interleukin-8 and Esophageal-Neoplasms

Esophageal cancer (EC) is one of the most lethal malignancies of the digestive tract and remains to be improved poor prognosis. Two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), are major characteristics of EC. Deep understanding about both subtypes is essential to overcome EC. Here, we focus on chemokines and their receptors as biomarkers and their current applications for the prognosis in EC. We reviewed relevant articles identified using PubMed database for the chemokines and their receptors in EC analyzed by immunohistochemistry. The primary objective is to summarize evidences for them as prognostic biomarkers in EC. A total of twenty-one articles were reviewed after exclusion. Most studies have been done in ESCC, and less in EAC. CXCL12 and its receptor CXCR4 have been shown in both subtypes as biomarkers. CXCR7, CXCL8 and its receptor CXCR2, and CCL21 and its receptor CCR7 have been examined in ESCC. Although it was a small number of reports, CXCL10, CCL4, and CCL5 have been indicated to have anti-tumor effects in ESCC. Chemokines and their receptors have the potential to be the biomarkers in EC. Comparative studies between ESCC and EAC will reveal the similarity and difference in these two subtypes of EC. These studies may indicate whether these molecules play important roles in both subtypes or are unique to one or another.

Topics: Adenocarcinoma; Age Factors; Biomarkers; Chemokine CCL21; Chemokine CXCL12; Chemokines; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Gender Identity; Humans; Immunohistochemistry; Interleukin-8; Male; Prognosis; Receptors, CXCR; Receptors, CXCR4; Receptors, Interleukin-8B

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Gastroesophageal reflux disease (GERD) is one of the most common problems in clinical practice today. It is widely believed that functional and structural abnormalities of the gastroesophageal junction as well as an abnormal exposure to gastroduodenal contents are the main contributors to its pathogenesis. Novel findings of the inflammatory process in GERD suggest a far more complex process involving multifaceted inflammatory mechanisms. This review summarizes knowledge about the expression of inflammatory mediators in GERD and their potential cellular sources and provides an integrated concept of disease pathogenesis. In addition we evaluate the contribution of inflammatory mediators to well-known complications of GERD, namely motility abnormalities, fibrosis, and carcinogenesis. Novel findings regarding the pathophysiology of esophageal inflammation should enhance our understanding of GERD and its complications and provide new treatment insights.

Topics: Animals; Endothelial Cells; Esophageal Motility Disorders; Esophageal Neoplasms; Esophagitis; Esophagogastric Junction; Fibrosis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Mesoderm; Platelet Activating Factor; Reactive Oxygen Species

It has been suggested that the blood clotting initiator protein, tissue factor (TF), participates in tumor growth, metastasis and angiogenesis. In addition, a family of G protein-coupled-receptors known as protease-activated receptors (PARs) has also been implicated in tumor biology. These receptors might be activated by blood coagulation proteases thus eliciting a number of pro-tumoral responses, including the expression of interleukin-8 (IL-8). Therefore, in this study we analyzed the expression of TF, PAR-1, PAR-2 and IL-8 genes in patients with esophageal cancer, one of the most aggressive neoplastic diseases. Total RNA was extracted from tissue samples (tumor and the corresponding normal mucosa) obtained from patients submitted to esophagectomy or endoscopy and further analyzed by semi-quantitative reverse transcriptase-polymerase (RT-PCR) and/or real-time quantitative PCR (qPCR). Expression of full-length transmembrane TF was significantly higher in tumor samples whereas no differences were observed in alternatively spliced TF transcripts. Tumor tissue showed increased mRNA levels for PAR-1 but not PAR-2. Remarkably, IL-8 expression was not detected in most normal tissues but showed very high expression in tumor samples. As expected, qPCR revealed greater differences in the expression pattern of all transcripts analyzed but the general profile was very similar to that observed by RT-PCR. Altogether our data suggest a possible role for blood clotting proteins in the biology of human esophageal cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Brazil; Esophageal Neoplasms; Esophagectomy; Esophagoscopy; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Middle Aged; Receptor, PAR-1; Receptor, PAR-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thromboplastin; Up-Regulation

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

To explore the influence of different ways of blood transfusion on the expression levels of interleukins (IL) and tumor necrosis factor-α (TNF-α) inperi-operative patients with esophageal cancer.. A total of 80 patients with esophageal cancer who underwent radical operations were selected as study patients and randomly divided into an observation group (treated with autologous blood transfusion) and control group (with homologous blood transfusion). Changes of intra-operative indexes and peri-operative blood indexes, from hemoglobin (Hb) and hematocrit value (Hct), to levels of inflammatory factors like interleukins-6 (IL-6), IL-8, IL-10 and tumor necrosis factor-α (TNF-α) were compared.. Operations for patients in both groups were successfully conducted, and no significant differences in mean surgical duration and intra-operative hemorrhage volume, fluid infusion volume and blood transfusion volume were detected (p>0.05). Compared with values before surgery, Hb and Hct levels decreased significantly while white blood cell count (WBC) increased 1, 5 and 7 d after operation (p<0.05, p<0.01). In addition, WBC was apparently higher in observation group than in control group 5 and 7 d after operation (p<0.01). Compared with before surgery, in the observation group, levels of IL-6, IL-8 and IL-10 had no significant differences after operation (P>0.05), but TNF-α level increased y (p<0.01), whereas in control group, IL-6 level had no significant difference (p>0.05), IL-8 level decreased obviously (p<0.05), IL-10 level increased markedly first and then decreased gradually as time passed but its level remained elevated (p<0.01), and TNF-α level increased first and then decreased, and there was no significant difference 7 d after operation (p>0.05).. Decreased IL-8 and increased IL-10 levels are two important reasons forimmunosuppression after homologous blood transfusion, whereas autologous blood transfusion can alleviate this while increasing the TNF-α level, which also has potential to improve anti-tumor immunity in the human body.

Topics: Adult; Aged; Blood Transfusion; Case-Control Studies; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Neoplasm Staging; Perioperative Care; Postoperative Complications; Prognosis; Transfusion Reaction; Tumor Necrosis Factor-alpha

Minimally invasive esophagectomy (MIE) has been advantageous for lowering pulmonary complications compared with open approaches.(1) However, pulmonary complications remain the most common morbidity after surgical resection of esophageal cancer.(2,3) The aim of this prospective, randomized, controlled, clinical trial was designed to see whether low tidal volume (VT) could further minimize pulmonary complications after MIE.. Between June 2011 and July 2012, a total of 101 patients who underwent MIE received left-lung ventilation during thoracoscopic esophagectomy. All patients received left-lung ventilation during thoracoscopic esophagectomy. Patients were randomly assigned to a low VT (5 mL/kg + 5 cm H2O positive end-expiratory pressure) preserved ventilation (PV) group (n = 53) and a conventional VT (8 mL/kg) controlled ventilation (CV) group (n = 48) in the thoracic stage. Alveolar lavage fluid was harvested from the ventilated lung at intubation and at 18 hours after surgery for analysis of interleukin (IL)-1ß, IL-6, and IL-8 levels. Clinical characteristics, including patient demographics, operation features, and changes in oxygenation index, were recorded and analyzed. Pulmonary complications were identified and statistically compared between the 2 groups.. The clinical characteristics and operation features were comparable between the 2 groups. IL-1ß, IL-6, and IL-8 expressions in preoperative alveolar lavage fluid were similar between the 2 groups. Significantly lower IL expressions were observed in the PV group than those in the CV group at 18 hours after MIE (IL-1ß, 25.42 ± 31.01 vs 94.96 ± 118.24 pg/mL; IL-6, 30.86 ± 75.78 vs 92.99 ± 72.90 pg/mL; IL-8, 258.75 ± 188.24 vs 403.95 ± 151.44 pg/mL; all P < .05). The 18-hour postoperative oxygenation index was lower in the CV group than that in the PV group (292.85 ± 28.74 vs 326.35 ± 34.43; P = .046). Pulmonary complications were observed in 18 cases of our series, occurring more frequently on the ventilation side (right, 6 cases; and left, 12 cases). All patients were cured by conservative therapy without severe sequelae. The occurrence of pulmonary complications in the PV group was lower than that in the CV group (9.43% vs 27.08%; P = .021).. Lung injury due to intraoperative single-lung ventilation may contribute to pulmonary complications after MIE. Low VT ventilation could decrease ventilation-associated lung inflammation, thus minimizing pulmonary complications after MIE. Further studies, based on a larger volume of populations, are required to confirm these findings.

Topics: Bronchoalveolar Lavage Fluid; Chi-Square Distribution; China; Esophageal Neoplasms; Esophagectomy; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung; Positive-Pressure Respiration; Prospective Studies; Thoracoscopy; Tidal Volume; Time Factors; Treatment Outcome; Ventilator-Induced Lung Injury

A prolonged period of one-lung ventilation(OLV) is required during thoracic surgery and this may activate cytokine release and cause lung inflammatory response. The lung protective ventilatory strategy has reduced lung and systemic cytokine release and achieved remarkable curative effect in patients with acute respiratory distress syndrome (ARDS). This study was to investigate the effect of the lung protective ventilatory strategy on proinflammatory cytokine release during OLV in patients underwent thoracic surgery.. Forty patients underwent esophagectomy were randomly divided into conventional ventilation (CV) group (n=20) and protective ventilation (PV) group (n=20). In CV group, all patients received two-lung ventilation (TLV) and OLV with a tidal volume (VT) of 10 mL/kg and an inspiration/expiration ratio (I/E) of 1:1.5. In PV group, all patients received TLV with a VT of 10 mL/kg and an I/E ratio of 1:1.5, and received OLV with a VT of 5-6 mL/kg and an I/E ratio of 1:1, along with positive end-expiratory pressure (PEEP) preset at 3-5 cm H2O. Blood samples of 3 mL were extracted at three time courses, which were after tracheal intubation (T1), 120 min after OLV (T2) and 24 h after operation (T3), to analyze concentrations of interleukin (IL)-6 and IL-8 in the two groups. Values of airway peak pressure (Ppeak), airway plateau pressure (Pplat), and airway resistance(Raw)were also recorded using side stream spirometry.. In CV group, concentrations of IL-6 and IL-8 at T2 [(269.4+/-57.2) ng/L, (180.8+/-35.0) ng/L] and T3[(335.8+/-98.7) ng/L,(178.5+/-18.3) ng/L] were significantly increased as compared with those at T1 [(17.0+/-5.4) ng/L,(18.2+/-2.8) ng/L](P<0.05). In PV group, concentrations of IL-6 and IL-8 at T2 [(209.3+/-55.7) ng/L], (115.3+/-71.5) ng/L] and T3 [(278.2+/-100.8) ng/L,(124.2+/-40.1) ng/L] were significantly increased as compared with those at T1[(20.0+/-7.1) ng/L,(15.3+/-3.6) ng/L] (P<0.05). Concentrations of IL-6 and IL-8 at T2 and T3 were significantly higher in CV group than in PV group (P<0.05). Ppeak, Pplat and Raw at T2 were significantly higher in CV group [(33.6+/-4.6 cmH2O,(21.5+/-3.1) cmH2O, (26.3+/-2.1) cmH2O.L(-1).S(-1)] than in PV group [(26.7+/-3.5) cmH2O, (12.4+/-2.1) cmH2O, (18.3+/-2.3) cmH2O.L(-1).S(-1)](P<0.05).. Concentrations of IL-6 and IL-8 are increased during and after OLV in thoracic surgery. The lung protective ventilatory strategy can reduce the airway pressure and airway resistance during OLV, decrease the release of IL-6 and IL-8, and inhibit lung inflammatory responses during OLV and postoperatively.

Topics: Adult; Aged; Airway Resistance; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Positive-Pressure Respiration; Pulmonary Ventilation; Respiratory Distress Syndrome; Tidal Volume

To examine the effect of ulinastatin (UTI) on the inflammatory responses induced by oesophagectomy.. Forty patients with esophageal cancer (without serious hypertension, heart disease, or respiratory function impairment, including 34 men and 6 women aged 46 to 70 years) scheduled for oesophagectomy via left thoracotomy were randomly divided into control group (n=20) and UTI group (n=20). Anesthesia induction and perioperative management followed the same protocols in the two groups, and in UTI group, patients received 5000 U/kg UTI while those in the control group were given the same volume of saline. Before operation (T(1)), 10 min after recovery of two-lung ventilation (T(2)), and 24 h (T(3)) and 48 h (T(4)) after operation, the venous blood sample was taken from the internal jugular vein and the plasma was separated and stored at -70 degrees C for later analysis of IL-6 and IL-8 with enzyme-linked immunosorbent assay (ELISA). The bronchoalveoar lavage fluid (BAFL) was also collected at T(1) and T(2) for IL-6 and IL-8 detection.. IL-6, IL-8 levels in the plasma and BALF collected at T(2)-T(4) increased significantly as compared with those in samples collected at T(1), and their peak concentration inplasma and BALF samples were similar. IL-6 and IL-8 levels in the UTI group were significantly lower than those in the control group during the time points of T(2)-T(4).. Inflammatory responses occur during and after oesophagectomy, which can be inhibited with UTI.

Topics: Adult; Aged; Esophageal Neoplasms; Esophagectomy; Female; Glycoproteins; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pneumonia; Postoperative Complications; Treatment Outcome; Trypsin Inhibitors

Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy.. The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time).. Plasmatic levels of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1beta, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15-0.40] vs. 0.56 [0.38-0.89] pg/ml, P < 0.001; 91 [61-117] vs. 189 [127-294] pg/ml, P < 0.001; and 30 [22-45] vs. 49 [29-69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13-0.30] vs. 0.43 [0.34-0.54] pg/ml, P < 0.001; 54 [36-89] vs. 116 [78-208] pg/ml, P < 0.001; 16 [11-24] vs. 35 [28-53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 +/- 38 vs. 171 +/- 57 min, P < 0.001).. A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.

Topics: Aged; Esophageal Neoplasms; Esophagectomy; Female; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Positive-Pressure Respiration; Prospective Studies; Respiration, Artificial; Systemic Inflammatory Response Syndrome; Tidal Volume; Tumor Necrosis Factor-alpha

The purpose of this study is to examine the effects of neutrophil elastase inhibitor on postoperative cytokine levels in patients after esophagectomy.. Fifteen patients were divided into two groups; group 1: 9 patients receiving neutrophil elastase inhibitor (0.2 mg x kg(-1) x hr(-1) from the admission to ICU to extubation), group 2: 6 patients as a control. We measured neutrophil elastase activity, interleukin 1-beta, interleukin 6 and interleukin 8 preoperatively, just after the admission to ICU, and 24, 48 and 72 hours after the surgery.. There were significant differences in neutrophil elastase activity and interleukin 8 in group 1 24 hours after the surgery, compared with those in group 2. The time necessary for mechanical ventilation in group 1 was shorter than that in group 2 (group 1: 44.7 +/- 24.7 hrs, group 2: 112.8 +/- 90.3 hrs, P = 0.048).. The administration of neutrophil elastase inhibitor may be useful for patients after esophagectomy to reduce overexpression of plasma cytokine levels after surgery.

Topics: Cytokines; Esophageal Neoplasms; Esophagectomy; Glycine; Humans; Interleukin-8; Leukocyte Elastase; Lung Diseases; Postoperative Complications; Postoperative Period; Respiration, Artificial; Serpins; Sulfonamides; Time Factors

Oesophageal surgery causes morbidity and mortality from respiratory complications. We tested the possibility that prostaglandin E1 (PGE1) could reduce inflammatory cytokine responses and improve gas exchange after oesophagectomy.. We randomized 14 patients into two groups. One group received PGE1 20 ng kg(-1) min(-1) i.v. during anaesthesia (PGE1 group) and the other group did not (control group). Anaesthesia was maintained with sevoflurane and epidural anaesthesia. During oesophagectomy, ventilation of one lung was carried out with a double-lumen bronchial tube. The patients were extubated on or after the first postoperative day. Blood samples were taken at induction of anaesthesia, at the end of thoracotomy, at the end of the operation, 2 h after surgery and on the first day after surgery.. The groups were similar for ASA physical status, age, FEV1%, operation time, duration of thoracotomy, intraoperative fluid volume and blood loss. The arterial blood gas and arterial pressure during surgery were also similar in the PGE1 and control groups. However, the PaO2/FiO2 ratio on the first day after surgery was significantly greater in the PGE1 group compared with the control group. Serum concentrations of IL-6 and IL-8 increased after surgery in both groups. IL-6 was significantly less in the PGE1 group at the end of the operation and 2 h after the operation.. Intraoperative PGE1 reduced IL-6 production in patients undergoing oesophagectomy and oxygenation was better in the postoperative period.

Topics: Aged; Alprostadil; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-6; Interleukin-8; Intraoperative Care; Male; Middle Aged; Oxygen; Partial Pressure; Postoperative Period; Pulmonary Gas Exchange

We have previously reported the beneficial effects of immediate enteral nutrition (EN) after esophageal cancer surgery. This randomized control study was conducted to determine whether immediate EN is beneficial or not for patients whose thoracic ducts were ligated, as well as those whose thoracic ducts were preserved.. Thirty-nine patients who underwent radical resection of the esophageal cancer entered this trial. After stratifying into two groups--patients whose thoracic ducts were preserved [D(+)] and those whose thoracic ducts were ligated [D(-)], they were randomly divided into two groups--the patients who received early EN and those who received parenteral nutrition (PN) followed by delayed enteral feeding. Thus, the number of patients in the D(+)-EN group, D(+)-PN group, D(-)-EN group and D(-)-PN group were 13, 12, 7 and 7, respectively. The mortality and morbidity rates, and several blood chemistries were compared between the EN groups and the PN groups.. Total lymphocyte count showed a significant early increase and serum c-reactive protein (CRP) was significantly decreased in the D(+)-EN group compared to the D(+)-PN group. However those differences were not observed between the D(-) groups. Serum total bilirubin was significantly decreased in the both EN groups compared to the PN groups. The mortality and morbidity rates were not different between the EN group and the PN group in the D(+) patients and also in the D(-) patients.. Patients whose thoracic ducts were ligated did not obtain any other benefit from early enteral feeding except for bilirubin metabolism. Early enteral feeding is not recommended for patients whose thoracic ducts are ligated during radical resection of a cancer in the thoracic esophagus.

Topics: Aged; Bilirubin; C-Reactive Protein; Carcinoma; Diuresis; Enteral Nutrition; Esophageal Neoplasms; Female; Humans; Interleukin-6; Interleukin-8; Lymphocyte Count; Male; Middle Aged; Parenteral Nutrition; Postoperative Complications; Thoracic Duct; Thoracic Surgical Procedures; Treatment Outcome

Postoperative tissue injury and immunosuppression can occur after major surgery. In this study, we explore the potential benefits of administering a protease inhibitor to treat immunosuppression caused by surgical stress.. Sixteen patients with esophageal cancer were preoperatively allocated at random into two equal groups. A urinary trypsin inhibitor, ulinastatin (UTI), was intravenously administered to the treatment (UTI) group at a dose of 150,000 U every 12 h from the start of surgery until postoperative day 5, whereas the control group received a placebo. One unit of UTI was defined as the amount of UTI necessary to inhibit the activity of 2 microg of bovine pancreatic trypsin by 50%. We measured the plasma levels of polymorphonuclear neutrophil elastase, interleukin 8, circulating T lymphocyte subsets, and mitogenic activity and in vitro production of tumor necrosis factor alpha in lipopolysaccharide-stimulated whole blood.. The postoperative serum value of polymorphonuclear neutrophil elastase was significantly lower in the UTI group, but the interleukin 8 concentrations did not significantly vary between the two groups. On the other hand, the severity of the postoperative immunosuppression was reduced in the UTI group, and immune functions, such as the numbers of T lymphocytes, the mitogenic activity of lymphocytes, and the level of tumor necrosis factor alpha production in whole blood, recovered significantly earlier in the UTI group.. These data suggest that a protease-modulating therapy may be a new strategy for the treatment of surgical stress induced immune dysfunction.

Topics: Aged; Esophageal Neoplasms; Female; Glycoproteins; Humans; Immune Tolerance; Interleukin-8; Male; Middle Aged; Neutrophils; Postoperative Period; Stomach; Stress, Physiological; T-Lymphocyte Subsets; Trypsin Inhibitors; Tumor Necrosis Factor-alpha

Granulocyte colony-stimulating factor (G-CSF) has been shown to effectively stimulate granulopoiesis, in both neutropenic and in non-neutropenic patients. Recently, other effects of G-CSF on the immune system have attracted interest in treating non-neutropenic patients with a high risk of severe infection. In this phase II trial, we measured the effects of G-CSF on the serum cytokine levels in patients with esophageal cancer undergoing esophagectomy. Twenty subsequent patients (study group, 19 evaluable) received G-CSF (rhG-CSF, Filgrastim) at standard doses (300 microg or 480 microg) subcutaneously 2 days before and up to 7 days after surgery. G-CSF was well tolerated. Leukocytes increased from 7600/microl at study entry (day -2) to a maximum of 45 100/microl (day 6). In the study patients, we found a highly significant (P<0.001) postoperative increase of G-CSF, IL-1ra, sTNFRp55 and sTNFRp75 as compared with the baseline level. In contrast, IL-8 levels were decreased by a factor of 6.8; there were no changes in the very low TNF-alpha levels. The comparison of the study group with a control group of 21 cancer patients undergoing major surgery who were not treated with G-CSF showed significant differences in the serum levels of G-CSF, sTNFRp55, sTNFRp75, and IL-1ra, respectively. There was no infection in the study group up to 10 days after surgery as compared with 29.9% in a historical control group (P=0.008). Thus, the induction of anti-inflammatory cytokines and the downregulation of pro-inflammatory cytokines by G-CSF might be a promising adjuvant treatment of infectious complications in patients undergoing esophagectomy.

Topics: Adenocarcinoma; Adolescent; Adult; Antigens, CD; Carcinoma, Squamous Cell; Case-Control Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Leukocytes; Male; Middle Aged; Prospective Studies; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Sialoglycoproteins; Time Factors; Tumor Necrosis Factor-alpha

Esophageal cancer (EC) is a malignancy with poor prognosis and high mortality. Hypoxic microenvironment has also been proved to be an important feature of tumors. Herein, we mainly studied the influence of hypoxia-treated tumor-associated macrophages (TAMs) on EC malignant phenotype and related molecular mechanism. In this paper, we found that hypoxic macrophages contributed to EC cell proliferation, cell cycle progression, and metastasis. Besides, the hypoxia treatment expedited the transformation of macrophages into M2 polarization. The level of interleukin (IL)-8 was boosted in macrophages after hypoxia treatment. Moreover, hypoxia treatment heightened IL-8 secretion by macrophages via positively regulating hypoxia-inducible factor-1α (HIF-1α) expression. The IL-8 secreted by hypoxic macrophages facilitated EC cell proliferation, cell cycle progression, and metastasis by elevating ligand of programmed death 1 (PD-L1) expression. In the end, IL-8 also expedited EC tumorigenesis in vivo. In conclusion, HIF-1α/IL-8 axis in hypoxic macrophages could expedite EC advancement by upregulating PD-L1 level, which might deliver a novel thought for EC cure.

Topics: B7-H1 Antigen; Cell Line, Tumor; Esophageal Neoplasms; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-8; Macrophages; Tumor Microenvironment

Although Barrett's metaplasia of the esophagus (BE) is the only known precursor lesion to esophageal adenocarcinomas (EACs), drivers of cellular transformation in BE remain incompletely understood. We use an artificial intelligence-guided network approach to study EAC initiation and progression. Key predictions are subsequently validated in a human organoid model, in patient-derived biopsy specimens of BE, a case-control study of genomics of BE progression, and in a cross-sectional study of 113 patients with BE and EACs. Our model classified healthy esophagus from BE and BE from EACs in several publicly available gene expression data sets (n = 932 samples). The model confirmed that all EACs must originate from BE and pinpointed a CXCL8/IL8↔neutrophil immune microenvironment as a driver of cellular transformation in EACs and gastroesophageal junction adenocarcinomas. This driver is prominent in White individuals but is notably absent in African Americans (AAs). Network-derived gene signatures, independent signatures of neutrophil processes, CXCL8/IL8 expression, and an absolute neutrophil count (ANC) are associated with risk of progression. SNPs associated with changes in ANC by ethnicity (e.g., benign ethnic neutropenia [BEN]) modify that risk. Findings define a racially influenced immunological basis for cell transformation and suggest that BEN in AAs may be a deterrent to BE→EAC progression.

Topics: Adenocarcinoma; Artificial Intelligence; Barrett Esophagus; Case-Control Studies; Cell Transformation, Neoplastic; Cross-Sectional Studies; Esophageal Neoplasms; Esophagogastric Junction; Ethnicity; Humans; Interleukin-8; Tumor Microenvironment

Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett's Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma. To that end, we analyzed the expression of the rate-limiting enzyme, carnitine palmytoyltransferase 1A (CPT1A), in human tissues and cell lines representing different stages in the sequence from normal squamous esophagus to cancer. We determined uptake of palmitic acid, the most abundant fatty acid in human serum, with fluorescent dye-labeled lipids as well as functional consequences of stimulation with palmitic acid relevant to Barrett's tumorigenesis, e.g., proliferation, characteristics of stemness and IL8 mediated inflammatory signaling. We further employed different mouse models including a genetic model of Barrett's esophagus based on IL1β overexpression in the presence and absence of a high fat diet and deoxycholic acid to physiologically mimic gastrointestinal reflux in the mice. Together, our data demonstrate that CPT1A is upregulated in Barrett's tumorigenesis and that experimental palmitic acid is delivered to mitochondria and associated with increased cell proliferation and stem cell marker expression.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Carcinogenesis; Carnitine; Carnitine O-Palmitoyltransferase; Cell Proliferation; Cell Transformation, Neoplastic; Deoxycholic Acid; Esophageal Neoplasms; Fluorescent Dyes; Gastroesophageal Reflux; Humans; Interleukin-8; Mice; Obesity; Palmitic Acid

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a chronic inflammatory state that can progress through a series of transformative dysplastic states before tumor development. While molecular and genetic changes of EAC tumors have been studied, immune microenvironment changes during Barrett's progression to EAC remain poorly understood. In this study, we identify potential immunologic changes that can occur during BE-to-EAC progression. RNA sequencing (RNA-Seq) analysis on tissue samples from EAC patients undergoing surgical resection demonstrated that a subset of chemokines and cytokines, most notably IL6 and CXCL8, increased during BE progression to EAC. xCell deconvolution analysis investigating immune cell population changes demonstrated that the largest changes in expression during BE progression occurred in M2 macrophages, pro-B cells, and eosinophils. Multiplex immunohistochemical staining of tissue microarrays showed increased immune cell populations during Barrett's progression to high-grade dysplasia. In contrast, EAC tumor sections were relatively immune poor, with a rise in PD-L1 expression and loss of CD8+ T cells. These data demonstrate that the EAC microenvironment is characterized by poor cytotoxic effector cell infiltration and increased immune inhibitory signaling. These findings suggest an immunosuppressive microenvironment, highlighting the need for further studies to explore immune modulatory therapy in EAC.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; CD8-Positive T-Lymphocytes; Chemokines; Cytokines; Disease Progression; Esophageal Neoplasms; Humans; Immune Tolerance; Immunohistochemistry; Interleukin-6; Interleukin-8; Macrophages; RNA-Seq; T-Lymphocytes, Regulatory; Tumor Microenvironment

The inflammatory cytokine IL-8 and its receptor CXCR2 are key signalling pathway molecules in cancer development. We hypothesized that IL-8/CXCR2 signalling promotes tumour progression in oesophageal squamous cell carcinoma (ESCC) patients.. We examined the relationship between IL-8/CXCR2 expression and clinicopathological factors by immunohistochemistry in samples from 63 patients with resectable ESCC. The effects of IL-8/CXCR2 signalling on cell proliferation and gene expression were examined in vitro and in vivo using ESCC cell lines.. Increased IL-8/CXCR2 signalling was associated with shorter overall survival (p<0.05) and recurrence-free survival (p<0.05) in ESCC patients. Multivariate analysis identified IL-8/CXCR2 expression as a prognostic factor for surgically treated ESCC (p<0.05). In vitro, IL-8 exposure or over-expression significantly enhanced ESCC cell proliferation. SB225002, a CXCR2-specific antagonist, and IL-8 siRNA significantly suppressed cell proliferation.. IL-8/CXCR2 expression is an independent prognostic factor for surgically treated ESCC, and IL-8/CXCR2 signalling contributes to ESCC cell proliferation.

Topics: Aged; Animals; Cell Line, Tumor; Cell Proliferation; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Mice; Middle Aged; Neoplasm Transplantation; Phenylurea Compounds; Prognosis; Receptors, Interleukin-8B; RNA, Small Interfering; Signal Transduction; Survival Analysis; Up-Regulation

Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC.. In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown.. The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001).. CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.

Topics: cdc25 Phosphatases; Cell Line, Tumor; Cell Survival; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Frizzled Receptors; Gene Knockdown Techniques; Humans; Immunohistochemistry; In Vitro Techniques; Interleukin-8; Male; Middle Aged; Minichromosome Maintenance Complex Component 4; Progression-Free Survival; Proportional Hazards Models; RNA, Small Interfering; Survival Rate; Up-Regulation

Although the clinical outcome of esophageal cancer has recently improved, the relapse rate remains high for all disease stages. At present, there is no diagnostic method to predict the long-term outcome for esophageal cancer. In this study, we evaluated serum preoperative proinflammatory cytokine levels and investigated the correlation between preoperative interleukin-6 (IL-6) and IL-8 levels and survival of patients with esophageal cancer.. Between 2008 and 2015, we evaluated preoperative serum cytokine levels in 122 patients who underwent esophagectomy for esophageal cancer. Serum IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. We investigated the relationship between serum cytokine levels and the response to chemotherapy and survival.. The preoperative IL-6 levels were significantly associated with shorter recurrence-free survival (RFS, p = 0.001) and overall survival (OS, p = 0.001) after esophagectomy. Higher IL-8 levels were significantly associated with RFS (p = 0.018). In the multivariate analysis, age, preoperative chemotherapy, lymph node metastasis, serum C-reactive protein (CRP) levels and serum IL-6 levels (hazard ratio (HR), 2.888; p = 0.049) were significantly independent prognostic factors of RFS. Additionally, age, pathological stage, and serum IL-6 levels (HR, 3.247; p = 0.027) were shown to be significantly independent prognostic factors of OS. Serum IL-6 levels were significantly higher in the non-responder group (pathological response pGrade0 and pGrade1) after neoadjuvant therapy.. High preoperative serum IL-6 levels are associated with a poor response to chemotherapy or chemoradiotherapy and poor prognosis after esophagectomy. Preoperative serum IL-6 levels may be a useful independent prognostic marker for esophageal cancer patients.

Topics: Aged; Biomarkers, Tumor; C-Reactive Protein; Chemoradiotherapy; Drug Therapy; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-6; Interleukin-8; Japan; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Outcome Assessment, Health Care; Preoperative Care; Prognosis; Retrospective Studies; Survival Analysis

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with frequent recurrence even after curative resection. The tumor microenvironment, which consists of non-cancer cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), was recently reported to promote several cancers, including ESCC. However, the role of CAF as a coordinator for tumor progression in ESCC remains to be elucidated. In our immunohistochemical investigation of ESCC tissues, we observed that the intensity of expression of two CAF markers-alpha smooth muscle actin (αSMA) and fibroblast activation protein (FAP)-in the tumor stroma was significantly correlated with the depth of tumor invasion, lymph node metastasis, advanced pathological stage, and poor prognosis. We co-cultured human bone marrow-derived mesenchymal stem cells (MSCs) with ESCC cells and confirmed the induction of FAP expression in the co-cultured MSCs. These FAP-positive MSCs (which we defined as CAF-like cells) promoted the cell growth and migration of ESCC cells and peripheral blood mononuclear cell-derived macrophage-like cells. CAF-like cells induced the M2 polarization of macrophage-like cells. A cytokine array and ELISA revealed that CAF-like cells secreted significantly more CCL2, Interleukin-6, and CXCL8 than MSCs. These cytokines promoted the migration of tumor cells and macrophage-like cells. The silencing of FAP in CAF-like cells attenuated cytokine secretion. We compared cell signaling of MSCs, CAF-like cells, and FAP-silenced CAF-like cells; PTEN/Akt and MEK/Erk signaling were upregulated and their downstream targets, NF-κB and β-catenin, were also activated with FAP expression. Silencing of FAP attenuated these effects. Cytokine secretion from CAF-like cells were attenuated by inhibitors against these signaling pathways. These findings indicate that the collaboration of CAFs with tumor cells and macrophages plays a pivotal role in tumor progression, and that FAP expression is responsible for the tumor promotive and immunosuppressive phenotypes of CAFs.

Topics: Actins; Cancer-Associated Fibroblasts; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemokine CCL2; Endopeptidases; Esophageal Neoplasms; Esophagus; Gelatinases; Humans; Interleukin-6; Interleukin-8; Japan; MAP Kinase Signaling System; Membrane Proteins; Mesenchymal Stem Cells; Serine Endopeptidases; Tumor Microenvironment

C-X-C motif chemokine 8 (CXCL-8), known as interleukin-8, is a pro-inflammatory cytokine which acts as a chemotactic factor, mainly for leukocytes. CXCL-8 is produced by malignant cells, and therefore it can stimulate the growth and progression of various neoplasms, including oesophageal cancer (OC). The aim of the current study was to measure serum concentrations of chemokine CXCL-8 in OC patients and establish whether this protein might be considered a potential candidate for a tumor marker in the diagnosis and progression of OC. The study included 50 OC subjects (32 patients with squamous cell carcinoma of oesophagus-OSCC, 18 patients with adenocarcinoma-OAC) and 26 healthy volunteers. Serum CXCL-8 concentrations were measured using immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetric method, while classical tumor marker levels were measured using chemiluminescent immunoassay. CXCL-8 concentrations were significantly higher in OC patients compared to healthy controls. We demonstrated significant differences between CXCL-8 concentrations and depth of tumor invasion (T factor) in OC patients and OSCC subgroup. In addition, CXCL-8 levels were found to correlate positively with T factor and CRP concentrations. The diagnostic sensitivity, negative predictive value and the area under ROC curve (AUC) of CXCL-8 were higher than those of classical tumor markers. Our findings suggest the potential usefulness of CXCL-8 in the diagnosis and progression of OC. However, due to the non-specific nature of this chemokine, further research is needed to clarify the usefulness of CXCL-8 as a tumor marker of OC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnostic Tests, Routine; Esophageal Neoplasms; Female; Humans; Immunoassay; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Serum

Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Progression from BE to cancer is associated with obesity, possibly due to increased abdominal pressure and gastroesophageal reflux disease, although this pathogenic mechanism has not been proven. We investigated whether environmental or dietary factors associated with obesity contribute to the progression of BE to EAC in mice.. Tg(ED-L2-IL1RN/IL1B)#Tcw mice (a model of BE, called L2-IL1B mice) were fed a chow (control) or high-fat diet (HFD) or were crossbred with mice that express human interleukin (IL) 8 (L2-IL1B/IL8 mice). Esophageal tissues were collected and analyzed for gene expression profiles and by quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry. Organoids were established from BE tissue of mice and cultured with serum from lean or obese individuals or with neutrophils from L2-IL1B mice. Feces from mice were analyzed by 16s ribosomal RNA sequencing and compared to 16s sequencing data from patients with dysplasia or BE. L2-IL1B were mice raised in germ-free conditions.. L2-IL1B mice fed an HFD developed esophageal dysplasia and tumors more rapidly than mice fed the control diet; the speed of tumor development was independent of body weight. The acceleration of dysplasia by the HFD in the L2-IL1B mice was associated with a shift in the gut microbiota and an increased ratio of neutrophils to natural killer cells in esophageal tissues compared with mice fed a control diet. We observed similar differences in the microbiomes from patients with BE that progressed to EAC vs patients with BE that did not develop into cancer. Tissues from dysplasias of L2-IL1B mice fed the HFD contained increased levels of cytokines that are produced in response to CXCL1 (the functional mouse homolog of IL8, also called KC). Serum from obese patients caused organoids from L2-IL1B/IL8 mice to produce IL8. BE tissues from L2-IL1B mice fed the HFD and from L2-IL1B/IL8 mice contained increased numbers of myeloid cells and cells expressing Cxcr2 and Lgr5 messenger RNAs (epithelial progenitors) compared with mice fed control diets. BE tissues from L2-IL1B mice raised in germ-free housing had fewer progenitor cells and developed less dysplasia than in L2-IL1 mice raised under standard conditions; exposure of fecal microbiota from L2-IL1B mice fed the HFD to L2-IL1B mice fed the control diet accelerated tumor development.. In a mouse model of BE, we found that an HFD promoted dysplasia by altering the esophageal microenvironment and gut microbiome, thereby inducing inflammation and stem cell expansion, independent of obesity.

Topics: Adenocarcinoma; Adult; Aged; Animals; Barrett Esophagus; Carcinogenesis; Diet, High-Fat; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagus; Feces; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Obesity; Organoids; Serum; Time Factors; Tissue Culture Techniques

The aim of the present study was to investigate the role of G‑protein coupled receptor 120 (GPR120) in esophageal cancer and explore the related mechanisms. The expression of GPR120 in esophageal cancer tissues was examined by immunohistochemistry. Correlation analysis was performed to investigate the association between the level of GPR120 and clinical parameters. The expression of GPR120 was evaluated in esophageal cancer cell lines and the effects of GPR120 on cell proliferation, clone formation, migration and invasion were evaluated in an in vitro cell model and an in vivo ectopic tumor nude mice model. In addition, the effect of GPR120 on epithelial‑mesenchymal transition (EMT), PI3K and I‑κB pathway, as well as angiogenesis and inflammation‑related cytokines was explored in order to elucidate the underlying mechanisms. Significantly increased expression of GPR120 was observed in esophageal cancer tissues compared to normal tissues. The expression of GPR120 was significantly related with histological grade, TNM stage and lymph node metastasis. GPR120 knockdown significantly decreased cell proliferation, clone formation, migration and invasion in vitro and decreased tumor growth in vivo. Furthermore significantly increased levels of E‑cadherin and decreased levels of N‑cadherin and vimentin, decreased level of Akt phosphorylation and I‑κB phosphorylation, as well as decreased levels of vascular endothelial growth factor (VEGF), interleukin‑8 (IL‑8) and cyclooxygenase‑2 (Cox‑2) and its corresponding protein PGE2 were observed as the underlying mechanisms. In conclusion, we observed an increased level of GPR120 in esophageal cancer tissues, which served as a positive regulator of the development and progression of esophageal cancer. Multiple mechanisms including EMT, PI3K and I‑κB pathway, as well as angiogenesis and inflammation‑related cytokines were involved.

Topics: Animals; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclooxygenase 2; Disease Progression; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Humans; I-kappa B Proteins; Interleukin-8; Lymphatic Metastasis; Mice; Mice, Nude; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled; Signal Transduction; Vascular Endothelial Growth Factor A

The aim of this study is to evaluate the efficacy of insulin-like growth factor 1 receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive patients as well as explore the molecular-resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1 receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot. And the antitumor effect of Linsitinib and JSH-23, an inhibitor of nuclear factor-κB transcriptional activity, was analyzed both as single agent and in combination in ESCC. Apoptosis, cell viability, and clonogenic survival analysis were also investigated. The sensitivity of Linsitinib was relatively variable in patient-derived primary ESCC cells as well as in human commercial cell lines. And the downstream AKT/mTOR and ERK signaling pathways were inhibited by Linsitinib, while phosphorylation level of NF-κB p65 was obviously activated to reduce apoptosis effect in Linsitinib-resistant cell lines. Most importantly, blockage of NF-κB activity by JSH-23 could sensitize resistant cells to Linsitinib treatment. Results from this study demonstrated that the intrinsic resistance to Linsitinib was predominantly mediated by NF-κB activation in ESCC. Moreover, combination of Linsitinib and JSH-23 as therapy provides a novel strategy to overcome resistance to Linsitinib in ESCC.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Extracellular Signal-Regulated MAP Kinases; Humans; Imidazoles; Interleukin-6; Interleukin-8; NF-kappa B; Phenylenediamines; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Pyrazines; RNA, Messenger; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Cells, Cultured

The incidence of esophageal adenocarcinoma (EAC) is rapidly increasing in western countries. The overall mortality of this disease remains high with a 5-year survival rate of less than 20%, despite remarkable advances in the care of patients with EAC. Galectin-9 (Gal-9) is a tandem-repeat type galectin that exerts anti-proliferative effects on various cancer cell types. The aim of the present study was to evaluate the effects of Gal-9 on human EAC cells and to assess the expression of microRNAs (miRNAs) associated with the antitumor effects of Gal-9 in vitro. Gal-9 suppressed the proliferation of the EAC cell lines OE19, OE33, SK-GT4, and OACM 5.1C. Additionally, Gal-9 treatment induced apoptosis and increased the expression levels of caspase-cleaved cytokeratin 18, activated caspase-3 and activated caspase-9. However, it did not promote cell cycle arrest by reducing cell cycle-related protein levels. Furthermore, Gal-9 increased the level of the angiogenesis-related protein interleukin-8 (IL-8) and markedly altered miRNA expression. Based on these findings, Gal-9 may be of clinical use for the treatment of EAC.

Topics: Adenocarcinoma; Apoptosis; Autophagy; Caspase 3; Caspase 9; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Esophageal Neoplasms; Galectins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Keratin-18; MicroRNAs; Mutation; Oligonucleotide Array Sequence Analysis; Recombinant Proteins

Barrett's esophagus, a metaplasia resulting from a long-standing reflux disease, and its progression to esophageal adenocarcinoma (EAC) are characterized by activation of pro-inflammatory pathways, induced by cytokines.. An in vitro cell culture system representing the sequence of squamous epithelium (EPC1 and EPC2), Barrett's metaplasia (CP-A), dysplasia (CP-B) to EAC (OE33 and OE19) was used to investigate TNF-α-mediated induction of interleukin-8 (IL-8).. IL-6 and IL-8 expressions are increasing with the progression of Barrett's esophagus, with the highest expression of both cytokines in the dysplastic cell line CP-B. IL-8 expression in EAC cells was approx. 4.4-fold (OE33) and eightfold (OE19) higher in EAC cells than in squamous epithelium cells (EPC1 and EPC2). The pro-inflammatory cytokine TNF-α increased IL-8 expression in a time-, concentration-, and stage-specific manner. Furthermore, TNF-α changed the EMT marker profile in OE33 cells by decreasing the epithelial marker E-cadherin and increasing the mesenchymal marker vimentin. The anti-inflammatory compound curcumin was able to repress proliferation and to activate apoptosis in both EAC cell lines.. The increased basal expression levels of IL-8 with the progression of Barrett's esophagus constrain NFκB activation and its contribution in the manifestation of Barrett's esophagus. An anti-inflammatory compound, such as curcumin, could create an anti-inflammatory microenvironment and thus potentially support an increase chemosensitivity in EAC cells.

Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Barrett Esophagus; Cell Line; Curcumin; Disease Progression; Drug Evaluation, Preclinical; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Humans; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha; Vimentin

Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF-κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF-κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF-κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF-κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF-κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention.

Topics: Adenocarcinoma; Bile Acids and Salts; Cell Line, Tumor; Esophageal Neoplasms; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; I-kappa B Kinase; Interleukin-8; NF-kappa B; Transcription Factor AP-1

Esophagectomy for esophageal cancer is one of the most invasive operative procedures. Surgical stress induces the release of proinflammatory cytokines, and overproduction induces a systemic inflammatory response syndrome, which may lead to acute lung injury and multiple organ dysfunction syndrome. In addition, surgical stress may cause immunosuppression, which may affect not only perioperative mortality but also long-term survival.. Between 2006 and 2013, levels of perioperative serum cytokines were evaluated in 90 patients who underwent esophagectomy for esophageal carcinoma. The serum interleukin (IL)-6, IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assays. We reviewed and assessed medical records, including cytokine profiles, and determined the factors affecting postoperative serum cytokine levels.. These cytokine levels peaked on postoperative day 1 and decreased gradually. Of the clinicopathologic factors, a thoracoscopic approach was a significant factor in attenuating IL-6 and IL-8 levels on postoperative day 1 in multivariate analysis, and a longer operative time was a significant factor in increasing these levels. During postoperative days 3-7, the thoracoscopic approach and early enteral nutrition were significant factors in attenuating serum cytokine changes in multivariate analysis, and postoperative infectious complications were significant factors in increasing these levels.. The thoracoscopic approach and early enteral nutrition could attenuate the cytokine change after esophagectomy, and a longer operative time and postoperative infectious complication could increase it. We should undertake strategies to minimize the surgical stress to reduce potential short-term and long-term consequences for patients.

Topics: Carcinoma, Squamous Cell; Cytokines; Enteral Nutrition; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Neoplasm Staging; Operative Time; Perioperative Care; Postoperative Complications; Prognosis

Barrett's esophagus (BE) is known to progress to esophageal adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4 has been linked to inflammation-associated carcinogenesis. We aimed to determine the expression and functional activity of TLR4 in the esophagus and whether TLR4 activation in BE could promote carcinogenesis by inducing COX-2 expression.. TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux esophagitis and normal squamous esophagus biopsies was assessed using real-time PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To evaluate the effect of TLR4 activation, NF-κB activation, IL8 secretion and expression and COX-2 expression were determined.. TLR4 expression was significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF-κB activation and a dose-dependent increase of IL8 secretion and mRNA expression. The induction of IL8 was more evident in BE compared to normal squamous esophagus. Upon LPS stimulation, COX-2 expression increased significantly in ex vivo cultured BE biopsies, which was observed in both epithelium and lamina propria cells. However, no effect was found in duodenum and normal squamous esophagus biopsies.. TLR4 activation in BE results in a strong increase in COX-2 and may contribute to malignant transformation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Cyclooxygenase 2; Esophageal Neoplasms; Esophagitis, Peptic; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; NF-kappa B; Precancerous Conditions; RNA, Messenger; Tissue Culture Techniques; Toll-Like Receptor 4; Up-Regulation; Young Adult

The aim of this study was to find disease-associated genes and gene functions in esophageal squamous cell carcinoma (ESCC) with DNA microarrays. We downloaded the gene expression profile GSE20347 from the Gene Expression Omnibus database including 17 ESCC and 17 matched normal adjacent tissue samples. Compared with normal samples, the probe level data were pre-processed and the differentially expressed genes (DEGs) were identified (FDR <0.05, and |logFC|>2) with packages in R language. The selected DEGs were further analyzed with bioinformatic methods. After an interaction network of DEGs was constructed by STRING, we selected the most important hub gene through network topological analysis (including node degree, clustering coefficient and path length) and analyzed functions and pathways of the hub gene network. A total of 538 genes were filtered as DEGs between normal and disease samples, and we selected the gene TSPO as the most important hub gene. Among its interactors, the CTSK gene and the IL8 gene participated in the toll-like receptor signaling pathway which is closely related to tumor occurrence. The TSPO gene and its interactors may affect the cancer-specific gene expression by participating in the toll-like receptor signaling pathway. Our discovery may be useful in investigating the complex interacting mechanisms underlying the disease. However, further experiments are still needed to confirm our result.

Topics: Carcinoma, Squamous Cell; Cathepsin K; Computational Biology; Databases, Nucleic Acid; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Humans; Interleukin-8; Oligonucleotide Array Sequence Analysis; Protein Interaction Maps; Receptors, GABA; Signal Transduction

Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Survival; Chemokine CXCL1; Chemokines, CXC; Esophageal Neoplasms; Humans; Interleukin-8; Neoplasm Metastasis; Neovascularization, Pathologic; Receptors, Interleukin-8; Receptors, Interleukin-8B

Interleukin-6 (IL-6) has been associated with disease progression and poor prognosis in esophageal carcinoma. The aim of this study was to investigate the possible influence of IL-6 on the biological activities of esophageal carcinoma cells in terms of invasiveness. The human esophageal carcinoma cell line, KYSE170, was transfected with a plasmid vector expressing IL-6, and a stable transfectant overexpressing IL-6 was established. Invasiveness was evaluated by an invasion assay and compared between IL-6 and control transfectants. The invasiveness of the IL-6 transfectant was significantly higher than that of the control transfectant, and was significantly reduced by IL-6-specific siRNA. In reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, IL-8 expression was significantly higher in the IL-6 transfectant than in the control transfectant, whereas the expression of Hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF) was not different. IL-8 expression in the IL-6 transfectant was significantly inhibited by IL-8-specific siRNA, whereas IL-6 expression was not. In addition, the invasiveness of the IL-6 transfectant was significantly reduced by IL-8-specific siRNA. These results indicate that the overexpression of IL-6 increases the invasiveness of KYSE170 esophageal carcinoma cells and IL-6-induced IL-8 plays a predominant role in increasing invasiveness.

Topics: Blotting, Western; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Gene Transfer Techniques; Genetic Vectors; Hepatocyte Growth Factor; Humans; Interleukin-6; Interleukin-8; Neoplasm Invasiveness; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

CXCL-8, known as proinflammatory cytokine interleukin (IL)-8, and its receptor, CXCR-2, are expressed in various cancer cells. CXCL-8/CXCR-2 network is believed to be involved in angiogenesis, growth, and invasion of tumor cells. To date, the clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we investigated the role of CXCL- 8/CXCR-2 network in ESCC.. The subjects included 78 patients with primary ESCC. We examined CXCL-8 and CXCR-2 expression in surgically resected specimens using immunohistochemistry. The association between CXCL-8/CXCR-2 expression and level of preoperative serum cytokines, C-reactive protein (CRP), coagulation factors, clinicopathologic background factors, and survival of ESCC patients was assessed.. Thirty-seven (47%) and 36 (46%) patients were positive for CXCL-8 and CXCR-2 expression, respectively. Both CXCL-8 and CXCR-2 were expressed in 26 patients (33%). We compared the results of these 26 patients [CXCL-8(+)/CXCR-2(+) group] with those of the other group (n = 52). The depth of invasion (pT factor; P < .001), lymph node metastasis (pN factor; P = .001), pathologic stage (P < .001), lymphatic invasion (P = .010), and venous invasion (P = .001) were significantly more advanced in the CXCL-8(+)/CXCR-2(+) group compared with the other group. Preoperative IL-6, IL-8, CRP, fibrin/fibrinogen degradation product, and fibrinogen levels in the CXCL-8(+)/CXCR-2(+) group were also significantly higher than those in the other group (P = .046, .009, .029, .010, and <.001, respectively). The CXCL-8(+)/CXCR-2(+) group also showed a significantly lower recurrence-free survival (RFS; P < .001) and disease-specific survival (P = .008). As per Cox's hazards model, CXCL-8/CXCR-2 expression (hazard ratio, 2.89; P = .008) was independent predictive factor for RFS.. Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression, metastasis, higher preoperative levels of proinflammatory cytokines, CRP, activation of exogenous coagulation factors, and poor prognosis in ESCC patients. These results indicate that overexpression of both CXCL-8 and CXCR-2 may be a useful marker for predicting the outcome in ESCC patients, and more important, has potential in becoming a critical diagnostic marker for selection of appropriate treatments.

Topics: Aged; Carcinoma, Squamous Cell; Cytokines; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Prognosis; Receptors, Interleukin-8B

Adiponectin, an adipocyte-derived hormone with anti-inflammatory and antitumor activity, inhibits esophageal adenocarcinoma (EAC) cell proliferation and induces apoptosis. Chronic inflammation is a key process involved in initiation and progression of EAC, but the roles and mechanisms of adiponectin in inflammation have not been fully understood in EAC. We aimed to analyze the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on inflammatory factors' expression and explore the roles of ROS/NF-κB signaling pathway in adiponectin-regulated inflammation in EAC cells. It was found that f-Ad and g-Ad differently regulated both mRNA and protein levels of TNF-α, IL-8, and IL-6 in a dose-dependent manner in OE19 cells. g-Ad apparently induced TNF-α, IL-8, and IL-6 production, which was inhibited by PDTC or NAC, and increased intracellular ROS levels and NF-κB p65 activation, whereas f-Ad significantly suppressed production of inflammatory factors and NF-κB p65 activation and also decreased the intracellular ROS levels. In conclusion, the study demonstrated that g-Ad exerts a proinflammatory effect whereas f-Ad appears to induce an anti-inflammatory effect in a ROS/NF-κB-dependent manner in OE19 cells.

Topics: Adenocarcinoma; Adiponectin; Cell Line, Tumor; Esophageal Neoplasms; Humans; Inflammation; Interleukin-6; Interleukin-8; NF-kappa B; Reactive Oxygen Species; Recombinant Proteins; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha

Esophageal cancer is the seventh leading cause of cancer death in males in USA, and there is a strong link has been demonstrated between inflammation and esophageal cancer, interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p-p38 MAPK.. Malignant esophageal tissue and blood samples were obtained from 65 operated untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression visualized by immunohistochemistry, Real time RT-PCR for IL-32 mRNA expression, NF-κB phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-α, IL-1β, IL-6 and IL-8) concentration in the patient's sera.. IL-32 expression was increased in immunohistochemical staining for malignant esophageal tissue and it's correlated with the relative expression level of IL-32 mRNA P=0.007, the P-NF-κB level elevated in tumor tissue compared with control and no difference in the total NF-κB level P=0.003 while the IL-32 up-regulated the P-pNF-κB in the esophageal tumor P=0.005. There is increase in p-p38MAPK activation underlying IL-32 expression in tumor P=0.004, but no change in total p38 MAPK in malignant esophagus. The plasma level of IL-32 expression was increased in malignant esophageal patients P=0.01, with increased in the levels of the cytokines TNF-α, IL-6, and IL-1βP<0.05.. Understanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-κB and up-regulation of p-p38MAPK may or may not prove to be a therapeutic target, or a biomarker, and future studies will finally answer this hypothesis generated.

Topics: Aged; Esophageal Neoplasms; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Male; MAP Kinase Signaling System; Middle Aged; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; RNA, Messenger; Tumor Necrosis Factor-alpha

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

Topics: Adult; Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Neoplasm Staging; Postoperative Complications; Respiratory Distress Syndrome; Thoracotomy

The nematode Spirocerca lupi (S. lupi) induces sarcoma in the dog oesophagus in about 25% of cases. The aim of this study was to compare the differences in the cytokine milieu between dogs with neoplastic (n=29) and non-neoplastic disease (n=49) and age- and gender-matched healthy controls (n=25). We measured IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, GM-CSF and MCP-1 in a specific canine multiplex immunoassay kit. Cytokine concentrations were compared between the different groups using the Kruskal-Wallis test followed by Dunn's test. Only IL-8 and IL-18 showed significant differences in their plasma concentration among the three groups. Kruskal-Wallis test revealed a significant (p=0.001) difference in IL-8 concentration between the neoplastic group (634pg/ml), the non-neoplastic (429 pg/ml) and the control groups (150 pg/ml). Post-test analysis revealed a significance difference between the two S. lupi groups and the control group (p<0.01). The highest IL-18 concentration was found in the non-neoplastic group (53 pg/ml), followed by the control group (46 pg/ml) and finally the neoplastic group (33 pg/ml). IL-18 concentrations were significantly higher in the non-neoplastic group than in the neoplastic group (p=0.05). The increased IL-8 in the spirocercosis groups is consistent with the neutrophilic infiltrate in spirocercosis lesions and in those of other inflammatory-induced neoplasias such as Barret's oesophagus and Helicobacter gastritis. IL-18 showed negative regulatory effect in several worm infections and it is possible that it plays the same role in spirocercosis, allowing the worm to evade the host response and to induce neoplastic transformation.

Topics: Animals; Biomarkers; Cytokines; Dog Diseases; Dogs; Esophageal Neoplasms; Female; Interleukin-18; Interleukin-8; Male; Sarcoma; Spirurida Infections; Thelazioidea

The development of Barrett's esophagus and its progression to adenocarcinoma are clearly linked to reflux of acid and bile. Our objective in this study was to develop an optimized ex vivo biopsy culture technique to study the molecular signaling events induced after insult with individual refluxate constituents. We illustrate the utility of this method by showing results for NF-kB centered cell signaling, and compare the results with those obtained from esophageal cell lines. We show that upregulation of the two NF-kB target genes show differences in pH preference, with IL-8 being preferentially upregulated by DCA at neutral pH, and IkB being upregulated by neutral DCA, acidic DCA, and acid alone. This was found to be true in both cell lines and biopsy cultures. The maximum responses were noted in both models when mixed reflux (DCA at pH 6) was utilized, perhaps reflecting the pH preference of DCA (pKa 6.2). Both the optimized ex vivo models, and the in vitro cell lines show that bile and acid are capable of inducing NF-kB dependent gene expression, with some interesting differences in preferred transcriptional target. In conclusion, in both cells and cultured biopsies, similar reflux driven gene expression changes were noted, with maximum effects noted with DCA exposures at pH 6.

Topics: Adenocarcinoma; Barrett Esophagus; Cell Line, Tumor; Cholagogues and Choleretics; Deoxycholic Acid; Esophageal Neoplasms; Gene Expression; Humans; Hydrogen-Ion Concentration; I-kappa B Proteins; In Vitro Techniques; Interleukin-8; NF-kappa B p50 Subunit; Signal Transduction; Up-Regulation

The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms.. Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression.. We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods.. PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001).. This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Endostatins; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Esophagectomy; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Prognosis; Receptor, PAR-1; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

The present study compared the ability of different berry types to prevent chemically-induced tumorigenesis in the rat esophagus. We also determined if berries influence the levels of inflammatory cytokines in the serum of carcinogen-treated rats.. Rats were treated with the carcinogen N-nitrosomethylbenzylamine (NMBA) for 5 weeks, then placed on diets containing 5% of either black or red raspberries, strawberries, blueberries, noni, açaí or wolfberry until the end of the study. The effects of the berries on tumor incidence, multiplicity and size were determined, as well as their effects on the levels of selected inflammatory cytokines in serum.. All berry types were about equally effective in inhibiting NMBA-induced tumorigenesis in the rat esophagus. They also reduced the levels of the serum cytokines, interleukin 5 (IL-5) and GRO/KC, the rat homologue for human interleukin-8 (IL-8), and this was associated with increased serum antioxidant capacity.. Seven berry types were about equally capable of inhibiting tumor progression in the rat esophagus in spite of known differences in levels of anthocyanins and ellagitannins. Serum levels of IL-5 and GRO/KC (IL-8) may be predictive of the inhibitory effect of chemopreventive agents on rat esophageal carcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Body Weight; Chemoprevention; Dimethylnitrosamine; Eating; Esophageal Neoplasms; Fruit; Humans; Interleukin-5; Interleukin-8; Male; Phytotherapy; Rats; Rats, Sprague-Dawley

Chemokines influence tumor progression through regulation of leukocyte chemotaxis, angiogenesis, and metastasis. In this study, the regulated expression of angiogenic (stromal cell-derived factor [SDF]-1/CXCL12 and interleukin [IL]-8/CXCL8) and angiostatic (platelet factor [PF]-4var/CXCL4L1 and inducible protein [IP-10]/CXCL10) chemokines was examined in human colorectal and esophageal cancer. In HCT 116 and HCT-8 colorectal adenocarcinoma cells, the production of IL-8 immunoreactivity was up-regulated by IL-1beta, tumor necrosis factor (TNF)-alpha, the toll-like receptor (TLR) ligands double-stranded RNA and peptidoglycan and phorbol ester. Increased PF-4 and synergistic IL-8 and IP-10 induction in carcinoma cells after stimulation with IL-1beta plus TNF-alpha or interferon-gamma was demonstrated by enzyme-linked immunosorbent assay, quantitative reverse transcriptase polymerase chain reaction, or immunocytochemistry. In addition, IL-8 from HT-29 colorectal adenocarcinoma cells was molecularly identified as intact chemokine, as well as NH(2)-terminally truncated, more active IL-8(6-77). The presence of PF-4var, SDF-1, and vascular endothelial growth factor (VEGF) was evidenced by immunohistochemistry in surgical samples from 51 patients operated on for colon adenocarcinoma (AC), esophageal AC, or esophageal squamous cell carcinoma (SCC). PF-4var was strongly detected in colorectal cancer, whereas its expression in esophageal cancer was rather weak. Staining for SDF-1 was almost negative in esophageal SCC, whereas a more intense and frequent staining was observed in AC of the esophagus and colon. Staining for VEGF was moderately to strongly positive in all 3 types of cancer, although less prominent in esophageal AC. The heterogenous expression of angiogenic (IL-8, SDF-1) as well as angiostatic (IP-10, PF-4var) chemokines not only within the tumor and between the different cases but also between the different tumor cell types may indicate a distinct role of the various chemokines in the complex process of tumor development.

Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemokine CXCL12; Colon; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagus; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Mucous Membrane; Neovascularization, Pathologic; Platelet Factor 4; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A

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

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

Esophagogastric cancers have high recurrence rates with lymph nodes being a common pattern. Pre-treatment anemia has been reported an independent prognostic factor of treatment failure regardless of treatment strategy, particularly associated with poor locoregional control. A causative relationship between anemia - tumor hypoxia - tumor aggressiveness mediated by angiogenesis up-regulation is advocated, yet remains controversial.. To determine whether and how the pre-treatment anemia is associa-ted with various aspects of disease aggressiveness and to evaluate the possible involvement of angiogenesis mediators.. In 111 esophagogastric cancer patients we investigated the association of pre-treatment hemoglobin concentration and anemia presence with cancer-related, patients-related features and laboratory parameters including angiogenic factors: vascular endothelial growth factors A and C, interleukin-8 and midkine. Serum levels of angiogenic factors were assessed with immunoenzymatic tests.. Histology, disease stage, regional metastasis and dissemination in general, malnutrition and angiogenesis represented by midkine were found to correlate with anemia presence and hemoglobin concentration, while tumor extension, patient's age and sex accounted only for anemia presence. A tendency towards hemoglobin correlation with VEGF-A and Il-8 was also observed. Midkine, tumor histology and malnutrition were found to exert an independent effect on pre-treatment hemoglobin concentration and anemia presence in esophagogastric cancer patients. Hemoglobin level of 12 g/dL was found an optimal cut-off value for discrimination between localized and disseminated cancers.. Even a mild pre-treatment anemia is associated with cancers metastasizing especially to regional lymph nodes, which seems to be mediated by some of studied angiogenic factors.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Angiogenesis Inducing Agents; Cytokines; Esophageal Neoplasms; Female; Hemoglobins; Humans; Interleukin-8; Lymphatic Metastasis; Male; Middle Aged; Midkine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C

The presence of lymph node metastasis (LNM) is an important factor in clinical evaluation of esophageal cancer patients. Biological markers able to support detection of metastatic lymph nodes are sought after. Interleukin-8 (IL-8) is overexpressed by many cancers and involved in cancer dissemination. We investigated the relationship between circulating IL-8 and clinicopathological features of esophageal squamous cell carcinoma (ESCC), and evaluated the diagnostic potential of IL-8, with reference to the key angiogenic and lymphangiogenic factors: vascular endothelial growth factors A and C (VEGF-A and VEGF-C). We found elevated IL-8 levels in ESCC patients, correlated with tumor size and cancer dissemination, especially LNM. Circulating IL-8 correlated with lymphangiogenic VEGF-C rather then angiogenic VEGF-A. The association weakened in metastatic cancers, suggesting divergent mechanism of IL-8 involvement in the dissemination process. The cytokine levels correlated with platelets and neutrophils, pointing at these cells as possible sources of circulating IL-8. We demonstrated IL-8 that positively correlated with inflammation status of ESCC patients. Circulating IL-8 was a better indicator of ESCC dissemination than VEGF-A or VEGF-C. Yet, the detection rates were not satisfactory enough to allow for the recommendation of IL-8 determination as an adjunct to the clinical evaluation of lymph node involvement in ESCC patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Interleukin-8; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C

Surgery remains the only curative therapy for esophageal cancer. The objective of the current study was to evaluate the impact of laparoscopic transhiatal esophagectomy versus open transhiatal esophagectomy on both inflammatory and immunological responses.. Seventeen patients undergoing laparoscopic or open surgery were included in the study. The postoperative inflammatory response was assessed by measuring WBC count and CRP, IL-6, IL-8, soluble TNF I and II receptor, and elastase levels. The postoperative immune function was assessed by measuring the monocyte HLA-DR expression. LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) were measured to evaluate bacterial translocation.. The IL-6 level increased significantly more in the patients who received open surgery as compared with the laparoscopic group. Both LBP and BPI increased predominantly in the laparoscopic group as compared with the group who received open surgery. No difference was found in HLA-DR expression between the two groups.. Although both laparoscopic and conventional esophageal resections result in an activation of the inflammatory response, this study suggests that this response could be less pronounced after the laparoscopic approach. However, in the laparoscopic group higher LBP and BPI levels were seen, suggesting an increased endotoxemia. We postulate that the persistently elevated abdominal pressure results in a loss of mucosal barrier function, resulting in bacterial translocation. The cellular acidification of the cells of the peritoneum induced by CO(2) insufflation, however, blunts the expected inflammatory response.

Topics: Acute-Phase Proteins; Adenocarcinoma; Antimicrobial Cationic Peptides; Bacterial Translocation; Blood Proteins; C-Reactive Protein; Carcinoma, Squamous Cell; Carrier Proteins; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; HLA-DR Antigens; Humans; Interleukin-6; Interleukin-8; Laparoscopy; Leukocyte Count; Male; Membrane Glycoproteins; Middle Aged; Pancreatic Elastase; Receptors, Tumor Necrosis Factor

To determine if immunohistochemistry (IHC) could be used to monitor nuclear factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre-malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa. The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA and protein levels were assessed in oesophageal tissues.. IHC was employed using an antibody against the nuclear localisation sequence (NLS) of the p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function, changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were also assessed in the histological sequence using real-time PCR. More global expression changes were also studied using membrane arrays.. IHC was effective at monitoring overall NF-kappaB activity and IL-8 abundance. This method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in specific cell types. There were significant increases in nuclear NF-kappaB activity and IL-8 abundance across the histological series. Gene expression analysis also showed consistent up-regulation of IL-8, confirming the IHC data and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF-kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues. Down-regulation of I-kappaB gene expression may partly explain increased NF-kappaB activity.. IHC, using antibodies against the NLS of p65, may be useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is amenable to high-throughput screening (whereas traditional electrophoretic mobility shift assay methods are not), this may lead to the development of a better screening tool for early cancer risk.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Carrier Proteins; Disease Progression; Esophageal Neoplasms; Humans; Interleukin-8; NF-kappa B; Polymerase Chain Reaction; Precancerous Conditions; Transcription Factor RelA; Up-Regulation

Chronic inflammation of esophageal mucosa secondary to refluxed gastric juice increases gene expression of interleukin 8 (IL-8). Antireflux surgery can reduce this overexpression.. Prospective analysis of archival paraffin-embedded tissue.. Academic tertiary medical center.. One hundred eight patients with reflux symptoms were classified according to pH monitoring and endoscopic and histologic findings. Twenty patients did not have reflux or mucosal injury; 47 had reflux disease (16 esophagitis and 31 Barrett's esophagus), 20 had dysplasia, and 21 had adenocarcinoma. Microdissection was performed to exclude inflammatory cells and stromal tissue. After RNA isolation and reverse transcription, IL-8 messenger RNA expression was measured using quantitative real-time polymerase chain reaction. All patients with reflux disease had Nissen fundoplication with biopsies at matched levels within the esophagus preoperation and postoperation.. Expression of IL-8 was increased in patients with reflux compared with those without reflux. Patients with the highest IL-8 expression were those with Barrett's dysplasia and adenocarcinoma (P<.001). In patients with reflux, Nissen fundoplication led to significantly decreased IL-8 expression compared with preoperative levels in esophagitis (P = .01) and Barrett's esophagus (P = .03).. Interleukin 8 messenger RNA expression increases during the progression of reflux disease from normal squamous mucosa to esophageal adenocarcinoma. Elimination of reflux with Nissen fundoplication significantly reduces IL-8 expression in both squamous and Barrett's mucosa. These results demonstrate that effective antireflux surgery can modulate the gene expression of esophageal mucosa and may impact the natural history of reflux disease.

Topics: Adenocarcinoma; Barrett Esophagus; Case-Control Studies; Esophageal Neoplasms; Esophagectomy; Esophagitis, Peptic; Fundoplication; Gastroesophageal Reflux; Humans; Interleukin-8; RNA, Messenger

To study the changes of serum interleukin-2 (IL-2), interleukin-8 (IL-8) and immunoglobulin (IgG, IgA, IgM) in patients with esophageal cancer, and to probe the relationship between the levels of IL-2, IL-8, IgG, IgA and IgM and the progress of cancer.. The serum levels of IL-2 and IL-8 were detected by enzyme-linked immunosorbent assay for 72 case of primary esophageal cancer, 68 advanced esophageal cancer and 120 healthy controls, and the level of immunoglobulin (IgG, IgA, IgM) in patients with esophageal cancer was dynamically observed.. The IL-2 level in patients with early esophageal cancer [(1.69 +/- 0.53) ng/ml] or late esophageal cancer [(1.11 +/- 0.60) ng/ml] was lower than the control group [(2.78 +/- 0.51) ng/ml] (P < 0.01), the late esophageal cancer group was lower than early esophageal cancer group (P < 0.05). The level of IL-8 in patients with early esophageal cancer [(85.48 +/- 6.14) ng/L] or late esophageal cancer [(121.41 +/- 6.22) ng/L] was much higher than the control group [(54.48 +/- 12.20) ng/L] (P < 0.01), the late esophageal cancer group was much higher than early esophageal cancer group (P < 0.01); There was correlation between the levels of IL-2 and IL-8 and the worsen-extent of the tumour in patients with early esophageal cancer or late esophageal cancer. But the level of IgG [(12.23 +/- 2.50) g/L], IgM [(1.60 +/- 0.80) g/L] in the patients with esophageal cancer compared with the level of IgG [(11.65 +/- 3.70) g/L], IgM [(1.46 +/- 0.71) g/L] in the health control group have no significant difference (P > 0.05), the level of IgA [(3.50 +/- 1.10) g/L] in patients with esophageal cancer Compared with the control group [(1.88 +/- 1.08) g/L] has significant difference (P < 0.01), and along with the worsen-extent of the tumor in patients the level of IgA has the increased tendency.. The IL-8 might accelerate the pathogenesis of esophageal cancer, and the IL-2 might restrain. The positive correlation between the level of IgA and the patients with esophageal cancer is observed in this study; the immune maladjustment of IL-2, IL-8 and IgA might be correlative to esophageal cancer, and the IL-2, IL-8 and IgA levels might be an available index for the severity of esophageal cancer, Which may be of some help for clinic practitioners to judge the progress, curative effect and prognosis of the cancer.

Topics: Adult; Aged; Case-Control Studies; Esophageal Neoplasms; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Interleukin-2; Interleukin-8; Male; Middle Aged; Neoplasm Staging

The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood.. To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB.. Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay.. Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative.. The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Biopsy; Electrophoresis; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagitis; Female; Gastroesophageal Reflux; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; Male; Metaplasia; Middle Aged; NF-kappa B; Precancerous Conditions; Prospective Studies

The objectives of this study were: 1) to examine the expression of macrophage migration inhibitory factor (MIF) in esophageal squamous cell carcinoma (ESCC); 2) to see if a relationship exists between MIF expression, clinicopathologic features, and long-term prognosis; and 3) to ascertain the possible biologic function of MIF in angiogenesis.. MIF has been linked to fundamental processes such as those controlling cell proliferation, cell survival, angiogenesis, and tumor progression. Its role in ESCC, and the correlation of MIF expression and tumor pathologic features in patients, has not been elucidated.. The expression of MIF in tumor and nontumor tissues was examined by immunohistochemical staining. Concentrations of MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in patients' sera and in the supernatant of tumor cells culture were examined by ELISA. Correlations with clinicopathologic factors were made.. In 72 patients with ESCC, intracellular MIF was overexpressed in esophagectomy specimens. The expression of MIF correlated with both tumor differentiation and lymph node status. The median survival in the low-MIF expression group (<50% positively stained cancer cells on immunohistochemistry) and high expression group (>/=50% positively stained cancer cells) was 28.3 months and 15.8 months, respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7% and 12.1%, respectively. MIF expression was related to microvessel density; increased MIF serum levels also correlated with higher serum levels of VEGF. In addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose-dependent increase in VEGF and IL-8 secretion.. These results demonstrate, for the first time, that human esophageal carcinomas express and secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve as an autocrine factor in angiogenesis and thus play an important role in the pathogenesis of ESCC.

Topics: Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Squamous Cell; Cohort Studies; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunohistochemistry; Interleukin-8; Lymph Nodes; Macrophage Migration-Inhibitory Factors; Male; Neoplasm Staging; Probability; Prognosis; Proportional Hazards Models; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Treatment Outcome; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Esophageal adenocarcinoma is increasing in incidence; it relates to chronic gastroesophageal reflux, it is difficult to cure, and treatment modalities increasingly use chemotherapy and radiation therapy prior to resectional surgery. Nuclear factor-kappa B (NF-kappaB) is a pleiotropic transcription factor that regulates several genes for cytokines and enzymes involved in inflammation and immunity, and we have previously described sequential expression of NF-kappaB from the normal esophagus through Barrett's metaplasia to adenocarcinoma. The aim of this exploratory study was to assess the NF-kappaB status and cytokine profiles pre- and post-chemoradiotherapy for esophageal adenocarcinoma. Fresh biopsy specimens obtained from 20 patients with esophageal adenocarcinoma and normal adjacent squamous epithelium were obtained pre-, during and post-chemoradiotherapy, and NF-kappaB expression was analyzed by electrophoretic mobility shift assay. The cytokine protein content of interleukin-1 beta (IL-1beta) and interleukin-8 (IL-8) of tissue homogenates was measured using the ELISA technique. NF-kappaB was constitutively activated in tumor tissues from esophageal adenocarcinoma but was not detected in adjacent normal esophageal mucosa. Elevated levels of IL-1beta and IL-8 were significantly (P < 0.05) higher in tumor tissues compared to control tissues. Patients with a major or complete pathological response (responders) were associated with absence of activated NF-kappaB from nuclear extracts after treatment. Moreover, IL-1beta and IL-8 levels were significantly (P < 0.05) down-regulated in tumor tissues from patients who demonstrated a complete pathological response. No differences in NF-kappaB, IL-1beta and IL-8 levels were detected pre- and post-treatment in patients who did not have a major or complete pathological response (non-responders). The study suggests that monitoring of molecular and cytokine patterns in patients undergoing this neoadjuvant regimen may help subselect the cohort that derives most benefit from the multimodal approach.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Cisplatin; Down-Regulation; Epithelium; Esophageal Neoplasms; Esophagectomy; Esophagus; Female; Fluorouracil; Humans; Interleukin-1; Interleukin-8; Male; Neoadjuvant Therapy; NF-kappa B; Radiotherapy Dosage; Radiotherapy, Adjuvant; Remission Induction

Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features and the role of HGF in ESCC.. One hundred and forty-nine patients with ESCC were studied. Pretherapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8). The function of HGF was shown by invasion chamber assay.. Pretherapy serum HGF was found to be significantly higher in patients with ESCC than in control subjects. The levels of HGF correlated significantly with advanced tumor metastasis stage and survival. Multivariate analyses showed that serum HGF level in cell migration was an independent prognostic factor. Increased HGF serum levels correlated positively with serum levels of VEGF and IL-8. Our results also showed that HGF was overexpressed in ESCC tissues and cell lines. In vitro study showed that HGF could stimulate ESCC cell to express VEGF and IL-8 and markedly enhance invasion and migration of ESCC cells. Furthermore, HGF-induced IL-8 and VEGF expression was dependent on extracellular signal-regulated kinase signaling pathways. The inhibition of extracellular signal-regulated kinase activation reduced HGF-mediated IL-8 and VEGF expression.. Our results suggest that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC. HGF may be involved in the progression of ESCC as an autocrine/paracrine factor via enhancing angiogenesis and tumor cell invasion and migration.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Movement; Disease Progression; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagus; Female; Hepatocyte Growth Factor; Humans; Interleukin-8; Male; MAP Kinase Signaling System; Neovascularization, Pathologic; Prognosis; Proto-Oncogene Proteins c-met; Vascular Endothelial Growth Factor A

To examine the changes in blood-soluble phospholipase A(2)-IIA levels caused by surgical stress and postoperative infections.. We retrospectively analyzed a prospective database of 40 patients who underwent esophagectomy for esophageal cancer. Nine of these patients had a postoperative infection (E Inf(+) group), and 31 did not have a postoperative infection (E Inf(-) group). The blood sPLA(2)-IIA level was measured using a radioimmunoassay, and whole blood was stimulated with lipopolysaccharide (LPS) to examine the sPLA(2)-IIA production.. In the E Inf(-) group, the blood sPLA(2)-IIA levels peaked on postoperative day (POD) 3 then decreased gradually thereafter. Receiver-operator characteristic statistics based on the sPLA(2)-IIA values on POD 5, which are used to classify postoperative infectious complications, revealed an area under the curve of 0.789. However, stimulation of peripheral blood cells with LPS did not induce the production of sPLA(2)-IIA.. During the early postoperative phase, blood sPLA(2)-IIA levels increase according to the surgical stress. Soluble PLA(2)-IIA may be produced at the site of infection or in the liver, but not in the circulating blood. Sustained elevation of the serum sPLA(2)-IIA level, observed even after POD 3, seems to represent a response to postoperative infection.

Topics: Biomarkers; Colonic Neoplasms; Esophageal Neoplasms; Esophagectomy; Female; Group II Phospholipases A2; Humans; Infections; Interleukin-6; Interleukin-8; Male; Middle Aged; Phospholipases A; Phospholipases A2; Postoperative Complications; Radioimmunoassay; ROC Curve; Stress, Physiological

Barrett's oesophagus patients accumulate chromosomal defects during the histological progression to cancer, one of the most prominent of which is the amplification of the whole of chromosome 4. We aimed to study the role that the transcription factor NF-kappaB, a candidate cancer- promoting gene, present on chromosome 4, plays in Barrett's oesophagus, using OE33 cells as a model. Specifically, we wanted to determine if NF-kappaB was activated by exposure to bile acid (deoxycholic acid) in oesophageal cells. We employed pathway specific cDNA microarrays and real-time PCR, to first identify bile acid induced genes and specifically to investigate the role of NF-kappaB. An NF-kappaB reporter system was used, as well as an inhibitor of NF-kappaB (pyrrolidine dithiocarbamate) to confirm the activation of NF-kappaB by bile. We show that physiological levels of DCA (100-300 microM) were capable of activating NF-kappaB in OE33 cells and inducing NF-kappaB target gene expression (particularly IkappaB and IL-8). Other gene expression abnormalities were also shown to be induced by DCA. Importantly, preliminary experiments showed that NF-kappaB activation by bile occurred at neutral pH, but not at acid pH. Acidic bile did however cause over-expression of the c-myc oncogene, as reported previously. Hence, we present data showing that NF-kappaB may be a key mediator of carcinogenesis in bile exposed Barrett's tissues. In addition, neutral bile acids appear to play a significant part in reflux induced gene expression changes. We postulate that the activation of the survival factor NF-kappaB by bile may be linked to the previous cytogenetic data from our laboratory showing the amplification of NF-kappaB's chromosome (chromosome 4), during Barrett's cancer progression. Hence chromosome 4 amplification may provide a survival mechanism for bile exposed oesophageal tissues via NF-kappaB.

Topics: Adenocarcinoma; Barrett Esophagus; Deoxycholic Acid; Esophageal Neoplasms; Esophagus; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Proteins; Interleukin-8; NF-kappa B

We previously reported that vascular endothelial growth factor (VEGF) expression correlates with vessel density in human esophageal squamous cell carcinomas. However, tumor angiogenesis is not controlled simply by the presence of VEGF, and is likely regulated by several angiogenic factors produced by tumor and host cells. The goal of the present study was to determine the angiogenic profile of precancerous and cancerous lesions of the esophagus. Expression of mRNAs for VEGF, platelet derived endothelial cell growth factor (PD-ECGF), basic fibroblast growth factor (bFGF), and interleukin (IL)-8 was examined in six esophageal carcinoma cell lines and fresh biopsy specimens from 16 patients with invasive esophageal carcinoma by RT-PCR. Immunohistochemical analyses with antibodies against VEGF, PD-ECGF, bFGF, and IL-8 were performed on archival specimens of 60 normal esophageal mucosa, 11 dysplasias and 49 carcinomas of the esophagus. Microvessels were stained with anti-CD34 antibody and quantified by counting the number of vessels in a x200 field in the most vascularized areas of the tumor. Esophageal carcinoma cell lines and tumor tissues expressed mRNAs for one or more these angiogenic factors at various levels. An initial increase in vessel density and enhanced expression of PD-ECGF and VEGF were observed in dysplastic epithelium. Vessel density was significantly higher in more advanced lesions. bFGF and IL-8 were not expressed in dysplasias and mucosal carcinomas, but expression was increased in late stage squamous cell carcinoma. These findings suggest that the angiogenic switch is a very early event in the development of invasive carcinoma. Several different angiogenic factors produced by tumor cells and host cells may regulate angiogenesis during different steps of esophageal carcinogenesis.

Topics: Base Sequence; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Primers; Esophageal Neoplasms; Fibroblast Growth Factor 2; Humans; Interleukin-8; Neovascularization, Pathologic; Precancerous Conditions; RNA, Messenger; Thymidine Phosphorylase; Vascular Endothelial Growth Factor A

The molecular mechanisms responsible for the progression of malignant transformation in Barrett's esophagus (BE) are still poorly understood. This study was undertaken (1) to investigate the gene and protein expression of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARgamma), interleukin-8 (IL-8), hepatocyte growth factor (HGF), gastrin, and its receptor (CCK-2) in the Barrett's epithelium; (2) to analyze the activity of NFkappaB in Barrett's esophagus with low-grade dysplasia; and (3) to assess the effects of PPARgamma ligand (ciglitazone) and gastrin on cell proliferation in the cell line derived from esophageal adenocarcinoma (OE-33). COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expression levels relative to the control gene encoding GAPDH were analyzed by RT-PCR and Western blot in specimens of BE with low-grade dysplasia (n = 20) and compared with that in the normal squamous esophageal mucosa from the middle portion of the esophagus (n = 20). In vitro experiments included the incubation of cell line OE-33 with ciglitazone (1-15 microM) and gastrin (100 nM). NFkappaB activity in biopsies specimens was measured by highly sensitive ELISA. COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expressions were significantly increased in BE compared with normal squamous esophageal mucosa. NFkappaB activity was significantly upregulated in BE. Ciglitazone inhibited cell proliferation of OE-33 cells as assessed by BrdU and this effect was attenuated partly by gastrin. (1) COX-2, PPARgamma, HGF, gastrin, and its receptor are significantly upregulated in BE, suggesting a possible role for these factors in Barrett's carcinogenesis; (2) the increased NFkappaB activity is probably linked to increased IL-8 and COX-2 expression; and (3) PPARgamma ligands might be useful as a new therapeutic option in the prevention and treatment of Barrett's carcinoma.

Topics: Aged; Aged, 80 and over; Barrett Esophagus; Blotting, Western; Cyclooxygenase Inhibitors; Disease Progression; Esophageal Neoplasms; Female; Gastrins; Hepatocyte Growth Factor; Humans; Hypoglycemic Agents; Interleukin-8; Male; Middle Aged; Mucous Membrane; NF-kappa B; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Thiazolidinediones; Transcription Factors

The population of Linxian in north central China is at high risk for gastric cardia adenocarcinoma (GCC) and esophageal squamous cell carcinoma (ESCC), and chronic inflammation may contribute to this risk. Interleukin-8 (IL8), a potent chemoattractant, has three well-characterized single nucleotide polymorphisms (SNP), one (-251) of which alters transcriptional activity. Four well-described SNPs in the two IL8 receptors, IL8RA and IL8RB, have been associated with inflammation. We conducted a case-cohort study in the Nutrition Intervention Trials (Linxian, China) to assess the association between these SNPs and incident GCC (n = 90) and ESCC (n = 131). IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models. The homozygous variants of IL8 -251 and +396 were associated with 2-fold increased relative risks for GCC, but the highest risk observed was for the AGT/AGC haplotype of IL8 -251/+396/+781 (relative risk, 4.14; 95% confidence interval, 1.31-13.1). Variation within IL8 was not associated with ESCC. Few subjects had variation at the IL8RA SNP and no significant associations were observed for IL8RB SNPs or haplotypes with either GCC or ESCC. We conclude that variation in IL8 seems to increase the risk for GCC but not ESCC in this high-risk population. These variants could confer an altered IL8 expression pattern or interact with environmental factors to increase the risk for inflammation and GCC.

Topics: Adenocarcinoma; Adult; Aged; Cardia; China; Esophageal Neoplasms; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Receptors, Interleukin-8B; Risk Factors; Stomach Neoplasms

To evaluate the role of inducible nitric oxide (NO) synthase (iNOS) and inflammatory cytokines in alveolar macrophages (AMs) after esophagectomy in the pathogenesis of acute lung injury.. Prospective, exploratory, open-labeled clinical study.. Intensive care unit and operating room in a university hospital.. Thirteen patients receiving esophagectomy with carcinoma of the esophagus (postesophagectomy group), ten patients just before the surgery (preoperation group), and seven patents receiving surgery less invasive than esophagectomy (other surgery group) were selected.. Bronchoalveolar lavage fluid (BALF) and blood samples were obtained from study groups.. The AMs in the BALF collected from each group were stained immunohistochemically with antibodies against iNOS, interleukin (IL)-6, and IL-8. The intensities of these expressions were determined by semiquantitative cytofluorometric system. NOx (NO2- + NO3-), IL-6, and IL-8 levels in the BALF and plasma were measured concurrently. The expressional intensities of iNOS, IL-6, and IL-8 in AMs obtained from the postesophagectomy group were maximal 24 hrs after the skin incision and significantly more evident than those from other groups. The IL-6, IL-8, and NOx levels in BALF and IL-6 and IL-8 levels in plasma in the postesophagectomy patients were also elevated. The intensities of iNOS and inflammatory cytokines expressions in AMs were closely related to postoperative respiratory failure.. The activation of topical alveolar macrophages may be involved in the pathogenesis of pulmonary complications in the postoperative period after esophagectomy.

Topics: Aged; Bronchoalveolar Lavage Fluid; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunohistochemistry; Interleukin-6; Interleukin-8; Macrophages, Alveolar; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrous Oxide; Prospective Studies

We investigated whether or not interleukin-8 (IL-8) and granulocyte elastase (GE) can be associated with pulmonary complication after esophagectomy (the most common cause of postoperative death).. We measured serial changes in the IL-8 concentration and GE activity in the plasma and bronchoalveolar lavage fluid (BALF) of 17 patients who had undergone esophagectomy, and examined the relationship between these mediators and postoperative pulmonary complication.. Pulmonary complication occurred in 6 patients (35%, Pneum+ group). Plasma IL-8 increased at the end of the surgery then decreased, but there was no significant difference between the Pneum+ group and the group without pulmonary complication (11[65%], Pneum- group). IL-8 and GE in BALF were significantly higher in the Pneum+ group than in the Pneum- group on days 1 and 3 after the operation. There was a significant and positive correlation between IL-8 and GE in BALF.. Our results indicate that IL-8 and GE in BALF may be useful for the prediction of postoperative pulmonary complication.

Topics: Aged; Bronchoalveolar Lavage Fluid; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-8; Leukocyte Elastase; Lung Diseases; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Predictive Value of Tests

Perioperative increases in the levels of cytokines and polymorphonuclear leukocyte elastase (PMN-E) have been shown to be related to degree of surgical trauma.. We measured the changes in levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and PMN-E in the perioperative period in patients undergoing thoracoscopic esophagectomy (n = 15) and conventional transthoracic esophagectomy (n = 15) for thoracic esophageal cancer.. Both IL-6 and IL-8 increased markedly immediately after transthoracic esophagectomy and thereafter, but only a slight increase was observed after the thoracoscopic procedure (IL-6: p = 0.047; IL-8: p = 0.03). A difference was also seen in the pattern of changes in PMN-E. Levels of PMN-E increased immediately after transthoracic esophagectomy and continued to be high up to the 3rd postoperative day, but they remained low after the thoracoscopic procedure and showed no increase (p

Topics: Cytokines; Esophageal Neoplasms; Esophagectomy; Female; Humans; Interleukin-6; Interleukin-8; Leukocyte Elastase; Leukocytes; Male; Middle Aged; Perioperative Care; Postoperative Period; Thoracoscopy

Proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with major surgery. We investigated the profile of proinflammatory cytokines and the association of cytokine levels with myocardial function after esophagectomy. We studied 12 patients who underwent subtotal esophagectomy. One patient died of multiple organ failure. This patient had the largest interleukin-6 (IL-6) level of all the subjects. IL-6 levels increased from 14.9 +/- 8.7 pg/mL to 498.4 +/- 294.3 pg/mL (P < 0.05) at 6 h postoperatively. Interleukin-8 (IL-8) levels also significantly increased postoperatively. Right ventricular ejection fraction (RVEF) decreased from 44% +/- 1% to 36% +/- 2% (P < 0.05) and 37% +/- 2% (P < 0.05) at 6 h and 12 h postoperatively. Stroke volume index (SVI) decreased significantly at the end of operation and at 6 h and 12 h postoperatively. The changes of RVEF and SVI showed an independent negative correlation with the IL-6 level (r = -0.70, P < 0.001 and r = -0.62, P < 0.001, respectively). In contrast, the change of RVEF and SVI was not correlated with the IL-8 level. Esophagectomy is associated with transient depression of myocardial function. IL-6 may contribute to this postoperative myocardial dysfunction.. We examined the association between myocardial function and proinflammatory cytokines after esophagectomy. Interleukin-6 may be the cytokine that most sensitively reflects the postoperative myocardial dysfunction.

Topics: Carcinoma, Squamous Cell; Epinephrine; Esophageal Neoplasms; Esophagectomy; Female; Hemodynamics; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Norepinephrine; Stroke Volume; Ventricular Dysfunction, Left

Topics: Esophageal Neoplasms; Esophagus; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Postoperative Period