Clinical significance of changes of TLR4/MyD88/NF-κB signaling pathway in peripheral blood mononuclear cells of gastric cancer patients with Helicobacter pylori infection

Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III–IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies.

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xpression and clinical significance of chemokine receptor in peripheral blood mononuclear cells in patients with primary biliary cirrhosis

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2009.00142 ◽

2009 ◽

Vol 29 (2) ◽

pp. 142-146

Author(s):

Zhi-jun HAN ◽

Chuan-yong WU ◽

Ting-wang JIANG ◽

Yu-jie TANG ◽

Ye ZHOU ◽

...

Keyword(s):

Primary Biliary Cirrhosis ◽

Clinical Significance ◽

Peripheral Blood Mononuclear Cells ◽

Chemokine Receptor ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Biliary Cirrhosis ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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POS0430 EXPRESSION AND CLINICAL SIGNIFICANCE OF AUTOPHAGY-RELATED GENES IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3562 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 443.2-443

Author(s):

Y. F. Qing ◽

J. Zheng ◽

S. B. Wang ◽

F. Dai ◽

Y. Jiang ◽

...

Keyword(s):

Systemic Sclerosis ◽

Clinical Significance ◽

Normal Control ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Beclin 1 ◽

Peripheral Blood Mononuclear ◽

Mesenchymal Transition ◽

Blood Mononuclear Cells

Background:Growing evidences have demonstrated that autophagy is a powerful regulators in the pathogenesis of fibrosis and autoimmune diseases. Autophagy abnormalities in SSc involve abnormal autophagy-related protein and autophagy-related gene polymorphism[1-2], however there is a few reports on the expression and clinical significance of autophagy-related genes.Objectives:To investigate the expression and clinical significance of autophagy-related genes LC-3 mRNA, Becline-1 mRNA, Agt-3 mRNA, Agt-5 mRNA, Agt-12 mRNA and Agt-16L1 mRNA in peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc).Methods:51 cases of SSc and 60 cases of normal control were received from the Affiliated Hospital of North Sichuan Medical College, and autophagy-related genes were detected by RT-PCR. SPSS19.0 statistical software was used to compare the expression of autophagy-related genes between groups and analyze the relationship between autophagy-related genes and clinical data, P<0.05 was considered statistically significantResults:LC-3, Becline-1, and Agt-3 were highly expressed in SSc compared with normal control [LC-3: 0.78(0.60) ×10-3 vs. 0.52(0.54) ×10-3; Beclin-1: 6.68(3.56)×10-3 vs. 5.22(3.54)×10-3; Agt-3: 17.58(12.33)×10-3 vs. 11.00(4.56)×10-3, P<0.05], however Agt-5, Agt-12 and Agt-16L1 of autophagy-related genes were not statistically significant [AGT-5: 6.67(3.58) ×10-3 vs. 6.67(2.64) ×10-3; AGT-12: 8.64(5.56)×10-3 vs. 8.57(4.66)×10-3; Agt-16L1: 2.69(2.19)×10-3 vs. 2.52(2.26)×10-3] (Figure 1). Beclin-1 and Agt-5 high expressed in SSc with the positive of anti-SSA/Ro antibody. LC-3 was positively correlated with Age(r=0.662) and ESR(r=0.355) (all P<0.05).Conclusion:Autophagy-related genes were increased in PBMC of SSc, and were correlated with Age, ESR and autoantibody, suggested that autophagy is a key feature in the pathogenesis of systemic sclerosis.Figure 1.The relative expression of autophagy-related genesReferences:[1]LIU C, ZHOU X, LU J, et al. Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia[J]. Rheumatology, 2019;58(11):1966–1975.[2]Mayes M D, Bossini-Castillo L, Gorlova O, et al. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis[J]. The American Journal of Human Genetics, 2014,94(1):47-61.DOI:10.1016/j.ajhg.2013.12.002.Disclosure of Interests:None declared

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α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05170-6 ◽

2021 ◽

Author(s):

S. Schumann ◽

U. Eberlein ◽

C. Lapa ◽

J. Müller ◽

S. Serfling ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Cancer Patients ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Absorbed Dose ◽

Peripheral Blood Mononuclear ◽

Absorbed Doses ◽

Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

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