leptin and Stomach-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

Leptin, an adipocyte-derived hormone and its receptor (ObR) expressed in the hypothalamus are well known as an essential regulator of appetite and energy expenditure. Obesity induces abundant leptin production, however, reduced sensitivity to leptin leads to the development of metabolic disorders, so called leptin resistance. The stomach has been identified as an organ that simultaneously expresses leptin and ObR. Accumulating evidence has shown gastric leptin to perform diverse functions, such as those in nutrient absorption and carcinogenesis in the gastrointestinal system, independent of its well-known role in appetite regulation and obesity. Overexpression of leptin and phosphorylated ObR is implicated in gastric cancer in humans and in murine model, and diet-induced obesity causes precancerous lesions in the stomach in mice. While the underlying pathomechanisms remain unclear, leptin signaling can affect gastric mucosal milieu. In this review, we focus on the significant role of the gastric leptin signaling in neoplasia and tumorigenesis in stomach in the context of hereditary and diet-induced obesity.

Topics: Animals; Carcinogenesis; Humans; Leptin; Obesity; Receptors, Leptin; Stomach Neoplasms

Obesity is an important public health problem worldwide. It increases the risk of many chronic diseases such as diabetes and cardiovascular diseases. Meanwhile, obesity is a major risk factor for several types of cancer including gastric cancer. Possible mechanisms linking obesity with gastric cancer may include obesity associated gastro-oesophageal reflux, insulin resistance, altered levels of adiponectin, leptin, ghrelin, and an abnormally increased blood level of insulin-like growth factor (IGF). Helicobacter pylori (H. pylori) infection is a well-recognized risk factor for peptic ulcer and gastric cancer. Recent studies have revealed an increased prevalence of H. pylori infection in obese patients, providing another clue for the increased incidence of gastric cancer in obese population. If this connection can be confirmed in animal models and a large cohort of patients, then eradicating H. pylori together with life style modification in obese individuals may help prevent the development of gastric cancer in the increasingly obese population.

Topics: Adiponectin; Animals; Gastroenteritis; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Obesity; Risk Factors; Signal Transduction; Stomach Neoplasms

Gastric carcinoma is a rare but important malignancy. The link between leptin, a cytokine that is elevated in obese individuals, and cancer development has been proposed. It is noted that leptin and its receptor may play a positive role in the progression in gastric cancer. However, the exact mechanism resulting form the interaction between leptin and leptin receptor has never been clarified. Here, the author used a new gene ontology technology to predict the molecular function and biological process due to the interaction between leptin and leptin receptor. Comparing to leptin and leptin receptor, the leptin-leptin receptor poses the same function and biological process as leptin receptor. This can confirm that leptin receptor has a significant suppressive effect on the expression of leptin. Loss of hormone activity and disturbance of normal cell signaling pathway of leptin can be seen. Blocking of receptor might be rational therapeutic strategy.

Topics: Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin; Stomach 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; 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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

The purpose of this study is to compare the effect of diabetes control induced by Roux-en-Y gastrojejunostomy(RY) vs Billroth-I reconstruction(BI) after distal gastrectomy in patients with early gastric cancer(EGC) and type 2 diabetes(T2DM). Forty EGC patients with T2DM, aged 20-80 years, who were expected to undergo curative distal gastrectomy were randomized 1:1 to RY(n = 20) or BI(n = 20). Diabetes medication status, biochemical and hormonal data including blood glucose, HbA1c, insulin, C-peptide, HOMA-IR, ghrelin, leptin, GLP-1, PYY, and GIP were evaluated for 12 months after surgery. Although pre- and postoperative 12-month fasting and postprandial glucose levels did not show a significant difference, HbA1c, C-peptide, and HOMA-IR levels were significantly improved at 12 months after surgery in both BI and RY groups. Sixty percent of RY patients and 20% of BI patients decreased their medication satisfying FBS<126 mg/dL and HbA1c<6.5% and 5% of BI patients stopped their medication satisfying the criteria of FBS<126 mg/dL and HbA1c<6.0%. The improvement patterns were more sustainable with less fluctuation in RY than in BI. On hormonal analysis, ghrelin and leptin levels were decreased and PYY and GIP levels were increased at 12 months after surgery in both groups without significant difference according to the reconstruction type and diabetic improvement status except ghrelin. In gastric cancer surgery, RY reconstruction showed better and more durable diabetes control compared to BI during the first year after surgery. Gastric cancer surgery led to decreased ghrelin and leptin and increased PYY and GIP, which might have a role in improving insulin resistance and glucose homeostasis.

Topics: Aged; Diabetes Mellitus, Type 2; Duodenum; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Male; Middle Aged; Peptide YY; Prospective Studies; Stomach; Stomach Neoplasms; Treatment Outcome

Gastric cancer patients who undergo gastrectomy suffer from a post-gastrectomy syndrome that includes weight loss, dumping syndrome, reflux esophagitis, alkaline gastritis, and finally malnutrition. It is important to ameliorate the post-gastrectomy symptoms to restore postoperative quality of life (QoL). The aim of this study was to investigate the effect of rikkunshito, a Japanese herbal medicine, on postoperative symptoms and ghrelin levels in gastric cancer patients after gastrectomy.. Twenty-five patients who had undergone gastrectomy received 2.5 g of rikkunshito before every meal for 4 weeks, and a drug withdrawal period was established for the next 4 weeks. Changes in gastrointestinal hormones, including ghrelin, and appetite visual analog scale scores were measured, and QoL was estimated by using the European Organization for Research and Treatment of Cancer core questionnaire QLQ-C30. The Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS) scoring system was used to evaluate gastrointestinal symptoms after gastrectomy.. Sixteen men and nine women (mean age 61.9 years) were enrolled in the study. All patients had either stage I (n = 24) or II (n = 1) disease and had undergone either distal gastrectomy (n = 17) or total gastrectomy (n = 8) by a laparoscopy-assisted approach. The mean ratio of the acyl-/total ghrelin concentration increased significantly after rikkunshito administration (Pre: 7.8 ± 2.1, 4 weeks: 10.5 ± 1.7 %, p = 0.0026). The total DAUGS score, as well as the scores reflecting limited activity due to decreased food consumption, reflux symptoms, dumping symptoms, and nausea and vomiting significantly improved after rikkunshito administration.. The present study demonstrated a significant attenuation of gastrointestinal symptoms after gastrectomy by treatment with rikkunshito. Rikkunshito is potentially useful to minimize gastrointestinal symptoms after gastrectomy.

Topics: Aged; Appetite; Drugs, Chinese Herbal; Dumping Syndrome; Esophagitis, Peptic; Female; Ghrelin; Humans; Insulin-Like Growth Factor I; Leptin; Male; Medicine, East Asian Traditional; Middle Aged; Postgastrectomy Syndromes; Quality of Life; Stomach Neoplasms

Obesity is a risk factor for various types of cancer. Leptin, an adipocyte‑derived hormone, may stimulate the proliferation of gastric cancer cells. However, the effect of leptin and underlying mechanism in gastric cancer remain unclear. In the present study, the role of leptin in gastric cancer was evaluated. The effect of leptin on the JAK‑STAT and MEK signaling pathways was investigated in gastric cancer cells using wound‑healing and cell invasion assays, immunoblotting and inhibition studies. Cancer‑initiating cells derived from gastric cancer cells were used to investigate the effect of leptin on the maintenance of stemness and epithelial‑mesenchymal transition (EMT) by immunoblotting. Clinicopathological characteristics including the serum leptin level and overall survival (OS) were analyzed in patients with (n=23) and without (n=23) obesity. Leptin induced the migration and invasion of gastric cancer cells by activating AKT and ERK and upregulating vascular endothelial growth factor (VEGF). Leptin increased the mRNA and protein levels of markers of stemness (CD44) and the EMT (Snail and N‑cadherin). Pharmacological inhibitors of the JAK‑STAT and MEK signaling pathways decreased leptin‑induced migration and invasion, and the expression of VEGF. Obesity was associated with an elevated leptin level and body mass index was positively correlated with the leptin level (P=0.001 for both). The 5‑year OS rate was not significantly different between the two groups (P=0.098). Leptin stimulates the migration and invasion of gastric cancer cells by activating the JAK‑STAT and MEK pathways, and contributes to the maintenance of cancer stemness and metastatic potential. The present findings support an adverse effect of obesity in gastric cancer. Consequently, targeting of leptin‑associated signaling pathways may have therapeutic potential for gastric cancer.

Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Humans; Leptin; Mitogen-Activated Protein Kinase Kinases; Neoplastic Stem Cells; Obesity; Stomach Neoplasms; Vascular Endothelial Growth Factor A

Topics: Adenocarcinoma; Animals; Carcinogenesis; Cell Proliferation; Gastric Mucosa; Hyperplasia; Leptin; Male; Methylnitronitrosoguanidine; Rats; Rats, Sprague-Dawley; Stomach; Stomach Neoplasms

Leptin may support the proliferation and hinder the apoptosis of tumor cells. Although leptin expression has been studied in several human tumors, its potential clinical significance remains uncertain in patients with gastric carcinoma. Furthermore, the majority of available findings have been determined from preclinical studies using stomach carcinoma tissue section and, to date, few studies have evaluated the clinical significance of leptin in the serum or plasma of gastric carcinoma patients. In the current study, the serum concentration of soluble leptin was assessed in gastric carcinoma patients, and its contributions to the clinical parameters and prognosis of patients were determined. A total of 63 pathologically confirmed gastric cancer patients and 30 healthy subjects were enrolled in the study and circulating leptin levels in the serum of all subjects were determined by ELISA. The serum leptin concentrations were significantly lower in the gastric cancer patients compared with the healthy control group (P = 0.009). In the gastric cancer patients, the clinical features of patient age, sex, lesion localization, histopathology, pathological grade, stage of disease, and serum tumor markers including lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 19-9 were not correlated with serum leptin concentration. Furthermore, no association was observed between serum leptin concentration and responsiveness to chemotherapy (P = 0.51), and leptin level had no apparent prognostic role in clinical outcome (P = 0.57). In conclusion, although it was not predictive or prognostic, serum leptin level may be a valuable diagnostic indicator in patients with gastric carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Leptin; Male; Middle Aged; Prognosis; Stomach Neoplasms

Depression is the most common psychiatric disorder among cancer patients. Studies have not only highlighted that leptin and its receptor (LepRb) are independent poor prognostic factors in gastric cancer (GC) patients but also shown that the leptin-LepRb is necessary for antidepressant-like behaviors. In this study, we examined the serum and tissue leptin-LepRb expression in GC patients. Enzyme-linked immunosorbent assay showed that depressive GC patients had significantly higher serum leptin-LepRb than healthy donors. Leptin-LepRb levels in GC tissues were also significantly higher than in matched paracarcinoma tissues using real-time RT-PCR. Moreover, we observed that both serum and tissue leptin-LepRb were significantly higher in depressive GC patients than those in nondepressive GC patients. Further, the patients with high tumor stage tend to have higher leptin-LepRb mRNA levels than that with low tumor stage. Together, our findings suggest that leptin-LepRb plays an important role in the pathogenesis and depression in GC. Leptin-LepRb therefore could be a potential diagnostic marker and therapeutic target in GC patients with depression.

Topics: Adolescent; Adult; Aged; Depression; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation, Neoplastic; Humans; Leptin; Male; Middle Aged; Prognosis; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Stomach Neoplasms; Young Adult

To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice.. Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor (IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcription-polymerase chain reaction and western blotting.. The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic (db/db) mice relative to the control (db/m) mice. The incidence of gastric dysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor mRNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP.. LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.

Topics: Adiponectin; Animals; Blood Glucose; Body Weight; Carcinogenesis; Cell Transformation, Neoplastic; Diabetes Mellitus, Experimental; Drugs, Chinese Herbal; Immunohistochemistry; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Ki-67 Antigen; Leptin; Male; Methylnitrosourea; Mice; Stomach Neoplasms

Topics: Abdomen; Humans; Insulin Resistance; Leptin; Obesity; Obesity, Morbid; Pediatric Obesity; Stomach; Stomach Neoplasms; Stomach Ulcer; Upper Gastrointestinal Tract

Antiangiogenic treatment is at the horizon in the palliative treatment of gastric cancer (GC), but data on proangiogenic biomarkers are still limited. The aim of this study was to analyze five proteins with a function in tumor angiogenesis: vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), follistatin, leptin, and platelet endothelial cell adhesion molecule 1 (CD31) in peripheral blood and corresponding tumor tissue.. From 2008-2010, tumor tissue (n = 76) and corresponding preoperative serum (n = 69) of patients with localized GC were collected; 45 had perioperative chemotherapy. Protein serum or tumor lysate levels of these factors were measured by an angiogenesis multiplex immunoassay and correlated with response and survival.. Serum Ang-2 had prognostic relevance in the whole study population (P = 0.027). In subgroup analysis, serum VEGF and Ang-2 had prognostic relevance in primarily resected patients (P = 0.028; P = 0.048) but no association was found in neoadjuvantly treated patients. Follistatin concentration in the tumor tissue was associated with prognosis in all patients (P = 0.019). Tumor VEGF concentrations were correlated with histopathologic response (P = 0.011), with patients showing >50% remaining tumor having higher VEGF concentrations. The tissue Ang-2/VEGF ratio was significantly correlated with both clinical and histopathologic response (P = 0.029, P = 0.009). Additionally, the level of leptin in the tissue was associated with clinical response: nonresponding patients had higher leptin levels than those of responding patients (P = 0.032).. Our results show the importance of angiogenetic factors in serum and tumor tissue in GC for prognosis and treatment response. Further trials in larger patient populations are warranted for a further evaluation of proangiogenetic factors as biomarkers in gastrointestinal cancer.

Topics: Adenocarcinoma; Angiogenic Proteins; Angiopoietin-2; Biomarkers, Tumor; Female; Follistatin; Germany; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Platelet Endothelial Cell Adhesion Molecule-1; Prognosis; Prospective Studies; ROC Curve; Stomach; Stomach Neoplasms; Vascular Endothelial Growth Factor A

We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.

Topics: Cell Line, Tumor; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Leptin; Male; Middle Aged; Signal Transduction; Stomach Neoplasms

Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chromosomes, Human, Pair 4; Cytokines; Female; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Insulin; Stomach Neoplasms; Toll-Like Receptor 1; Toll-Like Receptor 10; Young Adult

Our previous study indicates that leptin enhances gastric cancer (GC) invasion. However, the exact effect of leptin on GC metastasis and its underlying mechanism remain unclear. Intercellular adhesion molecule-1 (ICAM-1), a major molecule in stabilising cell-cell and cell-extracellular matrix interactions, is overexpressed and has crucial roles in tumour metastasis.. Here, we investigated leptin and ICAM-1 expression in GC tissues. Furthermore, we characterised the influence of leptin on ICAM-1 expression in GC cells and elucidated the underlying mechanism.. Leptin and ICAM-1 were overexpressed in GC tissues, and a strong positive correlation was observed. They were also related with clinical stage or lymph node metastasis. Furthermore, leptin induced GC cell (AGS and MKN-45) migration by upregulating ICAM-1, and knockdown of ICAM-1 by small interference RNA (siRNA) blocked this process. Cell surface ICAM-1, as well as soluble ICAM-1 (sICAM-1), was also enhanced by leptin. Moreover, leptin increased ICAM-1 expression through Rho/ROCK pathway, which was attenuated by pharmacological inhibition of Rho (C3 transferase) or its downstream effector kinase Rho-associated protein kinase (ROCK) (Y-27632).. Our findings indicate that leptin enhances GC cell migration by increasing ICAM-1 through Rho/ROCK pathway, which might provide new insight into the significance of leptin in GC.

Topics: Adult; Aged; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; rho GTP-Binding Proteins; rho-Associated Kinases; Signal Transduction; Stomach Neoplasms; Tumor Cells, Cultured

Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Cell Line, Tumor; Cell Proliferation; Female; Gastric Mucosa; Humans; Immunohistochemistry; Leptin; Male; MAP Kinase Signaling System; Middle Aged; Obesity; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Stomach; Stomach Neoplasms; Vascular Endothelial Growth Factor A

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

Leptin acts on its receptor (ObR) in the hypothalamus to inhibit food intake and energy expenditure. Leptin and ObR are also expressed in the gastrointestinal tract; however, the physiological significance of leptin signaling in the gut remains uncertain. Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback regulator of ObR-mediated signaling in the hypothalamus. We now show that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3b-SOCS3 cKO) mice developed gastric tumors by enhancing leptin production and the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not in the bowels by 2 months of age, even though the SOCS3 deletion occurred in both the epithelium of stomach and bowels. The tumors developed in the absence of the inflammatory response and all cKO mice died within 6 months. These tumors displayed pathology and molecular alterations, such as an increase in MUC2 (Mucin 2, oligomeric mucus/gel-forming) and TFF3 (trefoil factor 3), resembling human intestinal-type gastric tumors. Administration of antileptin antibody to T3b-SOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer.

Topics: Adenocarcinoma; Animals; Antibodies; Antineoplastic Agents; Carcinogenesis; Cells, Cultured; Disease Models, Animal; Drug Evaluation, Preclinical; Gastric Mucosa; Humans; Injections, Intraperitoneal; Intestinal Mucosa; Leptin; Mice; Mice, Transgenic; Neoplasms, Experimental; Protein Kinases; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Stomach; Stomach Neoplasms; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Leptin overexpression is closely correlated with gastric cancer (GC) invasion, but its exact effect and the underlying mechanism in tumorigenesis remain poorly understood. Membrane type 1-matrix metalloproteinase (MT1-MMP), a surface-anchored 'master switch' proteinase, is overexpressed and plays crucial roles in tumor invasion. Here, we characterized the influence of leptin on the generation and surface localization of MT1-MMP in GC and elucidated its molecular mechanisms. Our results revealed that leptin promoted GC cell invasion in vitro by upregulating MT1-MMP expression. Furthermore, cell surface biotinylation assay and flow cytometry demonstrated that the surface expression of MT1-MMP was also enhanced by leptin, and knockdown of kinesin family member 1B (KIF1B, a microtubule plus end-directed monomeric motor protein) by small interference RNA inhibited this process. Notably, coimmunoprecipitation analysis indicated that leptin enhanced the interaction of MT1-MMP with KIF1B in a time-dependent manner, which consequently contributed to GC cell invasion. Moreover, leptin increased MT1-MMP or KIF1B expression by the protein kinase B (AKT) pathway and extracellular signal-regulated kinase 1/2 partially participated in this process. However, only AKT was implicated in the leptin-mediated membrane localization of MT1-MMP. Immunohistochemistry analysis revealed that leptin, MT1-MMP and KIF1B are overexpressed in GC tissues, and they positively correlated with clinical stage and lymph node metastasis. These observations indicate that this regulatory network exists in vivo. Taken together, our findings suggest that leptin is an effective intracellular stimulator of MT1-MMP and that leptin-enhanced cell surface localization of MT1-MMP is dependent on KIF1B, which consequently plays a critical role in GC invasion.

Topics: Cell Line, Tumor; Female; Humans; Kinesins; Leptin; Male; MAP Kinase Signaling System; Matrix Metalloproteinase 14; Middle Aged; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt; Stomach Neoplasms; Up-Regulation

Quercetin affects the expressions of leptin and its receptor in human gastric cancer MGC-803 cells and JAK-STAT pathway.. The cultured MGC-803 cells were divided into three groups:. the cultured cells without quercetin, and Quercetin group: the cultured cells with quercetin(40 μmol/L), and AG490group: the cultured cells with AG490(40 μmol/L)The expressions of Leptin, Leptin receptor and P-STAT3 were detected in protein level by immunocytochemical and Western bloting method respectively. The expressions of Leptin, Leptin receptor were detected in mRNA level by RT-PCR method. MGC-803 cell cycle was arrest by flow cytometry (FCM); MGC-803 cell apoptosis ratio by apoptotic marker An-necxinV.. The protein expression of Leptin, Leptin receptor, P-STAT3 and the the mRNA expression of Leptin and Leptin receptor were significantly increased (P<0.05), compared with the control group.There was the rectilinear correlation relationship not only between Leptin and P-STAT3 protein(r=0.741, P<0.05) but also between Leptin receptor and P-STAT3 protein(r=0.693, P<0.05). FCM analysis showed that quercetin arrested MGC-803 cells at the G2/M phase, The ratio of apoptotic and necrosic cells increased with added quercetin concentration.. Quercetin could inhibit the Proliferation of MGC-803 cells. It is probably relevant to the down-regulation the expressions of Leptin and Leptin receptor protein, Leptin mRNA and Leptin receptor mRNA by JAK-STAT pathway.

Topics: Antioxidants; Apoptosis; Cell Cycle; Cell Line, Tumor; Humans; Janus Kinases; Leptin; Quercetin; Receptors, Leptin; Signal Transduction; STAT Transcription Factors; Stomach Neoplasms

We conducted this study to evaluate the expression of leptin and its receptor, OB-Rb in gastric cancer and their relationship to clinicopathological features, VEGF and HER-2 expression, as well as the prognostic value. One hundred and ten gastric cancer specimens were detected for leptin, OB-Rb, VEGF and HER-2 by immunohistochemistry (IHC), and 96 specimens of normal gastric mucosa served as the control. The expression level of leptin, OB-Rb and HER-2 in gastric tissues were significantly higher than normal tissues (49.1% vs. 34.0%, 60.9% vs. 46.0%, 19.1% vs. 8.0%, P<0.05). There was a correlation between the expression of leptin and HER-2, both of which were significantly associated with invasion depth, lymph node metastasis, AJCC stage and VEGF expression. However, there was no correlation between OB-Rb expression and all clinicopathological features. Cox regression analyses showed that age, tumor size, histological grade, serosa invasion, AJCC stage, chemotherapy, leptin and HER-2 overexpression were prognostic factors. The survival of patients with leptin positive expression was significantly poorer than those with negative expression (OS: 20.0 months vs. 32.5 months, FPS: 12.0 months vs. 18.0 months, P<0.01). Leptin, rather than OB-Rb, played an important role in the progression and angiogenesis of gastric cancer, and was a prognostic factor for poor outcome.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Follow-Up Studies; Gastric Mucosa; Humans; Leptin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Receptor, ErbB-2; Stomach Neoplasms; Survival Analysis; Up-Regulation

To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients.. One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control.. The expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors.. HER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Follow-Up Studies; Gastrectomy; Humans; Leptin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Leptin; Stomach Neoplasms; Survival Rate; Tumor Burden; Vascular Endothelial Growth Factor A

In 2005, a Japanese epidemiological study showed that increase in plasma glucose levels is a risk factor for gastric cancer. However, no animal model has hitherto shown any association between diabetes mellitus and neoplasia in the stomach. Diabetic (db/db) mice have obese and diabetic phenotypes, including hyperglycemia, because of disruption of the leptin receptor. In the present study, effects of hyperglycemia and/or hyperinsulinemia on the development of proliferative lesions were therefore examined in db/db mice given N-methyl-N-nitrosourea (MNU). A total of 120 mice were assigned to four groups: Group A, 40 db/db mice with MNU; Group B, 40 + /db mice with MNU; Group C, 30 misty (wild-type) mice with MNU; Group D, 10 db/db mice without MNU. MNU was given at 60 ppm in drinking water for 20 weeks. Subgroups of animals were sacrificed at weeks 21 and 30 and blood samples were collected to measure glucose, insulin, leptin, and adiponectin concentrations. The removed stomachs were fixed in formalin, and embedded in paraffin for histological examination and immunohistochemistry. At week 30 in Groups A, B, C and D, hyperplasia was observed in 100, 79, 57, and 0%, and dysplasia in 91, 43, 71, and 0%, respectively. Adenocarcinomas and pepsinogen-altered pyloric glands (PAPG), putative preneoplastic lesions, were observed only in Group A, at an incidence of 45%. The serum levels of insulin and leptin were also elevated in Group A. Gastric carcinogenesis by MNU was enhanced in db/db mice, possibly in association with hyperinsulinemia and hyperleptinemia.

Topics: Adenocarcinoma; Animals; Body Weight; Carcinogens; Diabetes Complications; Disease Models, Animal; Gastric Mucosa; Insulin; Leptin; Male; Methylnitrosourea; Mice; Mice, Inbred Strains; Precancerous Conditions; Stomach Neoplasms

Serological screening for gastric cancer (GC) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking.. To evaluate in a case-control study whether serum leptin levels correlate with intestinal metaplasia (IM) and can serve as a tool to identify patients at high risk for GC.. Cases were patients with a previous diagnosis of IM or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens I/II, gastrin, and Helicobacter pylori. Receiver operating characteristic (ROC) curves and their area under the curve (AUC) were provided to compare serum leptin levels with other serological markers.. One hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 pg/mL versus 81.9 pg/mL in controls (p = .01). After adjustment for age, sex and BMI, leptin levels remained higher in cases than in controls (p < .005). In multivariate analysis, male sex (p = .002), age (<0.001), low pepsinogen levels (p = .004) and high leptin levels (p = .04) were independent markers for the presence of IM. In addition, a ROC curve including age, sex and pepsinogen I levels had an AUC of 0.79 (95% CI (0.73-0.85)). Adding serum leptin levels increased the AUC to 0.81 (95% CI (0.75-0.86)).. High leptin levels are associated with an increased risk of IM. Moreover, serum leptin levels are a significant independent marker for the presence of IM. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Intestines; Leptin; Male; Metaplasia; Middle Aged; Risk Factors; Stomach Neoplasms; Young Adult

To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.. Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer-induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated.. Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P < 0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted.. These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

Topics: Adipokines; Adiponectin; Adult; Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Cachexia; Case-Control Studies; Female; Ghrelin; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prealbumin; Prospective Studies; Resistin; Serum Albumin; Severity of Illness Index; Stomach Neoplasms; Time Factors

The relationship between the expression of leptin in the tissue of gastric cancer and the clinicopathological features as well as patients' outcome were investigated.. Sixty-one gastric cancer specimens were investigated by immunohistochemical studies with anti-leptin and anti-vascular endothelial growth factor (VEGF) antibodies and by monitoring patients for at least 3 years after surgery.. A positive rate of leptin expression was significantly associated with Borrmann classification (Borrmann type 1 and type 2 68.2% vs Borrmann type 3 and type 4 or unclassified 35.3%), tumor histology (well differentiated tumors 87.5% vs poorly differentiated tumors 48.9%), lymph node metastasis (with 69.0% vs without 36.8%) and stage (stage III + IV 69.0% vs stage I + II 36.8%). There was a significant association between leptin expression and VEGF expression. In the poorly differentiated group, the overall survival rate for patients with a weak expression of leptin (histochemistry score <0.5) was significantly higher than that in patients with a strong expression (histochemistry score =0.5). The Cox proportional hazards model identified serosal involvement, tumor size, metastasis, tumor histology, leptin expression, lymph node metastasis, age and postoperative chemotherapy as significant prognostic factors.. The expression of leptin in the tissue of gastric cancer was significantly associated with tumor histology, Borrmann classification, lymph node metastasis and stage of gastric cancer. In patients with poorly differentiated gastric cancer, a poor prognosis was found in those with a strong expression of leptin.

Topics: Carcinoma; Humans; Immunohistochemistry; Leptin; Lymphatic Metastasis; Stomach Neoplasms; Survival Rate; Vascular Endothelial Growth Factor A

Body weight loss is a common but one of the most serious sequelae after gastrectomy. Ghrelin, a novel gastric hormone that up-regulates body weight through appetite control and metabolic reaction, seems to be affected by gastric surgery.. Early postoperative alteration of serum ghrelin was evaluated at days 3 and 7 after gastrectomy for 13 hospital patients. In 64 outpatients who had previously undergone total gastrectomy (TG: 26 patients) or distal gastrectomy (DG: 38 patients) 4.6 months to 136 months (average, 41 months) earlier, the association between their serum ghrelin and leptin levels and postoperative body weight was investigated.. Serum ghrelin declined immediately and greatly after TG to 12% of the preoperative level (day 3 and day 7), whereas the decline was less significant after DG at 39% (day 3) and 56% (day 7). In outpatients, serum ghrelin after TG was very low compared with the control (18.6 fmol/mL versus 92.1 fmol/mL, P<0.0001), irrespective of the period after surgery, whereas the level after DG recovered and was equivalent to the control (73.4 fmol/mL, P=0.355). Body weight loss was more apparent in TG patients than in DG patients, showing postoperative reduction of body mass index (DeltaBMI) -3.940 versus -1.949 (P<0.0001). Serum leptin concentration, reflecting the systemic fat volume, significantly correlated with BMI in both TG and DG patients, and tended to be lower in TG patients than in DG patients (800 pg/mL versus 1158 pg/mL, P=0.236).. Persistent decline of serum ghrelin and body weight was observed commonly after total gastrectomy. Further study is needed as to whether or not ghrelin administration can improve the body weight level for these patients.

Topics: Aged; Anastomosis, Roux-en-Y; Female; Gastrectomy; Gastroenterostomy; Ghrelin; Humans; Leptin; Male; Middle Aged; Outpatients; Peptide Hormones; Postoperative Complications; Stomach Neoplasms; Weight Loss

Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding behavior. The presence of leptin in stomach epithelium was recently demonstrated in the rat and humans, and gastric leptin has been linked to the control of meal size, local inflammatory responses, and paracrine and autocrine functions through leptin receptors in the stomach. We compared the expression patterns of leptin and of the long variant of the leptin receptor (Ob-Rb) between areas with non-ulcerated mucosa and with hyperplastic polyps, adenoma, or adenocarcinoma to evaluate the expression relative to different disease states. Leptin and Ob-Rb were expressed in hyperplastic polyps, adenoma, and adenocarcinoma. In the gastric adenocarcinoma, leptin was expressed significantly less in the poorly differentiated and diffuse-type groups than in the well-differentiated and moderately differentiated groups or in the intestinal type. Based upon our findings, we suggest the possibility that leptin expression can have a pathophysiologic role about the differentiation or growth pattern of gastric adenocarcinoma. A further series of experiments is necessary to elucidate the pathophysiological role of leptin in the differentiation of gastric adenocarcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Gastric Mucosa; Humans; Leptin; Middle Aged; Stomach; Stomach Neoplasms

To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia.. By immunohistochemical staining using specific antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features.. Both normal gastric epithelium and carcinoma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R-positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a significant correlation with the level of leptin expression. The expression levels of both leptin and OB-R tended to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic invasion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis.. Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.

Topics: Adenocarcinoma; Aged; Carcinoma, Signet Ring Cell; Disease Progression; Female; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Leptin; Lymphatic Metastasis; Male; Middle Aged; Receptors, Cell Surface; Receptors, Leptin; Stomach Neoplasms

The gp130(757F/F) mouse is a well-characterized and robust model of distal gastric tumorigenesis displaying many of the characteristics of human intestinal type gastric cancer. Key to the development of tumors in this model, and in many examples of human tumor development, is hyperactivation of the transcription factor STAT3. This study addressed the requirement for STAT3 activation in tumor initiation and characterized some of the genes downstream of STAT3 required for tumor development. Furthermore, the interaction among STAT3, the microbial environment, and tumorigenesis was evaluated.. The role of STAT3 in gastric tumor development was assessed in detail in gp130(757F/Y757F):STAT3(+/-) mice displaying reduced STAT3 activity. Tumor size was quantified morphologically, and the effects on endocrine cell populations, neovascularization, and inflammatory cell infiltration as well as the outcome of STAT3 activation on transcription of a number of genes relevant in growth and inflammation were quantified.. Loss of one STAT3 allele in gp130(757F/F) mice reduced the frequency and rate of tumor development because of inhibition of proliferation-induced glandular hyperplasia. There was also a concomitant reduction in the degree of inflammatory infiltration and cytokine and chemokine expression, angiogenesis, and expression of metalloproteinases and growth factors. Antimicrobial treatment of gp130(757F/F) mice slowed tumor growth coincident with reduced macrophage and neutrophil infiltration.. Activation of STAT3 and the microbial environment are pivotal for gastric tumor initiation and development in the gp130(757F/F) mouse, thus supporting the notion that STAT3 activation may play a role in human gastric cancer development.

Topics: Animals; Cell Division; Cell Movement; Cytokine Receptor gp130; Disease Models, Animal; Extracellular Matrix; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation, Neoplastic; Leptin; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neovascularization, Pathologic; Neutrophils; Phosphorylation; Pyloric Antrum; Somatostatin; STAT3 Transcription Factor; Stomach Neoplasms

Although leptin is known to induce proliferative response in gastric cancer cells, the mechanism(s) underlying this action remains poorly understood. Here, we provide evidence that leptin-induced gastric cancer cell proliferation involves activation of STAT and ERK2 signaling pathways. Leptin-induced STAT3 phosphorylation is independent of ERK2 activation. Leptin increases SHP2 phosphorylation and enhances binding of Grb2 to SHP2. Inhibition of SHP2 expression with siRNA but not SHP2 phosphatase activity abolished leptin-induced ERK2 activation. While JAK inhibition with AG490 significantly reduced leptin-induced ERK2, STAT3 phosphorylation, and cell proliferation, SHP2 inhibition only partially reduced cancer cell proliferation. Immunostaining of gastric cancer tissues displayed local overexpression of leptin and its receptor indicating that leptin might be produced and act locally in a paracrine or autocrine manner. These findings indicate that leptin promotes cancer growth by activating multiple signaling pathways and therefore blocking its action at the receptor level could be a rational therapeutic strategy.

Topics: Cell Proliferation; DNA-Binding Proteins; Enzyme Activation; Humans; Leptin; Mitogen-Activated Protein Kinase 1; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms; Trans-Activators

Leptin is known to act as a growth factor through the Janus-activated kinase (JAK)/signal transducer and activator of transcription signaling pathway as well as the mitogen-activated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors (Ob-R) at the protein level. We found that leptin, even at as low as 0.1 ng/mL, induced significant tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Time-course experiments revealed that phosphorylation was maximal after 5 minutes of stimulation and declined thereafter. We also revealed that tyrosine phosphorylation of EGFR induced by leptin was significantly attenuated by two inhibitors, an EGFR tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This indicates that the pathway of EGFR transactivation induced by leptin is dependent on proteolytically released EGFR ligands. Leptin induced JAK2 activation and extracellular signal-regulated kinase (ERK) 1/2 activation in these gastric cancer cells, both of which occurred after the peak of EGFR transactivation. Pretreatment of gastric cancer cells with AG1478 significantly reduced the degree of phosphorylation of both JAK2 and ERK1/2. These findings indicate the involvement of EGFR transactivation in the activation of JAK2 and ERK1/2. Our results reveal that EGFR transactivation is involved in the leptin signaling pathway in gastric cancer cells, which extends the physiologic action of leptin beyond its central effects in the hypothalamus to regulate body weight.

Topics: Cell Line, Tumor; Dipeptides; ErbB Receptors; Humans; Janus Kinase 2; Leptin; MAP Kinase Signaling System; Metalloproteases; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Protease Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Quinazolines; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins; Stomach Neoplasms; Transcriptional Activation; Tyrphostins

To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.. Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.. Dual expression of leptin and leptin receptor were detected in 80% (16/20) intestinal metaplasia, 86.3% (25/30) mild gastric epithelial dysplasia, 86.7% (26/30) moderate gastric epithelial dysplasia, 93.3% (28/30) severe gastric epithelial dysplasia, 91.3% (55/60) intestinal-type gastric adenocarcinoma and 30.0% (9/30) diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma (c2 = 37.022, P<0.01).. Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.

Topics: Adenocarcinoma; Humans; Immunohistochemistry; Leptin; MAP Kinase Signaling System; Phosphatidylinositol 3-Kinases; Precancerous Conditions; Receptors, Cell Surface; Receptors, Leptin; Stomach Neoplasms

Serum leptin level is associated with appetite and energy expenditure in healthy individuals. We aimed to evaluate the serum leptin concentration and the other factors which may be associated with weight loss in patients with advanced gastrointestinal cancer.. Forty-four patients with advanced gastrointestinal cancer (25 gastric and 19 colorectal cancer) and 25 healthy controls were enrolled. Serum leptin levels were measured as ng/ml via enzyme linked immuno-sorbent assay (ELISA) method in all subjects. The difference in serum leptin concentration between cancer and control group, the factor associated with its serum level and the relationship between serum leptin concentration and weight loss was evaluated.. Serum leptin concentration of cancer group was significantly lower than controls (p = 0.002). Female subjects had significantly higher serum leptin concentration than male subjects in control group (p = 0.01), while not in cancer group (p > 0.05). Serum leptin concentration was significantly related with gender in controls (p = 0.023, beta = 0.479), while no gender difference was observed in cancer group (p > 0.05). No relationship was found between serum leptin concentration and weight loss percentage in cancer group in linear regression analysis (p > 0.05). No significant difference was observed in serum leptin concentrations between colon and gastric cancer sub-groups (p > 0.05).. Independently from the site of gastrointestinal tract, serum leptin concentration in advanced gastrointestinal cancer is lower than controls and it is not a determinant factor in weight loss. In contrast to healthy subjects, gender does not effect the serum leptin concentration in patients with advanced gastrointestinal cancer.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Leptin; Male; Middle Aged; Reference Values; Regression Analysis; Sex Distribution; Stomach Neoplasms; Weight Loss

Although the majority of circulating ghrelin originates from the stomach, no prospective study of the proportion of ghrelin derived from the stomach has been reported. Patients with early gastric cancer who underwent gastric resection were divided into three groups according to the extent and site of gastric resection: subtotal gastrectomy group (n = 24), proximal gastrectomy group (n = 4), and total gastrectomy group (n = 12). Patients with advanced gastric cancer who underwent gastrojejunostomy without gastrectomy served as the bypass group (n = 5). Blood samples were collected from all patients preoperatively, at 1 h after gastric resection or gastrojejunostomy, and on postoperative d 1, 3, and 7. The plasma ghrelin level was determined in all samples and expressed as a percentage of the preoperative level. In the bypass group, no significant drop in the ghrelin level was observed at 1 h after gastrojejunostomy, and the ghrelin level remained stable through postoperative d 7. In the subtotal gastrectomy group, the ghrelin concentration reached a nadir of 38.8 +/- 12.9% of preoperative levels at 1 h after gastric resection and then gradually increased to 88.1 +/- 13.2% by postoperative d 7. In the proximal gastrectomy group, the nadir ghrelin level was 24.5 +/- 15.4% at 1 h after gastric resection and was followed by a gradual recovery. However, the recovery rate was slower than that in the subtotal gastrectomy group, with the ghrelin level reaching only 47.6 +/- 18.8% by postoperative d 7 (P < 0.05). In the total gastrectomy group, the nadir ghrelin level was 28.6 +/- 11.1% at 1 h after gastric resection and remained at 30.0 +/- 13.2% until postoperative d 7. These results suggest that compensatory ghrelin production can occur in the remnant stomach after the surgical removal of part of the stomach and that the proximal fundus is more important than the distal antrum and body in terms of the capacity for ghrelin production. The principal site of ghrelin production is clearly the stomach, which contributes 70% of the circulating ghrelin concentration.

Topics: Adult; Aged; Female; Gastrectomy; Ghrelin; Human Growth Hormone; Humans; Leptin; Male; Middle Aged; Peptide Hormones; Stomach Neoplasms

In order to investigate the effect of serum leptin and its potential as a parameter for the accessment of nutritional status of patients with cancer, serum leptin concentration, body mass index (BMI), blood erythrocyte, hemoglobin, serum albumin, lipid and lipoprotein concentration of 325 cancer patients and 66 healthy controls are meatured. The incidence of patients with BMI < 18.5, hypoalbumia, anemia, hypercholesterolemia, and hypertriglyceridemia is 23%, 14%, 42%, 17.2%, and 21.4% respectively. The incidence of patients with BMI < 18.5 in pulmonary carcinoma is obviously lower than that of those with gastric carcinoma (P = 0.022). The incidence of patients with hyperglycosemia and hypertriglyceridemia in pulmonary carcinoma is obviously higher than that of those with gastric carcinoma (P = 0.003 and P = 0.029 respectively). Serum leptin concentration in the patients with malnutrition is significantly lower than that of those with no malnutrition and that of those obese patients (P = 0.000). There is no significant difference in serum leptin concentration between patients with cancer and healthy control persons with same gender and with BMI value ranged from 18.5 to 25. It is shown that the BMI, gender and serum albumin concentration are all influencing factors to the serum leptin concentration and the serum leptin concentration is significantly correlated with BMI, gender and serum albumin concentrations (r = 0.599-0.698, P = 0.000). The above mentioned results from this study indicate that there is a high anemia incidence of patients with cancer. Serum leptin concentration can reflect the changes in BMI and nutritional status of the patients with cancer. The serum leptin concentration has the potential of being a parameter for assessing nutritional status of the patients with cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Nutritional Status; Stomach Neoplasms

Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium.. The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin.. Surgically resected human stomach tissues were subjected to immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to check for the presence of leptin in the human gastric epithelium. A total of 201 H pylori positive patients with chronic gastritis underwent eradication therapy for H pylori and were examined for the effect of infection cure in terms of body mass index (BMI) and serum leptin levels. Biopsy specimens from the gastric fundic mucosa were obtained from 40 of the 201 patients before and three months after eradication therapy. These samples were subjected to quantitative RT-PCR to examine the effect of eradication therapy on leptin expression in the gastric fundic mucosa.. Leptin immunoreactive cells were detected in the lower half of the gastric fundic glands and a leptin PCR product was also found in the gastric fundic mucosa. H pylori infection significantly increased gastric leptin expression. In addition, cure of H pylori infection significantly reduced gastric leptin expression, with a concomitant increase in BMI. In contrast, serum leptin levels did not change significantly after cure of H pylori infection.. Leptin is present in the human gastric mucosa. Gastric leptin may play a role in weight gain after eradication of H pylori infection. Gastric leptin may have a local rather than systemic action.

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Biomarkers; Biopsy; Body Mass Index; Case-Control Studies; Clarithromycin; Drug Therapy, Combination; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Omeprazole; Reverse Transcriptase Polymerase Chain Reaction; Statistics, Nonparametric; Stomach Neoplasms

Leptin is an important regulator of food intake and energy expenditure. Initially it was thought to be expressed exclusively in and secreted by adipocytes. Recently, leptin expression was also noted in other tissues, including rat gastric mucosa. Information on leptin and leptin receptor expression in the human stomach is lacking.. To investigate expression of leptin and its corresponding receptors in human gastric epithelial cells.. Fundic and antral gastric mucosal biopsies, primary cultures of human gastric epithelial cells, and the human gastric cancer cell line AGS were screened for expression of leptin and different leptin receptor isoform mRNA by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa.. mRNA of leptin and its four receptor isoforms (huOB-R, long receptor isoform; huB219.1-3, short receptor isoforms) was detected in gastric mucosal biopsies, cultured human gastric epithelial cells, and gastric cancer cells. Immunohistochemistry demonstrated that chief as well as parietal cells were reactive to leptin and leptin receptors.. Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine effect of leptin on gastric epithelial cell function.

Topics: Biopsy; Carrier Proteins; Cells, Cultured; Gastric Mucosa; Humans; Leptin; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Tumor Cells, Cultured