In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer

1991 ◽  
Vol 32 (6) ◽  
pp. 335-341 ◽  
Author(s):  
Yoshinori Nio ◽  
Takahiro Shiraishi ◽  
Michihiko Tsubono ◽  
Hideki Morimoto ◽  
Chen-Chiu Tseng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Blood ◽  
Immunomodulating Effect ◽  
Spleen Lymphocytes

scholarly journals CD137 Agonist Induces Gastric Cancer Cell Apoptosis by Enhancing The Functions of CD8+ T Cells via NF-κB Signaling

2020 ◽  
Author(s):  
Ben-Shun Hu ◽  
Tian Tang ◽  
Tie-Long Wu ◽  
Ying-Yue Sheng ◽  
Yu-Zheng Xue
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
T Cells ◽  
Real Time ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Nuclear Translocation ◽  
Granzyme B ◽  
Ifn Γ

Abstract Background: CD137 is identified as a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis has not been studied yet. Methods: Foxp3+ and CD8+ T cells in GCs were investigated by immunohistochemistry (IHC). CD137 expression in GCs was detected by flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cells proliferation and p65 expression were explored by flow cytometry. p65 nuclear translocation was analyzed by IF. IL-10, TGF-β, IFN-γ, Perforin and Granzyme B were detected by real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with the CD137 agonist in vitro. Apoptosis of the primary GC cells was detected by flow cytometry. Results: Our data demonstrated that GC tumors show characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. CD137 agonist promoted CD8+ T cells proliferation and increased the secretion of IFN-γ, Perforin and Granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that CD137 agonist could induce NF-κB nuclear translocation in CD8+ T cells. Conclusion: Our results demonstrate that CD137 agonist can induce primary GC cell apoptosis by enhancing CD8+ T cells via activating NF-κB signaling.

scholarly journals Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5562
Author(s):  
Juliette Palle ◽  
Laure Hirsch ◽  
Alexandra Lapeyre-Prost ◽  
David Malka ◽  
Morgane Bourhis ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Checkpoint Inhibitors ◽  
Interleukin 10 ◽  
Tube Formation ◽  
Antibody Treatment

Elucidating mechanisms involved in tumor-induced immunosuppression is of great interest since it could help to improve cancer immunotherapy efficacy. Here we show that Hepatocyte Growth Factor (HGF), a pro-tumoral and proangiogenic factor, and its receptor c-Met are involved in regulatory T cells (Treg) accumulation in the peripheral blood of gastric cancer (GC) patients. We observed that c-Met is expressed on circulating monocytes from GC patients. The elevated expression on monocytes is associated with clinical parameters linked to an aggressive disease phenotype and correlates with a worse prognosis. Monocyte-derived dendritic cells from GC patients differentiated in the presence of HGF adopt a regulatory phenotype with a lower expression of co-stimulatory molecules, impaired maturation capacities, and an increased ability to produce interleukin-10 and to induce Treg differentiation in vitro. In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation. Rilotumumab decreased circulating Treg in GC patients. Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.

scholarly journals Level of N6-Methyladenosine in Peripheral Blood RNA: A Novel Predictive Biomarker for Gastric Cancer

2020 ◽  
Vol 66 (2) ◽  
pp. 342-351 ◽  
Author(s):  
Lichen Ge ◽  
Nan Zhang ◽  
Zhuojia Chen ◽  
Jiaxi Song ◽  
Yingmin Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Human Peripheral Blood ◽  
Xenograft Model ◽  
Area Under The Curve ◽  
Predictive Biomarker ◽  
Gastric Disease

Abstract Background Dysregulation of N6-methyladenosine (m6A) is associated with various human diseases including cancer. This study aimed to evaluate the level of m6A as a biomarker for gastric cancer (GC) diagnosis. Methods Peripheral blood samples were collected from 100 GC patients, 30 benign gastric disease (BGD) patients, and 75 healthy controls (HCs). Levels of m6A in total RNA and expression of m6A-related proteins were analyzed. Results The m6A levels in peripheral blood RNA were significantly increased in the GC group compared with those in the BGD or HC groups; moreover, levels increased with the progression and metastasis of GC and decreased in GC patients after surgery. The area under the curve (AUC) for m6A in the GC group was 0.929 (95% CI, 0.88–0.96), which is markedly greater than the AUCs for carcinoembryonic antigen (CEA; 0.694) and carbohydrate antigen 199 (CA199; 0.603). The combination of CEA and CA199 with m6A improved the AUC to 0.955 (95% CI, 0.91–0.98). The expressions of m6A demethylases ALKBH5 and FTO were significantly downregulated in the GC group compared with the HC group. Coculture with GC cells increased the m6A of RNA in promyelocytic (HL-60) and monocytic (THP-1) leukemia cells and nontumorigenic human peripheral blood B lymphocyte cells (PENG-EBV). Furthermore, a xenograft model enhanced the m6A in peripheral blood RNA of mice. Accordingly, expressions of ALKBH5 and FTO were decreased both in vitro and in vivo. Conclusions Level of m6A in peripheral blood RNA is a promising noninvasive diagnostic biomarker for GC patients.

The Effect of Partial Splenectomy on Platelet Production in Mice

1981 ◽  
Vol 46 (03) ◽  
pp. 602-603 ◽  
Author(s):  
H Bessler ◽  
I Notti ◽  
M Djaldetti
Keyword(s):  
Peripheral Blood ◽  
Blood Platelets ◽  
Operative Procedures ◽  
Partial Splenectomy ◽  
Splenic Lymphocytes ◽  
Platelet Production ◽  
Platelet Number ◽  
Spleen Lymphocytes

SummaryThe effect of total and partial splenectomy on the number and production of circulating platelets was studied in mice. Five days after total and partial splenectomy the number of the peripheral blood platelets increased by 87% and 60%, respectively and the incorporation of 75selenium methionine (75Se-Met) into platelets was enhanced indicating that the thrombocytosis was due to increased platelet production. The results obtained by the two operative procedures were compared.Since previous work from our laboratory has shown that a factor produced by splenic lymphocytes affects the platelet number in mice, it is suggested that the differences in the number of circulating platelets observed in animals after total and partial splenectomy may reflect a difference in the number of spleen lymphocytes removed.

Role of vitamin C in gastric cancer

2018 ◽  
Vol 01 (1) ◽  
Author(s):  
Takalkar U Vidyadhar
Keyword(s):  
Gastric Cancer ◽  
Vitamin C ◽  
Gastric Juice ◽  
Oxidative Dna Damage ◽  
Preventive Measure ◽  
Dietary Factors ◽  
Preventive Strategy ◽  
H Pylori

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

Apoptosis and proliferation ofperipheral blood T-cells as alternative processes in pathogenesis of diabetes mellitus type 1

2019 ◽  
Vol 1 (4) ◽  
pp. 16-20 ◽  
Author(s):  
A. V. Lugovaya ◽  
N. M. Kalinina ◽  
V. Ph. Mitreikin ◽  
Yu. P. Kovaltchuk ◽  
A. V. Artyomova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
High Risk ◽  
Peripheral Blood ◽  
Cellular Response ◽  
Proliferative Potential ◽  
Autoreactive T Cells ◽  
Alternative Processes

Apoptosis, along with proliferation, is a form of lymphocyte response to activating stimuli. In the early stages of cell differentiation, the apoptotic response prevails and it results to the formation of tolerance to inductor antigen. Mature lymphocytes proliferate in response to stimulation and it means the initial stage in the development of the immune response. Since in this case apoptosis and proliferation acts as alternative processes, their ratio can serve as a measure of the effectiveness of the cellular response to activating signals. The resistance of autoreactive T-cells to apoptosis is the main key point in the development of type 1 diabetes mellitus (T1DM). Autoreactive T-cells migrates from the bloodstream to the islet tissue of the pancreas and take an active part in b cells destruction. The resistance of autoreactive effector T-cells to apoptosis may suggest their high proliferative potential. Therefore, the comparative evaluation of apoptosis and proliferation of peripheral blood lymphocytes can give a more complete picture of their functional state and thus will help to reveal the causes of ineffective peripheral blood T-ceiis apoptosis in patients with T1DM and will help to understand more deeply the pathogenesis of the disease. in this article, the features of proliferative response of peripheral blood T-cells in patients with T1DM and in individuals with high risk of developing T1DM have been studied. Apoptosis of T-cell subpopulations has been investigated. The correlation between the apoptotic markers and the intensity of spontaneous and activation- induced in vitro T-cells proliferation of was revealed. it was determined, that autoreactive peripheral blood T-cells were resistant to apoptosis and demonstrated the increased proliferative potential in patients with T1DM and in individuals with high risk of developing T1DM.

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