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https://www.readbyqxmd.com/read/28070996/distribution-and-differentiation-of-myeloid-derived-suppressor-cells-after-fluid-resuscitation-in-mice-with-hemorrhagic-shock
#1
Jiu-Kun Jiang, Wen Fang, Liang-Jie Hong, Yuan-Qiang Lu
OBJECTIVE: To investigate the distribution and differentiation of myeloid-derived suppressor cells (MDSCs) in hemorrhagic shock mice, which are resuscitated with normal saline (NS), hypertonic saline (HTS), and hydroxyethyl starch (HES). METHODS: BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups (n=8) in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs (M-MDSCs), and granulocytic/neutrophilic MDSCs (G-MDSCs) in peripheral blood nucleated cells (PBNCs), spleen single-cell suspension, and bone marrow nucleated cells (BMNCs)...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28068097/characterization-of-phase-separation-propensity-for-amorphous-spray-dried-dispersions
#2
Daniel McNamara, Shawn Yin, Duohai Pan, George Crull, Peter Timmins, Balvinder Vig
A generalized screening approach, applying isothermal calorimetry at 37°C 100%RH, to formulations of spray dried dispersions (SDDs) for two active pharmaceutical ingredients (APIs) (BMS-903452 and BMS-986034) is demonstrated. APIs 452 and 034, with similar chemotypes, were synthesized and promoted during development for oral dosing. Both APIs were formulated as SDDs for animal exposure studies using the polymer hydroxypropylmethlycellulose acetyl succinate M grade (HPMCAS M). 452 formulated at 30% (wt/wt%) was an extremely robust SDD that was able to withstand 40°C 75%RH open storage conditions for 6 months with no physical evidence of crystallization or loss of dissolution performance...
January 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28062672/repurposing-antiestrogens-for-tumor-immunotherapy
#3
Thomas Welte, Xiang H-F Zhang, Jeffrey M Rosen
Svoronos and colleagues observed estrogen receptor alpha-positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs...
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28060224/granulocytic-myeloid-derived-suppressor-cells-increased-in-early-phases-of-primary-hiv-infection-depending-on-trail-plasma-level
#4
N Tumino, M T Bilotta, C Pinnetti, A Ammassari, A Antinori, F Turchi, C Agrati, R Casetti, V Bordoni, E Cimini, I Abbate, M R Capobianchi, F Martini, A Sacchi
BACKGROUND: It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. METHODS: Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled...
January 2, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28052991/myeloid-derived-suppressor-cells
#5
REVIEW
Dmitry I Gabrilovich
Myeloid cells developed evolutionarily as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master-tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC). These cells are closely related to neutrophils and monocytes. MDSCs are not present in the steady state of healthy individuals and appear in cancer and in pathologic conditions associated with chronic inflammation or stress...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28051364/the-role-of-myeloid-derived-suppressor-cells-in-viral-infection
#6
Megan A O'Connor, Jessica L Rastad, William R Green
Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells that are well described as potent immune regulatory cells during human cancer and murine tumor models. Reports of MDSCs during viral infections remain limited, and their association with immunomodulation of viral diseases is still being defined. Here, we provide an overview of MDSCs or MDSC-like cells identified during viral infections, including murine viral models and human viral diseases. Understanding the similarities and/or differences of virally induced versus tumor-derived MDSCs will be important for designing future immunotherapeutic approaches...
January 4, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28050790/first-in-human-study-of-the-antibody-dr5-agonist-ds-8273a-in-patients-with-advanced-solid-tumors
#7
Andres Forero, Johanna C Bendell, Prasanna Kumar, Linda Janisch, Michael Rosen, Qiang Wang, Catherine Copigneaux, Madhuri Desai, Giorgio Senaldi, Michael L Maitland
Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid tumors. Methods The study comprised dose escalation and dose expansion cohorts. The dose escalation cohorts intended to determine the safety and to identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to characterize the pharmacokinetics and pharmacodynamics by a conventional 3 + 3 design (starting at 2 mg/kg and escalating through 8, 16 and 24 mg/kg once every 3 weeks)...
January 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#8
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28024516/-progress-of-experimental-research-on-differentiation-of-muscle-derived-stem-cells-into-haematopoietic-lineages-in-vitro-review
#9
Juan-Juan Wang, Xiao-Ning Gao, Shan-Shan Chen, Pan-Pan Zhang, Tao Wang, Hao-Ying Dou
Muscle-derived stem cells (MDSC) are a population of multipotent stem cells in the muscular tissue. It provide an excellent prospect of hemopathy treatment due to their superiorities, such as rich sources, convenient material resource and a high survival rate after transplantation and so on. However, there are great differences in sampling, separation, purification, and proliferation when MDSC were cultured in vitro. In addition, the proliferation conditions of the MDSC in vitro are yet unclear. The related regulatory mechanisms, which MDSC transformed into haematopoietic cells, need to be investigated...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28009291/myeloid-derived-suppressor-cells-are-controlled-by-regulatory-t-cells-via-tgf-%C3%AE-during-murine-colitis
#10
Cho-Rong Lee, Yewon Kwak, Taewoo Yang, Jung Hyun Han, Sang-Heon Park, Michael B Ye, Wongeun Lee, Kyu-Young Sim, Jung-Ah Kang, Yong-Chul Kim, Sarkis K Mazmanian, Sung-Gyoo Park
Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β)...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28008175/cll-cell-mediated-mdsc-induction-by-exosomal-mir-155-transfer-is-disrupted-by-vitamin-d
#11
H Bruns, M Böttcher, M Qorraj, M Fabri, S Jitschin, J Dindorf, L Busch, R Jitschin, A Mackensen, D Mougiakakos
Leukemia accepted article preview online, 23 December 2016. doi:10.1038/leu.2016.378.
December 23, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28007981/frontline-science-myeloid-derived-suppressor-cells-mdscs-facilitate-maternal-fetal-tolerance-in-mice
#12
Suzanne Ostrand-Rosenberg, Pratima Sinha, Chas Figley, Ramses Long, DoHwan Park, Darryl Carter, Virginia K Clements
During successful pregnancy, a woman is immunologically tolerant of her genetically and antigenically disparate fetus, a state known as maternal-fetal tolerance. How this state is maintained has puzzled investigators for more than half a century. Diverse, immune and nonimmune mechanisms have been proposed; however, these mechanisms appear to be unrelated and to act independently. A population of immune suppressive cells called myeloid-derived suppressor cells (MDSCs) accumulates in pregnant mice and women. Given the profound immune suppressive function of MDSCs, it has been suggested that this cell population may facilitate successful pregnancy by contributing to maternal-fetal tolerance...
December 22, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28006751/mir-375-ameliorates-sepsis-by-downregulating-mir-21-level-via-inhibiting-jak2-stat3-signaling
#13
Bo Sheng, Lei Zhao, Xuefeng Zang, Jie Zhen, Wei Chen
Accumulating evidences have confirmed that miRNAs have important roles in sepsis. Myeloid-derived suppressor cells (MDSCs) enhance late sepsis development through immunosuppression in mice. Here, the functions and mechanisms of miR-375 in sepsis were revealed. We found that miR-375 level was downregulated but miR-21 level was upregulated in sepsis patients and that their levels were correlated negatively. Importantly, ectopic expression of miR-375 could decrease the number of sepsis Gr1+CD11b+ MDSCs in mice...
December 19, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27999750/reprogramming-the-lung-microenvironment-by-inhaled-immunotherapy-fosters-immune-destruction-of-tumor
#14
Valentino Le Noci, Michele Sommariva, Monica Tortoreto, Nadia Zaffaroni, Manuela Campiglio, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Due to their constant exposure to inhaled antigens, lungs represent a particularly immunosuppressive environment that limits excessive immune responses; however, cancer cells can exploit this unique environment for their growth. We previously described the ability of aerosolized CpG-ODN combined with Poly(I:C) (TLR9 and TLR3 agonists, respectively) to promote antitumor immunity in a B16 melanoma lung metastasis model. Here, we explored the possibility of improving the therapeutic efficacy of TLR9/TLR3 agonist combinations by including in the inhalant either an antibody directed to both Ly6G and Ly6C markers to locally deplete myeloid-derived suppressive cells (MDSCs) or IFNα to directly activate the natural killer (NK) and macrophage innate immune cells in the lung...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999748/impact-of-myeloid-derived-suppressor-cell-on-kupffer-cells-from-mouse-livers-with-hepatocellular-carcinoma
#15
Stéphanie Lacotte, Florence Slits, Lorenzo A Orci, Jeremy Meyer, Graziano Oldani, Vaihere Delaune, Carmen Gonelle-Gispert, Philippe Morel, Christian Toso
Kupffer cells represent the first line of defense against tumor cells in the liver. Myeloid-derived suppressor cells (MDSC) have recently been observed in the liver parenchyma of tumor-bearing animals. The present study investigates the function of the MDSC subsets, and their impact on Kupffer cell phenotype and function. RIL-175 mouse hepatocellular carcinoma (HCC) cells were injected into the median liver lobe of C57BL/6 mice. Three weeks later, the median lobe hosting the tumor nodule was removed, and Kupffer cells and MDSCs were sorted from the remaining liver...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999739/tlr7-based-cancer-immunotherapy-decreases-intratumoral-myeloid-derived-suppressor-cells-and-blocks-their-immunosuppressive-function
#16
Thibaud Spinetti, Lorenzo Spagnuolo, Inès Mottas, Chiara Secondini, Marina Treinies, Curzio Rüegg, Christian Hotz, Carole Bourquin
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999738/the-interplay-of-epigenetic-therapy-and-immunity-in-locally-recurrent-or-metastatic-estrogen-receptor-positive-breast-cancer-correlative-analysis-of-encore-301-a-randomized-placebo-controlled-phase-ii-trial-of-exemestane-with-or-without-entinostat
#17
Yusuke Tomita, Min-Jung Lee, Sunmin Lee, Saori Tomita, Saranya Chumsri, Scott Cruickshank, Peter Ordentlich, Jane B Trepel
Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27987020/bio-hmgb1-from-breast-cancer-contributes-to-m-mdsc-differentiation-from-bone-marrow-progenitor-cells-and-facilitates-conversion-of-monocytes-into-mdsc-like-cells
#18
Zhaoliang Su, Ping Ni, Peng She, Yueqin Liu, Seidu A Richard, Wenlin Xu, Haitao Zhu, Jia Wang
Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4(+) and CD8(+) T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients...
December 16, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27974456/kinetics-of-myeloid-derived-suppressor-cell-frequency-and-function-during-simian-immunodeficiency-virus-infection-combination-antiretroviral-therapy-and-treatment-interruption
#19
Sandra E Dross, Paul V Munson, Se Eun Kim, Debra L Bratt, Hillary C Tunggal, Ana L Gervassi, Deborah H Fuller, Helen Horton
During chronic lentiviral infection, poor clinical outcomes correlate both with systemic inflammation and poor proliferative ability of HIV-specific T cells; however, the connection between the two is not clear. Myeloid-derived suppressor cells (MDSC), which expand during states of elevated circulating inflammatory cytokines, may link the systemic inflammation and poor T cell function characteristic of lentiviral infections. Although MDSC are partially characterized in HIV and SIV infection, questions remain regarding their persistence, activity, and clinical significance...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27965309/selective-targeting-of-myeloid-derived-suppressor-cells-in-cancer-patients-using-ds-8273a-an-agonistic-trail-r2-antibody
#20
George Dominguez, Thomas C Condamine, Sridevi Mony, Ayumi Hashimoto, Fang Wang, Qin Liu, Andres Forero, Johanna C Bendell, Robert Witt, Neil Hockstein, Prasanna Kumar, Dmitry Gabrilovich
PURPOSE: Myeloid-derived suppressor cells (MDSC) one of the major contributors to immune suppression in cancer. We recently have demonstrated that MDSC are sensitive to TRAIL receptor 2 (TRAIL-R2) agonist. The goal of this study was to clinically test the hypothesis that targeting TRAIL-R2 can selectively eliminate MDSC. EXPERIMENTAL DESIGN: The TRAIL-R2 agonistic antibody (DS-8273a) has been tested in 16 patients with advanced cancers enrolled in a phase 1 trial...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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