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Proliferation t cells

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https://www.readbyqxmd.com/read/28538176/tonic-lat-hdac7-signals-sustain-nur77-and-irf4-expression-to-tune-naive-cd4%C3%A2-t-cells
#1
Darienne R Myers, Tannia Lau, Evan Markegard, Hyung W Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, John P Huizar, Julie Zikherman, David J Erle, Weiguo Zhang, Eric Verdin, Jeroen P Roose
CD4(+) T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4(+) T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#2
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535649/-cancer-associated-fibroblasts-regulate-the-chemoresistance-of-lung-cancer-cell-line-a549-via-sdf-1-secretion
#3
F Zou, Z H Zhang, Y T Zhang, J Q Zhao, X L Zhang, C L Wen, X Y Song, W M Zhou
Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535645/-effect-of-rapamycin-and-chloroquine-on-osteosarcoma
#4
W D Liu, W Sun, Y Q Hua, S G Wang, Z D Cai
Objective: To investigate the combination effect of anti-tumor agent rapamycin and anti-autophagy agent chloroquine on osteosarcoma. Methods: The inhibition effect of rapamycin or chloroquine and combination of both on human osteosarcoma cell line 143B measured with CCK-8 box.The combination index at different concentration was calculated, and the synergism effect range was analysed.The effect of combined therapy on cell cycle and apoptosis via flow cytometric was analyzted.Setting up murine subcutaneous xenograft model, the combination effect of antitumor in vivo observed...
May 23, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535628/-expression-and-clinical-significance-of-long-non-coding-rna-ccat1-in-gastric-cancer
#5
T Shan, Y G Chen, B Hong, H Zhou, J Z Xia
Objective: To investigate the expression and clinical significance of long non-coding RNA colon cancer associated transcript-1 (CCAT1) in gastric cancer (GC), and to further explore the effect of CCAT1 on cell proliferation of GC. Methods: The mRNA expressions of CCAT1 in GC tissues and matched adjacent normal tissues from 62 patients who received resection for gastric carcinoma between January 2013 and May 2015 in Nanjing Medical University Affiliated Wuxi Second Hospital and expressions in GC cell lines were assessed by quantitative real-time PCR (qRT-PCR)...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535598/antarctic-seals-molecular-biomarkers-as-indicators-for-pollutant-exposure-health-effects-and-diet
#6
K Lehnert, L Weirup, K C Harding, T Härkönen, O Karlsson, J Teilmann
Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden...
May 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28534937/the-inhibitory-effect-of-meg3-mir-214-aifm2-axis-on-the-growth-of-t-cell-lymphoblastic-lymphoma
#7
Fang-Yi Fan, Rui Deng, Hai Yi, Hao-Ping Sun, Yan Zeng, Guang-Cui He, Yi Su
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534509/a-novel-interaction-of-pak4-with-ppar%C3%AE-to-regulate-nox1-and-radiation-induced-epithelial-to-mesenchymal-transition-in-glioma
#8
D Kesanakurti, D Maddirela, Y K Banasavadi-Siddegowda, T-H Lai, Z Qamri, N K Jacob, D Sampath, S Mohanam, B Kaur, V K Puduvalli
Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#9
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534337/-mir-145-inhibits-drug-resistance-to-oxaliplatin-in-colorectal-cancer-cells-through-regulating-g-protein-coupled-receptor-98
#10
Qiang Fu, Jing Cheng, Jindai Zhang, Yonglei Zhang, Xiaobing Chen, Jianguo Xie, Suxia Luo
OBJECTIVE: To predict and identify the target gene of miR-145, and to explore the underlying mechanism of the inhibition of miR-145 on drug resistance to Oxaliplatin (L-OHP) in human colorectal cancer cells. METHODS: L-OHP-resistant human colorectal cancer cell line (HCT116/L-OHP) was established in vitro by exposing to increased concentrations of L-OHP in cell culture medium. MiR-145-mimics and its negative control (NC-miRNA) were transfected into HCT116/L-OHP cells using liposome to establish HCT116/L-OHP(mimics) over-expressing miR-145 and HCT116/L-OHP(NC)...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534291/ultra-sensitive-measurement-of-il-17a-and-il-17f-in-psoriasis-patient-serum-and-skin
#11
Catherine Soderstrom, Gabriel Berstein, Weidong Zhang, Hernan Valdez, Lori Fitz, Max Kuhn, Stephanie Fraser
Interleukin 17 is a family of cytokines that play a central role in many autoimmune and inflammatory diseases. IL-17A has been implicated as a key driver of psoriasis, mediating a chronic cycle of T-cell activation, keratinocyte proliferation and angiogenesis. It has been hypothesized that expression of IL-17A and the related cytokine IL-17F could be used as predictive biomarkers for therapeutic response, though they have been difficult to measure locally or in circulation because of their low abundance. We developed ultrasensitive methods for measuring IL-17A and IL-17F in human serum samples and found that serum from psoriasis patients had higher and a broader range of concentrations of both IL-17 proteins compared to healthy volunteers...
May 22, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#12
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533525/cellular-responses-to-t-2-toxin-and-or-deoxynivalenol-that-induce-cartilage-damage-are-not-specific-to-chondrocytes
#13
Yang Lei, Zhao Guanghui, Wang Xi, Wang Yingting, Lin Xialu, Yu Fangfang, Mary B Goldring, Guo Xiong, Mikko J Lammi
The relationship between T-2 toxin and deoxynivalenol (DON) and the risk of Kashin-Beck disease is still controversial since it is poorly known about their selectivity in cartilage damage. We aimed to compare the cytotoxicity of T-2 toxin and DON on cell lines representative of cell types encountered in vivo, including human chondrocytes (C28/I2), human hepatic epithelial cells (L-02) and human tubular epithelial cells (HK-2). In addition, we determined the distribution of T-2 toxin and DON in Sprague-Dawley (SD) rats after a single dose exposure...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533469/the-phenotype-and-function-of-myeloid-derived-suppressor-cells-induced-by-porphyromonas-gingivalis-infection
#14
Lingkai Su, Qingan Xu, Ping Zhang, Suzanne M Michalek, Jannet Katz
Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, has been reported to induce the expansion of myeloid-derived suppressor cells (MDSC); however, little is known regarding the subpopulations of MDSC expanded by Pg infection. Flow cytometry was used to evaluate bone marrow and spleen cells from mice infected with Pg and controls for surface expression of CD11b, Ly6G and Ly6C. To characterize the phenotype of MDSC subpopulations induced by infection, cells were sorted based on the differential expression of Ly6G and Ly6C...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533445/lung-cd4-tissue-resident-memory-t-cells-mediate-adaptive-immunity-induced-by-previous-infection-of-mice-with-bordetella-pertussis
#15
Mieszko M Wilk, Alicja Misiak, Róisín M McManus, Aideen C Allen, Marina A Lynch, Kingston H G Mills
Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis, but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (TRM) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 TRM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#16
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#17
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#18
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28532104/in-situ-synthesis-and-characterization-of-hydroxyapatite-natural-rubber-composites-for-biomedical-applications
#19
T A Dick, L A Dos Santos
In this work, a biomimetic synthesis reaction for the production of hydroxyapatite (HA)/natural rubber (NR) composites is presented. HA was synthesized in the presence of solubilized NR in tetrahydrofuran (THF), which permits that negatively charged domains in proteins and lipids in NR work as nucleation sites for hydroxyapatite. The mechanical and physicochemical properties of composites containing 10, 20 and 30wt% HA were studied. NR influenced HA crystallite morphology, shape and size and was able to disperse the HA particles in THF...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531813/immunomodulatory-function-of-whole-human-umbilical-cord-derived-mesenchymal-stem-cells
#20
Hao Zhang, Yanling Tao, Haihui Liu, Saisai Ren, Bin Zhang, Hu Chen
Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73(+), CD90(+), CD105(+), and CD34(-), CD45(-), HLA-DR(-)) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8(+) T cells markedly decreased and CD4(+) T cells changed lightly...
May 19, 2017: Molecular Immunology
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