keyword
MENU ▼
Read by QxMD icon Read
search

T cell inhibitory pathway

keyword
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#1
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919885/trypanosoma-cruzi-evades-the-complement-system-as-an-efficient-strategy-to-survive-in-the-mammalian-host-the-specific-roles-of-host-parasite-molecules-and-trypanosoma-cruzi-calreticulin
#2
REVIEW
Galia Ramírez-Toloza, Arturo Ferreira
American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28902599/the-potential-role-of-inhibitory-receptors-in-the-treatment-of-psoriasis
#3
Neha Shah, Sabina Sandigursky, Adam Mor
Psoriasis is a common autoimmune disorder that affects the skin. Approximately 30% of individuals with psoriasis will develop inflammatory arthritis, often in the setting of human leukocyte antigen B27. Both forms of disease are thought to be the result of prolonged inflammation mediated by T lymphocytes, dendritic cells, and keratinocytes. While there are treatments aimed at immunomodulation, targeting T cell co-inhibitory receptors signaling pathways may provide therapeutic benefit. This review will discuss in detail four T cell co-inhibitory receptors and their potential application for the treatment of psoriasis and psoriatic arthritis...
May 2017: Bulletin of the Hospital for Joint Diseases
https://www.readbyqxmd.com/read/28881633/peroxiredoxin-6-overexpression-attenuates-lipopolysaccharide-induced-acute-kidney-injury
#4
Dong Hun Lee, Ju Ho Park, Sang Bae Han, Do Young Yoon, Yu Yeon Jung, Jin Tae Hong
Peroxiredoxin 6 (PRDX6) is a member of the PRDX family of antioxidant enzymes and correlated with inflammatory response. Therefore, we investigated the role of PRDX6 during lipopolysaccharide (LPS)-induced acute kidney injury. Both 3 months aged PRDX6-overexpressing transgenic mice (PRDX6 mice) and wild type (WT) mice had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg)., PRDX6 mice showed decreased mortality and renal injury following LPS challenge compared to WT mice. Furthermore, infiltration of macrophages, T-cells and neutrophils, and the number of apoptotic cells were more decreased by LPS treatment in PRDX6 mice than in WT mice...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881285/structures-and-biochemical-evaluation-of-silver-i-5-5-diethylbarbiturate-complexes-with-bis-diphenylphosphino-alkanes-as-potential-antimicrobial-and-anticancer-agents
#5
Veysel T Yilmaz, Ceyda Icsel, Jenaidullah Batur, Seyma Aydinlik, Pinar Sahinturk, Muhittin Aygun
New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag2(barb)2(μ-dppm)2] (1), [Ag2(barb)2(μ-dppe)(DMSO)2] (2) and [Ag2(barb)2(μ-dppp)2] (3) were binuclear, while [Ag(barb)(μ-dppb)]n (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies...
August 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28865357/check-point-inhibitors-as-therapies-for-infectious-diseases
#6
REVIEW
Maureen A Cox, Robert Nechanitzky, Tak W Mak
The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients. While still in early stages, basic and clinical data suggest that blockade of CTLA-4 and PD-1 can be beneficial in the treatment of chronic HIV, HBV, and HCV infection, as well as other chronic maladies. Furthermore, novel inhibitory receptors such as Tim-3, LAG-3, and TIGIT are the potential next wave of check points that can be manipulated for the treatment of chronic infection...
August 30, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28854230/heterologous-expression-of-anti-apoptotic-human-14-3-3%C3%AE-%C3%AE-enhances-iron-mediated-programmed-cell-death-in-yeast
#7
Rawan Eid, David R Zhou, Nagla T T Arab, Eric Boucher, Paul G Young, Craig A Mandato, Michael T Greenwood
The induction of Programmed Cell Death (PCD) requires the activation of complex responses involving the interplay of a variety of different cellular proteins, pathways, and processes. Uncovering the mechanisms regulating PCD requires an understanding of the different processes that both positively and negatively regulate cell death. Here we have examined the response of normal as well as PCD resistant yeast cells to different PCD inducing stresses. As expected cells expressing the pro-survival human 14-3-3β/α sequence show increased resistance to numerous stresses including copper and rapamycin...
2017: PloS One
https://www.readbyqxmd.com/read/28851628/pde8-controls-cd4-t-cell-motility-through-the-pde8a-raf-1-kinase-signaling-complex
#8
Chaitali P Basole, Rebecca K Nguyen, Katie Lamothe, Amanda Vang, Robert Clark, George S Baillie, Paul M Epstein, Stefan Brocke
The levels of cAMP are regulated by phosphodiesterase enzymes (PDEs), which are targets for the treatment of inflammatory disorders. We have previously shown that PDE8 regulates T cell motility. Here, for the first time, we report that PDE8A exerts part of its control of T cell function through the V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase signaling pathway. To examine T cell motility under physiologic conditions, we analyzed T cell interactions with endothelial cells and ligands in flow assays...
August 26, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28842430/switching-of-the-substrate-specificity-of-protein-tyrosine-phosphatase-n12-by-cyclin-dependent-kinase-2-phosphorylation-orchestrating-2-oncogenic-pathways
#9
Hui Li, Duxiao Yang, Shanglei Ning, Yinghui Xu, Fan Yang, Rusha Yin, Taihu Feng, Shouqing Han, Lu Guo, Pengju Zhang, Wenjie Qu, Renbo Guo, Chen Song, Peng Xiao, Chengjun Zhou, Zhigang Xu, Jin-Peng Sun, Xiao Yu
The protein tyrosine phosphatase N (PTPN)-12 is a multifunctional protein and has elicited much research attention because its decreased protein level has been associated with poor prognosis of several types of cancers. Recently, we have solved the crystal structure of the phosphatase domain of PTPN12, which disclosed a specific PTPN12-insert-loop harboring a cyclin-dependent kinase (CDK)-2 phosphorylation site. However, the functional significance of this phosphorylation is undefined. In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions...
August 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28834746/pdl1-signals-through-conserved-sequence-motifs-to-overcome-interferon-mediated-cytotoxicity
#10
Maria Gato-Cañas, Miren Zuazo, Hugo Arasanz, Maria Ibañez-Vea, Laura Lorenzo, Gonzalo Fernandez-Hinojal, Ruth Vera, Cristian Smerdou, Eva Martisova, Imanol Arozarena, Claudia Wellbrock, Diana Llopiz, Marta Ruiz, Pablo Sarobe, Karine Breckpot, Grazyna Kochan, David Escors
PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28830352/jak-inhibitor-has-the-amelioration-effect-in-lupus-prone-mice-the-involvement-of-ifn-signature-gene-downregulation
#11
Keigo Ikeda, Kunihiro Hayakawa, Maki Fujishiro, Mikiko Kawasaki, Takuya Hirai, Hiroshi Tsushima, Tomoko Miyashita, Satoshi Suzuki, Shinji Morimoto, Naoto Tamura, Kenji Takamori, Hideoki Ogawa, Iwao Sekigawa
BACKGROUND: We previously reported that JAK-STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE. RESULTS: We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4(+) T cells (SLE mice) and CD3(+) T cells (human SLE patients) were measured by DNA microarray and qRT-PCR...
August 22, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28829194/cd19-lo-cd27-hi-plasmablasts-suppress-harmful-th17-inflammation-through-interleukin-10-pathway-in-colorectal-cancer
#12
Hui Mao, Fei Pan, Zhiyong Wu, Zhikuan Wang, Yanhua Zhou, Pengfei Zhang, Miaomiao Gou, Guanghai Dai
The enrichment of CD20(+) and CD138(+) immune cells were previously associated with improved survival in colorectal cancer (CRC). We previously discovered that the resected tumors in CRC patients were highly enriched with interleukin (IL)-10-producing CD19(lo)CD27(hi) plasmablasts with potential suppressor functions. It is still unknown what roles the CD19(lo)CD27(hi) plasmablasts play in CRC patients. In this study, we first demonstrated that B cells from peripheral blood mononuclear cells (PBMCs) could be stimulated to resemble tumor-infiltrating plasmablasts using a coculture containing Caco-2 and heat-killed bacteria...
August 22, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#13
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28815947/olive-oil-phenolics-prevent-oxysterol-induced-pro-inflammatory-cytokine-secretion-and-ros-production-in-human-pbmcs-through-modulation-of-p38-and-jnk-pathways
#14
Gessica Serra, Monica Deiana, Jeremy P E Spencer, Giulia Corona
SCOPE: The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the pro-inflammatory effects induced by dietary and endogenous oxysterols in ex-vivo immune cells. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilised and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol (HT), tyrosol (TYR) and homovanillic alcohol (HVA)...
August 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28813410/identification-of-cmtm6-and-cmtm4-as-pd-l1-protein-regulators
#15
Riccardo Mezzadra, Chong Sun, Lucas T Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E W Logtenberg, Maarten Slagter, Elisa A Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M Horlings, Lodewyk F A Wessels, Christian U Blank, Yanling Xiao, Albert J R Heck, Jannie Borst, Thijn R Brummelkamp, Ton N M Schumacher
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28810531/mir-146a-overexpression-effectively-improves-experimental-allergic-conjunctivitis-through-regulating-cd4-cd25-t-cells
#16
Yang Yang, Xiaolong Yin, Jinglin Yi, Xiaowei Peng
OBJECTIVE: To study the mechanism of miR-146a in the regulation of allergic conjunctivitis (AC) through CD4(+)CD25(-)T cells. METHODS: BALB/c mice were sensitized with ragweed pollen (RW) and alum, and then challenged with RW. Eosinophil infiltration was determined using Giemsa assay. ELISA assay was performed to examine the level of antigen-specific IgE in the serum and cytokine levels in splenocytes. The expression of miR-146a was measured by qRT-PCR. Flow cytometric analysis was used to analyze the percentage of CD4(+)CD25(-)T cells and Tregs...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#17
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28802125/novel-4-3-4-oxo-5-2-oxoindolin-3-ylidene-thiazolidin-2-ylidene-amino-benzenesulfonamides-synthesis-carbonic-anhydrase-inhibitory-activity-anticancer-activity-and-molecular-modelling-studies
#18
Wagdy M Eldehna, Mahmoud F Abo-Ashour, Alessio Nocentini, Paola Gratteri, Ibrahim H Eissa, Mohamed Fares, Omnia E Ismael, Hazem A Ghabbour, Mahmoud M Elaasser, Hatem A Abdel-Aziz, Claudiu T Supuran
Herein we report the synthesis of two series of novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides (4a-m and 7a-g). All the newly prepared sulfonamides were in vitro investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IV and IX, using a stopped-flow CO2 hydrase assay. In particular, hCA isoforms II and IX (tumor-associated) were more susceptible to inhibition by the synthesized derivatives, with KIs in the range of 2...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#19
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 17, 2017: Nature
https://www.readbyqxmd.com/read/28792090/distinct-activation-mechanisms-trigger-the-trypanocidal-activity-of-dna-damaging-prodrugs
#20
Emma Louise Meredith, Ambika Kumar, Aya Konno, Joanna Szular, Sam Alsford, Karin Seifert, David Horn, Shane R Wilkinson
Quinone-based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl-1,4-benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections...
August 9, 2017: Molecular Microbiology
keyword
keyword
115212
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"