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T cell inhibitory pathway

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https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#1
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28076331/a-short-term-intervention-with-selenium-affects-expression-of-genes-implicated-in-the-epithelial-to-mesenchymal-transition-in-the-prostate
#2
Dieuwertje E G Kok, Lambertus A L M Kiemeney, Gerald W Verhaegh, Jack A Schalken, Emile N J T van Lin, J P Michiel Sedelaar, J Alfred Witjes, Christina A Hulsbergen-van de Kaa, Pieter Van't Veer, Ellen Kampman, Lydia A Afman
In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo)...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28063927/deubiquitinase-usp12-promotes-lps-induced-macrophage-responses-through-inhibition-of-i%C3%AE%C2%BAb%C3%AE
#3
Tapan Kumar Singh Nayak, Neeraja P Alamuru-Yellapragada, Kishore V L Parsa
Post translational modifications, ubiquitination and its reversal by deubiquitination play an important role in regulating innate immune system. USP12 is a poorly studied deubiquitinase reported to regulate T-cell receptor signaling however the functional role of USP12 in macrophages, the principal architects of inflammation, is unknown. Thus, in this study we probed the involvement of USP12 in macrophage mediated inflammatory responses using bacterial endotoxin, LPS, as the model system. Here, we observed that the expression of USP12 was altered in time dependent manner in LPS stimulated RAW 264...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28062735/the-ability-of-btk-inhibitors-to-sequester-y551-and-prevent-phosphorylation-determines-potency-for-inhibition-of-fcr-but-not-b-cell-receptor-signaling
#4
Andrew T Bender, Anna Gardberg, Albertina Pereira, Theresa Johenson, Yin Wu, Roland Grenningloh, Jared Head, Federica Morandi, Philipp Haselmayer, Lesley Liu-Bujalski
Bruton's tyrosine kinase (Btk) is expressed in a variety of hematopoietic cells. Btk has been demonstrated to regulate signaling downstream of the B cell receptor (BCR), Fc receptors (FcR), and toll like receptors (TLRs). Btk has become an attractive drug target as Btk inhibition may provide significant efficacy by blocking multiple disease mechanisms simultaneously. Consequently, a large number of Btk inhibitors have been developed. The compounds have diverse binding modes and both reversible and irreversible inhibitors have been developed...
January 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28052118/tgf-%C3%AE-3-inhibits-antibody-production-by-human-b-cells
#5
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Yuta Kochi, Haruka Tsuchiya, Mineto Ota, Toshihiko Komai, Mariko Inoue, Kaoru Morita, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus...
2017: PloS One
https://www.readbyqxmd.com/read/28052035/brca1-iris-overexpression-promotes-and-maintains-the-tumor-initiating-phenotype-implications-for-triple-negative-breast-cancer-early-lesions
#6
Abhilasha Sinha, Bibbin T Paul, Lisa M Sullivan, Hillary Sims, Ahmed El Bastawisy, Hend F Yousef, Abdel-Rahman N Zekri, Abeer A Bahnassy, Wael M ElShamy
Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039272/micafungin-alters-the-amino-acid-nucleic-acid-and-central-carbon-metabolism-of-candida-albicans-at-subinhibitory-concentrations-novel-insights-into-mechanisms-of-action
#7
Aspasia Katragkou, Michael Williams, Sandi Sternberg, Dennis Pantazatos, Emmanuel Roilides, Thomas J Walsh
BACKGROUND: Echinocandins are an important class of antifungal agents in the treatment of invasive candidiasis. However, little is known about the metabolomic effects of echinocandins on Candida We therefore performed LC-high-resolution MS (LC-HRMS)-based metabolomics profiling of the response of Candida albicans cells to increasing concentrations of micafungin to determine the metabolic response of Candida to micafungin subinhibitory injury. METHODS: Isolates of C...
December 30, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28029652/tumor-suppressor-blu-promotes-trail-induced-apoptosis-by-downregulating-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-carcinoma
#8
Jiahui Zhou, Zunnan Huang, Ziyou Wang, Shumin Liu, Alf Grandien, Ingemar Ernberg, Zhiwei He, Xiangning Zhang
A putative tumor suppressor BLU mapped on the chromosomal 3p21 region, is frequently lost in human tumors including nasopharyngeal carcinoma (NPC). To explore the underlying mechanism of tumor suppression by BLU, its potential to promote apoptosis induced by TRAIL, an effector molecule elaborated by natural killer-T (NKT) cells was investigated. BLU was re-expressed in NPC-derived HNE1 cells by recombinant adenoviral infection and the cells were challenged with recombinant TRAIL. The growth inhibition of BLU was assayed and apoptosis was examined by flow cytometry-based tetramethylrhodamine ethyl ester (TMRE) and annexin V staining, cleavage of pro-caspase-8 and poly ADP ribose polymerase (PARP)...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28018348/pd-l1-is-not-constitutively-expressed-on-tasmanian-devil-facial-tumor-cells-but-is-strongly-upregulated-in-response-to-ifn-%C3%AE-and-can-be-expressed-in-the-tumor-microenvironment
#9
Andrew S Flies, A Bruce Lyons, Lynn M Corcoran, Anthony T Papenfuss, James M Murphy, Graeme W Knowles, Gregory M Woods, John D Hayball
The devil facial tumor disease (DFTD) is caused by clonal transmissible cancers that have led to a catastrophic decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The first transmissible tumor, now termed devil facial tumor 1 (DFT1), was first discovered in 1996 and has been continually transmitted to new hosts for at least 20 years. In 2015, a second transmissible cancer [devil facial tumor 2 (DFT2)] was discovered in wild devils, and the DFT2 is genetically distinct and independent from the DFT1...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#10
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018338/the-pd1-pd-l1-2-pathway-from-discovery-to-clinical-implementation
#11
REVIEW
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28017495/oral-squamous-cell-carcinoma-suppressed-antitumor-immunity-through-induction-of-pd-l1-expression-on-tumor-associated-macrophages
#12
Canhua Jiang, Fulai Yuan, Jie Wang, Limeng Wu
Oral squamous cell carcinoma (OSCC) is the most common solid tumor in the oral cavity. Development and progression of OSCC is associated with the elevated presence of inhibitory M2 type tumor-associated macrophages (TAMs). However, the underlying mechanism leading to the enrichment of M2 TAMs and the pathway through which TAMs foster tumor progression are still unclear. In this study, we harvested TAMs and tumor cells from primary OSCC resections of stage II and stage III patients. We showed that compared to peritumoral macrophages, TAMs presented upregulated expression of PD-L1 and elevated capacity in inducing T cell apoptosis...
December 14, 2016: Immunobiology
https://www.readbyqxmd.com/read/28009988/a-neutralized-human-lmp1-igg-inhibits-enktl-growth-by-suppressing-the-jak3-stat3-signaling-pathway
#13
Yuan Mao, Jun Wang, Mingzhi Zhang, Weifei Fan, Qi Tang, Siping Xiong, Xiaojun Tang, Juqing Xu, Lin Wang, Shu Yang, Suyao Liu, Li Xu, Yan Chen, Lin Xu, Rong Yin, Jin Zhu
Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL)...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27987522/-interleukin-2-signaling-pathway-regulating-molecules-in-systemic-lupus-erythematosus
#14
Q Guo, X Y Chen, Y Su
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease, which characterized by complex immunological abnormalities and multiple tissue and organ damages. The etiology and pathogenesis of SLE have not been entirely recognized. Genetic, environmental and viral infections and other factors might be related to the pathogenetic mechanisms of SLE. Interleukin-2 (IL-2) is a critical cytokine produced by T cells upon activation and is important for the generation of T regulatory cells and activation-induced cell death...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27974925/new-pharmacological-strategies-in-rheumatic-diseases
#15
REVIEW
Schiotis Re, Buzoianu Ad, Mureșanu Df, Suciu S
Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania...
July 2016: Journal of Medicine and Life
https://www.readbyqxmd.com/read/27965942/attenuation-of-rankl-induced-osteoclast-formation-via-p38-mediated-nfatc1-signaling-pathways-by-extract-of-euphorbia-lathyris-l
#16
Ju-Hee Kang, Hyojung Lim, Ji-Eun Jeong, Mijung Yim
BACKGROUND: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL...
November 2016: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/27965674/molecular-and-cellular-characterization-of-human-cd8-t-suppressor-cells
#17
REVIEW
Zheng Xu, Sophey Ho, Chih-Chao Chang, Qing-Yin Zhang, Elena-Rodica Vasilescu, George Vlad, Nicole Suciu-Foca
Bidirectional interactions between dendritic cells and Ag-experienced T cells initiate either a tolerogenic or immunogenic pathway. The outcome of these interactions is of crucial importance in malignancy, transplantation, and autoimmune diseases. Blockade of costimulation results in the induction of T helper cell anergy and subsequent differentiation of antigen-specific CD8(+) T suppressor/regulatory cells (Ts). Ts, primed in the presence of inhibitory signals, exert their inhibitory function in an antigen-specific manner, a feature with tremendous clinical potential...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27965071/a-betulinic-acid-derivative-sh479-inhibits-collagen-induced-arthritis-by-modulating-t-cell-differentiation-and-cytokine-balance
#18
Shijie Chen, Yang Bai, Zhen Li, Kunhang Jia, Yunyun Jin, Bei He, Wen-Wei Qiu, Changsheng Du, Stefan Siwko, Huaqing Chen, Mingyao Liu, Jian Luo
The ideal therapeutic drug for rheumatoid arthritis (RA) should not only inhibit inflammation, but also prevent articular joint damage and particularly inhibit osteoclastogenesis. Betulinic acid (BA) is a natural pentacyclic triterpene that has displayed moderate anti-inflammatory and anti-osteoclastogenesis activities in various experimental systems, suggesting that BA or its derivatives could have an inhibitory effect on RA. In this study, we screened BA derivatives and found a heterocyclic ring-fused BA derivative, SH479, which had greater inhibitory effect than BA on Th17 differentiation...
December 11, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27959918/the-presence-persistence-and-functional-properties-of-plasmodium-vivax-duffy-binding-protein-ii-antibodies-are-influenced-by-hla-class-ii-allelic-variants
#19
Flora S Kano, Flávia A Souza-Silva, Leticia M Torres, Barbara A S Lima, Taís N Sousa, Jéssica R S Alves, Roberto S Rocha, Cor J F Fontes, Bruno A M Sanchez, John H Adams, Cristiana F A Brito, Douglas E V Pires, David B Ascher, Ana Maria Sell, Luzia H Carvalho
BACKGROUND: The human malaria parasite Plasmodium vivax infects red blood cells through a key pathway that requires interaction between Duffy binding protein II (DBPII) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). A high proportion of P. vivax-exposed individuals fail to develop antibodies that inhibit DBPII-DARC interaction, and genetic factors that modulate this humoral immune response are poorly characterized. Here, we investigate if DBPII responsiveness could be HLA class II-linked...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27959380/sequencing-and-bioinformatics-analysis-of-the-differentially-expressed-genes-in-herniated-discs-with-or-without-calcification
#20
Jia Shao, Miao Yu, Liang Jiang, Fengliang Wu, Xiaoguang Liu
The purpose of this study was to detect the differentially expressed genes between ossified herniated discs and herniated discs without ossification. In addition, we sought to identify a few candidate genes and pathways by using bioinformatics analysis. We analyzed 6 samples each of ossified herniated discs (experimental group) and herniated discs without ossification (control group). Purified mRNA and cDNA extracted from the samples were subjected to sequencing. The NOISeq method was used to statistically identify the differentially expressed genes (DEGs) between the 2 groups...
January 2017: International Journal of Molecular Medicine
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