INFLAMMATORY DISORDERS. THE COEXISTENCE OF ENDOMETRIOSIS AND AUTOIMMUNITY IS A WELL-KNOWN OCCURRENCE. RECENT RESEARCH RESULTS INDICATE REGULATORY T-CELL (TREG) ALTERATIONS IN ENDOMETRIOSIS, AND AN INCREASED NUMBER OF HIGHLY ACTIVE TREGS AND MACROPHAGES HAVE BEEN FOUND IN PERITONEAL FLUID FROM WOMEN WITH ENDOMETRIOSIS. ELIMINATION OF THE REGULATORY FUNCTION OF T CELLS AND AN IMBALANCE BETWEEN T HELPER CELLS OF THE TH1 AND TH2 TYPES HAVE BEEN REPORTED IN THE ENDOMETRIA OF WOMEN WITH ENDOMETRIOSIS-ASSOCIATED INFERTILITY. THIS REVIEW AIMS TO PRESENT THE STATE OF THE ART IN RECOGNITION EPIGENETIC REPROGRAMMING OF T CELLS AS THE KEY FACTOR IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS IN THE CONTEXT OF T-CELL-RELATED AUTOIMMUNITY. THE NEW POTENTIAL THERAPEUTIC APPROACHES BASED ON EPIGENETIC MODULATION AND/OR ADOPTIVE TRANSFER OF T CELLS WILL ALSO BE OUTLINED. 2022 19 506 46 ASSOCIATION OF ENDOMETRIOSIS WITH CARDIOVASCULAR DISEASE: GENETIC ASPECTS (REVIEW). CARDIOVASCULAR DISEASE (CVD) COMPRISES A BROAD SPECTRUM OF PATHOLOGICAL CONDITIONS THAT AFFECT THE HEART OR BLOOD VESSELS, INCLUDING SEQUELAE THAT ARISE FROM DAMAGED VASCULATURE IN OTHER ORGANS OF THE BODY, SUCH AS THE BRAIN, KIDNEYS OR EYES. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY DISEASE OF THE ARTERIAL INTIMA AND IS THE PRIMARY CAUSE OF CORONARY ARTERY DISEASE, PERIPHERAL VASCULAR DISEASE, HEART ATTACK, STROKE AND RENAL PATHOLOGY. IT REPRESENTS A LEADING CAUSE OF MORTALITY WORLDWIDE AND THE LOSS OF HUMAN PRODUCTIVITY THAT IS MARKED BY AN ALTERED IMMUNE RESPONSE. ENDOMETRIOSIS IS A HERITABLE, HETEROGENEOUS, COMMON GYNECOLOGICAL CONDITION INFLUENCED BY MULTIPLE GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS, AFFECTING UP TO 10% OF THE FEMALE POPULATION OF CHILDBEARING AGE, CAUSING PAIN AND INFERTILITY; IT IS CHARACTERIZED BY THE ECTOPIC GROWTH OF ENDOMETRIAL TISSUE OUTSIDE THE UTERINE CAVITY. OF NOTE, EPIDEMIOLOGICAL DATA OBTAINED THUS FAR HAVE SUGGESTED A LINK BETWEEN ENDOMETRIOSIS AND THE RISK OF DEVELOPING CVD. THE SIMILARITIES OBSERVED IN SPECIFIC MOLECULAR AND CELLULAR PATHWAYS OF ENDOMETRIOSIS AND CVD MAY BE PARTIALLY EXPLAINED BY A SHARED GENETIC BACKGROUND. THE PRESENT REVIEW PRESENTS AND DISCUSSES THE SHARED GENETIC FACTORS WHICH HAVE BEEN REPORTED TO BE ASSOCIATED WITH THE DEVELOPMENT OF BOTH DISORDERS. 2023 20 3697 31 INFLAMMATORY MARKERS IN CANCER: POTENTIAL RESOURCES. CANCER IS A LEADING CAUSE OF DEATH WORLDWIDE AND A MAJOR BURDEN ON DEVELOPING AND LESS DEVELOPED COUNTRIES OF THE WORLD WITH LIMITED RESOURCES FOR PREVENTION AND EFFECTIVE TREATMENT OF CANCER. ALTHOUGH CANCER IS MULTIFACTORIAL IN ORIGIN, VARIOUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST THAT CHRONIC INFLAMMATION HAS AN IMPORTANT ROLE IN ALL STAGES OF CANCER, FROM INITIATION TO PROGRESSION AND EVEN SURVIVAL OF THE PATIENT. INFLAMMATORY PRODUCTS LIKE CYTOKINES, CHEMOKINES, LEUCOCYTES, PROSTAGLANDINS, CYCLOOXYGENASE, REACTIVE OXYGEN AND NITROGEN SPECIES, METALLOPROTEINASE INDUCE GENETIC AND EPIGENETIC CHANGES IN NORMAL CELLS DAMAGING ITS DNA, INHIBITING ITS REPAIR, ALTERING TRANSCRIPTION FACTORS, PREVENTING APOPTOSIS, AND STIMULATING ANGIOGENESIS, AND THUS RESULTING IN CARCINOGENESIS. THUS, THESE INFLAMMATORY MEDIATORS HAVE A POTENTIAL ROLE TO BECOME CANCER BIOMARKERS FOR ALL STAGES OF CANCER AS MANY OF THEM CAN BE MEASURED IN A COST-EFFECTIVE MANNER. HOWEVER, LARGE SCALE PROSPECTIVE TRIALS ARE REQUIRED TO VALIDATE THESE POTENTIAL CANCER BIOMARKERS. NONETHELESS, A TRANSITION FROM POTENTIAL TO PRACTICAL UTILIZATION OF THESE MARKERS WILL BE AN EFFECTIVE TOOL FOR THE AMELIORATION OF CANCER BURDEN AND MORTALITY IN A RESOURCE LIMITED SETTING. 2020