Body fat is an important source of adipokine, which is associated with energy balance and inflammatory and immune responses. However, the role of adipokines in coronary artery complications in Kawasaki disease (KD) has not yet been fully explained. We investigated whether serum adipokine level can be a useful marker for patients with KD who are at higher risk of developing coronary artery lesion (CAL). We measured adipokine levels and other inflammatory parameters in 40 patients with KD, 32 febrile controls, and 15 afebrile controls. Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and other laboratory parameters were also measured before and after intravenous immunoglobulin therapy, and in the convalescent phase. At admission, the serum resistin levels in KD children were significantly higher than those in controls (177.56 ng/mL in KD children, 76.48 ng/mL in febrile controls, and 17.95 ng/mL in afebrile controls). In patients with KD, resistin levels were significantly associated with decreased hemoglobin levels (P=0.049) and increased IL-6 levels (P=0.014). The serum IL-6 levels were significantly higher and body mass index was significantly lower in the group of KD with CALs than those without CALs (228.26 ng/mL vs. 39.18 ng/mL and 15.09 vs. 16.60, respectively). In conclusion, resistin is significantly elevated in KD patients, although it has no prognostic value of predicting coronary artery lesion in the acute stage.
Biological Markers/*blood ; Child ; Child, Preschool ; Coronary Vessels/pathology ; Echocardiography ; Female ; Hemoglobins/analysis ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Inflammation/blood/immunology ; Interleukin-6/*blood ; Male ; Mucocutaneous Lymph Node Syndrome/*blood/pathology ; Resistin/*blood ; Tumor Necrosis Factor-alpha/*blood

Dirofilaria immitis (heartworm) infections affect domestic dogs, cats, and various wild mammals with increasing incidence in temperate and tropical areas. More sensitive antibody detection methodologies are required to diagnose asymptomatic dirofilariasis with low worm burdens. Applying current transcriptomic technologies would be useful to discover potential diagnostic markers for D. immitis infection. A filarial homologue of the mammalian translationally controlled tumor protein (TCTP) was initially identified by screening the assembled transcriptome of D. immitis (DiTCTP). A BLAST analysis suggested that the DiTCTP gene shared the highest similarity with TCTP from Loa loa at protein level (97%). A histidine-tagged recombinant DiTCTP protein (rDiTCTP) of 40 kDa expressed in Escherichia coli BL21 (DE3) showed immunoreactivity with serum from a dog experimentally infected with heartworms. Localization studies illustrated the ubiquitous presence of rDiTCTP protein in the lateral hypodermal chords, dorsal hypodermal chord, muscle, intestine, and uterus in female adult worms. Further studies on D. immitis-derived TCTP are warranted to assess whether this filarial protein could be used for a diagnostic purpose.
Animal Structures/chemistry ; Animals ; Antibodies, Helminth/blood ; Antigens, Helminth/chemistry/*genetics/immunology/*isolation & purification ; Cloning, Molecular ; Dirofilaria immitis/chemistry/*genetics/immunology ; Disease Models, Animal ; Dogs ; Escherichia coli/genetics ; Gene Expression ; Molecular Sequence Data ; Molecular Weight ; Recombinant Fusion Proteins/chemistry/genetics/immunology/isolation & purification ; Sequence Analysis, DNA ; Tumor Markers, Biological/chemistry/*genetics/immunology/*isolation & purification

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.
Actins/immunology/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Antibodies/immunology ; Carcinoembryonic Antigen/blood ; Colorectal Neoplasms/*diagnosis/mortality/pathology ; Disease-Free Survival ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/immunology/*metabolism ; Middle Aged ; Neoplasm Staging ; Phenotype ; Prognosis ; S100 Proteins/immunology/*metabolism ; Tumor Markers, Biological/metabolism

Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an uncommon, aggressive, and malignant tumor with a poor patient outcome. Its occurrence in the lesser sac is a rare event and to the best of our knowledge, has not been previously described. The present case was clinically and radiologically misdiagnosed as a pancreatic tumor/gastrointestinal stromal tumor. Histopathology revealed a tumor with "small round cells" that were positive for CD99, confirming the diagnosis of ES/PNET. This report highlights the importance of considering Ewing's sarcoma in the differential diagnosis of intraabdominal, extraintestinal masses.
Antigens, CD/analysis ; Biopsy ; Cell Adhesion Molecules/analysis ; *Diagnostic Errors ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neuroectodermal Tumors, Primitive, Peripheral/*diagnosis/immunology/pathology/therapy ; Pancreatic Neoplasms/*diagnosis ; Peritoneal Neoplasms/*diagnosis/immunology/pathology/therapy ; Predictive Value of Tests ; Sarcoma, Ewing/*diagnosis/immunology/pathology/therapy ; Tomography, X-Ray Computed ; Tumor Markers, Biological/analysis

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.
Adenoviridae ; Antigen Presentation/genetics ; Antigens, Neoplasm/immunology ; Carcinoma/*therapy ; Cell Line, Tumor ; Colorectal Neoplasms/*therapy ; Cytotoxicity, Immunologic/genetics ; Dendritic Cells/immunology ; Humans ; *Immunotherapy, Adoptive ; Interferon-gamma/secretion ; Lymphocyte Activation/genetics ; Proteins/genetics/*metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transduction, Genetic ; Transgenes/genetics ; Tumor Markers, Biological/immunology

In carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA) and diverse carcinoma components showing luminal (ductal) or non-luminal (myoepithelial) differentiation coexist. To elucidate the clinicopathological implications of cellular differentiation in CXPA and the potential role of p53, vascular endothelial growth factor (VEGF), c-erbB-2, c-kit, and glucose transporter 1 (Glut-1) in carcinogenesis, we analyzed 11 CXPAs with luminal differentiation (CXPAs-LD) and 6 CXPAs with non-luminal differentiation (CXPAs-NLD) and compared protein expressions in residual PAs and carcinomas by immunohistochemistry. Among the CXPAs-LD, 5 were invasive and 8 were histologically high-grade tumors. The 5-year survival rate was 72.7%. P53, c-erbB-2, VEGF, and Glut-1 were more immunoreactive in carcinoma components than in PAs (P = 0.008, 0.004, 0.002, and 0.024, respectively); c-erbB-2 overexpression was associated with high histological grade (P = 0.024). Carcinoma components frequently lacked c-kit expression (P = 0.009). CXPAs-NLD were all low-grade and invasive with a larger mean tumor size (5.2 cm) than CXPAs-LD (3.3 cm) (P = 0.040). The patients remained disease-free without significant immunohistochemical expression. The immunoprofiles and clinical course of CXPA differed according to cellular differentiation. Therefore, it is important to report the histological subtype and to assess potential biomarkers in diagnostic and therapeutic trials.
Adenoma, Pleomorphic/*immunology/metabolism/*pathology ; Adult ; Aged ; Carcinoma/*immunology/metabolism/*pathology ; Cell Differentiation ; Female ; Glucose Transport Proteins, Facilitative/metabolism ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism ; Receptor, erbB-2/metabolism ; Salivary Gland Neoplasms/*immunology/metabolism/*pathology ; Tumor Markers, Biological/*analysis ; Tumor Suppressor Protein p53/metabolism ; Vascular Endothelial Growth Factor A/metabolism

The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28< or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.
Adult ; Aged ; Anemia/*blood ; Anti-Bacterial Agents/blood ; Antimicrobial Cationic Peptides/*blood ; Arthritis, Rheumatoid/*blood/immunology/*physiopathology ; Biological Markers/blood ; Female ; Humans ; Interleukin-1beta/blood/immunology ; Interleukin-6/blood/immunology ; Male ; Middle Aged ; Protein Precursors/*blood ; *Severity of Illness Index ; Tumor Necrosis Factor-alpha/blood/immunology

BACKGROUND: Inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6 play an important role in pathophysiology of rheumatoid arthritis (RA). We investigated the possibility whether TNFalpha and IL-6 could be used as an objective marker reflecting treatment response in RA. METHODS: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) together with TNFalpha and IL-6 were measured in 159 specimens obtained from 95 RA patients. RA patients were divided into pre-treatment, methotrexate (MTX) and non-MTX groups by treatment regimen and into inactive and active groups by disease activity. The agreement between changes in marker levels and treatment response, and the correlation between each marker were analyzed. RESULTS: IL-6 was higher in active than in inactive group of patients in all three different treatment subgroups, but TNFalpha was not different between the two groups. IL-6 showed a better agreement with treatment response (MTX group, K=0.58; non-MTX group, K=0.21) than ESR or CRP, whereas TNFalpha did not show an agreement with treatment response. IL-6 was correlated with both ESR (r=0.22) and CRP (r=0.54), but TNFalpha was correlated only with ESR (r=0.21). CONCLUSIONS: Unlike TNFalpha, IL-6 reflects disease activity of RA and shows a better agreement with treatment response than ESR or CRP, indicating that it has an association with clinical features of RA. Therefore IL-6 could be used as an additional marker in the evaluation of treatment response when markers like ESR or CRP show results discordant from clinical features.
Adult ; Arthritis, Rheumatoid/diagnosis/*drug therapy/immunology ; Biological Markers/blood ; Blood Sedimentation ; C-Reactive Protein/analysis ; Female ; Humans ; Interleukin-6/*blood ; Methotrexate/therapeutic use ; Middle Aged ; Rheumatoid Factor/blood ; Tumor Necrosis Factor-alpha/*blood

Carcinosarcoma of the esophagus is a rare malignancy accounting for approximately 1-2% of all esophageal neoplasms. It presents as a bulky intraluminal polypoid lesion mainly in the mid to lower esophagus, which harbors both carcinomatous and sarcomatous components histologically. It often presents relatively early because of its rapid intraluminal growth. We report the case of a 69-year-old man who had suffered from dysphagia for 1 month. He was previously admitted to the hospital due to corrosive esophagitis caused by ingestion of acetic acid. Endoscopy and radiological studies revealed a bulky polypoid mass with superficial ulcerations and mucosal friability, measuring 10 cm in length approximately, in the mid-esophagus. Subtotal esophagectomy with esophagogastrostomy was done. Microscopically it was composed of sarcomatous component intermingled with squamous cell carcinoma. Immunohistochemical stains reveal cytokeratin, 34betaE12, and p63 positivity in the nests of carcinoma, and desmin and vimentin positivity in the spindle cells of sarcomatous stoma.
Aged ; Carcinosarcoma/*diagnosis/pathology/surgery ; Esophageal Neoplasms/*diagnosis/pathology/surgery ; Esophagectomy ; Esophagitis/chemically induced ; Humans ; Male ; Tomography, X-Ray Computed ; Tumor Markers, Biological/immunology

BACKGROUND: The aberrant, leukemia-associated antigen expression patterns allow us to discriminate leukemic blasts from normal precursor cells. Our major goal was to determine a guideline for the detection of minimal residual disease using CD20+/CD34+ and myeloid Ag+/CD19+ combination in the bone marrow of acute leukemia in complete remission (CR) after chemotherapy. METHODS: Bone marrow samples from 117 patients with acute leukemia in complete remission after chemotherapy and from 22 healthy controls were immunophenotyped by triple staining and measured by flow cytometry. RESULTS: The CD20+/CD34+ cells in the large lymphocyte gate (R1) ranged from 0% to 3.24% (0.8+/-0.82%, P=0.000) in CD20+/CD34+ B-lineage ALL CR (N=31), from 0.03% to 4.2% (0.7+/-0.83%, P=0.000) in CD20-/CD34- B-lineage ALL CR (N=66), from 0.1% to 0.96% (0.45+/-0.32%, P=0.016) in T-ALL CR (N=10), and from 0.02% to 0.48% (0.18+/-0.15%, P=0.776) in AML CR (N=10). The CD13,33+/CD19+ cells in R1 gate ranged from 0% to 2.69% (0.37+/-0.48%, P<0.001) in CD13,33+/CD19+ B-lineage ALL CR (N=31), from 0% to 1.8% (0.31+/-0.28%, P<0.001) in CD13,33-/CD19+B-lineage ALL CR (N=65), from 0.02% to 0.64% (0.29+/-0.22%, P=0.071) in T-ALL CR (N=9), and from 0% to 0.17% (0.07+/-0.09%, P=0.341) in AML CR (N=3). CONCLUSIONS: Using an immunophenotypic method for the detection of early relapse or minimal residual disease of B-lineage ALL bone marrow in CR after chemotherapy, different cutoff values should be applied according to antigen combination and gating. When the proportion of aberrant antigen combination was less than 5% in large lymphocyte gate, the results should be interpreted with caution.
Acute Disease ; Antigens, CD/*metabolism ; Antigens, CD19/metabolism ; Antigens, CD20/metabolism ; Antigens, CD34/metabolism ; Antigens, Differentiation, Myelomonocytic/analysis/metabolism ; Bone Marrow Cells/*classification/metabolism ; Flow Cytometry ; Hematopoietic Stem Cells/classification/metabolism ; Humans ; Immunophenotyping ; Leukemia/*diagnosis/drug therapy ; Leukemia, Myeloid, Acute/diagnosis/drug therapy ; Neoplasm, Residual ; Remission Induction ; Tumor Markers, Biological/immunology