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https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#1
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28418921/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#2
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418913/accumulation-of-myeloid-derived-suppressor-cells-mdscs-induced-by-low-levels-of-il-6-correlates-with-poor-prognosis-in-bladder-cancer
#3
Guoliang Yang, Wenyan Shen, Yan Zhang, Mengyao Liu, Lianhua Zhang, Qiang Liu, Hui Hui Lu, Juanjie Bo
Bladder cancer (BC) is one of the most commonly occurring cancers, with a high recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here, we analyzed the markers and significance of myeloid-derived suppressor cells (MDSCs) for BC development and progression. MDSC markers were examined in peripheral blood from 113 BC patients and 20 healthy volunteers. We identified CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC patients. We also demonstrated that MDSC numbers are higher in BC patients than healthy donors, and that MDSC numbers correlate with the clinical grade, stage, and poor prognosis...
March 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417112/lectin-type-oxidized-ldl-receptor-1-distinguishes-population-of-human-polymorphonuclear-myeloid-derived-suppressor-cells-in-cancer-patients
#4
Thomas Condamine, George A Dominguez, Je-In Youn, Andrew V Kossenkov, Sridevi Mony, Kevin Alicea-Torres, Evgenii Tcyganov, Ayumi Hashimoto, Yulia Nefedova, Cindy Lin, Simona Partlova, Alfred Garfall, Dan T Vogl, Xiaowei Xu, Stella C Knight, George Malietzis, Gui Han Lee, Evgeniy Eruslanov, Steven M Albelda, Xianwei Wang, Jawahar L Mehta, Meenakshi Bewtra, Anil Rustgi, Neil Hockstein, Robert Witt, Gregory Masters, Brian Nam, Denis Smirnov, Manuel A Sepulveda, Dmitry I Gabrilovich
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses in cancer and have been directly implicated in promotion of tumor progression. However, the heterogeneity of these cells and lack of distinct markers hampers the progress in understanding of the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation we determined that low density PMN-MDSC and high density neutrophils from the same cancer patients had a distinct gene profile...
August 2016: Science Immunology
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#5
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412745/neutrophil-count-is-associated-with-myeloid-derived-suppressor-cell-level-and-presents-prognostic-value-of-for-hepatocellular-carcinoma-patients
#6
Xing Li, Yan-Fang Xing, Ai-Hua Lei, Qiang Xiao, Zhi-Huan Lin, Ying-Fen Hong, Xiang-Yuan Wu, Jie Zhou
Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC)...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411578/differential-effects-of-low-dose-fludarabine-or-5-fluorouracil-on-the-tumor-growth-and-myeloid-derived-immunosuppression-status-of-tumor-bearing-mice
#7
Manuchehr Abedi-Valugerdi, Wenyi Zheng, Fadwa Benkessou, Ying Zhao, Moustapha Hassan
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a key role in the suppression of the innate and adaptive immunity. Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to reduce the tumor size by depleting MDSCs. Here, we asked whether the purine analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma model, we demonstrated that in mice with advanced tumors (where MDSC-induced suppression was present), treatment with a single low-dose Flu (25, 50, 100mg/kg) elevated the numbers of splenic MDSCs and serum arginase activity, and simultaneously, increased the tumor growth (only the highest dose)...
April 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28400539/mass-cytometry-deep-phenotyping-of-human-mononuclear-phagocytes-and-myeloid-derived-suppressor-cells-from-human-blood-and-bone-marrow
#8
Mikael Roussel, P Brent Ferrell, Allison R Greenplate, Faustine Lhomme, Simon Le Gallou, Kirsten E Diggins, Douglas B Johnson, Jonathan M Irish
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274...
April 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28382931/monocytic-and-granulocytic-myeloid-derived-suppressor-cells-differentially-regulate-spatiotemporal-tumour-plasticity-during-metastatic-cascade
#9
Maria Ouzounova, Eunmi Lee, Raziye Piranlioglu, Abdeljabar El Andaloussi, Ravindra Kolhe, Mehmet F Demirci, Daniela Marasco, Iskander Asm, Ahmed Chadli, Khaled A Hassan, Muthusamy Thangaraju, Gang Zhou, Ali S Arbab, John K Cowell, Hasan Korkaya
It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype...
April 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28381543/setd1b-activates-inos-expression-in-myeloid-derived-suppressor-cells
#10
Priscilla S Redd, Mohammed Ibrahim, John D Klement, Sarah K Sharman, Amy V Paschall, Dafeng Yang, Asha Nayak-Kapoor, Kebin Liu
Inducible nitric oxide synthase (iNOS) generates nitric oxide (NO) in myeloid cells that acts as a defense mechanism to suppress invading microorganisms or neoplastic cells. In tumor-bearing mice, elevated iNOS expression is a hallmark of myeloid-derived suppressor cells (MDSC). MDSCs use NO to nitrate both the T cell receptor and STAT1, thus inhibiting T cell activation and the anti-tumor immune response. The molecular mechanisms underlying iNOS expression and regulation in tumor-induced MDSCs are unknown...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28378599/liposomal-microparticle-injection-can-induce-myeloid-derived-suppressor-cells-mdsc-like-cells-in-vivo
#11
Hiroshi Azuma, Yoichiro Yoshida, Hironori Takahashi, Emi Ishibazawa, Hiroya Kobayashi, Hiromi Sakai, Daisuke Takahashi, Mitsuhiro Fujihara
CONTEXT: Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that function as immunosuppressive cells in various pathological conditions. Membrane-derived microvesicles are thought to be involved in MDSC induction. Earlier reports have described that injection of considerable amount of liposome into rat can suppress Con A-induced splenic T-cell proliferation. Liposome-internalized cells expressing CD11b/c suppress T-cell proliferation. Nitric oxide (NO) appears to be involved in the suppression...
April 5, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28372154/effect-of-salt-on-the-glass-transition-of-condensed-tapioca-starch-systems
#12
Lillian Chuang, Naksit Panyoyai, Robert A Shanks, Stefan Kasapis
This work examines the effect of including hydrated NaCl and CaCl2 (up to 6% w/w) on the physicochemical properties of condensed tapioca starch. Samples were prepared by hot pressing at 120°C to produce condensed systems that covered a range of moisture contents from 7.34% w/w (23% relative humidity) to 19.52% w/w (75% relative humidity). Tensile storage modulus and heat flow measurements were taken using DMA and MDSC, which were accompanied by FTIR, WAXD and ESEM. Increasing the salt level enhances the mechanical strength of starch in the glassy state and shifts the glass transition temperature to a higher value...
August 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28364000/anti-pd-l1-efficacy-can-be-enhanced-by-inhibition-of-myeloid-derived-suppressor-cells-with-a-selective-inhibitor-of-pi3k%C3%AE-%C3%AE
#13
Ruth J Davis, Ellen C Moore, Paul E Clavijo, Jay Friedman, Harrison A Cash, Zhong Chen, Christopher Silvin, Carter Van Waes, Clint T Allen
Checkpoint inhibitors are relatively inefficacious in head and neck cancers, despite an abundance of genetic alterations and a T cell-inflamed phenotype. One significant barrier to efficacy may be the recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment. Here we demonstrate functional inhibition of MDSC with IPI-145, an inhibitor of PI3Kδ and PI3Kγ isoforms which enhances responses to PD-L1 blockade. Combination therapy induced CD8+ T lymphocyte-dependent primary tumor growth delay and prolonged survival only in T cell-inflamed tumor models of head and neck cancers...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28356386/the-granulocyte-progenitor-stage-is-a-key-target-of-irf8-mediated-regulation-of-myeloid-derived-suppressor-cell-production
#14
Colleen S Netherby, Michelle N Messmer, Lauren Burkard-Mandel, Sean Colligan, Austin Miller, Eduardo Cortes Gomez, Jianmin Wang, Michael J Nemeth, Scott I Abrams
Alterations in myelopoiesis are common across various tumor types, resulting in immature populations termed myeloid-derived suppressor cells (MDSCs). MDSC burden correlates with poorer clinical outcomes, credited to their ability to suppress antitumor immunity. MDSCs consist of two major subsets, monocytic and polymorphonuclear (PMN). Intriguingly, the latter subset predominates in many patients and tumor models, although the mechanisms favoring PMN-MDSC responses remain poorly understood. Ordinarily, lineage-restricted transcription factors regulate myelopoiesis that collectively dictate cell fate...
March 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28352304/myeloid-derived-suppressor-cells-and-myeloid-regulatory-cells-in-cancer-and-autoimmune-disorders
#15
Prince Amoah Barnie, Pan Zhang, Hongxiang Lv, Dan Wang, Xiaolian Su, Zhaoliang Su, Huaxi Xu
Myeloid-derived suppressor cells (MDSCs) were originally described as a heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts. In recent years, increasing number of studies have described various populations of myeloid cells with MDSC-like properties in murine models of cancer and autoimmune diseases. These studies have observed that the populations of MDSCs are increased during inflammation and autoimmune conditions. In addition, MDSCs can effectively suppress T cell responses and modulate the activity of natural killer cells and other myeloid cells...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#16
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344880/protective-function-of-interleukin-27-in-colitis-associated-cancer-via-suppression-of-inflammatory-cytokines-in-intestinal-epithelial-cells
#17
Bijun Cui, Shen Lu, Lihua Lai, Yiwei Xie, Jia He, Yue Xue, Peng Xiao, Ting Pan, Luoquan Chen, Yang Liu, Xuetao Cao, Qingqing Wang
Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344866/cd13-hi-neutrophil-like-myeloid-derived-suppressor-cells-exert-immune-suppression-through-arginase-1-expression-in-pancreatic-ductal-adenocarcinoma
#18
Jing Zhang, Xiongfei Xu, Min Shi, Ying Chen, Danghui Yu, Chenyan Zhao, Yan Gu, Biao Yang, Shiwei Guo, Guiling Ding, Gang Jin, Chin-Lee Wu, Minghua Zhu
Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28338007/human-immunodeficiency-virus-type-1-myeloid-derived-suppressor-cells-inhibit-cytomegalovirus-inflammation-through-interleukin-27-and-b7-h4
#19
Ankita Garg, Rodney Trout, Stephen A Spector
HIV/CMV co-infected persons despite prolonged viral suppression often experience persistent immune activation, have an increased frequency of myeloid derived suppressor cells (MDSC) and are at increased risk for cardiovascular disease. We examined how HIV MDSC control CD4(+) T cell IFNγ response to a CMVpp65 peptide pool (CMVpp65). We show that HIV/CMV co-infected persons with virologic suppression and recovered CD4(+) T cells compared to HIV(-)/CMV(+) controls exhibit an increase in CD4(+)CX3CR1(+)IFNγ(+) cells in response to CMVpp65; MDSC depletion further augmented CD4(+)CX3CR1(+)IFNγ(+) cells and IFNγ production...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337051/a-novel-cd48-based-analysis-of-sepsis-induced-mouse-myeloid-derived-suppressor-cell-compartments
#20
Bei Jia, Chenchen Zhao, Guoli Li, Yaxian Kong, Yaluan Ma, Qiuping Wang, Beibei Wang, Hui Zeng
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells that expands dramatically in many disease states and can suppress T-cell responses. MDSCs mainly include monocytic and granulocytic subpopulations that can be distinguished in mice by the expression of Ly6G and Ly6C cell surface markers. This identification system has been validated in experimental tumor models, but not in models of inflammation-associated conditions such as sepsis. We challenged growth factor independent 1 transcription repressor green fluorescent protein (Gfi1:GFP) knock-in reporter mice with cecal ligation and puncture surgery and found that CD11b(+)Ly6G(low)Ly6C(high) MDSCs in this sepsis model comprised both monocytic and granulocytic MDSCs...
2017: Mediators of Inflammation
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