1 3697 113 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 2 2704 23 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 3 2676 40 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 4 5373 42 RECENT ADVANCES IN UNDERSTANDING THE ROLE OF DIET AND OBESITY IN THE DEVELOPMENT OF COLORECTAL CANCER. COLORECTAL CANCER (CRC) IS A MAJOR CAUSE OF PREMATURE DEATH IN THE UK AND MANY DEVELOPED COUNTRIES. HOWEVER, THE RISK OF DEVELOPING CRC IS WELL RECOGNISED TO BE ASSOCIATED NOT ONLY WITH DIET BUT ALSO WITH OBESITY AND LACK OF EXERCISE. WHILE EPIDEMIOLOGICAL EVIDENCE SHOWS AN ASSOCIATION WITH FACTORS SUCH AS HIGH RED MEAT INTAKE AND LOW INTAKE OF VEGETABLES, FIBRE AND FISH, THE MECHANISMS UNDERLYING THESE EFFECTS ARE ONLY NOW BEING ELUCIDATED. CRC DEVELOPS OVER MANY YEARS AND IS TYPICALLY CHARACTERISED BY AN ACCUMULATION OF MUTATIONS, WHICH MAY ARISE AS A CONSEQUENCE OF INHERITED POLYMORPHISMS IN KEY GENES, BUT MORE COMMONLY AS A RESULT OF SPONTANEOUSLY ARISING MUTATIONS AFFECTING GENES CONTROLLING CELL PROLIFERATION, DIFFERENTIATION, APOPTOSIS AND DNA REPAIR. EPIGENETIC CHANGES ARE OBSERVED THROUGHOUT THE PROGRESS FROM NORMAL MORPHOLOGY THROUGH FORMATION OF ADENOMA, AND THE SUBSEQUENT DEVELOPMENT OF CARCINOMA. THE REASONS WHY THIS ACCUMULATION OF LOSS OF HOMOEOSTATIC CONTROLS ARISES ARE UNCLEAR BUT CHRONIC INFLAMMATION HAS BEEN PROPOSED TO PLAY A CENTRAL ROLE. OBESITY IS ASSOCIATED WITH INCREASED PLASMA LEVELS OF CHEMOKINES AND ADIPOKINES CHARACTERISTIC OF CHRONIC SYSTEMIC INFLAMMATION, AND DIETARY FACTORS SUCH AS FISH OILS AND PHYTOCHEMICALS HAVE BEEN SHOWN TO HAVE ANTI-INFLAMMATORY PROPERTIES AS WELL AS MODULATING ESTABLISHED RISK FACTORS SUCH AS APOPTOSIS AND CELL PROLIFERATION. THERE IS ALSO SOME EVIDENCE THAT DIET CAN MODIFY EPIGENETIC CHANGES. THIS PAPER BRIEFLY REVIEWS THE CURRENT STATE OF KNOWLEDGE IN RELATION TO CRC DEVELOPMENT AND CONSIDERS EVIDENCE FOR POTENTIAL MECHANISMS BY WHICH DIET MAY MODIFY RISK. 2011 5 1522 34 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 6 4429 34 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 7 6359 31 THE ROLE OF INFLAMMATION IN THE PATHOGENESIS OF LUNG CANCER. INTRODUCTION: IT IS REPORTED THAT CANCER MAY ARISE IN CHRONICALLY INFLAMED TISSUE. THERE IS MOUNTING EVIDENCE SUGGESTING THAT THE CONNECTION BETWEEN INFLAMMATION AND LUNG CANCER IS NOT COINCIDENTAL BUT MAY INDEED BE CAUSAL. THE INFLAMMATORY MOLECULES MAY BE RESPONSIBLE FOR AUGMENTED MACROPHAGE RECRUITMENT, DELAYED NEUTROPHIL CLEARANCE AND AN INCREASE IN REACTIVE OXYGEN SPECIES. THE CYTOKINES AND GROWTH FACTORS UNUSUALLY PRODUCED IN CHRONIC PULMONARY DISORDERS HAVE BEEN FOUND TO HAVE HARMFUL PROPERTIES THAT PAVE THE WAY FOR EPITHELIAL-TO-MESENCHYMAL TRANSITION AND TUMOR MICROENVIRONMENT. HOWEVER, THE ROLE OF INFLAMMATION IN LUNG CANCER IS NOT YET FULLY UNDERSTOOD. AREAS COVERED: THE ROLE OF CHRONIC INFLAMMATION IN THE PATHOGENESIS OF LUNG CANCER AND SOME OF THE POSSIBLE MECHANISMS INVOLVED, WITH PARTICULAR FOCUS ON INFLAMMATORY MEDIATORS, GENETIC AND EPIGENETIC ALTERATIONS, INFLAMMATORY MARKERS, TUMOR MICROENVIRONMENT AND ANTI-INFLAMMATORY DRUGS ARE DISCUSSED. A FRAMEWORK FOR UNDERSTANDING THE CONNECTION BETWEEN INFLAMMATION AND LUNG CANCER IS PROVIDED, WHICH MAY AFFORD THE OPPORTUNITY TO INTERCEDE IN SPECIFIC INFLAMMATORY DAMAGE MEDIATING LUNG CARCINOGENESIS AND THERAPEUTIC RESISTANCE. EXPERT OPINION: ADVANCES IN TUMOR IMMUNOLOGY SUPPORT THE CLINICAL IMPLEMENTATION OF IMMUNOTHERAPIES FOR LUNG CANCER. ALONG WITH THERAPEUTIC BENEFITS, IMMUNOTHERAPY PRESENTS THE CHALLENGES OF DRUG-RELATED TOXICITIES. GENE MODIFICATION OF IMMUNOCYTOKINE MAY LOWER THE ASSOCIATED TOXIC EFFECTS. 2011 8 3683 35 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 9 551 36 AUTOIMMUNITY AS AN ETIOLOGICAL FACTOR OF CANCER: THE TRANSFORMATIVE POTENTIAL OF CHRONIC TYPE 2 INFLAMMATION. RECENT EPIDEMIOLOGICAL STUDIES HAVE FOUND AN ALARMING TREND OF INCREASED CANCER INCIDENCE IN ADULTS YOUNGER THAN 50 YEARS OF AGE AND PROJECTED A SUBSTANTIAL RISE IN CANCER INCIDENCE OVER THE NEXT 10 YEARS IN THIS AGE GROUP. THIS TREND WAS EXEMPLIFIED IN THE INCIDENCE OF NON-CARDIA GASTRIC CANCER AND ITS DISPROPORTIONATE IMPACT ON NON-HISPANIC WHITE FEMALES UNDER THE AGE OF 50. THE TREND IS CONCURRENT WITH THE INCREASING INCIDENCE OF AUTOIMMUNE DISEASES IN INDUSTRIALIZED COUNTRIES, SUGGESTING A CAUSAL LINK BETWEEN THE TWO. WHILE AUTOIMMUNITY HAS BEEN SUSPECTED TO BE A RISK FACTOR FOR SOME CANCERS, THE EXACT MECHANISMS UNDERLYING THE CONNECTION BETWEEN AUTOIMMUNITY AND CANCER REMAIN UNCLEAR AND ARE OFTEN CONTROVERSIAL. THE LINK HAS BEEN ATTRIBUTED TO SEVERAL MEDIATORS SUCH AS IMMUNE SUPPRESSION, INFECTION, DIET, ENVIRONMENT, OR, PERHAPS MOST PLAUSIBLY, CHRONIC INFLAMMATION BECAUSE OF ITS WELL-RECOGNIZED ROLE IN TUMORIGENESIS. IN THAT REGARD, AUTOIMMUNE CONDITIONS ARE COMMON CAUSES OF CHRONIC INFLAMMATION AND MAY TRIGGER REPETITIVE CYCLES OF ANTIGEN-SPECIFIC CELL DAMAGE, TISSUE REGENERATION, AND WOUND HEALING. ILLUSTRATING THE CONNECTION BETWEEN AUTOIMMUNE DISEASES AND CANCER ARE PATIENTS WHO HAVE AN INCREASED RISK OF CANCER DEVELOPMENT ASSOCIATED WITH GENETICALLY PREDISPOSED INSUFFICIENCY OF CYTOTOXIC T LYMPHOCYTE-ASSOCIATED PROTEIN 4 (CTLA4), A PROTOTYPICAL IMMUNE CHECKPOINT AGAINST AUTOIMMUNITY AND ONE OF THE MAIN TARGETS OF CANCER IMMUNE THERAPY. THE TUMORIGENIC PROCESS TRIGGERED BY CTLA4 INSUFFICIENCY HAS BEEN SHOWN IN A MOUSE MODEL TO BE DEPENDENT ON THE TYPE 2 CYTOKINES INTERLEUKIN-4 (IL4) AND INTERLEUKIN-13 (IL13). IN THIS TYPE 2 INFLAMMATORY MILIEU, CROSSTALK WITH TYPE 2 IMMUNE CELLS MAY INITIATE EPIGENETIC REPROGRAMMING OF EPITHELIAL CELLS, LEADING TO A METAPLASTIC DIFFERENTIATION AND EVENTUALLY MALIGNANT TRANSFORMATION EVEN IN THE ABSENCE OF CLASSICAL ONCOGENIC MUTATIONS. THOSE FINDINGS COMPLEMENT A LARGE BODY OF EVIDENCE FOR TYPE 1, TYPE 3, OR OTHER INFLAMMATORY MEDIATORS IN INFLAMMATORY TUMORIGENESIS. THIS REVIEW ADDRESSES THE POTENTIAL OF AUTOIMMUNITY AS A CAUSAL FACTOR FOR TUMORIGENESIS, THE UNDERLYING INFLAMMATORY MECHANISMS THAT MAY VARY DEPENDING ON HOST-ENVIRONMENT VARIATIONS, AND IMPLICATIONS TO CANCER PREVENTION AND IMMUNOTHERAPY. 2021 10 928 22 CHRONIC INFLAMMATION, THE TUMOR MICROENVIRONMENT AND CARCINOGENESIS. CHRONIC INFLAMMATION OFTEN PRECEDES OR ACCOMPANIES A SUBSTANTIAL NUMBER OF CANCERS. INDEED, ANTI-INFLAMMATORY THERAPIES HAVE SHOWN EFFICACY IN CANCER PREVENTION AND TREATMENT. THE EXACT MECHANISMS THAT TURN A WOUND HEALING PROCESS INTO A CANCER PRECURSOR ARE TOPICS OF INTENSE RESEARCH. A PATHOGENIC LINK HAS BEEN IDENTIFIED BETWEEN INFLAMMATORY MEDIATORS, INFLAMMATION RELATED GENE POLYMORPHISMS AND CARCINOGENESIS. ANIMAL MODELS OF CANCER HAVE BEEN INSTRUMENTAL IN DEMONSTRATING THE DIVERSITY OF MECHANISMS THROUGH WHICH EVERY TUMOR COMPARTMENT AND TUMOR STAGE MAY BE AFFECTED BY THE UNDERLYING INFLAMMATORY PROCESS. IN THIS REVIEW, WE FOCUS ON THE INTERACTION BETWEEN CHRONIC INFLAMMATION, TUMOR STEM CELLS AND THE TUMOR MICROENVIRONMENT. WE SUMMARIZE THE PROPOSED MECHANISMS THAT LEAD TO THE RECRUITMENT OF BONE MARROW DERIVED CELLS AND EXPLORE THE GENETIC AND EPIGENETIC ALTERATIONS THAT MAY OCCUR IN INFLAMMATION ASSOCIATED CANCERS. 2009 11 2335 30 EPIGENETIC REGULATION OF INFLAMMATORY CYTOKINES AND ASSOCIATED GENES IN HUMAN MALIGNANCIES. INFLAMMATION IS A MULTIFACETED DEFENSE RESPONSE OF IMMUNE SYSTEM AGAINST INFECTION. CHRONIC INFLAMMATION HAS BEEN IMPLICATED AS AN IMMINENT THREAT FOR MAJOR HUMAN MALIGNANCIES AND IS DIRECTLY LINKED TO VARIOUS STEPS INVOLVED IN TUMORIGENESIS. INFLAMMATORY CYTOKINES, INTERLEUKINS, INTERFERONS, TRANSFORMING GROWTH FACTORS, CHEMOKINES, AND ADHESION MOLECULES HAVE BEEN ASSOCIATED WITH CHRONIC INFLAMMATION. NUMEROUS CYTOKINES ARE REPORTED TO BE ABERRANTLY REGULATED BY DIFFERENT EPIGENETIC MECHANISMS LIKE DNA METHYLATION AND HISTONE MODIFICATIONS IN TUMOR TISSUES, CONTRIBUTING TO PATHOGENESIS OF TUMOR IN MULTIPLE WAYS. SOME OF THESE CYTOKINES ALSO WORK AS EPIGENETIC REGULATORS OF OTHER CRUCIAL GENES IN TUMOR BIOLOGY, EITHER DIRECTLY OR INDIRECTLY. SUCH REGULATIONS ARE REPORTED IN LUNG, BREAST, CERVICAL, GASTRIC, COLORECTAL, PANCREATIC, PROSTATE, AND HEAD AND NECK CANCERS. EPIGENETICS OF INFLAMMATORY MEDIATORS IN CANCER IS CURRENTLY SUBJECT OF EXTENSIVE RESEARCH. THESE INVESTIGATIONS MAY HELP IN UNDERSTANDING CANCER BIOLOGY AND TO DEVELOP EFFECTIVE THERAPEUTIC STRATEGIES. THE PURPOSE OF THIS PAPER IS TO HAVE A BRIEF VIEW OF THE ABERRANT REGULATION OF INFLAMMATORY CYTOKINES IN HUMAN MALIGNANCIES. 2015 12 733 33 CANCER EPIGENETICS: LINKING BASIC BIOLOGY TO CLINICAL MEDICINE. CANCER EVOLUTION AT ALL STAGES IS DRIVEN BY BOTH EPIGENETIC ABNORMALITIES AS WELL AS GENETIC ALTERATIONS. DYSREGULATION OF EPIGENETIC CONTROL EVENTS MAY LEAD TO ABNORMAL PATTERNS OF DNA METHYLATION AND CHROMATIN CONFIGURATIONS, BOTH OF WHICH ARE CRITICAL CONTRIBUTORS TO THE PATHOGENESIS OF CANCER. THESE EPIGENETIC ABNORMALITIES ARE SET AND MAINTAINED BY MULTIPLE PROTEIN COMPLEXES AND THE INTERPLAY BETWEEN THEIR INDIVIDUAL COMPONENTS INCLUDING DNA METHYLATION MACHINERY, HISTONE MODIFIERS, PARTICULARLY, POLYCOMB (PCG) PROTEINS, AND CHROMATIN REMODELING PROTEINS. RECENT ADVANCES IN GENOME-WIDE TECHNOLOGY HAVE REVEALED THAT THE INVOLVEMENT OF THESE DYSREGULATED EPIGENETIC COMPONENTS APPEARS TO BE EXTENSIVE. MOREOVER, THERE IS A GROWING CONNECTION BETWEEN EPIGENETIC ABNORMALITIES IN CANCER AND CONCEPTS CONCERNING STEM-LIKE CELL SUBPOPULATIONS AS A DRIVING FORCE FOR CANCER. EMERGING DATA SUGGEST THAT ASPECTS OF THE EPIGENETIC LANDSCAPE INHERENT TO NORMAL EMBRYONIC AND ADULT STEM/PROGENITOR CELLS MAY HELP FOSTER, UNDER THE STRESS OF CHRONIC INFLAMMATION OR ACCUMULATING REACTIVE OXYGEN SPECIES, EVOLUTION OF MALIGNANT SUBPOPULATIONS. FINALLY, UNDERSTANDING MOLECULAR MECHANISMS INVOLVED IN INITIATION AND MAINTENANCE OF EPIGENETIC ABNORMALITIES IN ALL TYPES OF CANCER HAS GREAT POTENTIAL FOR TRANSLATIONAL PURPOSES. THIS IS ALREADY EVIDENT FOR EPIGENETIC BIOMARKER DEVELOPMENT, AND FOR PHARMACOLOGICAL TARGETING AIMED AT REVERSING CANCER-SPECIFIC EPIGENETIC ALTERATIONS. 2011 13 1958 32 EPIGENETIC AGING AND COLORECTAL CANCER: STATE OF THE ART AND PERSPECTIVES FOR FUTURE RESEARCH. ALTHOUGH TRANSLATIONAL RESEARCH HAS IDENTIFIED A LARGE NUMBER OF POTENTIAL BIOMARKERS INVOLVED IN COLORECTAL CANCER (CRC) CARCINOGENESIS, A BETTER UNDERSTANDING OF THE MOLECULAR PATHWAYS ASSOCIATED WITH BIOLOGICAL AGING IN COLORECTAL CELLS AND TISSUES IS NEEDED. HERE, WE AIM TO SUMMARIZE THE STATE OF THE ART ABOUT THE ROLE OF AGE ACCELERATION, DEFINED AS THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, IN THE DEVELOPMENT AND PROGRESSION OF CRC. SOME STUDIES HAVE SHOWN THAT ACCELERATED BIOLOGICAL AGING IS POSITIVELY ASSOCIATED WITH THE RISK OF CANCER AND DEATH IN GENERAL. IN LINE WITH THESE FINDINGS, OTHER STUDIES HAVE SHOWN HOW THE ASSESSMENT OF EPIGENETIC AGE IN PEOPLE AT RISK FOR CRC COULD BE HELPFUL FOR MONITORING THE MOLECULAR RESPONSE TO PREVENTIVE INTERVENTIONS. MOREOVER, IT WOULD BE INTERESTING TO INVESTIGATE WHETHER ABERRANT EPIGENETIC AGING COULD HELP IDENTIFY CRC PATIENTS WITH A HIGH RISK OF RECURRENCE AND A WORST PROGNOSIS, AS WELL AS THOSE WHO RESPOND POORLY TO TREATMENT. YET, THE APPLICATION OF THIS NOVEL CONCEPT IS STILL IN ITS INFANCY, AND FURTHER RESEARCH SHOULD BE ENCOURAGED IN ANTICIPATION OF FUTURE APPLICATIONS IN CLINICAL PRACTICE. 2020 14 3672 28 INFLAMMATION AND CANCER: AN ANCIENT LINK WITH NOVEL POTENTIALS. INFECTION AND CHRONIC INFLAMMATION CONTRIBUTE TO ABOUT 1 IN 4 OF ALL CANCER CASES. MEDIATORS OF THE INFLAMMATORY RESPONSE, E.G., CYTOKINES, FREE RADICALS, PROSTAGLANDINS AND GROWTH FACTORS, CAN INDUCE GENETIC AND EPIGENETIC CHANGES INCLUDING POINT MUTATIONS IN TUMOR SUPPRESSOR GENES, DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS, CAUSING ALTERATIONS IN CRITICAL PATHWAYS RESPONSIBLE FOR MAINTAINING THE NORMAL CELLULAR HOMEOSTASIS AND LEADING TO THE DEVELOPMENT AND PROGRESSION OF CANCER. RECENT DISCOVERY OF AN INTERACTION BETWEEN MICRORNAS AND INNATE IMMUNITY DURING INFLAMMATION HAS FURTHER STRENGTHENED THE ASSOCIATION BETWEEN INFLAMMATION AND CANCER. 2007 15 5738 34 SMOKING AND LUNG CANCER: THE ROLE OF INFLAMMATION. WORLDWIDE OVER 1 MILLION PEOPLE DIE DUE TO LUNG CANCER EACH YEAR. IT IS ESTIMATED THAT CIGARETTE SMOKING EXPLAINS ALMOST 90% OF LUNG CANCER RISK IN MEN AND 70 TO 80% IN WOMEN. CLINICALLY EVIDENT LUNG CANCERS HAVE MULTIPLE GENETIC AND EPIGENETIC ABNORMALITIES. THESE ABNORMALITIES MAY RESULT IN ACTIVATION OF ONCOGENES AND INACTIVATION OF TUMOR-SUPPRESSOR GENES. CHRONIC INFLAMMATION, WHICH IS KNOWN TO PROMOTE CANCER, MAY RESULT BOTH FROM SMOKING AND FROM GENETIC ABNORMALITIES. THESE MEDIATORS IN TURN MAY BE RESPONSIBLE FOR INCREASED MACROPHAGE RECRUITMENT, DELAYED NEUTROPHIL CLEARANCE, AND INCREASE IN REACTIVE OXYGEN SPECIES (ROS). THUS, THE PULMONARY ENVIRONMENT PRESENTS A UNIQUE MILIEU IN WHICH LUNG CARCINOGENESIS PROCEEDS IN COMPLICITY WITH THE HOST CELLULAR NETWORK. THE PULMONARY DISEASES THAT ARE ASSOCIATED WITH THE GREATEST RISK FOR LUNG CANCER ARE CHARACTERIZED BY ABUNDANT AND DEREGULATED INFLAMMATION. PULMONARY DISORDERS SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)/EMPHYSEMA ARE CHARACTERIZED BY PROFOUND ABNORMALITIES IN INFLAMMATORY AND FIBROTIC PATHWAYS. THE CYTOKINES AND GROWTH FACTORS ABERRANTLY PRODUCED IN COPD AND THE DEVELOPING TUMOR MICROENVIRONMENT HAVE BEEN FOUND TO HAVE DELETERIOUS PROPERTIES THAT SIMULTANEOUSLY PAVE THE WAY FOR BOTH EPITHELIAL-MESENCHYMAL TRANSITION (EMT) AND DESTRUCTION OF SPECIFIC HOST CELL-MEDIATED IMMUNE RESPONSES. FULL DEFINITION OF THESE PATHWAYS WILL AFFORD THE OPPORTUNITY TO INTERVENE IN SPECIFIC INFLAMMATORY EVENTS MEDIATING LUNG TUMORIGENESIS AND RESISTANCE TO THERAPY. 2008 16 4800 38 OBESITY AND INFLAMMATION: COLORECTAL CANCER ENGINES. THE PREVALENCE OF OBESITY CONTINUES TO INCREASE TO THE EXTENT THAT IT BECAME A WORLDWIDE PANDEMIC. AN ACCUMULATING BODY OF EVIDENCE HAS ASSOCIATED OBESITY WITH THE DEVELOPMENT OF DIFFERENT TYPES OF CANCER, INCLUDING COLORECTAL CANCER, WHICH IS A NOTORIOUS DISEASE WITH A HIGH MORTALITY RATE. AT THE MOLECULAR LEVEL, COLORECTAL CANCER IS A HETEROGENOUS DISEASE CHARACTERIZED BY A MYRIAD OF GENETIC AND EPIGENETIC ALTERATIONS ASSOCIATED WITH VARIOUS FORMS OF GENOMIC INSTABILITY (DETAILED IN SUPPLEMENTARY MATERIALS). RECENTLY, THE MICROENVIRONMENT HAS EMERGED AS A MAJOR FACTOR IN CARCINOGENESIS. OUR AIM IS TO DEFINE THE DIFFERENT MOLECULAR ALTERATIONS LEADING TO THE DEVELOPMENT OF COLORECTAL CANCER IN OBESE PATIENTS WITH A FOCUS ON THE ROLE OF THE MICROENVIRONMENT IN CARCINOGENESIS. WE ALSO HIGHLIGHT ALL EXISTENT MOLECULES IN CLINICAL TRIALS THAT TARGET THE ACTIVATED PATHWAYS IN OBESITY-ASSOCIATED COLORECTAL CANCER, WHETHER USED AS SINGLE TREATMENTS OR IN COMBINATION. OBESITY PREDISPOSES TO COLORECTAL CANCER VIA CREATING A STATE OF CHRONIC INFLAMMATION WITH DYSREGULATED ADIPOKINES, INFLAMMATORY MEDIATORS, AND OTHER FACTORS SUCH AS IMMUNE CELL INFILTRATION. A UNIFYING THEME IN OBESITY-MEDIATED COLORECTAL CANCER IS THE ACTIVATION OF THE PI3K/AKT, MTOR/MAPK, AND STAT3 SIGNALING PATHWAYS. DIFFERENT INHIBITORY MOLECULES TOWARDS THESE PATHWAYS EXIST, INCREASING THE THERAPEUTIC CHOICE OF OBESITY-ASSOCIATED COLON CANCER. HOWEVER, OBESE PATIENTS ARE MORE LIKELY TO SUFFER FROM CHEMOTHERAPY OVERDOSING. PREVENTING OBESITY THROUGH MAINTAINING A HEALTHY AND ACTIVE LIFESTYLE REMAINS TO BE THE BEST REMEDY. 2022 17 3038 31 GENOME ENGINEERING FOR OSTEOARTHRITIS: FROM DESIGNER CELLS TO DISEASE-MODIFYING DRUGS. BACKGROUND: OSTEOARTHRITIS (OA) IS A HIGHLY PREVALENT DEGENERATIVE JOINT DISEASE INVOLVING JOINT CARTILAGE AND ITS SURROUNDING TISSUES. OA IS THE LEADING CAUSE OF PAIN AND DISABILITY WORLDWIDE. AT PRESENT, THERE ARE NO DISEASE-MODIFYING OA DRUGS, AND THE PRIMARY THERAPIES INCLUDE EXERCISE AND NONSTEROIDAL ANTI-INFLAMMATORY DRUGS UNTIL TOTAL JOINT REPLACEMENT AT THE END-STAGE OF THE DISEASE. METHODS: IN THIS REVIEW, WE SUMMARIZED THE CURRENT STATE OF KNOWLEDGE IN GENETIC AND EPIGENETIC ASSOCIATIONS AND RISK FACTORS FOR OA AND THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. RESULTS: GENOME-WIDE ASSOCIATION STUDIES AND ANALYSIS OF EPIGENETIC MODIFICATIONS (SUCH AS MIRNA EXPRESSION, DNA METHYLATION AND HISTONE MODIFICATIONS) CONDUCTED ACROSS VARIOUS POPULATIONS SUPPORT THE NOTION THAT THERE IS A GENETIC BASIS FOR CERTAIN SUBSETS OF OA PATHOGENESIS. CONCLUSION: WITH RECENT ADVANCES IN THE DEVELOPMENT OF GENOME EDITING TECHNOLOGIES SUCH AS THE CRISPR-CAS9 SYSTEM, THESE GENETIC AND EPIGENETIC ALTERNATIONS IN OA CAN BE USED AS PLATFORMS FROM WHICH POTENTIAL BIOMARKERS FOR THE DIAGNOSIS, PROGNOSIS, DRUG RESPONSE, AND DEVELOPMENT OF POTENTIAL PERSONALIZED THERAPEUTIC TARGETS FOR OA CAN BE APPROACHED. FURTHERMORE, GENOME EDITING HAS ALLOWED THE DEVELOPMENT OF "DESIGNER" CELLS, WHEREBY THE RECEPTORS, GENE REGULATORY NETWORKS, OR TRANSGENES CAN BE MODIFIED AS A BASIS FOR NEW CELL-BASED THERAPIES. 2019 18 731 25 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 19 1010 27 CHRONICALLY ELEVATED PROLIFERATION AS A RISK FACTOR FOR NEOPLASIA. CHRONIC DISEASE CONDITIONS THAT ARE ASSOCIATED WITH ELEVATED PROLIFERATION ARE WELL ESTABLISHED AS RISK FACTORS FOR CANCER DEVELOPMENT. THESE MAY BE DUE TO VIRUSES (FOR EXAMPLE, IN THE CASE OF HEPATITIS AND LIVER CANCER), BACTERIAL INFECTIONS, PARASITE INFESTATION OR PHYSICAL TRAUMA. IN ADDITION TO THESE EXOGENOUS AGENTS THERE ARE ALSO METABOLIC ABNORMALITIES THAT CAN CONTRIBUTE, CAUSED BY GENETIC OR EPIGENETIC INFLUENCE. IN THE LATTER CASE, AN INCREASE IN SERUM LEVELS OF THE HORMONES OESTROGEN, TESTOSTERONE AND INSULIN MAY BE OF SPECIAL IMPORTANCE. THE PRESENT REVIEW CONCENTRATES ATTENTION ON FACTORS THAT INDUCE ELEVATED CELL TURNOVER AND FOR WHICH THERE IS EPIDEMIOLOGICAL AND/OR EXPERIMENTAL EVIDENCE OF A LINK WITH NEOPLASIA, WITH PARTICULAR STRESS ON THE INDIVIDUAL ORGAN OR TISSUE LEVEL. 1998 20 1180 34 CONVERGENCE OF GENETIC, NUTRITIONAL AND INFLAMMATORY FACTORS IN GASTROINTESTINAL CANCERS. GASTROINTESTINAL CANCERS ACCOUNT FOR 20% OF ALL CANCER INCIDENCES WORLDWIDE. COLORECTAL CANCER IS THE SECOND MOST COMMON CAUSE OF ALL CANCER-RELATED MORTALITY AND IS INCREASING IN WESTERN SOCIETIES. INFECTION AND INFLAMMATION CONTRIBUTE TO 15-20% OF ALL MALIGNANCIES, AND ARE PREDISPOSING RISK FACTORS FOR GASTROINTESTINAL CANCERS. HELICOBACTER PYLORI INFECTION IS COMMONLY ASSOCIATED WITH GASTRIC CANCERS, AND CHRONIC INFLAMMATION INCREASES THE RISK OF COLORECTAL CANCER BY 1% PER YEAR. MICRONUTRIENT STATUS AND COMMON GENETIC VARIATIONS IN HUMAN POPULATIONS MODIFY RISK FOR GASTROINTESTINAL CANCER. CHRONIC INFLAMMATION PROMOTES CARCINOGENESIS BY INDUCING GENE MUTATIONS, INHIBITING APOPTOSIS, AND STIMULATING ANGIOGENESIS AND CELL PROLIFERATION. INFLAMMATION ALSO INDUCES EPIGENETIC ALTERATIONS THAT ARE ASSOCIATED WITH CANCER DEVELOPMENT. TWO KEY GENES IN THE INFLAMMATORY PROCESS, CYCLOOXYGENASE-2 (COX-2) AND NUCLEAR FACTOR-KAPPA B (NF-KAPPAB), PROVIDE A MECHANISTIC LINK BETWEEN INFLAMMATION AND CANCER AND ARE TARGETS FOR CHEMOPREVENTION. DIETARY COMPONENTS, AND HUMAN GENETIC VARIATION THAT AFFECTS NUTRIENT UTILIZATION, CAN DIRECTLY MODIFY INFLAMMATORY PROCESSES AND/OR SUPPRESS GENOMIC ALTERATIONS THAT ARE THE MOLECULAR ANTECEDENTS OF CANCERS. THE PRESENT REPORT FOCUSES ON THE CONVERGENCE OF GENETIC, NUTRITIONAL, AND INFLAMMATORY FACTORS IN THE INITIATION AND PROGRESSION OF GASTROINTESTINAL CANCERS, AND THE EMERGING DIETARY STRATEGIES FOR CANCER PREVENTION. 2007