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https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-pro-tumorigenic-actions-via-neutrophil-elastase
#1
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer (PCa) and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here it is reported that granulocytic myeloid-derived suppressor cells (MDSCs) are the predominant tumor infiltrating cells in PCa xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28509406/high-heparin-content-surface-modified-polyurethane-discs-promote-rapid-and-stable-angiogenesis-in-full-thickness-skin-defects-through-vegf-immobilization
#2
M McLuckie, C A Schmidt, A Oosthuysen, N Sanchez-Macedo, H Merker, D Bezuidenhout, S P Hoerstrup, N Lindenblatt
Three-dimensional scaffolds have the capacity to serve as an architectural framework to guide and promote tissue regeneration. Parameters such as the type of material, growth factors, and pore dimensions are therefore critical in the scaffold's success. In this study, heparin has been covalently bound to the surface of macroporous polyurethane (PU) discs via two different loading methods in order to determine if the amount of heparin content had an influence on the therapeutic affinity loading and release of (VEGF165 ) in full thickness skin defects...
May 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28507805/generation-and-functional-characterization-of-mdsc-like-cells
#3
Annkristin Heine, Stefanie Andrea Erika Held, Jonas Schulte-Schrepping, Julia Friederike Andrea Wolff, Kathrin Klee, Thomas Ulas, Niklas Arndt Schmacke, Solveig Nora Daecke, Kati Riethausen, Joachim L Schultze, Peter Brossart
Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14(+)HLA-DR(low)phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28498847/paradoxical-myeloid-derived-suppressor-cell-reduction-in-the-bone-marrow-of-siv-chronically-infected-macaques
#4
Yongjun Sui, Blake Frey, Yichuan Wang, Rolf Billeskov, Shweta Kulkarni, Katherine McKinnon, Tracy Rourke, Linda Fritts, Christopher J Miller, Jay A Berzofsky
Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral immune responses, are expanded in the peripheral blood and tissues of patients/animals with cancer or viral infectious diseases. We here show that in chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin-CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated with SIV/AIDS disease progression...
May 12, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28492541/glycolysis-regulates-the-expansion-of-myeloid-derived-suppressor-cells-in-tumor-bearing-hosts-through-prevention-of-ros-mediated-apoptosis
#5
Shiou-Ling Jian, Wei-Wei Chen, Yu-Chia Su, Yu-Wen Su, Tsung-Hsien Chuang, Shu-Ching Hsu, Li-Rung Huang
Immunotherapy aiming to rescue or boost antitumor immunity is an emerging strategy for treatment of cancers. The efficacy of immunotherapy is strongly controlled by the immunological milieu of cancer patients. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with immunosuppressive functions accumulating in individuals during tumor progression. The signaling mechanisms of MDSC activation have been well studied. However, there is little known about the metabolic status of MDSCs and the physiological role of their metabolic reprogramming...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28471197/-circulating-myeloid-suppressor-cells-and-their-role-in-tumour-immunology
#6
K Pilatova, E Budinská, B Bensciková, R Nenutil, R Šefr, L Fedorová, B Hanáková, V Brychtová, L Zdražilová Dubská
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogenic population of multipotent progenitors of myeloid lineage. For their immunosuppressive effect, MDSC are responsible for tumour escape from the host immune surveillance. Furthermore, MDSCs support tumour by promotion of angiogenesis and metastasis. Membrane markers of human MDSCs are myeloid markers CD11b and CD13, these cells are HLA-Drlow/- and expression of CD15 or CD14 differentiate them into granulocytic (Gr-MDSCs) and monocytic (Mo-MDSCs), resp...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28466815/the-study-of-cd14-hla-dr-low-myeloid-drived-suppressor-cell-mdsc-in-peripheral-blood-of-peripheral-t-cell-lymphoma-patients-and-its-biological-function
#7
J Du, X Sun, Y Song
Peripheral T-cell lymphoma is the generic term of a group of heterogeneous disease in non-Hodgkin's lymphoma. To investigate the quantity of CD14+HLA-DR-/low MDSC and T cell subsets in peripheral blood of peripheral T cell lymphoma (PTCL) patients, and explore the biological functions of CD14+HLA-DR-/low MDSC in peripheral T-cell lymphoma. Flow cytometry was used to determine CD14+HLA-DR-/low MDSC and T cell subsets in peripheral blood of 33 peripheral T-cell lymphoma patients and 23 healthy cases; CD3 +T cells, CD14+HLA-DR-/low MDSC cells and HLA-DR+ cells were selected with magnetic activated cell sorting; Biotin-labeled micro magnetic beads (CD2 / CD3 / CD28) were used to stimulate amplification of CD3 + T cells, which were co-cultured and analyzed by flow cytometry for the effect of different concentrations of CD14+HLA-DR-/low MDSC on the proliferative activity of autologous CD3+ T cells...
March 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28464218/granulocytic-myeloid-derived-suppressor-cells-from-human-cord-blood-modulate-t-helper-cell-response-towards-an-anti-inflammatory-phenotype
#8
Natascha Köstlin, Margit Vogelmann, Bärbel Spring, Julian Schwarz, Judith Feucht, Christoph Härtel, Thorsten W Orlikowsky, Christian F Poets, Christian Gille
Infections are a leading cause of perinatal morbidity and mortality. The outstandingly high susceptibility to infections early in life is mainly attributable to the compromised state of the neonatal immune system. One important difference to the adult immune system is a bias towards T helper (Th) 2-responses in newborns. However, mechanisms regulating neonatal T-cell responses are yet incompletely understood. Granulocytic myeloid-derived suppressor cells (GR-MDSC) are myeloid cells with a granulocytic phenotype that suppress various functions of other immune cells and accumulate under physiological conditions during pregnancy in maternal and foetal blood...
May 2, 2017: Immunology
https://www.readbyqxmd.com/read/28462680/does-placental-mdsc-mediated-modulation-of-arginine-levels-help-protect-the-foetus-from-auxotrophic-pathogens
#9
Abdul Qader Tahir Ismail
Myeloid-derived suppressor cells (MDSCs) are immunosuppressive precursors of dendritic cells, macrophages and granulocytes. MDSCs normally quickly differentiate, but have elevated levels in chronic infection and cancer, where they help tumours evade the immune system through induction of T-cell dysfunction. MDSC levels are also raised in pregnancy, and in the neonate. During pregnancy they may help to prevent maternal rejection of the semiallogenic foetus. In the immediate postnatal period they may aid in allowing tolerance of gut microbiological colonisation and non-pathological environmental antigens...
May 2, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28455608/expansion-of-cd11b-ly6g-high-and-cd11b-cd49d-myeloid-cells-with-suppressive-potential-in-mice-with-chronic-inflammation-and-light-at-night-induced-circadian-disruption
#10
Yuliya V Perfilyeva, Nurshat Abdolla, Yekaterina O Ostapchuk, Raikhan Tleulieva, Vladimir C Krasnoshtanov, Nikolai N Belyaev
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases. SUBJECTS: 67 CD-1 mice and in vitro MDSC cultures...
April 28, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28455419/cxcl1-is-critical-for-pre-metastatic-niche-formation-and-metastasis-in-colorectal-cancer
#11
Dingzhi Wang, Haiyan Sun, Jie Wei, Bo Cen, Raymond N DuBois
Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as pre-metastatic niches, in certain distant organs before arrival of metastatic cells.  However, the mechanisms underlying the contributions of the primary tumor to pre-metastatic niche formation are not fully understood.  Here we demonstrate that colorectal carcinoma cells secrete VEGF-A, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor.  Elevation of CXCL1 in pre-metastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a pre-metastatic niche that ultimately promoted liver metastases...
April 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28454374/arsenic-trioxide-inhibits-tumor-induced-myeloid-derived-suppressor-cells-and-enhances-t-cell-activity
#12
Qingmin Gao, Jingwei Jiang, Zhaohui Chu, Hao Lin, Xinli Zhou, Xiaohua Liang
Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#13
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#14
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
#15
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
#16
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
#17
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
#18
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...
May 2, 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
#19
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)...
April 11, 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
#20
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
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