leptin and Esophageal-Neoplasms

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; Lasers, Semiconductor; Lenalidomide; Leptin; Lethal Dose 50; Levonorgestrel; Limit of Detection; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Lipopolysaccharides; Liquid Biopsy; Liver; Liver Abscess, Pyogenic; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Longevity; Lung Neoplasms; Luteolin; Lymph Nodes; Lymphocyte Activation; Macaca fascicularis; Macrophages; Mad2 Proteins; Magnetic Resonance Imaging; Male; Mammary Glands, Human; Manganese; Manganese Compounds; MAP Kinase Signaling System; Materials Testing; Maternal Health Services; MCF-7 Cells; Medicaid; Medicine, Chinese Traditional; Melanoma; Membrane Proteins; Mental Health; Mercury; Metal Nanoparticles; Metals, Heavy; Metformin; Methionine Adenosyltransferase; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Nude; Microalgae; Microbial Sensitivity Tests; Microglia; MicroRNAs; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses

Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.

Topics: Adenocarcinoma; Adipose Tissue; Esophageal Neoplasms; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Female; Humans; Leptin; Male; Sex Factors; Signal Transduction

There is increasing evidence that obesity may have pathophysiological effects that extend beyond its well-known co-morbidities; in particular its role in cancer has received considerable epidemiological support. As adipose tissue becomes strongly established as an endocrine organ, two of its most abundant and most investigated adipokines, leptin and adiponectin, are also taken beyond their traditional roles in energy homeostasis, and are implicated as mediators of the effects of obesity on cancer development. This review examines these adipokines in relation to the prostate, breast, colorectal, thyroid, renal, pancreatic, endometrial and oesophageal cancers, and how they may orchestrate the influence of obesity on the development of these malignancies.

Topics: Adiponectin; Body Mass Index; Breast Neoplasms; Colorectal Neoplasms; Endometrial Neoplasms; Esophageal Neoplasms; Female; Humans; Kidney Neoplasms; Leptin; Male; Neoplasms; Obesity; Pancreatic Neoplasms; Prostatic Neoplasms; Thyroid Neoplasms

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; Lasers, Semiconductor; Lenalidomide; Leptin; Lethal Dose 50; Levonorgestrel; Limit of Detection; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Lipopolysaccharides; Liquid Biopsy; Liver; Liver Abscess, Pyogenic; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Longevity; Lung Neoplasms; Luteolin; Lymph Nodes; Lymphocyte Activation; Macaca fascicularis; Macrophages; Mad2 Proteins; Magnetic Resonance Imaging; Male; Mammary Glands, Human; Manganese; Manganese Compounds; MAP Kinase Signaling System; Materials Testing; Maternal Health Services; MCF-7 Cells; Medicaid; Medicine, Chinese Traditional; Melanoma; Membrane Proteins; Mental Health; Mercury; Metal Nanoparticles; Metals, Heavy; Metformin; Methionine Adenosyltransferase; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Nude; Microalgae; Microbial Sensitivity Tests; Microglia; MicroRNAs; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses

To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development.. A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions) versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions) in inactive, overweight/obese (25.0-34.9 kg/m2) males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance [HOMA]). Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value.. Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80); 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control) was observed for waist circumference (-4.5 [95% CI -7.5, -1.4] cm; p < 0.01). Effects on primary outcomes were not statistically significant.. This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment.. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000401257.

Topics: Adenocarcinoma; Adiponectin; Barrett Esophagus; C-Reactive Protein; Case-Control Studies; Esophageal Neoplasms; Exercise; Humans; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Overweight; Risk Factors; Tumor Necrosis Factor-alpha

Currently, the global prevalence of obesity among the worlds adult population is about 650 million people, which makes it possible to consider this chronic metabolic disease as a non-infectious pandemic of the 21st century. It has been proven that obesity is associated with several gastroenterological diseases, while the mechanisms of these associations are extremely heterogeneous and multifactorial. Hypertrophy and hyperplasia of adipocytes in obesity lead to a change in the profile of adipokine production (a decrease in adiponectin, an increase in leptin), an increase in the production of pro-inflammatory cytokines (interleukin-1, 6, 8, tumor necrosis factor ), C-reactive protein, free fatty acids, as well as active forms of oxygen (superoxide radicals, H2O2). All the above induces the development of chronic slowly progressive inflammation, oxidative stress, and insulin resistance. In addition, peptides secreted by adipocytes (adiponectin, leptin, nesfatin-1 and apelin) can modulate gastrointestinal motility, acting both centrally and peripherally. The qualitative and quantitative changes in the intestinal microbiota observed in obese patients (increased Firmicutes and decreased Bacteroidetes) lead to a decrease in the production of short-chain fatty acids and an increase in the intestinal permeability due to disruption of intercellular tight junctions, which leads to increased translocation of bacteria and endotoxins into the systemic circulation. Numerous studies have demonstrated the association of obesity with diseases of the esophagus (gastroesophageal reflux disease, Barretts esophagus, esophageal adenocarcinoma, esophageal motility disorders), stomach (functional dyspepsia, stomach cancer), gallbladder (cholelithiasis, gallbladder cancer), pancreas (acute pancreatitis, pancreatic cancer), liver (non-alcoholic fatty liver disease, hepatocellular carcinoma), intestine (diverticular disease, irritable bowel syndrome, colorectal cancer).. В настоящее время глобальная распространенность ожирения среди взрослого населения мира составляет около 650 млн человек, что позволяет рассматривать данное хроническое заболевание обмена веществ как неинфекционную пандемию XXI в. Доказано, что ожирение ассоциировано с целым рядом заболеваний гастроэнтерологического профиля, при этом механизмы этих связей крайне гетерогенны и мультифакториальны. Гипертрофия и гиперплазия адипоцитов при ожирении приводят к изменению профиля продукции адипокинов (снижение адипонектина, повышение лептина), повышению продукции провоспалительных цитокинов (интерлейкин-1, 6, 8, фактор некроза опухоли ), С-реактивного белка, свободных жирных кислот, а также активных форм кислорода (супероксидные радикалы, H2O2). Все перечисленное индуцирует развитие хронического медленно прогрессирующего воспаления, оксидативного стресса, а также инсулинорезистентности. Помимо этого, пептиды, секретируемые адипоцитами (адипонектин, лептин, несфатин-1 и апелин), способны модулировать моторику желудочно-кишечного тракта, действуя как центрально, так и периферически. Наблюдаемые у пациентов с ожирением качественные и количественные изменения микробиоты кишечника (повышение Firmicutes и снижение Bacteroidetes) приводят к сокращению продукции короткоцепочечных жирных кислот и росту проницаемости кишечной стенки вследствие нарушения межклеточных плотных контактов, что ведет к повышенной транслокации бактерий и эндотоксинов в системный кровоток. Многочисленными исследованиями продемонстрирована ассоциация ожирения с заболеваниями пищевода (гастроэзофагеальная рефлюксная болезнь, пищевод Баррета, аденокарцинома пищевода, нарушения моторики пищевода), желудка (функциональная диспепсия, рак желудка), желчного пузыря (желчнокаменная болезнь, рак желчного пузыря), поджелудочной железы (острый панкреатит, рак поджелудочной железы), печени (неалкогольная жировая болезнь печени, гепатоцеллюлярная карцинома), кишечника (дивертикулярная болезнь, синдром раздраженного кишечника, колоректальный рак).

Topics: Acute Disease; Adipokines; Adiponectin; Adult; Apelin; Barrett Esophagus; C-Reactive Protein; Cytokines; Digestive System; Endotoxins; Esophageal Neoplasms; Fatty Acids, Nonesterified; Humans; Hydrogen Peroxide; Interleukin-1; Leptin; Obesity; Oxygen; Pancreatitis; Risk Factors; Superoxides; Tumor Necrosis Factors

Obesity is a risk factor for Barrett's oesophagus and oesophageal adenocarcinoma. Adipose tissue secretes the hormone leptin. Leptin is a growth factor for several cell types, including Barrett's cells and oesophageal adenocarcinoma cells. Statins are associated with reduced rates of Barrett's oesophagus and oesophageal cancer and exhibit anti-cancer effects in vitro. The mechanisms of these effects are not fully established. We have examined the effects of leptin and the lipid-soluble statin, atorvastatin, on signalling via monomeric GTP-binding proteins and Akt. Proliferation and apoptosis were assessed in OE33 cells. Akt activity was quantified by cell-based ELISA and in vitro kinase assay. Specific small-molecule inhibitors and a dominant-negative construct were used to reduce Akt activity. Small GTPases were inhibited using transfection of dominant-negative plasmids, prenylation inhibitors and pretreatment with atorvastatin. Leptin stimulated Akt activity and cell proliferation and inhibited camptothecin-induced apoptosis in an Akt-sensitive manner. Leptin induced phosphorylation of Bad and FOXO1 in an Akt-sensitive manner. Leptin activated Ras, Rac, RhoA and cdc42. Transfection of dominant-negative plasmids confirmed that leptin-induced Akt activation required Ras, RhoA cdc42 but not Rac. Atorvastatin inhibited leptin-induced activation of Ras, RhoA, cdc42 and Akt. Co-treatment with mevalonate prevented these effects of atorvastatin. The protein kinase Akt is essential to the growth-promoting and anti-apoptotic effects of leptin in oesophageal adenocarcinoma cells. Akt is activated via Ras-, Rho- and cdc42-dependant pathways. Atorvastatin reduces leptin-induced Akt activation by inhibiting prenylation of small GTPases. This may explain the reduced incidence of oesophageal adenocarcinoma in statin-users.

Topics: Atorvastatin; Cell Line, Tumor; Enzyme Activation; Esophageal Neoplasms; GTP Phosphohydrolases; Humans; Leptin; Proto-Oncogene Proteins c-akt

Esophageal adenocarcinoma (EAC) is one of the most common malignancies in the world which is associated the increased prevalence of obesity. In the context of obesity, leptin can directly contribute to progression of EAC. Adiponectin inhibits leptin-induced oncogenic signaling in EAC cells. However, the exact molecular mechanisms linking obesity, adipokines, and EAC remain far from completely understood. In the present study, we tested the role of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) in adiponectin-induced protective effects against leptin-induced EAC cell proliferation. We found that globular adiponectin (gAD) significantly inhibited leptin-induced increase of cell proliferation and decrease of apoptosis in OE 19 cells. Moreover, leptin-induced increase of UHRF1 expression was suppressed by gAD. Compared with normal controls, UHRF1 expression was markedly increased in EAC tissues and cell lines. Silence of UHRF1 increased the expression of cleaved caspase 3 and 9 and Bax, reduced the expression of Bcl-2, promoted apoptosis, and inhibited cell proliferation in OE 19 cells. Overexpression of UHRF1 significantly blocked gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of adiponectin receptor 1/2 (AdipoR1/2) could inhibit gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of AdipoR2, but not AdipoR1, suppressed gAD-induced decrease of UHRF1 expression in leptin-treated cells. The results indicated that gAD inhibited the prooncogenic effects of leptin via AdipoR2-mediated suppression of UHRF1. Our study provides novel insights into the role of UHRF1 in the development of EAC and the mechanism of antitumor effect of gAD.

Topics: Adenocarcinoma; Adiponectin; CCAAT-Enhancer-Binding Proteins; Cell Line, Tumor; Cell Proliferation; Esophageal Neoplasms; Humans; Leptin; Neoplasm Proteins; Receptors, Adiponectin; Ubiquitin-Protein Ligases

Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.

Topics: Actins; Adenocarcinoma; Adipocytes; Adipose Tissue; Aged; Antigens, CD; Cadherins; Cell Size; Culture Media, Conditioned; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Leptin; Lymphangiogenesis; Lymphatic Metastasis; Male; Membrane Glycoproteins; Middle Aged; Neovascularization, Pathologic; Obesity; Paracrine Communication; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Adiponectin; RNA, Messenger; Signal Transduction; Tissue Culture Techniques; Tumor Cells, Cultured

Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC.

Topics: Adiponectin; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Enzyme Activation; Esophageal Neoplasms; Humans; Janus Kinase 2; Leptin; Matrix Metalloproteinases; Models, Biological; Neoplasm Invasiveness; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Signal Transduction; STAT3 Transcription Factor

Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy.. Tumour biopsies from patients (n=14) with TNM stage IB-IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations.. We identified 520 genes with differential expression (Mann-Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin.. In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Growth Processes; Drug Resistance, Neoplasm; Esophageal Neoplasms; Female; Gene Expression Profiling; Humans; Leptin; Male; Middle Aged; Neoplasm Staging; Prognosis; RNA, Messenger; Stomach Neoplasms

To preliminarily investigate the expression and clinical significance of leptin and adiponectin in esophageal squamous cell carcinoma (ESCC).. The expression of leptin and adiponectin in ESCC and normal esophageal mucosal tissue was detected by immunohistochemical staining with tissue microarray. The correlation between leptin, adiponectin and clinicalpathological features was statistically analyzed.. The expression of leptin was significantly upregulated in the ESCC than in the normal esophageal mucosa tissue [65.6% (80/122) versus 27.5% (11/40), P < 0.001]. Expression of leptin was significantly correlated with lymph node involvement and advanced tumor stage (P = 0.009 and P = 0.043, respectively). Expression of adiponectin was significantly down-regulated in ESCC compared with that in normal esophageal mucosal tissue [22.1% (27/122) versus 47.5% (19/40), P = 0.002]. Expression of adiponectin was significantly correlated with lymph node involvement (P = 0.020). Correlation analysis showed a positive correlation between the expression of leptin and lymph node metastasis and TNM stage (r = 0.235 and r = 0.183, respectively), and a negative correlation between the expression of adiponectin and lymph node metastasis (r = -0.229). There was no significant correlation between the expressions of leptin and adiponectin (P > 0.05), and between the body mass index and the expression of leptin and adiponectin, and lymph node metastasis (P > 0.05 for all).. An imbalanced expression of adipocytokines exits in ESCC. The expression of leptin and adiponectin is correlated with lymph node metastasis and/or tumor stage. Therefore, imbalanced expression of leptin and adiponectin may have a potential role in the carcinogenesis and disease progression of ESCC.

Topics: Adiponectin; Carcinoma, Squamous Cell; Down-Regulation; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Leptin; Lymphatic Metastasis; Neoplasm Staging; Up-Regulation

Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes.. We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors.. Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA.. Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE.

Topics: Adenocarcinoma; Adiponectin; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers; Blood Glucose; Esophageal Neoplasms; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Assessment

Esophageal adenocarcinoma incidence is rapidly increasing which may be due to the growing incidence of Barrett's esophagus (BE) and obesity. The mechanisms linking obesity and progression of Barrett's carcinogenesis is poorly understood. The aim of the study was to evaluate the expression of adipokines receptors in BE and in normal squamous epithelium in the same patients in correlation with obesity parameters.. Expression of adiponectin receptors 1 and 2 protein (AdipoR1, AdipoR2) as well as leptin receptor protein (ObR) in biopsies from 27 BE and normal squamous epithelium (N) in the same patients as well as in obese and normal controls were assessed with Western-blot analysis. These correlations were confirmed with the quantitative RT-PCR (qRT-PCR). AdipoR1 and ObR protein levels were similar in BE mucosa and squamous epithelium in the same patients in Western-blot analysis (2303 vs. 2448 OB units; 106927 vs. 103390, respectively; p>0.05). RT-PCR analysis confirmed this observation for AdipoR1, R2 and ObR genes expression (0.11±0.08 vs. 0.19±0.24, p=0.78; 0.24±0.36 vs. 0.33±0.49, p=0.5375; 0.71±0.8 vs. 1.33±2.95, p=1.0; respectively). Using linear correlation analysis we found the positive correlation between AdipoR1 expression in Barrett's epithelium compared to squamous epithelium in the same patients (N) (r=0.5; p=0.008) and between ObR expression in BE and N (r=0.8; p<0.001). The AdipoR1 and ObR protein levels were significantly higher in BE patients compared to controls and obese controls (2303 vs. 895 vs. 1674 and OD units, p<0.05).. in opposite to the prior hypothesis adiponectin and leptin receptors activation in BE may be not caused by obesity.

Topics: Adenocarcinoma; Adiponectin; Adult; Aged; Barrett Esophagus; Epithelium; Esophageal Neoplasms; Female; Humans; Leptin; Male; Middle Aged; Obesity, Abdominal; Receptors, Adiponectin; Receptors, Leptin

Adipocytokines are adipocyte-secreted hormones associated with some malignancies. It has been reported that the impaired response of adipocytokines to body weight loss may play a role in the pathogenesis of cancer-induced cachexia. We investigated the association between adipocytokines with squamous cell carcinoma of the esophagus (SCCE).. The levels of body mass index (BMI) and adiponectin, leptin, resistin, visfatin and C-peptide in the blood at diagnosis were measured in 117 SCCE patients and 117 age- and sex-matched controls. Logistic regression models were employed to estimate odds ratio. One-way analysis was performed to examine the prevalence of variables between two or more groups. A non-parametric Spearman correlation test was conducted to examine the associations between BMI and other variables.. Adiponectin and BMI levels were significantly lower, and resistin level was significantly higher in the patients on multivariate analysis (P = 0.01, <0.01 and <0.01 respectively). BMI gradually decreased with stage progression, and resistin level gradually increased with stage progression (P < 0.01 for both). The inverse correlation between BMI and adiponectin was comparatively strong in the controls, but was weak in the patients. Leptin showed comparatively strong correlation with BMI in the controls, but was weakly correlated in the patients. The correlation between BMI and resistin or C-peptide was demonstrated weakly only in the controls, and visfatin did not correlate with BMI.. Resistin may be a biomarker for the progression of SCCE. In addition, the impaired responses to body weight loss of adiponectin and leptin in the patients with SCCE were suggested.

Topics: Adipokines; Adiponectin; Aged; Analysis of Variance; Biomarkers, Tumor; Body Mass Index; C-Peptide; Cachexia; Carcinoma, Squamous Cell; Case-Control Studies; Disease Progression; Esophageal Neoplasms; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Neoplasm Staging; Nicotinamide Phosphoribosyltransferase; Odds Ratio; Resistin

Prostaglandins are important in the progression of various gastrointestinal cancers including oesophageal adenocarcinoma (OAC). Cyclo-oxygenase (COX)-2 inhibitors reduce OAC prostaglandin production but also have potentially detrimental effects on vascular endothelial function by reducing prostacyclin production and increasing the risk of cardiovascular events. We have examined the effects of inhibiting microsomal prostaglandin synthase-1 (mPGES-1), the enzyme downstream of COX-2 in the prostaglandin synthetic cascade. In OAC cells, reduction of mPGES-1 with RNA interference blocked PGE2 production, inhibited serum-induced proliferation and enhanced apoptosis in the COX-2 expressing cell lines (OE33 and FLO) but had no effect in COX-2 deficient BIC-1 cells. Three different methods of inhibiting mPGES-1 (RNA interference, a novel small molecule inhibitor and the endogenous inhibitor 15-deoxy-Delta(12,14)-PGJ(2)) also blocked leptin induced mPGES-1 expression and PGE2 production and abolished the leptin-induced proliferative and anti-apoptotic effects in OE33 cells, without affecting COX-2 expression. The anti-proliferative effects were equivalent to those produced by COX-2 inhibitory concentrations of celecoxib and NS-398. However, unlike the two COX-2 inhibitors, mPGES-1 inhibition did not reduce endothelial prostacyclin production. In contrast to the effects of the COX-2 inhibitor celecoxib, mPGES-1 inhibition had no effects on Akt kinase activity in OAC cells. We conclude that inhibition of mPGES-1 has potentially beneficial effects in OAC without the potentially detrimental effects on vascular endothelial prostacyclin synthesis. We have also confirmed that celecoxib has anticancer actions separate from the inhibition of COX-2. Inhibition of mPGES-1 may be therapeutically useful in the treatment and prevention of OAC.

Topics: Adenocarcinoma; Apoptosis; Celecoxib; Cell Line, Tumor; Cell Proliferation; Cell Survival; Endothelial Cells; Epoprostenol; Esophageal Neoplasms; Humans; Intramolecular Oxidoreductases; Leptin; Prostaglandin-E Synthases; Pyrazoles; RNA, Small Interfering; Sulfonamides

We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract.

Topics: Adenocarcinoma; Anorexia; Body Mass Index; C-Reactive Protein; Cachexia; Carcinoma, Squamous Cell; Down-Regulation; Esophageal Neoplasms; Female; Gastrointestinal Tract; Hemoglobins; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Male; Serum Albumin; Syndrome; Tumor Necrosis Factor-alpha

Obesity increases the risk of developing oesophageal adenocarcinoma (OAC) as well as several other cancers. Leptin is secreted by adipocytes and serum leptin levels rise with body mass index. Leptin stimulates proliferation and inhibits apoptosis in OAC cells but the mechanisms are not fully elucidated, Transactivation of the epidermal growth factor receptor (EGFR) is an important signalling mechanism for G-protein-coupled receptors, but the relationship with leptin-type receptors has not been examined and the authors hypothesise that leptin-induced proliferation involves EGFR signalling. This study examines the effect of leptin on EGFR signalling in cultured cell lines. Leptin stimulated proliferation in four OAC lines expressing leptin receptors (OE33, OE19, BIC-1 and FLO) and this was abolished by specific EGFR inhibitors (PD153035 and AG1478). Leptin-induced proliferation was inhibited by neutralising antibodies to transforming growth factor-alpha (TGFalpha and HB-EGF) but not by anti-amphiregulin. Leptin significantly increased gene expression of HB-EGF and TGFalpha as measured by a quantitative real-time polymerase chain reaction (PCR) method but did not alter amphiregulin and EGFR gene expression. Leptin increased extracellular release of HB-EGF and TGFalpha and this was blocked by matrix metalloproteinase (MMP) inhibitors. The MMP inhibitors also abolished leptin-induced proliferation as well as leptin-induced EGFR tyrosine phosphorylation, but did not affect proliferation or EGFR activation induced by TGFalpha. The authors conclude that leptin stimulates OAC proliferation via increased gene expression of HB-EGF and TGFalpha, MMP-mediated extracellular release of HB-EGF and TGFalpha and subsequent activation of EGFR.

Topics: Adenocarcinoma; Amphiregulin; Autoantibodies; Cell Line, Tumor; Cell Proliferation; EGF Family of Proteins; ErbB Receptors; Esophageal Neoplasms; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Matrix Metalloproteinases; Quinazolines; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation; Transforming Growth Factor alpha; Tyrphostins

Obesity increases the risk of developing several cancers including oesophageal adenocarcinoma (OAC). Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia: we have hypothesised that these hormonal factors may contribute to the progression of OAC. We have examined the effects of leptin and adiponectin on proliferation of OAC cells. Leptin-stimulated proliferation in four different OAC lines (OE33, OE19, BIC-1 and FLO) and this was inhibited by globular but not full length adiponectin. All four OAC lines expressed both adiponectin-receptor isoforms (AdipoR1 and AdipoR2). Globular adiponectin also inhibited leptin-induced proliferation in rat IEC-18 cells which only expressed AdipoR1. Specific inhibitors of 5'-AMP-activated protein kinase (Compound C) and serine/threonine phosphatases (okadaic acid) and a specific siRNA to AdipoR1 blocked the anti-proliferative effects of adiponectin. Adiponectin inhibited leptin-induced Akt phosphorylation; this action was sensitive to okadaic acid but not to Compound C. Adiponectin deficiency may contribute to the promotion of OAC in obesity.

Topics: Adenocarcinoma; Adiponectin; AMP-Activated Protein Kinases; Animals; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Enzyme Inhibitors; Esophageal Neoplasms; Humans; Leptin; Multienzyme Complexes; Obesity; Okadaic Acid; Protein Isoforms; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Pyrazoles; Pyrimidines; Rats; Receptors, Adiponectin; RNA Interference

Obesity and gastro-oesophageal reflux are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and ERK phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and ERK inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis.

Topics: Acids; Adenocarcinoma; Apoptosis; Cell Proliferation; Cyclooxygenase 2; Enzyme Activation; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Extracellular Signal-Regulated MAP Kinases; Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin; Tumor Cells, Cultured

Obesity is an important risk factor for esophageal adenocarcinoma (EAC), and elevated serum leptin is characteristic of obesity. We hypothesized that leptin may have biological effects in promoting esophageal adenocarcinoma and examined the effects of leptin on the OE33 Barrett's-derived EAC line. Proliferation was assessed by dimethylthiazoldiphenyltetra-zoliumbromide and 5-bromo-2'-deoxyuridine incorporation assays and apoptosis by ELISA of intracellular nucleosomes. Intracellular signaling was examined using specific pharmacological inhibitors and direct detection of phosphorylated active kinases. Expression of the long and short leptin receptors by OE33 cells was confirmed by RT-PCR, Western blotting and immunocytochemistry. Leptin stimulated OE33 cell proliferation in a dose-dependent manner and inhibited apoptosis. These effects were dependent on cyclooxygenase (COX)-2 and replicated by adding prostaglandin E2 (PGE2). The effects of PGE2 and leptin were abolished by the EP-4 antagonist AH23848. ERK, p38 MAPK, phosphatidylinositol 3'-kinase/Akt, and Janus tyrosine kinase (JAK)-2 were activated upstream of COX-2 induction, whereas the epidermal growth factor receptor and c-Jun NH2-terminal kinase (JNK) were downstream of COX-2. The activation of ERK and Akt but not p38 MAPK was JAK2 dependent. PGE2 stimulated phosphorylation of JNK in an EGF receptor-dependent manner, and activation of the epidermal growth factor receptor required protein kinase C, src, and matrix metalloproteinase activities. We conclude that leptin stimulates cell proliferation and inhibits apoptosis in OAC cells via ERK, p38 MAPK, phosphatidylinositol 3'-kinase/Akt, and JAK2-dependent activation of COX-2 and PGE2 production. Subsequent PGE2-mediated transactivation of the epidermal growth factor receptor and JNK activation are essential to the leptin effects. These effects may contribute to the greatly increased risk of esophageal adenocarcinoma in obesity.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Cell Division; Cell Line, Tumor; Cyclooxygenase 2; Dinoprostone; Enzyme Activation; ErbB Receptors; Esophageal Neoplasms; Extracellular Signal-Regulated MAP Kinases; Humans; Janus Kinase 2; JNK Mitogen-Activated Protein Kinases; Leptin; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptors, Cell Surface; Receptors, Leptin; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP4 Subtype; Recombinant Proteins; RNA, Messenger; Transcriptional Activation

Body weight loss is observed commonly after esophagectomy with gastric tube reconstruction in thoracic esophageal cancer patients. The functional and anatomical alteration of the stomach by this surgery should affect ghrelin secretion, a novel gastric hormone that upregulates body weight through appetite control and metabolic reaction.. Early-phase postoperative alteration of serum ghrelin was measured before and at day 3 and day 7 after surgery in 9 patients. With 26 other patients, who had previously undergone surgery from 3 months to 67 months (mean, 25 months) before the present study period, the late-phase postoperative alteration of serum ghrelin was investigated along with postoperative body weight loss and serum leptin.. Serum ghrelin concentration, which was equivalent to the control group before surgery (88.6 fmol/mL vs 97.5 fmol/mL) significantly decreased by half at 3 and 7 days after surgery. Thereafter, the serum ghrelin decline continued in the outpatients within 1 year after surgery (58.8 fmol/mL), while it was marginal in those from 1 to 3 years after surgery (77.2 fmol/mL). Serum ghrelin was significantly higher than the control after 3 years (185.1 fmol/mL). Thus, a significant positive correlation was observed between ghrelin and time after surgery (P < .0001). Postoperative body weight loss was significant, averaged as DeltaBMI - 2.7 in the outpatients (P < .0001). Until 3 years after surgery, a significant correlation between ghrelin and postoperative body weight loss was observed (P = .0152), with those having higher serum ghrelin showing less body weight loss. Serum leptin correlated well with body weight (P = .0144), but not with postoperative time, the degree of body weight loss, or serum ghrelin concentration.. Gastric tube replacement for esophagectomy resulted in temporary reduction of ghrelin production, which is associated with body weight loss after surgery. The decline of ghrelin may play some role in the serious body weight loss after esophagectomy, thus encouraging clinical application of exogenous recombinant ghrelin for these patients.

Topics: Aged; Aged, 80 and over; Body Mass Index; Esophageal Neoplasms; Esophagectomy; Esophagoplasty; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Peptide Hormones; Quality of Life; Weight Loss

Oesophageal cancer patients with substantial weight loss have worse prognosis. Weight loss is often refractory to the nutritional support. Causes of the weight loss are multiple: oesophageal stricture, frequent alcohol abuse, cancer related cachexia. It may be a consequence of metabolic changes mediated by cytokines, hormones and tumour derived products. Leptin, a protein produced by adipocytes, is an important signalling molecule in energy regulation, metabolism of fatty acids and it can also augment tumour growth of various cancer cell lines. Enhanced intake of poly-unsaturated fatty acids may play an important role in the reversal of cancer related weight loss.. In this study we examined the nutritional status (pre-treatment weight-loss, actual weight, body mass index), serum levels of leptin, soluble leptin receptor, TNF-alpha, IGF-1 and plasma phosphatidyl-cholin fatty acids before the beginning of treatment, after the onset of treatment and shortly before its completion. In the group of 38 pts (33 men, 5 women), mean age 58 years, statistically significant mean pre-treatment weight-loss 8 kg and significant mean weight loss 2 kg after chemoradiotherapy was observed. Concomitant chemoradiation led to transient elevation of serum leptin level despite the weight loss during chemoradiotherapy. Significant changes in the distribution of fatty acids in plasmatic phosphatidyl-cholin were observed.. Our results show the possibility for direct influence of chemoradiotherapy on body weight regulation in advanced oesophageal cancer patients.

Topics: Adult; Aged; Combined Modality Therapy; Esophageal Neoplasms; Fatty Acids; Female; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Phosphatidylcholines; Receptors, Cell Surface; Receptors, Leptin; Tumor Necrosis Factor-alpha; Weight Loss

Eighty-five to 95% of esophageal cancer patients suffer dysphagia. Yet, few studies have focused on this symptom, and four 'myths' persist: (i) dysphagia cannot be measured; (ii) chemotherapy cannot palliate it; (iii) dysphagia predicts a poor prognosis; (iv) dysphagia is associated with a frustratingly insatiable appetite. Forty-four patients with metastatic esophageal cancer participated in this quality of life/translational component of a previously reported clinical trial. All were monitored for chemotherapy efficacy and toxicity and completed questionnaires on dysphagia and appetite at baseline and every 6 weeks. The appetite hormones, leptin and neuropeptide y, were also assessed. Forty-five per cent of patients could easily swallow solid foods; all others had varying dysphagia, thus enabling exploration of these four 'myths.' First, a single-item visual analog scale (Swallowing Scale), demonstrated excellent agreement with a previously validated questionnaire (81% at baseline), thus reminding us that dysphagia is measurable. Second, chemotherapy was associated with a trend towards improved dysphagia (P = 0.059). Third, dysphagia did not predict tumor response or survival. Fourth, dysphagia was not associated with appetite, leptin or neuropeptide y. This study helps to dispel these four 'myths' and underscores the need for further quality of life research on dysphagia.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Appetite; Cohort Studies; Deglutition Disorders; Esophageal Neoplasms; Female; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Prognosis; Quality of Life; Surveys and Questionnaires; Treatment Outcome

In the Western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastro-oesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However, there is no plausible biological mechanism of association between H. pylori, obesity, and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake, and body composition, was studied in H. pylori positive asymptomatic subjects.. Plasma ghrelin, leptin, and gastrin were measured for six hours after an overnight fast, before and after cure of H. pylori in 10 subjects. Twenty four hour intragastric acidity was also assessed.. After cure, median (95% confidence intervals) integrated plasma ghrelin increased from 1160.5 (765.5-1451) pg/ml x h to 1910.4 (1675.6-2395.6) pg/ml x h (p=0.002, Wilcoxon's rank sum test), a 75% increase. This was associated with a 14% increase in 24 hour intragastric acidity (p=0.006) and non-significant changes in leptin and gastrin. There was a significant positive correlation between plasma ghrelin and intragastric acidity (r(s) 0.44, p=0.05, Spearman's rank correlation).. After H. pylori cure, plasma ghrelin increased profoundly in asymptomatic subjects. This could lead to increased appetite and weight gain, and contribute to the increasing obesity seen in Western populations where H. pylori prevalence is low. This plausible biological mechanism links H pylori, through increasing obesity and GORD, to the increase in oesophageal adenocarcinoma observed in the West.

Topics: Adenocarcinoma; Adult; Esophageal Neoplasms; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Peptide Hormones; Radioimmunoassay

Leptin, a protein produced by adipocytes, is an important signaling molecule in energy regulation and food intake. Many obese patients have leptin resistance associated with increased circulating leptin. Leptin receptor activation downregulates many regulatory genes, including STAT-3 and PAP 1. Certain cancers are associated with obesity, including breast, prostate, and colon. Recent studies have shown that leptin stimulates proliferation of human colon cancer in vitro. We hypothesized that leptin would have stimulatory effects on other human cancers.. Human cancer cell lines from esophagus (KYSE410 and 150), breast (ZR75-1 and MCF-7), prostate (DU145 and PC-3), and pancreas (PANC-1, Mia-PaCa) were cultured using standard techniques. Leptin (0.4 ng/ml and 4.0 ng/ml) was added for 24 h and 48 h. Cell growth was determined by MTT assay. Statistical analysis was performed using analysis of variance.. Cancer cell lines demonstrated dose- and time-related responses to treatment. Leptin caused growth potentiation in breast, esophagus, and prostate cancer (P < 0.05). However, in both Mia-PaCa and PANC-1 pancreatic cancer cells, leptin inhibited growth (P < 0.05). This inhibitory effect peaked in PANC-1 at 48 h (78%).. We have shown for the first time that human cancer cells exhibit differential responses to treatment with leptin, depending upon organ of derivation. Both leptin and leptin antagonism have potential efficacy in cancer therapy, based on cellular origin. Further studies are warranted and ongoing.

Topics: Breast Neoplasms; Cell Division; Esophageal Neoplasms; Female; Humans; Leptin; Male; Neoplastic Processes; Pancreatic Neoplasms; Pancreatitis-Associated Proteins; Peptide Hormones; Prostatic Neoplasms; Tumor Cells, Cultured

Leptin is a hormone primarily produced by adipocytes and serum leptin is elevated in obese persons. One risk factor associated with adenocarcinoma of the esophagus is obesity. We hypothesized that leptin would have stimulatory effects on esophageal adenocarcinoma and alter apoptosis in vitro.. Barrett's esophageal adenocarcinoma cells (BIC-1 and SEG-1) were cultured with human recombinant leptin (80 ng/mL) for 24 hours. Cell growth was determined by MTT assay. Apoptosis and necrosis was measured after 16 hours of treatment with leptin using a Cell Death Kit.. Exogenous leptin stimulated cell proliferation in both cell lines. No changes in apoptosis or necrosis resulted between control and leptin-treated groups.. We have shown that leptin increases the proliferation of human esophageal adenocarcinoma, but does not alter cell apoptosis or necrosis. The data suggest that leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms. Leptin antagonism may have potential efficacy in esophageal cancer therapy.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Cell Division; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Humans; Leptin; Necrosis; Recombinant Proteins; Stimulation, Chemical; Tumor Cells, Cultured