leptin and Lung-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; 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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; 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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

Many studies have found that leptin is involved in tumorigenesis and the progression of lung cancer. However, these studies were inconsistent. Therefore, we performed a meta-analysis to investigate the role of leptin in the patients with lung cancer. A systematic literature search in the several databases and on commercial Internet search engines was carried out to identify studies published up to July 8, 2016. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were used to investigate the effect sizes. Finally, 21 eligible articles were included in the current meta-analysis. Overall, there is no relationship between levels of serum leptin and lung cancer. However, a subgroup analysis in high-study quality group found a weak association between serum leptin concentrations and lung cancer in Chinese (SMD=0.77, P=0.035). Additionally, the meta-analysis indicates that the serum leptin levels were lower in the weight-losing group than in the sustained weight group (SMD=-0.80, P=0.001). Further, there was evidence of a significant association between expression levels of leptin protein in tissue and lung cancer (OR=7.35, P<0.001). The present meta-analysis suggests that the serum and tissue leptin may be involved in the pathogenesis of lung cancer and tumor metastasis, especially among Chinese. However, the leptin may not appear to play an important role in cancer cachexia development.

Topics: Case-Control Studies; Humans; Leptin; Lung Neoplasms; Prognosis

Leptin system plays an important role in lung inflammation and tumorigenesis, but the precise function in the tumormicrovironment and the prognosis value of the leptin system in lung cancer have not been fully elucidated. This review will focus on the relationship between leptin system and non-small cell lung cancer (NSCLC), in which special attentions will be paid on the expression of leption and its receptor (LepR) in peripheral blood and tumor tissues, leptin-related signal transduction pathways, the interaction between leption and regulatory T cells (Treg) and the gene polymorphisms of leptin and leptin receptor, and possibly provide new strategies for diagnosis and treatment of NSCLC.. 瘦素系统在肺部炎症反应、癌症发生发展等过程中发挥重要作用，但是其在肿瘤微环境中的作用机理、对肺癌的诊断价值仍不明晰。本文就瘦素系统与非小细胞肺癌之间的关系，从瘦素及其受体在循环和肿瘤组织中的表达变化、瘦素信号转导通路、瘦素与调节性T细胞的相互作用和瘦素及其受体的基因多态性等方面进行叙述，以期为非小细胞肺癌的诊治提供新方法。

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Gene Expression Regulation, Neoplastic; Humans; Leptin; Lung Neoplasms; Receptors, Leptin; Signal Transduction

Leptin is a product of the obese (ob) gene and acts through its receptor Ob-R. Leptin is primarily known for its role as a hypothalamic modulator of food, especially in intake, energy balance, fat stores and body weight. Recent studies have shown that leptin may be involved in the development of respiratory diseases such as pulmonary artery hypertension, chronic obstructive pulmonary disease, lung neoplasms and asthma. Therefore, further studies are needed to elucidate the mechanisms accounting for the association between leptin and respiratory diseases, which may lead to the development of novel approaches to the prevention and treatment of these diseases. Here we give an overview of the distribution and physiological function of leptin and ob-R, and summarize the recent progress in the relationship between leptin and respiratory diseases.

Topics: Animals; Asthma; Humans; Leptin; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Tract Diseases

This is a short review focusing on leptin immunoinflammatory mechanisms that ultimately may contribute to lung cancer development. We explored the complex and intricate interaction of leptin with immune cells to propose a pathway of inflammation-associated lung cancer development.

Topics: Humans; Immunity, Innate; Leptin; Lung 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; 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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 aim of this study was to evaluate the expression and clinical significance of leptin in lung cancer.. 126 patients with lung cancer ranged from 30 to 83years of age were studied. Serum leptin levels were determined by ELISA. The mRNA and protein levels of leptin in normal and lung cancer tissues were measured by RT-PCR and immunohistochemistry. The relationships between leptin levels and clinicopathological factors were evaluated by Wilcoxon rank sum or Kruskal-Wallis H test.. Serum leptin levels in lung cancer patients were significantly higher compared to those in controls and leptin expression in lung cancer tissue was markedly increased than that in normal lung tissue (both P<0.050).. Determination of leptin levels might provide useful predictive information for lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; RNA, Messenger; RNA, Neoplasm

To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions.. The epidemiologic studies within SELECT will be based on 32,400 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500-2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components.. Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5alpha-reductase type II, CYP17, and beta-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin.. SELECT offers an excellent opportunity to conduct molecular epidemiologic investigations to assess gene-environment interactions and their role in prostate, lung, and colon carcinogenesis.

Topics: Colorectal Neoplasms; Double-Blind Method; Epidemiologic Studies; Genetic Markers; Gonadal Steroid Hormones; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Selenium; United States; Vitamin E

Leptin is a nutritional cytokine, and it is closely related to the progression of cancer. However, the detailed effect of leptin in lung cancer remains poorly known. We found leptin-induced A549 cell proliferation, migration, and invasion, which was reversed by epigallocatechin gallate (EGCG) from green tea. Currently, we found that leptin-triggered M2 polarization of tumor-associated macrophages was inhibited by EGCG. Then, to investigate the underlying mechanism effect of leptin on A549 cells was studied. Aberrant activities of STAT1 are implicated in cancer development. Based on the cancer genome atlas data, STAT1 acted as an oncogene in lung cancer and EGCG greatly reduced STAT1 expression in A549 cells. Ferroptosis is an iron-dependent nonapoptotic cell death. STAT1 served as a transcriptional activator for SLC7A11. EGCG restrained lung cancer cell growth induced by leptin via targeting STAT1-SLC7A11 mediated ferroptosis. A high-fat diet (HFD) feeding condition was combined with a multi-dose urethane-induced lung tumorigenesis model using C57BL/6J mice. Obesity was induced with a 60 kcal% HFD feeding. Serum leptin levels increased in urethane-administered and HFD-fed mice. Compared to the control diet-fed mice, the HFD-fed mice exhibited increased lung tumor burden and typical pro-tumorigenic STAT1 activation in lung tissues after urethane administration. In addition, HFD alters the gut microbiome by decreasing the abundance of Clostridia and by increasing the abundance of Deltaproteobacteria and Epsilonproteobacteria while EGCG exhibited a reversed effect. These findings suggested that leptin promoted the development of lung tumorigenesis in vitro and in vivo via mediating activation of the STAT-SLC7A11 pathway and gut microbiota.

Topics: Animals; Carcinogenesis; Diet, High-Fat; Gastrointestinal Microbiome; Leptin; Lung; Lung Neoplasms; Mice; Mice, Inbred C57BL; Obesity; Urethane

Only few ES-SCLC patients experience long-term survival benefit by maintenance IT. Adipokines-induced metabolic meta-inflammation has been related to enhanced responsiveness to IT in obese patients; however, their prognostic role in SCLC is currently controversial.. Pre-treatment CT scan was used for determining distribution of abdominal adiposity, and blood samples were collected at fasting for measuring glycemia, insulin, ghrelin, leptin and adipokines (TNF-α, IFN-γ, IL-6 and MCP-1). Patients with known history of DM type II or metabolic syndrome with HOMA index > 2.5 were considered insulin resistant (IR).. In ES-SCLC pts receiving maintenance IT, increased leptin concentration and higher leptin/visceral adipose tissue (VAT) ratio were significantly associated with prolonged PFS. By applying a hierarchical clustering algorithm, we identified a cluster of patients characterized by higher leptin values and lower pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) who experienced longer PFS (13.2 vs 8.05 months; HR: 0.42 [0.18-0.93] p = 0.02) and OS (18.04 vs 12.09 mo; HR: 0.53 [0.25-1.29] p = 0.07).. Adipokines can play a crucial role to determining effectiveness of anti-cancer immunotherapy. The role of metabolic immune dysfunctions needs further pre-clinical validation and is currently investigated in the larger prospective cohort.

Topics: Adipokines; Humans; Immunotherapy; Inflammation; Insulins; Interleukin-6; Leptin; Lung Neoplasms; Prospective Studies; Small Cell Lung Carcinoma; Tumor Necrosis Factor-alpha

Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.. Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.. Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.. Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.. 【中文题目：瘦素/ERK信号在云锡矿粉诱导
大鼠II型肺泡上皮细胞转化中的作用】 【中文摘要：背景与目的 目前，云南个旧锡矿有大量矿工从事开采工作，这种职业环境与接触粉尘颗粒、重金属、多环芳烃和放射性氡有关，大大增加了患肺癌的风险。本研究旨在探讨在云锡矿粉诱导大鼠肺泡II型上皮细胞（immortalized rat alveolar cells type II, RLE-6TN）恶性转化过程中，瘦素（leptin）及其介导的细胞外调节蛋白激酶（extracellular regulated protein kinase, ERK）信号通路所起的作用。方法 采用200 μg/mL的云锡矿粉隔代毒染RLE-6TN至第9代，建立毒染细胞模型，命名为R₂₀₀细胞，正常培养组命名为R细胞，通过Western blot法检测两种细胞leptin受体的表达情况。通过MTT法筛选出leptin及丝裂原活化蛋白激酶激酶（mitogen-activated protein kinase kinase, MEK）抑制剂（U0126）对R₂₀₀细胞的最佳作用浓度。自第20代起，将R组、R₂₀₀组细胞分别与leptin及MEK抑制剂U0126共培养，对各组细胞的形态改变进行观察，并利用苏木素-伊红（hematoxylin-eosin, HE）染色技术鉴别第40代细胞的形态学差异，通过刀豆凝集素A（concanavalin A, ConA）及锚着独立性生长实验法检测细胞恶性转化情况。通过Western blot法检测leptin作用后上皮细胞ERK信号通路的变化。结果 R组和R₂₀₀组细胞均表达leptin受体（OB-R）。与R₂₀₀组比较，当leptin浓度达100 ng/mL时，其促增殖效应最为显著，30 μmol/L U0126可抑制毒染细胞R₂₀₀增殖，与对照组相比具有统计学差异（P<0.05）。自第25代起，leptin诱导的R₂₀₀组（R₂₀₀L组）细胞形态发生变化，至第30代出现恶性转化，至第40代时恶性转化特征明显；而R₂₀₀组细胞及U0126诱导的R₂₀₀组（R₂₀₀LU组）细胞则在第40代时才出现恶性转化特征。R₂₀₀L组细胞凝集速度较R₂₀₀LU组快，其余各组细胞P30出现凝集，且随ConA浓度增加，细胞凝集速度加快。R₂₀₀L组细胞自P40可见克隆形成，克隆形成率为2.25‰±0.5‰，R₂₀₀LU组及R₂₀₀组未见克隆集落。R₂₀₀L组细胞pERK表达增强；加入U0126阻断后，R₂₀₀L组细胞pERK磷酸化水平降低。结论 Leptin可以促进云锡矿粉毒染肺上皮细胞的恶性转化，ERK信号通路可能是其促进云锡矿粉引发的肺泡II型上皮细胞转化的重要途径。
】 【中文关键词：瘦素；肺泡II型上皮细胞；转化；ERK信号通路】.

Topics: Alveolar Epithelial Cells; Animals; China; Dust; Epithelial Cells; Leptin; Lung Neoplasms; Mitogen-Activated Protein Kinase Kinases; Rats; Receptors, Leptin; Signal Transduction; Tin

Chemotherapeutic combinational approaches would be more efficient in decreasing toxicity of drug, preventing tumor progression in relation to either drug alone. Hence, the aim of this study is to constract magnetic PLGA/PEG nanoparticles (NPs) co-loaded with Metformin (Met) and Silibinin (Sil) to investigate their cytotoxicity as well as their impact on  mRNA expression levels of leptin and leptin receptor genes in A549 lung cancer cells.. The synthesized NPs were characterized by FTIR, FE-SEM, and VSM and then, MTT assay was utilized to assess and compare the cytotoxicity of various concentrations of the chemotheruptic molecules in pure and nanoformulated forms as well as in alone and combination state after 48 h exposure time. Moreover, the mRNA levels of leptin and its receptor genes expression were studied by quantitative real-time PCR. By co-encapsulation of Met and Sil into PLGA/PEG/ Fe3O4, cytotoxic efficiency of the compounds considerably augmented for all concentrations.. Cytotoxicity assay displayed that combination of Met and Sil had a synergistic concentration-dependent effect on A549 lung cancer cells. Moreover, qPCR data revealed that the expression levels of the leptin and leptin receptor was considerably reduced with increasing concentrations of drug-encapsulated magnetic NPs, especially Met/Sil-encapsulated PLGA/PEG/ Fe3O4 NPs.. Present preliminary study shows that co-incorporating Met, Sil, Fe3O4 into PLGA/PEG NPs might provide a more promising and safe treatment strategy for lung cancer.

Topics: A549 Cells; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Gene Expression Regulation, Neoplastic; Humans; Leptin; Lung Neoplasms; Magnetic Phenomena; Metformin; Nanoparticle Drug Delivery System; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Receptors, Leptin; Silybin

EGFR-TKIs such as erlotinib and gefitinib have been introduced into the first-line treatment for patients having a mutation of deletion in exon 19 or L858R missense mutations in exon 21. Almost all patients who respond to EGFR-TKIs at first place eventually develop acquired resistance after several months of therapy. The secondary mutations and bypass signaling activation are involved in the generation of the resistance. Hypoxia in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance including radiotherapy, chemotherapy and EGFR-TKI therapy. In this study, the effect of hypoxic cancer microenvironment in the bypass signaling activation was investigated. We found that bone marrow-derived mesenchymal stem cells (BMSCs) residing in the hypoxic solid cancer microenvironment highly produced molecules associated with adipocytes including adipokine leptin and IGFBPs. Leptin could induce the resistance of lung cancer cells to erlotinib through activating IGF-1R signaling. IGFBP2 counteracted the activation role of IGF-1 and induced erlotinib resistance by activating IGF-1R signaling in an IGF-1 independent manner. IGFBP2 had synergistic effect with leptin to induce erlotinib resistance. Leptin and IGFBP2 may be predictive factors for acquired resistance for EGFR-TKIs.

Topics: Adenocarcinoma of Lung; Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Bone Marrow; Cell Proliferation; Drug Resistance, Neoplasm; Erlotinib Hydrochloride; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; Insulin-Like Growth Factor Binding Protein 2; Leptin; Lung Neoplasms; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Receptor, IGF Type 1; Tumor Cells, Cultured; Tumor Microenvironment; Xenograft Model Antitumor Assays

A high energy intake contributes to obesity, a risk factor for cancer. We previously reported that an excessive intake of dietary fat enhances malignant spread in mice. This study tested the hypothesis that consumption of a diet with an excessive amount of sucrose enhances metastasis. In a spontaneous metastasis model of Lewis lung carcinoma (LLC), male C57BL/6 mice were maintained on an AIN93G, a high-fat, or a high-sucrose diet for the duration of the study. Pulmonary metastases from a primary tumor, established by a subcutaneous injection of LLC cells, were quantified. There were no differences in energy intake among the 3 groups. The percent body fat mass of the high-sucrose group, while higher than that of the AIN93G group, was lower than that of the high-fat group. The number and size of lung metastases were significantly higher in the high-fat group than in the AIN93G group; these measurements in the high-sucrose group remained similar to those in the AIN93G group. Hepatic concentrations of triacylglycerols and plasma concentrations of insulin, proinflammatory cytokines (leptin, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1) and angiogenic factors (vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1) in the high-sucrose group were significantly lower than those in the high-fat group. In conclusion, the high-sucrose diet does not enhance spontaneous metastasis of LLC. This null effect may be due to the inadequate production of tumorigenic proinflammatory cytokines and angiogenic factors by the high-sucrose diet compared to the high-fat diet.

Topics: Adipose Tissue; Angiogenesis Inducing Agents; Animals; Carcinoma, Lewis Lung; Chemokine CCL2; Cytokines; Diet; Diet, High-Fat; Dietary Fats; Dietary Sucrose; Energy Intake; Feeding Behavior; Insulin; Leptin; Liver; Lung Neoplasms; Male; Mice, Inbred C57BL; Plasminogen Activator Inhibitor 1; Tissue Inhibitor of Metalloproteinase-1; Triglycerides; Vascular Endothelial Growth Factor A

Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a "metabolocentric" approach in metastatic breast cancer therapy.

Topics: Acetyl-CoA Carboxylase; Acetylation; Animals; Breast Neoplasms; Disease Models, Animal; Female; HEK293 Cells; Humans; Leptin; Lung Neoplasms; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Recurrence, Local; Tissue Array Analysis

Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C).. Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used.. Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001).. Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.

Topics: Aged; Aged, 80 and over; Anorexia; Appetite; Carcinoma, Non-Small-Cell Lung; Cytokines; Dietary Supplements; Female; Ghrelin; Humans; Hypothalamus; Inflammation; Leptin; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged

The aim of the present study was to evaluate pre-treatment concentrations of leptin in patients with advanced lung cancer and to investigate possible associations between their levels and clinicopathological variables, response to therapy and overall survival.. There are 71 previously untreated patients with cytological or histological evidence of primary lung cancer who were admitted to the oncology department between November 2013 and August 2014. Forty-five healthy individuals with age, sex and BMI matching the lung cancer patients, were recruited to take part in the study as a control group. Leptin levels were measured quantitatively by using a microELISA kit.. The serum leptin levels at diagnosis were significantly lower in lung cancer patients than those in control subjects (4.75±4.91 ng/ml, 9.67±8.02 ng/ml; p<0.001). We did not find any significant difference in leptin values related to clinicopathological parameters such as ECOG PS, weight loss, histological type, disease stage and TNM classification. Nevertheless, we demonstrated a significant correlation between serum leptin levels and BMI in lung cancer patients (correlation coefficient: 0.303; p>0.010). The analysis of serum leptin values did not show any association with the overall survival of the patients.. Our results showed that the serum leptin level has no prognostic indications in advanced lung cancer patients. Leptin is decreased in lung cancer, and there is lack of correlation with tumour‑related factors including prognosis. Therefore, leptin is not a useful clinical marker in lung cancer (Tab. 2, Fig. 2, Ref. 22).

Topics: Aged; Biomarkers, Tumor; Body Mass Index; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Reference Values; Statistics as Topic

Lung cancer is an invasive and progressive, fatal disease with few treatment choices and poor overall survival rates in nonsurgical stages. Leptin (LEP), an adipocyte derivative cytokine, participates in carcinogenesis. Increased amounts of systemic and pulmonary LEP indicate lung cancer. Curcumin (CUR) and silibinin (SIL) are herbal compounds which have many anticancer properties, but they have hydrophobic structures and low solubility in water. In this study, evaluated CUR-SIL dual drug-loaded poly (ɛ-caprolactone) [PCL]-co-poly ethylene glycol (PEG) magnetic nanoparticles (MNPs) were used to determine the inhibitory effect on LEP gene expression. The physicochemical properties of free and CUR-SIL-loaded PCL-PEG were fully characterized. The cytotoxic effect of CUR-SIL-loaded PCL-PEG magnetic nanoparticles was determined by MTT assay. Afterward, the inhibition of LEP gene expression was specified through real-time PCR. Results indicated that CUR-SIL cytotoxicity is time- and dose-dependent. CUR-SIL loaded MNPs showed the IC50 limit in lower concentrations in comparison to net CUR-SIL. CUR-SIL loaded MNPs reduced LEP expression more than net CUR-SIL. These results revealed the possibilities of CUR-SIL-loaded MNPs as a natural and effective antitumor drug delivery system to fight lung tumors.

Topics: Cell Line, Tumor; Coated Materials, Biocompatible; Curcumin; Gene Expression Regulation, Neoplastic; Humans; Leptin; Lung Neoplasms; Magnetite Nanoparticles; Neoplasm Proteins; Polyesters; Polyethylene Glycols; Silybin; Silymarin

Leptin (LEP), an adipocyte-derived cytokine, has been reported to participate in carcinogenesis. Elevated levels of systemic and pulmonary LEP are associated with diseases related to lung injury and lung cancer. The purpose of the present study was to investigate if the LEP and leptin receptor (LEPR) gene polymorphisms are associated with lung cancer in a cohort of Turkish population. One hundred and sixty-two lung cancer patients and 130 healthy controls were included in the study. The genotypes of LEP gene -2548G > A and LEPR gene Q223R polymorphisms were determined using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. The genotype frequencies of LEP -2548G > A polymorphism showed statistically significant differences between lung cancer patients and controls (p = 0.007). GA + AA genotypes and A allele of LEP -2548G > A polymorphism was found to be susceptibility factors for lung cancer (p = 0.003, odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.32-4.10; p = 0.003, OR 1.65, 95 % CI 1.18-2.29, respectively). The genotype and allele frequencies of LEPR Q223R polymorphism did not show any statistically significant differences between lung cancer patients and controls (p = 0.782 and p = 0.762, respectively). Although AA-QQ and AA-QR combined genotypes of LEP -2548G > A-LEPR Q223R loci were significantly higher in lung cancer patients (p = 0.020 and p = 0.047, respectively), GG-QQ, GG-QR, and AA-RR combined genotypes were significantly higher in control group. As a result, susceptibility effects of LEP -2548G > A polymorphism alone or in combination with LEPR Q223R polymorphism on lung cancer were observed. Further studies are necessary to prove the association of LEP and LEPR gene polymorphisms with lung cancer.

Topics: Aged; Carcinoma; Female; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptors, Leptin

To study the leptin resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats.. An LCC rat model was established. Totally 40 rats were randomly divided into the normal control group, the LCC model group, the XD group, and the positive control group, 10 in each group. After LCC model was set up, rats in the LCC model group were administered with normal saline, 2 mL each time. Rats in the XD group were administered with XD at the daily dose of 2 mL. Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL. All medication lasted for 14 days. The general condition and tumor growth were observed. Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay. Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique.. Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P < 0.05). Compared with the LCC model groups, serum leptin levels significantly increased in the XD group (P < 0.01). Leptin receptor levels in the hypothalamus increased significantly in the LCC model group (P < 0.01). Increased receptor levels in the LCC model group indicated that either XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P < 0.01). There was also statistical difference between the XD group and the positive control group (P < 0.05). Contents of NPY was higher in the LCC model group than in the other groups with statistical difference (P < 0.05). There was no statistical difference in NPY between the normal control group and the rest 2 treatment groups (P > 0.05). There was statistical difference in POMC between the normal control group and the LCC model group (P < 0.05). POMC could be decreased in the XD group and the positive control group with statistical significance (P < 0.05), and it was more obviously decreased in the XD group (P < 0.05).. Leptin resistance existed in LCC rats. XD could increase serum leptin levels and reduce leptin receptor levels in the hypothalamus. LCC could be improved by elevating NPY contents in the hypothalamus and reducing POMC contents, promoting the appetite, and increasing food intake from the periphery pathway and the central pathway.

Topics: Animals; Cachexia; Drugs, Chinese Herbal; Eating; Humans; Hypothalamus; Leptin; Lung Neoplasms; Neuropeptide Y; Random Allocation; Rats; Rats, Sprague-Dawley

Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.

Topics: Adipokines; Adiponectin; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Down-Regulation; Female; Ghrelin; Humans; Kaplan-Meier Estimate; Leptin; Lung Neoplasms; Male; Middle Aged; Prognosis; Prospective Studies; Small Cell Lung Carcinoma; Up-Regulation

Leptin, an adipocyte-derived cytokine associated with obesity, has been reported to participate in carcinogenesis. Epithelial-mesenchymal transition (EMT) is also considered as a key event in tumor metastasis. The aim of this study is to investigate the mechanism of leptin in the promotion of EMT leading to metastasis in A549 lung cancer cells. We investigated the effect of leptin on migration of A549 cells using wound healing and transwell assays. The incidence of EMT in A549 cells was examined by real-time PCR and immunofluorescence staining. The expression of TGF-β in A549 cells was detected by real-time PCR, and blocking of TGF-β in A549 cells was achieved by siRNA techniques. Additional work was performed using 100 patient samples, which included samples from 50 patients diagnosed with lung cancer and an additional 50 patients diagnosed with lung cancer with metastatic bone lesions. Leptin expression was measured using immunohistochemistry techniques. We demonstrated that leptin can effectively enhance the metastasis of human lung cancer A549 cell line using both wound healing and transwell assays. We also found the incidence of EMT in A549 cells after leptin exposure. Furthermore, we detected the expression of TGF-β in A549 cells, which had been reported to play an important role in inducing EMT. We showed that leptin can significantly upregulate TGF-β at both the mRNA and protein levels in A549 cells. Using siRNA to block the expression of TGF-β in A549 cells, we confirmed the role of TGF-β in the promotion of metastasis and induction of EMT. Furthermore, we found that in patient samples leptin was present at higher levels in samples associated with diagnosis of lung cancer bone metastases tissue than lung cancer tissue. Our results indicated that leptin promoted the metastasis of A549 human lung cancer cell lines by inducing EMT in a TGF-β-dependent manner.

Topics: Bone Neoplasms; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Humans; Leptin; Lung Neoplasms; Neoplasm Metastasis; Real-Time Polymerase Chain Reaction; Transforming Growth Factor beta

Cancer cachexia is a devastating condition leading to loss of function and independence, decreased performance status, decreased quality of life, and poor prognosis. Adipokines play a role in a wide variety of physiological or pathological processes, including immunity and inflammation, in addition to having significant effects on metabolism and lipogenesis. The objective of the present study was to investigate the relationship of adipokines and systemic inflammation in weight-losing advanced-stage non-small-cell lung cancer (NSCLC) patients.. Sixty-three male NSCLC patients (stages III and IV) and 25 age- and sex-matched controls were included. NSCLC patients were further divided into subgroups as those with a>5% weight loss in last 6 months and those who did not. Serum leptin, adiponectin, and TNF-α concentrations were measured by ELISA using commercially available kits.. The positive acute-phase reactants (APR) CRP, leukocyte, ferritin, thrombocyte, and fibrinogen were higher in the NSCLC group. Serum albumin level (which is a negative APR) was lower in the cancer group, whereas there was no difference in transferrin level between the groups. TNF-α and leptin concentrations were similar in the cancer group and the control group, whereas adiponectin was lower in the cancer group. There was a difference in thrombocyte and transferrin levels between patients with and without weight loss, whereas CRP, TNF-α, and adiponectin levels were similar. Leptin was lower in weight-losing cancer patients. However, there was no correlation between adipokines and markers of systemic inflammation.. These results revealed a lack of association between adipokine levels and systemic inflammation with cancer cachexia.

Topics: Adiponectin; Aged; Aged, 80 and over; C-Reactive Protein; Cachexia; Carcinoma, Non-Small-Cell Lung; Ferritins; Fibrinogen; Humans; Leptin; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Platelet Count; Transferrin; Tumor Necrosis Factor-alpha

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.

Topics: Adiponectin; Aged; Antineoplastic Agents; Cachexia; Colorectal Neoplasms; Cytokines; Female; Follow-Up Studies; Ghrelin; Humans; Interferon-gamma; Interleukin-6; Leptin; Lung Neoplasms; Male; Middle Aged; Peptide Hormones; Prognosis; Prospective Studies; Survival Rate; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor that binds leptin. Leptin is an obesity-associated peptide hormone overexpressed in gestational trophoblastic disease (GTD). GTD encompasses several placental abnormalities that range from benign to malignant. Among GTD, molar placentas are characterized by excess proliferation, whereas gestational trophoblastic neoplasias (GTN) have characteristically aggressive invasion. We hypothesized that in GTD, Siglec-6 expression would increase with disease severity and that Siglec-6 and leptin would promote proliferation, inhibit apoptosis and/or promote invasion. Siglec-6 expression patterns were evaluated with particular attention to the diagnostic utility of Siglec-6 in GTD (controls: normal placentas (n=32), hydropic abortus placentas (n=7), non-GTD reproductive tract cancers (n=2); GTD: partial moles (PM; n=11), complete moles (n=24), GTN (n=6)). In normal placentas, Siglec-6 expression dramatically decreased after 8 weeks gestation. Complete molar placentas had significantly higher Siglec-6 expression than controls, but expression was not significantly different from PM. In GTN, Siglec-6 expression was low. These data suggest that Siglec-6 may have diagnostic utility for distinguishing complete moles from normal and hydropic abortus placentas. Functional studies in choriocarcinoma-derived BeWO cells demonstrated a complex interplay between Siglec-6 expression and leptin exposure. In cells lacking Siglec-6, leptin treatment promoted invasion, likely through interaction with LepR leptin receptor, without affecting proliferation or apoptosis. Siglec-6 expression promoted proliferation in a leptin-dependent manner, but protected cells from apoptosis and promoted invasion in a leptin-independent manner. We propose that Siglec-6 and leptin play a role in the aberrant properties characteristic of GTD, namely excess proliferation and invasion.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Gestational Trophoblastic Disease; Humans; Lectins; Leptin; Lung Neoplasms; Neoplasm Invasiveness; Placenta; Pregnancy; Vaginal Neoplasms; Young Adult

Metastin, the product of the KISS-1 gene, seems to represent a strong suppressant of metastasis for some types of cancer. The aim of this study is to explore whether circulating levels of metastin could be used as a marker for the metastatic potential of non-small cell lung cancer (NSCLC) as well as a diagnostic marker in NSCLC patients. The possible correlation between metastin and leptin circulating levels was also evaluated. Fasting serum levels of metastin and leptin were determined in 96 NSCLC patients at diagnosis (76 with metastatic disease and 21 with locally advanced disease) and 49 healthy volunteers using commercial available ELISA. Serum metastin levels presented no differences between NSCLC patients and healthy volunteers (1.18 ± 0.98 vs. 1.17 ± 0.39 ng/ml, P = 0.979) as well as between patients with metastatic and locally advanced disease (1.17 ± 1.05 vs. 1.21 ± 0.64 ng/ml, P = 0.872). There was no statistically significant correlation between circulating metastin and leptin levels in NSCLC patients and patients with locally advanced and metastatic disease. This study shows a lack of direct involvement of metastin in the diagnosis and metastatic potential of NSCLC.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kisspeptins; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Tumor Suppressor Proteins

Insulin resistance is closely associated with numerous metabolic disorders. Although studies have supported the importance of insulin resistance in carcinogenesis, the existing data have not established its relevance in the context of lung cancer. The aim of the present case-control study was to evaluate the association between insulin resistance and lung cancer after adjusting for possible confounders. Homeostasis model assessment of insulin resistance (HOMA-IR) and serum leptin and adiponectin levels were determined in 81 lung cancer cases and 162 age- and sex-matched controls; anthropometric and lifestyle variables were recorded. Mean HOMA-IR in the cases was more than 2-fold higher compared with the mean value of controls (P < .001). Among controls, HOMA-IR correlated positively with serum leptin (r = 0.16; P = .04), body mass index (r = 0.43; P = .0001), and waist-to-hip ratio (r = 0.21; P = .01) but negatively with serum adiponectin (r = -0.29; P = .0002). As expected, smoking was associated with an approximately 10-fold increase in lung cancer risk in multiple logistic regression models. A positive association between HOMA-IR, treated as continuous variable, and lung cancer (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.16-1.99, P = .002, model 1) was demonstrated, which persisted after adjustment for somatometric and lifestyle variables (OR = 2.36, 95% CI: 1.00-5.55, P = .05, model 2). When serum adiponectin was also taken into account, the association seemed fairly robust (OR = 2.58, 95% CI: 1.11-6.01, P = .03, model 3); on the contrary, when serum leptin was added, the association remained positive, but lost its statistical significance (OR = 1.76, 95% CI: 0.78-3.98, P = .17, model 4). In the fully adjusted model, HOMA-IR was still positively, but only marginally, associated with lung cancer risk (OR = 2.02, 95% CI: 0.88-4.65, P = .10, model 5). Insulin resistance may represent a meaningful risk factor for lung cancer.

Topics: Adiponectin; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

Apigenin, a common edible plant flavonoid, is a well characterised antioxidant. The adipokine leptin exerts proliferative and anti-apoptotic activities in a variety of cell types. In cancer cells, apigenin may induce a pro-apoptotic pathway whereas leptin has an anti-apoptotic role. The purpose of the study is to investigate the role of apigenin and of leptin/leptin receptor pathway on proliferation and on apoptosis in lung adenocarcinoma.. Immunocytochemistry, flow cytometry and RT-q-RT PCR, were used to investigate the expression and modulation of leptin receptors on the lung adenocarcinoma cell line A549 in presence or absence of apigenin and of leptin, alone or combined. Clonogenic test to evaluate cell proliferation was assessed. Exogenous leptin binding to its receptors by flow cytometry, reactive oxygen species (ROS) by dichlorofluorescein diacetate analysis, cell death by ethidium bromide and apoptosis by annexin V analysis were assessed. Apoptosis was assessed also in presence of lung adenocarcinoma pleural fluids (PF) (n=6).. A549 express leptin/leptin receptor pathway and its expression is upregulated by apigenin. Apigenin alone or combined with leptin significantly decreases cell proliferation and significantly increases the spontaneous release of ROS, with augmented cell death and apoptosis, this latter also in the presence of lung adenocarcinoma PF. Leptin alone significantly increases cell proliferation and significantly decreases cell death.. These results strongly suggest the potential utility of the flavonoid apigenin in the complementary therapeutic approach of patients with lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apigenin; Apoptosis; Cell Growth Processes; Cell Line, Tumor; Cell Survival; Humans; Leptin; Lung Neoplasms; Receptors, Leptin

High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice.. The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion.. Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion.. Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Body Weight; Cell Movement; Cell Proliferation; Complement C5a; Cyclin A; Cyclin D1; Cyclin-Dependent Kinase 2; Cytokines; Dietary Fats; Energy Intake; Female; Interleukin-16; Ki-67 Antigen; Leptin; Leukocyte Common Antigens; Liver Neoplasms; Lung; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Obesity; Platelet Endothelial Cell Adhesion Molecule-1

The human epidermal growth factor receptor 2 (HER-2) and leptin/OB-R system have been reported to be intertwined in several cancer types. However, limited research has been conducted with regard to this interaction in lung cancers. In this study, we investigated the relationship between the expression levels of these proteins and the development, progression and prognosis of non-small-cell lung cancer (NSCLC).. The expression of leptin, OB-Rb and HER-2 was evaluated in 100 NSCLC specimens by immunohistochemistry, with normal lung tissue as controls. The relationships between their expression levels and clinicopathological factors were evaluated by correlation analysis. Univariate and multivariate analyses were used to determine the associations between the expression levels of these proteins and the survival of NSCLC patients.. Leptin was expressed in 71 and 25% (P < 0.05) of NSCLC and normal lung tissues, respectively, while OB-Rb was expressed in 62 and 31% (P < 0.05), respectively. Overexpression of HER-2 was detected in 53% of NSCLC tissues versus 0% of normal lung tissues (P < 0.05). A significant association was found between the expression levels of leptin and OB-Rb (P = 0.024), and between tumor-node-metastasis (TNM) stage and HER-2 expression (P = 0.003). Univariate survival analysis showed that TNM stage (P < 0.001) and leptin expression (P = 0.009) influenced survival time. Multivariate analysis suggested that TNM stage [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.30-2.04, P < 0.001] and leptin expression (HR 1.69, 95% CI 1.01-2.80, P = 0.044) were independent prognostic factors for NSCLC.. The expression of leptin, OB-Rb and HER-2 was significantly higher in NSCLC tissues than in normal lung tissues. The expression of leptin is an independent prognostic factor for NSCLC.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Female; Humans; Leptin; Lung; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prognosis; Receptor, ErbB-2; Receptors, Leptin; Retrospective Studies

Topics: Humans; Leptin; Lung Neoplasms; Neoplasm Staging; Prognosis

Leptin is intimately intertwined in the molecular pathophysiology of several cancer types; with regard to lung cancer, however, limited research has been conducted, with overall conflicting results.. The present case-control study comprises 66 non-small-cell lung cancer (NSCLC) cases and 132 healthy controls matched for gender and age. Lifestyle, sociodemographic and medical history information has been obtained in addition to body mass index (BMI) measurements and weight change during the last 2 months. Serum leptin and adiponectin levels were determined following a standard protocol.. In multiple logistic regression analyses, elevated serum leptin emerged as a risk factor for NSCLC independent of central obesity, more pronounced after controlling for BMI and recent weight loss (odds ratio = 4.58, 95% confidence interval: 1.94-10.82). Additionally, smoking and animal foods consumption were strongly associated with the disease, whereas plant foods consumption showed a protective association.. The observed higher serum leptin levels in NSCLC cases might be attributed to direct or indirect effects mediated by cancer- or cachexia-related cytokines. In line with the growth-promoting properties of leptin in the lung tissue documented elsewhere, increased serum leptin concentration may represent a tumor-promoting event during non-small-cell lung carcinogenesis.

Topics: Animals; Body Mass Index; Carcinoma, Non-Small-Cell Lung; Diet; Greece; Humans; Leptin; Life Style; Lung Neoplasms; Meat; Middle Aged; Neoplasm Staging; Overweight; Reference Values; Risk Factors; Smoking; Weight Loss

Leptin, protein taking part in body mass regulation, might play a role in cancer cachexia development. The aim of the study was to measure leptin serum levels in cachectic, non-cachectic lung cancer patients, healthy controls and to correlate leptin concentration with nutritional status markers.. 40 lung cancer patients were enrolled into the study: 20 with cachexia, 20 without cachexia, and 10 healthy controls. Leptin serum concentration, body mass, BMI, arm circumference and skin triceps fold thickness were measured in each subject.. Serum leptin level in cachectic cancer patients was significantly lower than in non-cachectic and healthy controls. Leptin concentration correlated with body mass, arm circumference and skin triceps fold thickness.. Cachectic lung cancer patients have significantly lower serum leptin concentrations than non-cachectic patients and healthy controls which may suggest, that leptin does not play an important role in cancer cachexia development. Leptin levels positively correlate with good nutritional status markers. Non-cachectic lung cancer patients have similar leptin serum levels as healthy controls.

Topics: Adolescent; Adult; Aged; Biomarkers; Cachexia; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Nutritional Status; Young Adult

To investigate the regulation of leptin expression in human lung adenocarcinoma cells by hypoxia inducible factor-1 (HIF-1alpha) and the mechanism thereof.. Lung adenocarcinoma tissues were collected from 42 patients during operation and samples of corresponding adjacent lung tissue were obtained from 16 of the 42 specimens. The expression levels of HIF-1alpha and leptin were detected by immunohistochemical staining. Human lung adenocarcinoma cells of the line A549 cells were cultured for 0, 12, 24, and 48 h respectively, exposed to hypoxia induced by CoCl2. Other A549 cells were treated with GL331, a kind of HIF-1alpha inhibitor, of the concentrations of 0, 5, 10, or 20 micromol/L under normoxic condition for 24 h, and then were exposed to hypoxia induced by CoCl2 for 24 h. RT-PCR and Western-blotting were used to examine the mRNA and protein expression levels of HIF-1alpha and leptin in different groups.. Immunohistochemistry showed that the positive rates of HIF-1alpha and leptin in the lung adenocarcinoma tissue were 57.1% and 69.0% respectively, both significantly higher than those in the adjacent normal lung tissues (18.8% and 25.0% respectively, both P<0.01). The protein expression levels of HIF-1alpha in the hypoxia 0, 12, 24, and 48 h groups were 0.314+/-0.030, 0.552+/-0.027, 0.743+/-0.015, and 0.799+/-0.010 respectively, and the protein expression levels of leptin were 0.398+/-0.016, 0.633+/-0.036, 0.796+/-0.008, and 0.942+/-0.088 respectively, increasing in a time dependent manner too. The mRNA expression levels of leptin in the 4 hypoxia groups were 0.144+/-0.009, 0.336+/-0.017, 0.524+/-0.013, and 0.671+/-0.021 respectively, increasing in a time dependent manner, however, there was no significant differences in the mRNA expression levels of HIF-1alpha among the groups exposed to hypoxia for different courses of time (all P>0.05). The protein expression levels of HIF-1alpha and leptin, and the mRNA expression levels of leptin in the groups exposed to hypoxia for different courses of time were all significantly higher than those of the control (0 h hypoxia) group (all P<0.01). The mRNA and protein expression levels of leptin in the A549 cells exposed to GL331 and hypoxia were decreased dose-dependently.. The expression of leptin is up-regulated by hypoxia and regulated by HIF-1alpha.

Topics: Adenocarcinoma; Aged; Cell Hypoxia; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Adipose tissue secretes adipokines with proinflammatory and anti-inflammatory properties. Our aim was to assess the role of adipose tissue in generalized inflammatory state of advanced NSCLC patients and the possible use of leptin, adiponectin and resistin as diagnostic and prognostic markers. Correlation of adipose tissue with weight loss in advanced NSCLC patients was also studied. Fasting serum levels of leptin, adiponectin and resistin were determined in 101 advanced NSCLC patients (76 without weight loss and 25 with weight loss) and 51 healthy volunteers using commercially available ELISA. Adipokine serum levels were determined at diagnosis, at the end of first-line chemotherapy and at the time of disease progression for those who responded to treatment. Epidemiological, anthropometrical and laboratory data were assessed. Serum leptin and adiponectin levels presented no differences. Serum resistin levels were significantly increased in NSCLC patients after adjustment for age, sex and BMI. Multivariate analysis showed that these adipokines at diagnosis could not be used as predictive factors for overall survival or time to progression. Only serum resistin levels were associated with weight loss. Despite no direct involvement of leptin and adiponectin, resistin as a proinflammatory cytokine may play a role in the pathogenesis of weight loss in NSCLC patients.

Topics: Adiponectin; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Proportional Hazards Models; Prospective Studies; Resistin; Statistics, Nonparametric

One recent line of cancer research shows increasing interest for biological factor such as IL-2, TNF-alpha, and leptin, which have been found to participate in the development and progression of non-small cell lung cancer (NSCLC). The aim of this study was to measure IL-2, TNF-alpha, and leptin concentrations in the airways and in the systemic circle of patients with NSCLC, investigating the role of these factors in the lung tumors. We enrolled 32 patients (17 men, 71 +/- 7 years) with a histological diagnosis of NSCLC and 20 healthy ex-smoker controls, negative for computed tomography of the chest (14 men, 69 +/- 8 years). IL-2, TNF-alpha, and leptin levels were measured in the serum, the urine, the bronchoalveolar lavage, the induced sputum, and exhaled breath condensate (EBC) of patients enrolled by means of a specific enzyme immunoassay kit. Higher concentrations of IL-2, TNF-alpha and leptin were found in NSCLC patients than in controls (p < 0.0001). A statistically significant increase of IL-2, TNF-alpha, and leptin concentrations was observed in patients from stage I to stage III of NSCLC. These findings suggest that IL-2, TNF-alpha, and the leptin play an important role in the cancerogenesis of NSCLC. Their measure in the EBC could be proposed as noninvasive markers for an early detection of NSCLC and in the follow-up of this tumor.

Topics: Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; Breath Tests; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carcinoma, Non-Small-Cell Lung; Early Diagnosis; Female; Humans; Interleukin-2; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Sputum; Tumor Necrosis Factor-alpha

Leptin hormone and receptor have been associated to cancer development and were identified in lung tissue. In this study, a functional polymorphism in the 5' flanking region of the leptin gene (LEP -2548 G/A) was found to increase susceptibility for non-small cell lung cancer [odds ratio (OR), 1.97; 95% confidence interval (CI), 1.13-3.43]. Age-adjusted logistic regression analysis in men indicated an association of AA genotype with adenocarcinoma (OR, 4.29; CI, 1.64-11.72) and squamous cell carcinoma (OR, 3.19; CI, 1.26-8.13). Logistic regression analysis confirmed the AA genotype as an independent risk factor for lung cancer after adjustment for age and gender (OR, 2.57; CI, 1.34-4.92). The AA genotype was overrepresented only in patients with non-metastatic disease (OR, 1.86; CI, 1.13-3.04). Kaplan-Meier analysis demonstrated an earlier age of onset for lung cancer in AA carriers (P=0.023). Results suggest the existence of genetic susceptibility for lung cancer in carriers of this LEP functional polymorphism. Further studies are warranted to extend knowledge of leptin involvement in lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Genetic Predisposition to Disease; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length

Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis.

Topics: Animals; Carcinoma, Lewis Lung; Cell Line, Tumor; Hypoglycemic Agents; Killer Cells, Natural; Leptin; Luciferases; Lung; Lung Neoplasms; Lymphocyte Count; Melanoma, Experimental; Mice; Mice, Obese; Pioglitazone; Recombinant Proteins; Thiazolidinediones; Time Factors; Transfection

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-alpha, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-alpha immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-alpha (p < 0.001) and CRP (p < 0.001), and lower leptin (p = 0.021) levels in patients than in controls. Serum IL-6 cytokine (p = 0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-alpha, and CRP were all similar in lung cancer patients independently from severity of weight loss (p > 0.05). A direct relationship was found between serum IL-6 and TNF-alpha levels (r = 0.530, p = 0.004). We found that both serum leptin (p = 0.046) and IL-6 (p = 0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-alpha and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p = 0.06) related to a worse prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; C-Reactive Protein; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Leptin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Tumor Necrosis Factor-alpha; Vinblastine; Vinorelbine

In humans, leptin circulates in a free form and is also bound to macromolecules. The aim of the present study was to compare a rapid acid-ethanol precipitation (AEP) method of measuring bound leptin with the more laborious gel exclusion chromatography (GEC) reference procedure. Serum samples collected from healthy subjects and cancer patients were used in this comparison.. AEP and GEC methods for measuring leptin binding in serum (from 14 healthy volunteers and 14 patients with advanced non-small cell lung cancer) were adapted from previously published procedures.. Intra- and inter-assay precision of the AEP method were 6% (n = 10) and 8% (n = 10), respectively. Bland-Altman analysis of results obtained from the AEP and GEC methods indicated no significant difference in healthy controls. However, significantly higher results were obtained by the AEP method in the cancer patients.. Evaluation of the AEP method revealed that on examination of normal subjects the method was less precise than had previously been reported. Moreover, the method gave differing results in the cancer patients when compared with the GEC method. This study indicates that careful evaluation of any new method for measuring leptin binding requires comparison with a GEC method using the sample matrix of interest.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Chemistry, Clinical; Chromatography; Ethanol; Female; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Reproducibility of Results; Statistics as Topic

Topics: Anorexia; Anthropometry; C-Reactive Protein; Cachexia; Carcinoma, Non-Small-Cell Lung; Cytokines; Humans; Leptin; Lung Neoplasms; Nutritional Status; Predictive Value of Tests; Risk Factors

Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.

Topics: Acute-Phase Reaction; Adult; Aged; Antigens, CD; Cachexia; Carcinoma, Non-Small-Cell Lung; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-6; Leptin; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Receptors, Interleukin-2; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Time Factors; Tumor Necrosis Factor-alpha

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

1. Adipocyte-derived leptin is postulated to represent the afferent hormonal signal to the hypothalamus in a feedback mechanism that regulates fat mass. In this proposed feedback mechanism, increased fat mass leads to an elevated plasma leptin level that eventually induces a decrease in appetite and an increase in energy expenditure, and vice versa. 2. As anorexia and hypermetabolism play a role in the development of cancer cachexia, we investigated the hypothesis that underlying abnormalities in the leptin feedback mechanism (in particular relatively high plasma leptin levels or, on the other hand, a hypothalamic insensitivity to a fall in leptin levels) might be involved. For this purpose, total plasma leptin, body composition (fat mass and fat-free mass), appetite and resting energy expenditure were assessed in 21 male lung-cancer patients. 3. Total leptin was detectable in six patients and non-detectable in 15. In comparison with the latter, the patients with detectable leptin were characterized by a trend towards less weight loss (3.4% compared with 11.0%, P = 0.07), as being less underweight (body mass index 23.8 kg/m2 compared with 19.4 kg/m2, P = 0.004) and by a higher fat mass (21.4 kg compared with 9.7 kg, P = 0.001). Significant between-group differences in appetite and resting energy expenditure were lacking. 4. Based on these findings, we conclude that in cancer the afferent part of the leptin feedback mechanism functions normally and that, in particular, elevated leptin levels are not involved in the development of cachexia. Since the absence of plasma leptin was not associated with an increased appetite and decreased energy expenditure, disturbances in the hypothalamic part of the feedback mechanism are hypothesized.

Topics: Aged; Aged, 80 and over; Appetite; Body Composition; Cachexia; Energy Metabolism; Feedback; Humans; Leptin; Lung Neoplasms; Male; Middle Aged; Proteins