ABSTRACT
Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC-derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium-dependent phospholipid-binding protein, was expressed in a PC cell line (CFPAC-1)-derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC-derived exosomes and its involvement in PC biology.
Subject(s)
Exosomes/metabolism , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Proteome/metabolism , Algorithms , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Chromatography, Liquid , Cohort Studies , Databases, Protein , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Microscopy, Electron, Transmission , Signal Transduction/genetics , Tandem Mass SpectrometryABSTRACT
Several recent studies have found an increased prevalence of non-alcoholic fatty liver disease within psoriasis patients. The exact pathophysiological mechanisms behind these observations are unclear, but are likely related to the high prevalence of obesity and metabolic syndrome within this patient population. Chronic inflammation, mediated by either proinflammatory adipokines or skin-derived cytokines, may contribute to fatty liver disease development by increasing insulin resistance which in turn promotes hepatic lipid accumulation. These same adipokines in addition to hepatic cytokines may act on the skin to influence psoriasis disease severity.
Subject(s)
Fatty Liver/complications , Psoriasis/complications , Adipokines/metabolism , Adult , Fatty Liver/diagnostic imaging , Fatty Liver/metabolism , Female , Humans , Insulin Resistance , Lipid Metabolism , Liver/metabolism , Male , Middle Aged , Psoriasis/metabolism , UltrasonographyABSTRACT
To investigate the role of CpG sequences in anti-DNA induction, immunization experiments were performed in mice to assess the immunogenicity of native Escherichia coli (EC) and calf thymus (CT) in incomplete Freund's adjuvant. The effects of CpG sequences were further tested by comparing the adjuvant properties of a synthetic phosphorothioate oligonucleotide with a CpG motif to one with a GpC sequence. Both EC and CT DNA alone induced a limited anti-DNA response. For CT DNA, the addition of a CpG ODN significantly enhanced responses whereas for EC DNA, the presence of a CpG oligonucleotide (ODN) or control GpC ODN did not increase responses compared to EC DNA alone. Specificity analysis by ELISA indicated that these immunizations led to the generation of cross-reactive anti-DNA autoantibodies. These results thus extend the adjuvant effects of CpG sequences to self antigens and suggest mechanisms by which self and foreign antigens can interact in the generation of autoimmunity.
Subject(s)
Antibodies, Antinuclear/immunology , CpG Islands/immunology , Adjuvants, Immunologic , Animals , Antibody Specificity , Autoimmunity , Cattle , Escherichia coli , Immunization , Mice , Mice, Inbred BALB CSubject(s)
Antibodies, Monoclonal/pharmacology , B-Lymphocytes/immunology , CD4 Antigens/immunology , HLA-DR3 Antigen/immunology , Immunosuppression Therapy/methods , T-Lymphocytes/immunology , Tetanus Toxoid/immunology , Animals , Antibody Formation , CD4 Antigens/genetics , Enzyme-Linked Immunosorbent Assay , Humans , Immunity, Cellular , Immunosuppressive Agents/pharmacology , Mice , Mice, Knockout , Mice, TransgenicABSTRACT
1. Prostaglandin A-, prostaglandin E- and prostaglandin F-like substances were determined radioimmunologically in antral biopsy material obtained by endoscopy. 2. In patients with gastritis, the concentrations of prostaglandin (E+A)-like substances were six times as high and of prostaglandin F-like substances twice as high as in normal subjects. In chronic atrophic gastritis, the concentrations of prostaglandin (E+A)-like material was four times as high as in normal subjects whereas prostaglandin-F like material remained unchanged. In acute gastric ulcer, prostaglandin (E+A)-like material reached concentrations four times times higher than in normal subjects, accompanied by a fivefold increase of prostglandin F-like substances. After healing of the gastric ulcer, prostaglandins returned to normal values. 3. There was no correlation between gastrin and prostaglandins in all biopsy specimens.
Subject(s)
Gastric Mucosa/analysis , Prostaglandins/analysis , Stomach Diseases/metabolism , Adult , Aged , Duodenal Ulcer/metabolism , Female , Gastrins/analysis , Gastritis/metabolism , Humans , Male , Middle Aged , Prostaglandins A/analysis , Prostaglandins E/analysis , Prostaglandins F/analysis , Stomach Ulcer/metabolismABSTRACT
Mature granulocytes from six patients with myelocytic leukemia and monocytic cells from two patients with monocytic leukemia were damaged after incubation with leukocidin from Staphylococcus aureus. The immature granulocytes were not significantly affected. The lymphocytic cells from one patient with lymphocytic leukemia were not markedly damaged. The numbers of erythrocytes from all nine patients remained practically unchanged with lower concentrations of leukocidin.