Correlation of VEGF with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Hirokazu Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Vascular Permeability Factor ◽  
Reactive Protein ◽  
Cell Mediated Immune Response ◽  
Immunosuppressive Cells

582 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Vascular endothelial growth factor (VEGF), previously known as vascular permeability factor. 45 kDa protein, belongs to a family of platelet-derived growth factors. VEGF, inflammation-related protein, could contribute to the accumulation of immunosuppressive cells (MDSC, Treg, TAM, and Tie-2-expressingmonocytes) in tumor-bearing hosts through direct or indirect mechanisms. Methods: We tested the serum levels of VEGF by ELISA in 106 patients including 43 with gastric and 63 with colorectal cancer, and they were increased in advanced stages of gastric and colorectal cancer. Production of IL-17, pro-inflammatory cytokine, with a stimulation of PHA was measured by ELISA and MDSC (myeloid-derived suppressor cells), one of major immunosuppressing cells, was measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and SI (stimulation index) of blastogenic response of lymphocytes were used as markers of cell-mediated immune response. Results: The concentrations of VEGF were positively correlated with levels of MDSC, production of IL-17, NLR and CRP, and were inversely correlated with IL-12 production, SI and nutritional markers including prealbumin and retinol binding protein. The patients were both divided into two groups with a serum level of VEGF (330 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer were both significantly worse in patients with high levels of VEGF than in those with low VEGF although the differences were not significant in patients with stagesⅠand II. Conclusions: The results of the present study suggested that VEGF may have an impact on advancement and progression involving inflammation and serve as useful markers of the immune suppression involving MDSC, malnutrition and poor prognosis in patients with gastric and colorectal cancer.

Correlation of IL-17 with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 83-83 ◽  
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Daisuke Ujiie ◽  
Mai Ashizawa ◽  
Tomohiro Kikuchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Retinol Binding Protein ◽  
Reactive Protein ◽  
Th 17 ◽  
Cell Mediated Immune Response ◽  
Inflammatory Processes ◽  
Advanced Stages

83 Background: Although a causal relationship linking inflammation and cancer immunity is more widely accepted today, precise cell mechanisms mediating this relationship have not been elucidated. IL-17, a pro-inflammatory cytokine primarily secreted by T helper (Th)17 cells, has previously been associated with inflammatory processes in autoimmune disease. The presence of IL-17 and Th17 cells has been confirmed in various invasive cancers and recently linked to immunosuppression in cancer patients. We investigated systemic inflammation, immune suppression, malnutrition, and prognosis associated with IL-17 in patients with gastric and colorectal cancer. Methods: We measured IL-17 in 106 patients, including 43 with gastric and 63 with colorectal cancer, Production of IL-17 stimulated by PHA was measured by ELISA. MDSC (myeloid-derived suppressor cells), which significantly contribute to immunosuppression, were measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and the SI (stimulation index) of lymphocytes’ blastogenic response were used as markers of cell-mediated immune response. Results: Production of IL-17 increased in advanced stages of gastric and colorectal cancer. IL-17 positively correlated with levels of MDSC, serum concentrations of VEGF, NLR, and levels of CRP, and was inversely correlated with IL-12 production, SI, and nutritional markers including prealbumin and retinol binding protein. Patient cohorts were divided into two groups with IL-17 level (540 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer both significantly worse in patients with high production of IL-17 than in those with low IL-17, although the differences were not significant in patients at stages I and II. Conclusions: The present study suggests that IL-17 may reflect an inflammatory impact on the advancement and progression of cancer, and it may serve as useful marker of immune suppression involving MDSC, malnutrition, and poor prognosis in patients with gastric and colorectal cancer.

scholarly journals IL-17 and VEGF are increased and correlated to systemic inflammation, immune suppression, and malnutrition in patients with breast cancer

2017 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Kazunoshin Tachibana ◽  
Masahiko Shibata ◽  
Kenji Gonda ◽  
Yoshiko Matsumoto ◽  
Takahiro Nakajima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Function ◽  
Systemic Inflammation ◽  
Immune Suppression ◽  
Stimulation Index ◽  
Suppressor Cells ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Cell Mediated Immunity ◽  
The Status

Relationships between inflammation and innate immunity in cancer are widely accepted today; however, the precise cell mechanisms mediating these relationships have not yet been elucidated. Interleukin (IL)-17 is a proinflammatory cytokine that has been reported to induce inflammation in patients with autoimmune diseases. Myeloid-derived suppressor cells (MDSC) may contribute to the negative regulation of immune responses during cancer and inflammation. Vascular endothelial growth factor (VEGF) is reported to have multiple biological actions including increasing vascular permeability, neovascularization, and possible inhibition of immune function in malignant diseases. This study investigated the status of systemic inflammation and immune suppression associated with IL-17 and VEGF in patients with breast cancer. IL-17 production and the serum levels of VEGF were also increased in advanced stages of the disease. The production of IL-12, which induces Th1 cells, and the stimulation index (SI), which is a marker of cell-mediated immune function, were both shown to decrease along with disease advancement. Also, the production of IL-17 and the VEGF levels were both positively correlated with the levels of MDSC, the neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and were inversely correlated with IL-12 production and the SI. Nutritional markers, including prealbumin (PA), transferrin (TF), and retinol-binding protein (RBP), were also shown to be significantly lower in patients with high production of IL-17 or high levels of VEGF. These data clearly showed that IL-17 and VEGF, whose levels correlated with each other and with those of MDSC, were significantly associated with disease advancement, systemic inflammation, suppression of cell-mediated immunity including Th1 induction, and malnutrition.

Correlation of production of IL-17 with immune suppression relating myeloid-derived suppressor cells (MDSC) and nutritional damages in patients with digestive system cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 437-437
Author(s):  
Kenji Gonda ◽  
Masahiko Shibata ◽  
Takashi Yazawa ◽  
Rei Yashima ◽  
Takashi Kimura ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Immune Suppression ◽  
Th17 Cells ◽  
Digestive System ◽  
Suppressor Cells ◽  
Digestive Cancer ◽  
Cellular Mechanisms ◽  
Neutrophil Lymphocyte Ratio ◽  
Cell Mediated Immune Response ◽  
Inflammatory Bowel

437 Background: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cellular mechanisms mediating this relationship remain unclear. Th17 cells, which produce the proinflammatory cytokine IL-17, have been recognized as one of the key factors in regulation of inflammatory bowel disease and rheumatoid arthritis. Methods: This study demonstrated that, in patients with digestive system cancers including 7 patients with esophageal, 14 with gastric, 20 with colorectal, 5 with hepatocellular, 7 with cholangiocellular, and 7 with pancreatic carcinomas, IL-17 production was correlated with MDSC level and with markers for nutritional impairment, immune suppression and chronic inflammation. Results: IL-17 production was significantly higher in patients with all types of digestive cancer than in normal volunteers. In addition, IL-17 production levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio, and significantly inversely correlated with cell mediated immune response indicators (lymphocyte PHA-blastogenesis and IL-12 production) and patients’ nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. Conclusions: These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism for disease progression through enhancement of immune suppression or cachexia. Controlling activation of Th17 cells may prove to be a valuable strategy for treatment of patients with gastrointestinal cancer.

scholarly journals Assessment of Serum Levels of the Adipocytokine Chemerin in Colorectal Cancer Patients

2018 ◽  
Vol 37 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Manal M. Alkady ◽  
Phebe L. Abdel-Messeih ◽  
Neveen M. Nosseir
Keyword(s):  
Colorectal Cancer ◽  
Characteristic Curve ◽  
Serum Levels ◽  
Tumor Stage ◽  
Carbohydrate Antigen ◽  
Cancer Cell Growth ◽  
Reactive Protein ◽  
Stage Progression ◽  
Embryonic Antigen ◽  
Colorectal Cancer Patients

Summary Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment is very important for determining cancer cell growth and spreading. Chemerin, a newly identified adipokine secreted by adipose tissue, is known to be associated with obesity, metabolic syndrome, and insulin resistance. The present study was carried out to investigate the association between serum levels of chemerin and colorectal cancer. Thirty-two patients with colorectal cancer aged 57.6±6.5 years, and twenty age, sex and BMI matched healthy controls were included in the study. Serum che me rin levels were determined using enzyme linked immuno sorbent assay. C-reactive protein (CRP) levels were determined using a turbidimetric immunoassay. Carcino embryonic antigen (CEA) and carbohydrate antigen (CA 19-9) were measured by radioimmunoassay. Chemerin levels were found to be significantly higher in patients relative to the controls (P<0.001) and gradually increased with the TNM tumor stage progression. The mean CRP, CEA and CA 19-9 levels were also significantly higher in patients (P<0.001). There was a significant correlation between the serum levels of chemerin and the other measured parameters in CRC patients. The area under receiver operating characteristic curve (ROC) for serum chemerin was 1 at a cut-off value ≥ 161.5 with 100% sensitivity and 100% specificity. Conclusions: The observed results suggest that chemerin may have a potential role in the pathogenesis and progression of colorectal malignancy and may be a good biomarker of colorectal cancer and stage progression.

scholarly journals The Association of Simultaneous Increase in Interleukin-6, C Reactive Protein, and Matrix Metalloproteinase-9 Serum Levels with Increasing Stages of Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ismar Rasic ◽  
Velma Rebic ◽  
Azra Rasic ◽  
Goran Aksamija ◽  
Svjetlana Radovic
Keyword(s):  
Colorectal Cancer ◽  
Matrix Metalloproteinase ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Colorectal Carcinogenesis ◽  
Simultaneous Increase ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Metalloproteinase 9

Background. Tumor development and growth are driven in many cases by inflammatory cells, which can produce cytokines and other factors that can stimulate the development of the malignant process. The aim of this study was to evaluate interleukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), serum levels in patients with colorectal cancer (CRC), and their association with the stage of CRC. Methods. IL-6, MMP-9, and CRP serum levels were measured in 75 patients with CRC just before surgical treatment, as well as in 20 healthy individuals as controls. Surgically obtained tissue material was subjected to pathological analysis. Results. Significant increase in CRP and IL-6 serum concentration is associated with increasing stage of CRC (p <0.05), where MMP-9 serum level was significantly higher in stages III and IV compared to the stage II CRC. Significant correlation was found between IL-6 and MMP-9 serum levels (rho=0.478; p <0.001) as well as between IL-6 and CRP serum levels (rho=0.720; p <0.001) and between MMP-9 and CRP serum levels (rho=0.379; p <0.001). Serum levels of MMP-9 and CRP have been shown to be independent predictors of the CRC stage. Conclusion. Combined quantification of IL-6, MMP-9, and CRP serum levels seems to be a reliable index of inflammation-related processes during colorectal carcinogenesis.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document