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forkhead box p3 and indoleamine 2,3-dioxygenase co-expression in pakistani triple negative breast cancer patients

World Journal of Clinical Oncology 2020年第12期11卷 1018-1028页

作者： Kashif Asghar Asif Loya Iftikhar Ali Rana Muhammad Abu Bakar Asim Farooq Muhammad Tahseen Muhammad Ishaq Iqra Masood Muhammad Usman Rashid Department of Basic Science Research Shaukat Khanum Memorial Cancer Hospital and Research CentreLahorePunjab 54000Pakistan Department of pathology Shaukat Khanum Memorial Cancer Hospital and Research CentreLahorePunjab 54000Pakistan Department of Cancer Registry and Clinical Data Management Shaukat Khanum Memorial Cancer Hospital and Research CentreLahorePunjab 54000Pakistan Department of Clinical Research Shaukat Khanum Memorial Cancer Hospital and Research CentreLahorePunjab 54000Pakistan

BACKGROUND forkhead box p3(FOXp3)is a specific marker for immunosuppressive regulatory T(T-reg)cells.T-regs and an immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO),are associated with advanced disease in *** To evaluate the co-expression of FOXp3 and IDO in triple negative breast cancer(TNBC)with respect to hormone-positive breast cancer patients from *** Immunohistochemistry was performed to analyze the expression of FOXp3,IDO,estrogen receptor,progesterone receptor,and human epidermal growth factor receptor on tissues of breast cancer patients(n=100):Hormone-positive breast cancer(n=51)and TNBC(n=49).A total of 100 patients were characterized as FOXp3 negative vs positive and further categorized based on low,medium,and high IDO expression *** and multivariate logistic regression models were *** Out of 100 breast tumors,25%expressed FOXp3 positive T-regs.A significant coexpression of FOXp3 and IDO was observed among patients with TNBC(p=0.01)compared to those with hormone-positive breast *** variables were identified as significant independent risk factors for FOXp3 positive:IDO expression high(adjusted odds ratio(AOR)5.90;95%confidence interval(CI):1.22-28.64;p=0.03)and TNBC(AOR 2.80;95%CI:0.96-7.95;p=0.05).CONCLUSION Our data showed that FOXp3 positive cells might be associated with high expression of IDO in TNBC ***3 and IDO co-expression may also suggest its involvement in disease,and evaluation of FOXp3 and IDO expression in TNBC patients may offer a new therapeutic option.

关键词： forkhead box p3 Indoleamine 2,3-dioxygenase Triple negative breast cancer T-regs Immunotherapy Cancer

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protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats

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Chinese Journal of Integrative Medicine 2018年第4期24卷 278-283页

作者： SHEN Hong-bo HUO Ze-jun BAI Yun-jing HE Xiao-juan LI Chang-hong ZHAO Yu-kun GUO Qing-qing Department of Traditional Chinese Medicine Peking University Third Hospital Division of Rheumatology PLA Army General Hospital Institute of Basic Research in Clinical Medicine Academy of Chinese Medical Sciences Division of Rheumatology Peking University Third Hospital

Objective： To observe the effect of norcantharidin（NCTD） on collagen-induced arthritis（CIA） rats. Methods： Sixty Sprague-Dawley（SD） rats were randomly divided into 6 groups（n=10）： normal group, CIA model group（model group）, NCTD low-dose group [1.35 mg/（kg·d）], NCTD middle-dose group [2.7 mg/（kg·d）], NCTD high-dose group [5.4 mg/（kg·d）] and methotrexate（MTX） group [1.8 mg/（kg/w）]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin（H＆E） staining. The serum levels of interleukin（IL） 1β, IL-6, tumor necrosis factor（TNF）-α, vascular endothelial growth factor（VEGF）, IL-17 and transform growth factor（TGF） β were detected by enzyme linked immunosorbent assay（ELISA）. The mRNA expression of retinoid-related orphan nuclear receptor γ t（ROR γ t） and forkhead box p3（Foxp3） in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. Results： MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats＇ ankle joints compared with the model group（p〈0.05 or p〈0.01）. All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats（p〈0.05）. Only middle-and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats（p〈0.05）. However, NCTD has no effect on vascular endothelial growth factor（VEGF） level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group（p〈0.05）. The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group（p〈0.05）. Conclusion： NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.

关键词： norcantharidin collagen-induced arthritis cytokine Th17/Treg forkhead box p3 retinoid related orphan nuclear receptor γt

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CD4^(+)CD25^(+)but not CD4^(+)Foxp3^(+) T cells as a regulatory subset in primary biliary cirrhosis

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Cellular & Molecular Immunology 2010年第6期7卷 485-490页

作者： Dandan Wang Huayong Zhang Jun Liang Zhifeng Gu Qiang Zhou Xiangshan Fan Yayi Hou Lingyun Sun Department of Immunology and Rheumatology The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina Department of pathology The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina Immunology Laboratory Nanjing University Medical SchoolNanjingJiangsuChina

Increasing evidence indicates a role for regulatory T cells(Tregs)in the immune response and in autoimmune diseases,but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial,especially in patients with primary biliary cirrhosis(pBC).This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of pBC *** found that these patients demonstrated a reduction of CD4^(+)CD25^(+) T cells but elevated CD4^(+)Foxp3^(+) T cells in peripheral blood mononuclear cells(pBMCs)and CD41 T *** percentage of CD4^(+)CD25^(+) T cells in pBMCs was negatively correlated with elevated plasma interferon(IFN)-c levels.A liver-specific analysis showed that the frequency of Foxp31 Tregs,transforming growth factor(TGF)-b1 and IFN-c were increased in pBC *** findings suggest that an imbalance between CD4^(+)CD25^(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of pBC while the role of Foxp3 needs further investigation.

关键词： cytokines forkhead box p3 primary biliary cirrhosis regulatory T cells

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