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T cell inhibitory pathway

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https://www.readbyqxmd.com/read/28544747/k-ras-mutation-and-amplification-status-is-predictive-of-resistance-and-high-basal-pakt-is-predictive-of-sensitivity-to-everolimus-in-biliary-tract-cancer-cell-lines
#1
Yvonne Yeung, David K Lau, Fiona Chionh, Hoanh Tran, Janson W T Tse, Andrew J Weickhardt, Mehrdad Nikfarjam, Andrew M Scott, Niall C Tebbutt, John M Mariadason
Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signaling pathway is hyperactivated in a subset of BTCs and clinical activity to the mTOR inhibitor everolimus has been observed in some BTC patients. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28543637/evidence-of-the-immunomodulatory-role-of-dual-pi3k-mtor-inhibitors-in-graft-survival
#2
Valery Vilchez, Lilia Turcios, D Allan Butterfield, Mihail I Mitov, Cristin L Coquillard, Anthony J Brandon, Virgilius Cornea, Roberto Gedaly, Francesc Marti
The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of Rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative...
May 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28539667/strontium-loaded-titania-nanotube-arrays-repress-osteoclast-differentiation-through-multiple-signalling-pathways-in-vitro-and-in-vivo-studies
#3
Baoguo Mi, Wei Xiong, Na Xu, Hanfeng Guan, Zhong Fang, Hui Liao, Yong Zhang, Biao Gao, Xiang Xiao, Jijiang Fu, Feng Li
The loosening of implants is an important clinical issue, particularly for patients with osteoporosis. In these patients, an implant should preferably both promote osteoblast differentiation and repress osteoclastic resorption. In the present study, we fabricated coatings containing TiO2 nanotubes (NTs) incorporated with strontium (Sr) on titanium (Ti) surfaces through hydrothermal treatment. The amount of loaded Sr was controlled by hydrothermally treating the samples in a Sr(OH)2 solution for 1 and 3 h (samples NT-Sr1h and NT-Sr3h, respectively) and found that both types of NT-Sr samples inhibited osteoclast differentiation by reducing the expression of osteoclast marker genes...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534937/the-inhibitory-effect-of-meg3-mir-214-aifm2-axis-on-the-growth-of-t-cell-lymphoblastic-lymphoma
#4
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/28522830/inhibition-of-endocytic-lipid-antigen-presentation-by-common-lipophilic-environmental-pollutants
#5
Manju Sharma, Xiang Zhang, Shuangmin Zhang, Liang Niu, Shuk-Mei Ho, Aimin Chen, Shouxiong Huang
Environmental pollutants as non-heritable factors are now recognized as triggers for multiple human inflammatory diseases involving T cells. We postulated that lipid antigen presentation mediated by cluster of differentiation 1 (CD1) proteins for T cell activation is susceptible to lipophilic environmental pollutants. To test this notion, we determined whether the common lipophilic pollutants benzo[a]pyrene and diesel exhaust particles impact on the activation of lipid-specific T cells. Our results demonstrated that the expression of CD1a and CD1d proteins, and the activation of CD1a- and CD1d-restricted T cells were sensitively inhibited by benzo[a]pyrene even at the low concentrations detectable in exposed human populations...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#6
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507805/generation-and-functional-characterization-of-mdsc-like-cells
#7
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/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#8
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505536/design-synthesis-molecular-docking-and-cytotoxic-evaluation-of-novel-2-furybenzimidazoles-as-vegfr-2-inhibitors
#9
Mona A Abdullaziz, Heba T Abdel-Mohsen, Ahmed M El Kerdawy, Fatma A F Ragab, Mamdouh M Ali, Sherifa M Abu-Bakr, Adel S Girgis, Hoda I El Diwani
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21...
April 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28490670/leukotriene-b4-antagonism-ameliorates-experimental-lymphedema
#10
Wen Tian, Stanley G Rockson, Xinguo Jiang, Jeanna Kim, Adrian Begaye, Eric M Shuffle, Allen B Tu, Matthew Cribb, Zhanna Nepiyushchikh, Abdullah H Feroze, Roham T Zamanian, Gundeep S Dhillon, Norbert F Voelkel, Marc Peters-Golden, Jan Kitajewski, J Brandon Dixon, Mark R Nicolls
Acquired lymphedema is a cancer sequela and a global health problem currently lacking pharmacologic therapy. We have previously demonstrated that ketoprofen, an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory properties, effectively reverses histopathology in experimental lymphedema. We show that the therapeutic benefit of ketoprofen is specifically attributable to its inhibition of the 5-lipoxygenase metabolite leukotriene B4 (LTB4). LTB4 antagonism reversed edema, improved lymphatic function, and restored lymphatic architecture in the murine tail model of lymphedema...
May 10, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28482233/activated-akt-mtor-autophagy-in-local-t-cells-of-oral-lichen-planus
#11
Na Zhang, Jing Zhang, Ya-Qin Tan, Ge-Fei Du, Rui Lu, Gang Zhou
Oral lichen planus (OLP) is a chronic inflammatory disease regulated by T cell-mediated immune response. Autophagy and its major inhibitory pathway Akt/mTOR participate in T cell metabolism and homeostasis, which has been implicated in autoimmune diseases. In this study, the potential involvement of autophagy and its regulatory Akt/mTOR pathway were investigated in local T cells of OLP. The expression of Akt/mTOR pathway and autophagy-related proteins in OLP local lesions, as well as in T cells, were measured by immunohistochemistry and double-labeling immunofluorescence, respectively...
May 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28477140/chondroitin-sulfate-impairs-neural-stem-cell-migration-through-rock-activation
#12
Layla T Galindo, Mayara T V V Mundim, Agnes S Pinto, Gabrielly M D Chiarantin, Maíra E S Almeida, Marcelo L Lamers, Alan R Horwitz, Marinilce F Santos, Marimelia Porcionatto
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site...
May 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28469254/immune-checkpoint-protein-vista-critically-regulates-the-il-23-il-17-inflammatory-axis
#13
Na Li, Wenwen Xu, Ying Yuan, Natarajan Ayithan, Yasutomo Imai, Xuesong Wu, Halli Miller, Michael Olson, Yunfeng Feng, Yina H Huang, Mary Jo Turk, Samuel T Hwang, Subramaniam Malarkannan, Li Wang
V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an inhibitory immune-checkpoint molecule that suppresses CD4(+) and CD8(+) T cell activation when expressed on antigen-presenting cells. Vsir (-/-) mice developed loss of peripheral tolerance and multi-organ chronic inflammatory phenotypes. Vsir (-/-) CD4(+) and CD8(+) T cells were hyper-responsive towards self- and foreign antigens. Whether or not VISTA regulates innate immunity is unknown. Using a murine model of psoriasis induced by TLR7 agonist imiquimod (IMQ), we show that VISTA deficiency exacerbated psoriasiform inflammation...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28468652/-epicatechin-3-o-%C3%AE-d-allopyranoside-prevent-ovariectomy-induced-bone-loss-in-mice-by-suppressing-rankl-induced-nf-%C3%AE%C2%BAb-and-nfatc-1-signaling-pathways
#14
Hung-Bo Hsiao, Jin-Bin Wu, Wen-Chuan Lin
BACKGROUND: Davallia formosana Hayata is a herb that has been used in Chinese medicine to treat bone diseases, including arthritis, bone fractures and osteoporosis. The rhizome of D. formosana H. has been found to be rich in (-)-Epicatechin 3-O-β-D-allopyranoside (ECAP), which is considered to be the active component of the plant in terms of its antiosteoporotic effect. This study investigated the molecular mechanism of the antiosteoporotic property of ECAP isolated from the roots of D...
May 3, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28466814/association-of-leukemia-inhibitory-factor-gene-polymorphism-and-in-vitro-fertilization-outcome-in-a-population-in-northern-iran
#15
M Alipour, F Mashayekhi, Z Salehi
Several studies have been demonstrated that endometrial leukemia inhibitory factor (LIF) is important in embryo implantation. LIF is a secreted glycoprotein with a variety of biological functions including stimulation of cell proliferation, differentiation and survival that are all essential for blastocyete development and implantation. The LIF receptor activates several signaling pathways in diverse cell types, including Jak/STAT, MAPK and PI3-kinase pathways in the endometrium of fertile woman. It has been suggested that the initial lower expression of LIF in proliferative phase may be one of the causes for multiple failure of implantation...
March 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#16
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28461179/immune-characterization-of-the-programmed-death-receptor-pathway-in-high-risk-prostate%C3%A2-cancer
#17
Wesley Baas, Svetlana Gershburg, Danuta Dynda, Kristin Delfino, Kathy Robinson, Daotai Nie, Jennifer Holmes Yearley, Shaheen Alanee
BACKGROUND: Programmed cell death-1 (PD-1), a T-cell inhibitory receptor, and its ligand, PD-L1, have been reported to be expressed in many tumor types, and this expression has led to the development of many drugs targeting the PD-1 pathway. The objective of this study was to determine the expression of PD-1 and PD-L1 in high-grade prostate cancer tissues, and correlate the expression with disease and patient characteristics. MATERIALS AND METHODS: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed and scored from 0 to 5 on prostatectomy/biopsy tissue samples taken from 25 men with high-grade prostate cancer...
April 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28456467/dysfunctional-t-cell-metabolism-in-the-tumor-microenvironment
#18
REVIEW
Kathryn E Beckermann, Stephanie O Dudzinski, Jeffrey C Rathmell
Metabolic and signaling pathways are integrated to determine T cell fate and function. As stimulated T cells gain distinct effector functions, specific metabolic programs and demands are also adopted. These changes are essential for T cell effector function, and alterations or dysregulation of metabolic pathways can modulate T cell function. One physiological setting that impacts T cell metabolism is the tumor microenvironment. The metabolism of cancer cells themselves can limit nutrients and accumulate waste products...
April 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28454312/treatment-with-a-selenium-platinum-compound-induced-t-cell-acute-lymphoblastic-leukemia-lymphoma-cells-apoptosis-through-the-mitochondrial-signaling-pathway
#19
Feifei Wu, Wei Cao, Huaping Xu, Mingxia Zhu, Jing Wang, Xiaoyan Ke
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454090/peroxiredoxin-6-overexpression-attenuates-lipopolysaccharide-induced-acute-kidney-injury
#20
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...
April 10, 2017: Oncotarget
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