1 6331 118 THE ROLE OF COX-2 IN INTESTINAL INFLAMMATION AND COLORECTAL CANCER. COLORECTAL CANCER (CRC) IS A HETEROGENEOUS DISEASE, INCLUDING AT LEAST THREE MAJOR FORMS: HEREDITARY, SPORADIC AND COLITIS-ASSOCIATED CRC. A LARGE BODY OF EVIDENCE INDICATES THAT GENETIC MUTATIONS, EPIGENETIC CHANGES, CHRONIC INFLAMMATION, DIET AND LIFESTYLE ARE THE RISK FACTORS FOR CRC. AS ELEVATED CYCLOOXYGENASE-2 (COX-2) EXPRESSION WAS FOUND IN MOST CRC TISSUE AND IS ASSOCIATED WITH WORSE SURVIVAL AMONG CRC PATIENTS, INVESTIGATORS HAVE SOUGHT TO EVALUATE THE EFFECTS OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) AND SELECTIVE COX-2 INHIBITORS (COXIBS) ON CRC. THE EPIDEMIOLOGICAL STUDIES, CLINICAL TRIALS AND ANIMAL EXPERIMENTS INDICATE THAT NSAIDS ARE AMONG THE MOST PROMISING CHEMOPREVENTIVE AGENTS FOR THIS DISEASE. NSAIDS EXERT THEIR ANTI-INFLAMMATORY AND ANTITUMOR EFFECTS PRIMARILY BY REDUCING PROSTAGLANDIN PRODUCTION BY INHIBITION OF COX-2 ACTIVITY. IN THIS REVIEW, WE HIGHLIGHT BREAKTHROUGHS IN OUR UNDERSTANDING OF THE ROLES OF COX-2 IN CRC AND INFLAMMATORY BOWEL DISEASE. THESE RECENT DATA PROVIDE A RATIONALE FOR RE-EVALUATING COX-2 AS BOTH THE PROGNOSTIC AND THE PREDICTIVE MARKER IN A WIDE VARIETY OF MALIGNANCIES AND FOR RENEWING THE INTEREST IN EVALUATING RELATIVE BENEFITS AND RISK OF COXIBS IN APPROPRIATELY SELECTED PATIENTS FOR CANCER PREVENTION AND TREATMENT. 2010 2 4671 42 NEW INSIGHTS INTO THE MECHANISM OF ACTION OF ASPIRIN IN THE PREVENTION OF COLORECTAL NEOPLASIA. THE RESULTS OF CLINICAL STUDIES HAVE SHOWN THAT THE CHRONIC ADMINISTRATION OF ASPIRIN, EVEN AT THE LOWDOSES (75-100 MG DAILY) RECOMMENDED FOR THE PREVENTION OF CARDIOVASCULAR DISEASE, IS ASSOCIATED WITH A REDUCTION OF CANCER INCIDENCE AND MORTALITY, IN PARTICULAR COLORECTAL CANCER (CRC). THE MECHANISM OF ACTION OF ASPIRIN AS AN ANTINEOPLASTIC AGENT REMAINS CONTROVERSIAL. HOWEVER, DATA OF CLINICAL PHARMACOLOGY AND SEVERAL FEATURES OF THE CHEMOPREVENTIVE EFFECT OF ASPIRIN, EMERGED FROM CLINICAL TRIALS, SUGGEST THAT THE ANTIPLATELET EFFECT OF ASPIRIN PLAYS A CENTRAL ROLE IN ITS ANTICANCER EFFECTS. IN ADDITION TO THEIR CONTRIBUTION TO TUMOR METASTASIS, PLATELETS MAY PLAY A ROLE IN THE EARLY PHASES OF TUMORIGENESIS. IN RESPONSE TO LIFESTYLE AND ENVIRONMENT FACTORS, INTESTINAL EPITHELIAL DAMAGE/ DYSFUNCTION MAY BE ASSOCIATED WITH PLATELET ACTIVATION, INITIALLY AS A MECHANISM TO REPAIR THE DAMAGE. HOWEVER, IF THE PLATELET RESPONSE IS UNCONSTRAINED, IT MAY CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC INFLAMMATION. ALTOGETHER THESE EVENTS LEAD TO ALTER THE NORMAL FUNCTIONS OF INTESTINAL EPITHELIAL CELLS AND MAY TRANSLATE INTO CELLULAR TRANSFORMATION THROUGH SEVERAL MECHANISMS, INCLUDING THE OVEREXPRESSION OF CYCLOOXYGENASE(COX)-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR), WHICH ARE CONSIDERED EARLY EVENTS IN COLORECTAL TUMORIGENESIS. THUS, ANTIPLATELET AGENTS MAY PLAY A ROLE IN THE PREVENTION OF CRC BY MODIFYING EPIGENETIC EVENTS INVOLVED IN EARLY PHASES OF COLORECTAL TUMORIGENESIS. FINALLY, WE CARRIED OUT A CRITICAL REVIEW OF THE LITERATURE ON OFF-TARGET MECHANISMS OF ASPIRIN ACTION AS ANTICANCER DRUG. 2015 3 6325 50 THE ROLE OF ANTI-INFLAMMATORY DRUGS IN COLORECTAL CANCER. A LARGE BODY OF EVIDENCE INDICATES THAT GENETIC MUTATIONS, EPIGENETIC CHANGES, CHRONIC INFLAMMATION, DIET, AND LIFESTYLE ARE KEY RISK FACTORS FOR COLORECTAL CANCER (CRC). PREVENTION OF CRC HAS LONG BEEN CONSIDERED A PLAUSIBLE APPROACH FOR THE POPULATION AND INDIVIDUALS AT HIGH RISK FOR DEVELOPING THIS DISEASE. A SIGNIFICANT EFFORT HAS BEEN MADE IN THE DEVELOPMENT OF NOVEL DRUGS FOR BOTH PREVENTION AND TREATMENT OVER THE PAST TWO DECADES. THIS REVIEW HIGHLIGHTS RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN CRC PREVENTION AND ADJUVANT TREATMENT. MOREOVER, WE FOCUS ON THE MOLECULAR MECHANISMS UNDERLYING THE ANTITUMOR EFFECTS OF THESE DRUGS IN CRC. THE KNOWLEDGE OF HOW ANTI-INFLAMMATORY AGENTS INHIBIT CANCER FORMATION AND PROGRESSION MAY PROVIDE A RATIONALE FOR THE DEVELOPMENT OF MORE EFFECTIVE CHEMOPREVENTIVE AND CHEMOTHERAPEUTIC AGENTS WITH LESS TOXICITY. 2013 4 1180 31 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 5 45 31 A COMPREHENSIVE REVIEW ON RNA INTERFERENCE-MEDIATED TARGETING OF INTERLEUKINS AND ITS POTENTIAL THERAPEUTIC IMPLICATIONS IN COLON CANCER. COLON CANCER IS THE WORLD'S FOURTH LEADING CAUSE OF DEATH. IT IS CANCER OF THE LATTER PART OF THE LARGE INTESTINE, I.E. THE COLON. CHRONIC INFLAMMATION OVER A LONG PERIOD ALSO LEADS TO THE DEVELOPMENT OF CANCER. CANCER IN THE COLON REGION IS ARDUOUS TO DIAGNOSE AND IS DETECTED AT A LATER STAGE WHEN IT METASTASIZES TO OTHER PARTS OF THE BODY LIKE THE LIVER, LUNGS, PERITONEUM, ETC. COLON CANCER IS A GREAT EXAMPLE OF SOLID TUMOURS ASSOCIATED WITH CHRONIC INFLAMMATION. ALTHOUGH CONVENTIONAL THERAPIES ARE EFFECTIVE, THEY LOSE THEIR EFFECTIVENESS BEYOND A CERTAIN POINT. RELAPSE OF THE DISEASE OCCURS FREQUENTLY. RNA INTERFERENCE (RNAI) IS EMERGING AS A GREAT TOOL TO SPECIFICALLY ATTACK THE CANCER CELLS OF A TARGET SITE LIKE THE COLON. RNAI DEALS WITH EPIGENETIC CHANGES MADE IN THE DEFECTIVE CELLS WHICH ULTIMATELY LEADS TO THEIR DEATH WITHOUT HARMING THE HEALTHY CELLS. IN THIS REVIEW, TWO TYPES OF EPIGENETIC MODULATORS HAVE BEEN CONSIDERED, NAMELY SIRNA AND MIRNA, AND THEIR EFFECT ON INTERLEUKINS. INTERLEUKINS, A CLASS OF CYTOKINES, ARE MAJOR INFLAMMATORY RESPONSES OF THE BODY THAT ARE RELEASED BY IMMUNE CELLS LIKE LEUKOCYTES AND MACROPHAGES. SOME OF THESE INTERLEUKINS ARE PRO-INFLAMMATORY, THEREBY PROMOTING INFLAMMATION WHICH EVENTUALLY CAUSES CANCER. RNAI CAN PREVENT COLON CANCER BY INHIBITING PRO-INFLAMMATORY INTERLEUKINS. 2023 6 4732 40 NOVEL BIOMARKERS FOR INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER: AN INTERPLAY BETWEEN METABOLIC DYSREGULATION AND EXCESSIVE INFLAMMATION. PERSISTENT INFLAMMATION CAN TRIGGER ALTERED EPIGENETIC, INFLAMMATORY, AND BIOENERGETIC STATES. INFLAMMATORY BOWEL DISEASE (IBD) IS AN IDIOPATHIC DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION OF THE GASTROINTESTINAL TRACT, WITH EVIDENCE OF SUBSEQUENT METABOLIC SYNDROME DISORDER. STUDIES HAVE DEMONSTRATED THAT AS MANY AS 42% OF PATIENTS WITH ULCERATIVE COLITIS (UC) WHO ARE FOUND TO HAVE HIGH-GRADE DYSPLASIA, EITHER ALREADY HAD COLORECTAL CANCER (CRC) OR DEVELOP IT WITHIN A SHORT TIME. THE PRESENCE OF LOW-GRADE DYSPLASIA IS ALSO PREDICTIVE OF CRC. MANY SIGNALING PATHWAYS ARE SHARED AMONG IBD AND CRC, INCLUDING CELL SURVIVAL, CELL PROLIFERATION, ANGIOGENESIS, AND INFLAMMATORY SIGNALING PATHWAYS. CURRENT IBD THERAPEUTICS TARGET A SMALL SUBSET OF MOLECULAR DRIVERS OF IBD, WITH MANY FOCUSED ON THE INFLAMMATORY ASPECT OF THE PATHWAYS. THUS, THERE IS A GREAT NEED TO IDENTIFY BIOMARKERS OF BOTH IBD AND CRC, THAT CAN BE PREDICTIVE OF THERAPEUTIC EFFICACY, DISEASE SEVERITY, AND PREDISPOSITION TO CRC. IN THIS STUDY, WE EXPLORED THE CHANGES IN BIOMARKERS SPECIFIC FOR INFLAMMATORY, METABOLIC, AND PROLIFERATIVE PATHWAYS, TO HELP DETERMINE THE RELEVANCE TO BOTH IBD AND CRC. OUR ANALYSIS DEMONSTRATED, FOR THE FIRST TIME IN IBD, THE LOSS OF THE TUMOR SUPPRESSOR PROTEIN RAS ASSOCIATED FAMILY PROTEIN 1A (RASSF1A), VIA EPIGENETIC CHANGES, THE HYPERACTIVATION OF THE OBLIGATE KINASE OF THE NOD2 PATHOGEN RECOGNITION RECEPTOR (RECEPTOR INTERACTING PROTEIN KINASE 2 [RIPK2]), THE LOSS OF ACTIVATION OF THE METABOLIC KINASE, AMP ACTIVATED PROTEIN KINASE (AMPKALPHA1), AND, LASTLY, THE ACTIVATION OF THE TRANSCRIPTION FACTOR AND KINASE YES ASSOCIATED PROTEIN (YAP) KINASE, THAT IS INVOLVED IN PROLIFERATION OF CELLS. THE EXPRESSION AND ACTIVATION STATUS OF THESE FOUR ELEMENTS ARE MIRRORED IN IBD, CRC, AND IBD-CRC PATIENTS AND, IMPORTANTLY, IN MATCHED BLOOD AND BIOPSY SAMPLES. THE LATTER WOULD SUGGEST THAT BIOMARKER ANALYSIS CAN BE PERFORMED NON-INVASIVELY, TO UNDERSTAND IBD AND CRC, WITHOUT THE NEED FOR INVASIVE AND COSTLY ENDOSCOPIC ANALYSIS. THIS STUDY, FOR THE FIRST TIME, ILLUSTRATES THE NEED TO UNDERSTAND IBD OR CRC BEYOND AN INFLAMMATORY PERSPECTIVE AND THE VALUE OF THERAPEUTICS DIRECTED TO RESET ALTERED PROLIFERATIVE AND METABOLIC STATES WITHIN THE COLON. THE USE OF SUCH THERAPEUTICS MAY TRULY DRIVE PATIENTS INTO REMISSION. 2023 7 5554 36 ROLE OF EPIGENETICS IN TRANSFORMATION OF INFLAMMATION INTO COLORECTAL CANCER. MOLECULAR MECHANISMS ASSOCIATED WITH INFLAMMATION-PROMOTED TUMORIGENESIS HAVE BECOME AN IMPORTANT TOPIC IN CANCER RESEARCH. VARIOUS ABNORMAL EPIGENETIC CHANGES, INCLUDING DNA METHYLATION, HISTONE MODIFICATION, CHROMATIN REMODELING, AND NONCODING RNA REGULATION, OCCUR DURING THE TRANSFORMATION OF CHRONIC INFLAMMATION INTO COLORECTAL CANCER (CRC). THESE CHANGES NOT ONLY ACCELERATE TRANSFORMATION BUT ALSO LEAD TO CANCER PROGRESSION AND METASTASIS BY ACTIVATING CARCINOGENIC SIGNALING PATHWAYS. THE NF-KAPPAB AND STAT3 SIGNALING PATHWAYS PLAY A PARTICULARLY IMPORTANT ROLE IN THE TRANSFORMATION OF INFLAMMATION INTO CRC, AND BOTH ARE CRITICAL TO CELLULAR SIGNAL TRANSDUCTION AND CONSTANTLY ACTIVATED IN CANCER BY VARIOUS ABNORMAL CHANGES INCLUDING EPIGENETICS. THE NF-KAPPAB AND STAT3 SIGNALS CONTRIBUTE TO THE MICROENVIRONMENT FOR TUMORIGENESIS THROUGH SECRETION OF A LARGE NUMBER OF PRO-INFLAMMATORY CYTOKINES AND THEIR CROSSTALK IN THE NUCLEUS MAKES IT EVEN MORE DIFFICULT TO TREAT CRC. COMPARED WITH GENE MUTATION THAT IS IRREVERSIBLE, EPIGENETIC INHERITANCE IS REVERSIBLE OR CAN BE ALTERED BY THE INTERVENTION. THEREFORE, UNDERSTANDING THE ROLE OF EPIGENETIC INHERITANCE IN THE INFLAMMATION-CANCER TRANSFORMATION MAY ELUCIDATE THE PATHOGENESIS OF CRC AND PROMOTE THE DEVELOPMENT OF INNOVATIVE DRUGS TARGETING TRANSFORMATION TO PREVENT AND TREAT THIS MALIGNANCY. THIS REVIEW SUMMARIZES THE LITERATURE ON THE ROLES OF EPIGENETIC MECHANISMS IN THE OCCURRENCE AND DEVELOPMENT OF INFLAMMATION-INDUCED CRC. EXPLORING THE ROLE OF EPIGENETICS IN THE TRANSFORMATION OF INFLAMMATION INTO CRC MAY HELP STIMULATE FUTURES STUDIES ON THE ROLE OF MOLECULAR THERAPY IN CRC. 2019 8 5566 42 ROLE OF INFLAMMATION IN THE DEVELOPMENT OF COLORECTAL CANCER. CHRONIC INFLAMMATION CAN LEAD TO THE DEVELOPMENT OF MANY DISEASES, INCLUDING CANCER. INFLAMMATORY BOWEL DISEASE (IBD) THAT INCLUDES BOTH ULCERATIVE COLITIS (UC) AND CROHNMP'S DISEASE (CD) ARE RISK FACTORS FOR THE DEVELOPMENT OF COLORECTAL CANCER (CRC). MANY CYTOKINES PRODUCED PRIMARILY BY THE GUT IMMUNE CELLS EITHER DURING OR IN RESPONSE TO LOCALIZED INFLAMMATION IN THE COLON AND RECTUM ARE KNOWN TO STIMULATE THE COMPLEX INTERACTIONS BETWEEN THE DIFFERENT CELL TYPES IN THE GUT ENVIRONMENT RESULTING IN ACUTE INFLAMMATION. SUBSEQUENTLY, CHRONIC INFLAMMATION, TOGETHER WITH GENETIC AND EPIGENETIC CHANGES, HAVE BEEN SHOWN TO LEAD TO THE DEVELOPMENT AND PROGRESSION OF CRC. VARIOUS CELL TYPES PRESENT IN THE COLON, SUCH AS ENTEROCYTES, PANETH CELLS, GOBLET CELLS, AND MACROPHAGES, EXPRESS RECEPTORS FOR INFLAMMATORY CYTOKINES AND RESPOND TO TUMOR NECROSIS FACTOR-ALPHA (TNF-ALPHA), INTERLEUKIN-1 BETA (IL-1BETA), IL-6, AND OTHER CYTOKINES. AMONG THE SEVERAL CYTOKINES PRODUCED, TNF-ALPHA AND IL-1BETA ARE THE KEY PRO-INFLAMMATORY MOLECULES THAT PLAY CRITICAL ROLES IN THE DEVELOPMENT OF CRC. THE CURRENT REVIEW IS INTENDED TO CONSOLIDATE THE PUBLISHED FINDINGS TO FOCUS ON THE ROLE OF PRO-INFLAMMATORY CYTOKINES, NAMELY TNF-ALPHA AND IL-1BETA, ON INFLAMMATION (AND THE ALTERED IMMUNE RESPONSE) IN THE GUT, TO BETTER UNDERSTAND THE DEVELOPMENT OF CRC IN IBD, USING VARIOUS EXPERIMENTAL MODEL SYSTEMS, PRECLINICAL AND CLINICAL STUDIES. MOREOVER, THIS REVIEW ALSO HIGHLIGHTS THE CURRENT THERAPEUTIC STRATEGIES AVAILABLE (MONOTHERAPY AND COMBINATION THERAPY) TO ALLEVIATE THE SYMPTOMS OR TREAT INFLAMMATION-ASSOCIATED CRC BY USING MONOCLONAL ANTIBODIES OR APTAMERS TO BLOCK PRO-INFLAMMATORY MOLECULES, INHIBITORS OF TYROSINE KINASES IN THE INFLAMMATORY SIGNALING CASCADE, COMPETITIVE INHIBITORS OF PRO-INFLAMMATORY MOLECULES, AND THE NUCLEIC ACID DRUGS LIKE SMALL ACTIVATING RNAS (SARNAS) OR MICRORNA (MIRNA) MIMICS TO ACTIVATE TUMOR SUPPRESSOR OR REPRESS ONCOGENE/PRO-INFLAMMATORY CYTOKINE GENE EXPRESSION. 2021 9 3921 41 LINKING INFLAMMATION TO CELL CYCLE PROGRESSION. RISK OF GASTROINTESTINAL CANCERS IS CLOSELY RELATED TO INCREASED LEVELS OF OXIDANTS IN THE BALANCE BETWEEN OXIDANT AND ANTI-OXIDANT AGENTS. A POSSIBLE EXPLANATION OF THIS EPIDEMIOLOGICAL OBSERVATION IS THE LOCAL LOSS OF THE EPITHELIAL BARRIER FUNCTION WITH A FOCAL INFLAMMATORY RESPONSE. ACCORDINGLY, CHRONIC INFLAMMATORY DISEASES REPRESENT WELL-KNOWN RISK FACTORS FOR CANCER AND, ON THE OTHER HAND, IT IS KNOWN THAT ANTI-INFLAMMATORY AGENTS, DEMULCENTS AND ANTIOXIDANTS MARKEDLY INHIBIT THE DEVELOPMENT OF COLON CANCER IN ANIMAL MODELS AS WELL IN HUMANS. AT MOLECULAR LEVEL A KEY ROLE IN THE PROCESS THAT LINK INFLAMMATION TO CELLULAR TRANSFORMATION SEEMS TO BE PLAYED BY ACTIVATION OF CYCLOOXYGENASE-2 (COX-2) TOGETHER WITH PRODUCTION OF REACTIVE OXYGEN INTERMEDIATE (ROI). BOTH THESE EVENTS HAVE BEEN STRICTLY LINKED WITH CELL PROLIFERATION AND TRANSFORMATION, ALTHOUGH THE INTRACELLULAR PATHWAYS INVOLVED IN THESE PROCESSES ARE STILL NOT COMPLETELY UNDERSTOOD. THE UNCONTROLLED PROLIFERATION, WHICH IS A LANDMARK OF CELLULAR TRANSFORMATION, IS ACCOMPANIED BY THE DEREGULATION OF PROTEINS INVOLVED IN THE CONTROL OF CELL CYCLE CHECKPOINTS. ALTERED EXPRESSION AND FUNCTION OF CYCLOOXYGENASE AND NITRIC OXIDE SYNTHASE SEEM TO INFLUENCE, AMONG OTHERS, THE EXPRESSION OF PROTEINS INVOLVED IN THE REGULATION OF CELL CYCLE PROGRESSION. SIMILARLY, ANTI-INFLAMMATORY AND ANTIOXIDANT AGENTS MAY ALSO ACT ON THE EXPRESSION AND FUNCTION OF SEVERAL CELL CYCLE REGULATING PROTEINS. UNDERSTANDING THE MECHANISMS BY WHICH CHRONIC INFLAMMATION CONTRIBUTES TO GENETIC AND EPIGENETIC CHANGES INVOLVED IN THE REGULATION OF CRITICAL CELL CYCLE CHECKPOINTS MAY HELP TO DEVELOP MORE AND MORE SPECIFIC TREATMENT STRATEGIES FOR REDUCING MALIGNANT TRANSFORMATION OF THESE INFLAMMATORY DISEASES. 2004 10 3681 37 INFLAMMATION, DNA METHYLATION AND COLITIS-ASSOCIATED CANCER. INFLAMMATION CAN RESULT FROM A RANGE OF SOURCES INCLUDING MICROBIAL INFECTIONS, EXPOSURE TO ALLERGENS AND TOXIC CHEMICALS, AUTOIMMUNE DISEASE AND OBESITY. A WELL-BALANCED IMMUNE RESPONSE CAN BE ANTI-TUMORIGENIC; HOWEVER, A SUSTAINED OR CHRONIC INFLAMMATORY RESPONSE IS GENERALLY HARMFUL AS THE IMMUNE RESPONSE BECOMES DISTORTED. A CAUSAL LINK BETWEEN CHRONIC INFLAMMATION AND CANCER IS NOW WELL ACCEPTED AND MANY CHRONICALLY INFLAMED ORGANS OF THE GASTROINTESTINAL TRACT SHOW THIS ASSOCIATION. FOR EXAMPLE, PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING BOTH ULCERATIVE COLITIS AND CROHN'S DISEASE, HAVE A 2- TO 3-FOLD GREATER LIFETIME RISK OF DEVELOPING COLORECTAL CANCER COMPARED WITH THE GENERAL POPULATION. THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCER (CAC) IS THOUGHT TO BE MULTIFACETED AND IS PROBABLY DUE TO A COMBINATION OF GENETIC FACTORS, EPIGENETIC FACTORS AND THE DURATION, EXTENT AND SEVERITY OF DISEASE. RECENTLY, EPIGENETIC ALTERATIONS, IN PARTICULAR ALTERATIONS IN DNA METHYLATION, HAVE BEEN OBSERVED DURING INFLAMMATION AND INFLAMMATION-ASSOCIATED CARCINOGENESIS. THE MEDIATORS OF THIS, THE SIGNIFICANCE OF THESE CHANGES IN DNA METHYLATION AND THE EFFECT THIS HAS ON GENE EXPRESSION AND THE MALIGNANT TRANSFORMATION OF THE EPITHELIAL CELLS DURING IBD AND CAC ARE DISCUSSED IN THIS REVIEW. THE RECENT ADVANCES IN TECHNOLOGIES TO STUDY GENOME-WIDE DNA METHYLATION AND THE THERAPEUTIC POTENTIAL OF UNDERSTANDING THESE MOLECULAR MECHANISMS ARE ALSO HIGHLIGHTED. 2012 11 928 24 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 12 1237 44 CURCUMIN AND COLORECTAL CANCER: AN UPDATE AND CURRENT PERSPECTIVE ON THIS NATURAL MEDICINE. COLORECTAL CANCER (CRC) IS ONE OF MOST COMMON MALIGNANCIES WORLDWIDE AND ITS INCIDENCE IS STILL GROWING. IN SPITE OF RECENT ADVANCES IN TARGETED THERAPIES, THEIR CLINICAL EFFICACY HAS BEEN LIMITED, NON-CURATIVE AND UNAFFORDABLE. A GROWING BODY OF LITERATURE INDICATES THAT CRC IS A MULTI-MODAL DISEASE, WHERE A VARIETY OF FACTORS WITHIN THE TUMOR MICROENVIRONMENT PLAY A SIGNIFICANT ROLE IN ITS PATHOGENESIS. FOR INSTANCE, IMBALANCE IN GUT MICROBIAL PROFILES AND IMPAIRED INTESTINAL BARRIER FUNCTION CONTRIBUTE TO THE OVERALL INTESTINAL INFLAMMATION AND INITIATION OF CRC. MOREOVER, PERSISTENT CHRONIC INFLAMMATION FAVORS A TUMOR MICROENVIRONMENT FOR THE GROWTH OF CANCER. IN ADDITION, AUTOPHAGY OR 'SELF-EATING' IS A SURVEILLANCE MECHANISM INVOLVED IN THE DEGRADATION OF CELLULAR CONSTITUENTS THAT ARE GENERATED UNDER STRESSFUL CONDITIONS. CANCER STEM CELLS (CSCS), ON THE OTHER HAND, ENGAGE IN THE ONSET OF CRC AND ARE ABLE TO ENDOW CANCER CELLS WITH CHEMO-RESISTANCE. FURTHERMORE, THE ABERRANT EPIGENETIC ALTERATIONS PROMOTE CRC. THESE EVIDENCES HIGHLIGHT THE NEED FOR MULTI-TARGETED APPROACHES THAT ARE NOT ONLY SAFE AND INEXPENSIVE BUT OFFER A MORE EFFECTIVE ALTERNATIVE TO CURRENT GENERATION OF TARGETED DRUGS. CURCUMIN, DERIVED FROM THE PLANT CURCUMA LONGA, REPRESENTS ONE SUCH OPTION THAT HAS A LONG HISTORY OF ITS USE FOR A VARIETY OF CHRONIC DISEASE INCLUDING CANCER, IN INDIAN AYURVEDIC AND TRADITIONAL CHINESE MEDICINE. SCIENTIFIC EVIDENCE OVER THE PAST FEW DECADES HAVE OVERWHELMINGLY SHOWN THAT CURCUMIN EXHIBITS A MULTITUDE OF ANTI-CANCER ACTIVITIES ORCHESTRATED THROUGH KEY SIGNALING PATHWAYS ASSOCIATED WITH CANCER. IN THIS ARTICLE, WE WILL PRESENT A CURRENT UPDATE AND PERSPECTIVE ON THIS NATURAL MEDICINE - INCORPORATING THE BASIC CELLULAR MECHANISMS IT EFFECTS AND THE CURRENT STATE OF CLINICAL EVIDENCE, CHALLENGES AND PROMISE FOR ITS USE AS A CANCER PREVENTATIVE AND POTENTIAL ADJUNCT TOGETHER WITH MODERN THERAPIES FOR CRC PATIENTS. 2022 13 4458 35 MOLECULAR MECHANISMS OF ALCOHOL-INDUCED COLORECTAL CARCINOGENESIS. THE ETIOLOGY OF COLORECTAL CANCER (CRC) IS COMPLEX. APPROXIMATELY, 10% OF INDIVIDUALS WITH CRC HAVE PREDISPOSING GERMLINE MUTATIONS THAT LEAD TO FAMILIAL CANCER SYNDROMES, WHEREAS MOST CRC PATIENTS HAVE SPORADIC CANCER RESULTING FROM A COMBINATION OF ENVIRONMENTAL AND GENETIC RISK FACTORS. IT HAS BECOME INCREASINGLY CLEAR THAT CHRONIC ALCOHOL CONSUMPTION IS ASSOCIATED WITH THE DEVELOPMENT OF SPORADIC CRC; HOWEVER, THE EXACT MECHANISMS BY WHICH ALCOHOL CONTRIBUTES TO COLORECTAL CARCINOGENESIS ARE LARGELY UNKNOWN. SEVERAL PROPOSED MECHANISMS FROM STUDIES IN CRC MODELS SUGGEST THAT ALCOHOL METABOLITES AND/OR ENZYMES ASSOCIATED WITH ALCOHOL METABOLISM ALTER CELLULAR REDOX BALANCE, CAUSE DNA DAMAGE, AND EPIGENETIC DYSREGULATION. IN ADDITION, ALCOHOL METABOLITES CAN CAUSE A DYSBIOTIC COLORECTAL MICROBIOME AND INTESTINAL PERMEABILITY, RESULTING IN BACTERIAL TRANSLOCATION, INFLAMMATION, AND IMMUNOSUPPRESSION. ALL OF THESE EFFECTS CAN INCREASE THE RISK OF DEVELOPING CRC. THIS REVIEW AIMS TO OUTLINE SOME OF THE MOST SIGNIFICANT AND RECENT FINDINGS ON THE MECHANISMS OF ALCOHOL IN COLORECTAL CARCINOGENESIS. WE EXAMINE THE EFFECT OF ALCOHOL ON THE GENERATION OF REACTIVE OXYGEN SPECIES, THE DEVELOPMENT OF GENOTOXIC STRESS, MODULATION OF ONE-CARBON METABOLISM, DISRUPTION OF THE MICROBIOME, AND IMMUNOSUPPRESSION. 2021 14 2704 28 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 15 4800 41 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 16 6395 31 THE ROLE OF THE MEDIATORS OF INFLAMMATION IN CANCER DEVELOPMENT. EPIGENETIC DISORDERS SUCH AS POINT MUTATIONS IN CELLULAR TUMOR SUPPRESSOR GENES, DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS ARE NEEDED TO TRANSFORMATION OF NORMAL CELLS INTO CANCER CELLS. THESE EVENTS RESULT IN ALTERATIONS IN CRITICAL PATHWAYS RESPONSIBLE FOR MAINTAINING THE NORMAL CELLULAR HOMEOSTASIS, TRIGGERING TO AN INFLAMMATORY RESPONSE WHICH CAN LEAD THE DEVELOPMENT OF CANCER. THE INFLAMMATORY RESPONSE IS A UNIVERSAL DEFENSE MECHANISM ACTIVATED IN RESPONSE TO AN INJURY TISSUE, OF ANY NATURE, THAT INVOLVES BOTH INNATE AND ADAPTIVE IMMUNE RESPONSES, THROUGH THE COLLECTIVE ACTION OF A VARIETY OF SOLUBLE MEDIATORS. MANY INFLAMMATORY SIGNALING PATHWAYS ARE ACTIVATED IN SEVERAL TYPES OF CANCER, LINKING CHRONIC INFLAMMATION TO TUMORIGENESIS PROCESS. THUS, INFLAMMATORY RESPONSES PLAY DECISIVE ROLES AT DIFFERENT STAGES OF TUMOR DEVELOPMENT, INCLUDING INITIATION, PROMOTION, GROWTH, INVASION, AND METASTASIS, AFFECTING ALSO THE IMMUNE SURVEILLANCE. IMMUNE CELLS THAT INFILTRATE TUMORS ENGAGE IN AN EXTENSIVE AND DYNAMIC CROSSTALK WITH CANCER CELLS, AND SOME OF THE MOLECULAR EVENTS THAT MEDIATE THIS DIALOG HAVE BEEN REVEALED. A RANGE OF INFLAMMATION MEDIATORS, INCLUDING CYTOKINES, CHEMOKINES, FREE RADICALS, PROSTAGLANDINS, GROWTH AND TRANSCRIPTION FACTORS, MICRORNAS, AND ENZYMES AS, CYCLOOXYGENASE AND MATRIX METALLOPROTEINASE, COLLECTIVELY ACTS TO CREATE A FAVORABLE MICROENVIRONMENT FOR THE DEVELOPMENT OF TUMORS. IN THIS REVIEW ARE PRESENTED THE MAIN MEDIATORS OF THE INFLAMMATORY RESPONSE AND DISCUSSED THE LIKELY MECHANISMS THROUGH WHICH, THEY INTERACT WITH EACH OTHER TO CREATE A CONDITION FAVORABLE TO DEVELOPMENT OF CANCER. 2015 17 1522 38 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 4283 37 MICRORNA BIOMARKERS IN IBD-DIFFERENTIAL DIAGNOSIS AND PREDICTION OF COLITIS-ASSOCIATED CANCER. INFLAMMATORY BOWEL DISEASE (IBD) INCLUDES CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC). THESE ARE CHRONIC AUTOIMMUNE DISEASES OF UNKNOWN ETIOLOGY AFFECTING THE GASTROINTESTINAL TRACT. THE IBD POPULATION INCLUDES A HETEROGENEOUS GROUP OF PATIENTS WITH VARYING DISEASE COURSES REQUIRING PERSONALIZED TREATMENT PROTOCOLS. THE COMPLEXITY OF THE DISEASE OFTEN DELAYS THE DIAGNOSIS AND THE INITIATION OF APPROPRIATE TREATMENTS. IN A SUBSET OF PATIENTS, IBD LEADS TO COLITIS-ASSOCIATED CANCER (CAC). MICRORNAS ARE SINGLE-STRANDED REGULATORY NONCODING RNAS OF 18 TO 22 NUCLEOTIDES WITH PUTATIVE ROLES IN THE PATHOGENESIS OF IBD AND COLORECTAL CANCER. THEY HAVE BEEN EXPLORED AS BIOMARKERS AND THERAPEUTIC TARGETS. BOTH TISSUE-DERIVED AND CIRCULATING MICRORNAS HAVE EMERGED AS PROMISING BIOMARKERS IN THE DIFFERENTIAL DIAGNOSIS AND IN THE PROGNOSIS OF DISEASE SEVERITY OF IBD AS WELL AS PREDICTIVE BIOMARKERS IN DRUG RESISTANCE. IN ADDITION, KNOWLEDGE OF THE CELLULAR LOCALIZATION OF DIFFERENTIALLY EXPRESSED MICRORNAS IS A PREREQUISITE FOR DECIPHERING THE BIOLOGICAL ROLE OF THESE IMPORTANT EPIGENETIC REGULATORS AND THE CELLULAR LOCALIZATION MAY EVEN CONTRIBUTE TO AN ALTERNATIVE REPERTOIRE OF BIOMARKERS. IN THIS REVIEW, WE DISCUSS FINDINGS BASED ON RT-QPCR, MICROARRAY PROFILING, NEXT GENERATION SEQUENCING AND IN SITU HYBRIDIZATION OF MICRORNA BIOMARKERS IDENTIFIED IN THE CIRCULATION AND IN TISSUE BIOPSIES. 2020 19 3672 19 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 20 2335 26 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