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https://www.readbyqxmd.com/read/28192403/a-double-negative-feedback-loop-between-epcam-and-erk-contributes-to-the-regulation-of-epithelial-mesenchymal-transition-in-cancer
#1
N V Sankpal, T P Fleming, P K Sharma, H J Wiedner, W E Gillanders
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28174027/forkhead-box-p3-regulatory-t-cells-and-toll-like-receptor-2-co-expression-in-oral-squamous-cell-carcinoma
#2
H M Hussaini, V P B Parachuru, G J Seymour, A M Rich
BACKGROUND: The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3(+)cells, TLR2(+) cells and double-labelled FoxP3(+)TLR2(+) immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF)...
February 4, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28166225/the-composition-of-t-cell-subtypes-in-duodenal-biopsies-are-altered-in-coeliac-disease-patients
#3
Janni V Steenholt, Christian Nielsen, Leen Baudewijn, Anne Staal, Karina S Rasmussen, Hardee J Sabir, Torben Barington, Steffen Husby, Henrik Toft-Hansen
One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+) and the number of CD3+ CD4- CD8- double-negative (DN) T cells were elevated 6-7 fold in children with CD...
2017: PloS One
https://www.readbyqxmd.com/read/28159903/cd31-a-valuable-marker-to-identify-early-and-late-stages-of-t-cell-differentiation-in-the-human-thymus
#4
Marc Douaisi, Rachel S Resop, Maho Nagasawa, Joshua Craft, Beth D Jamieson, Bianca Blom, Christel H Uittenbogaart
Although CD31 expression on human thymocytes has been reported, a detailed analysis of CD31 expression at various stages of T cell development in the human thymus is missing. In this study, we provide a global picture of the evolution of CD31 expression from the CD34(+) hematopoietic precursor to the CD45RA(+) mature CD4(+) and CD8(+) single-positive (SP) T cells. Using nine-color flow cytometry, we show that CD31 is highly expressed on CD34(+) progenitors and stays high until the early double-positive stage (CD3(-)CD4(+)CD8α(+)β(-))...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159235/commercial-gold-nanocolloid-inhibits-synthesis-of-il-2-and-proliferation-of-porcine-t-lymphocytes
#5
Joanna Małaczewska, Roman Wójcik, Edyta Kaczorek, Wojciech Rękawek, Andrzej Krzysztof Siwicki
Recent intensive development of nanotechnology has broadened the use of noble metal nanocolloids in alternative medicine. Meanwhile, silver and copper nanoparticles are tested as potential feed additives in pig farming. Experiments on rodents prove that metal nanocolloids easily interact with macrophages and lymphocytes, although the specific nature of pigs' immune system means that rodent tests may not reflect fully the responsiveness of porcine T cells. Our purpose was to demonstrate the effect of a commercial gold nanocolloid on percentages and proliferation of T lymphocyte subpopulations and on IL-2 and IL-10 synthesis in porcine peripheral blood mononuclear cells tested in vitro...
February 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28149711/hepatic-caveolin-1-is-enhanced-in-cyp27a1-apoe-double-knockout-mice
#6
Line Zurkinden, Yosef T Mansour, Beatrice Rohrbach, Bruno Vogt, Hiten D Mistry, Geneviève Escher
Sterol 27-hydroxylase (CYP27A1) is involved in bile acid synthesis and cholesterol homoeostasis. Cyp27a1((-/-))/Apolipoprotein E((-/-)) double knockout mice (DKO) fed a western diet failed to develop atherosclerosis. Caveolin-1 (CAV-1), the main component of caveolae, is associated with lipid homoeostasis and has regulatory roles in vascular diseases. We hypothesized that liver CAV-1 would contribute to the athero-protective mechanism in DKO mice. Cyp27a1((+/+))/ApoE((-/-)) (ApoE KO), Cyp27a1((+/-))/ApoE((-/-)) (het), and DKO mice were fed a western diet for 2 months...
October 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28138401/t-cadherin-in-prostate-cancer-relationship-with-cancer-progression-differentiation-and-drug-resistance
#7
Boris Dasen, Tatjana Vlajnic, Chantal Mengus, Christian Ruiz, Lukas Bubendorf, Giulio Spagnoli, Stephen Wyler, Paul Erne, Thérèse J Resink, Maria Philippova
Prostate cancer represents the second leading cause of cancer-related death in men. T-cadherin (CDH13) is an atypical GPI-anchored member of the cadherin family of adhesion molecules. Its gene was reported to be downregulated in a small series of prostate tumours. T-cadherin protein expression/localisation in prostate tissue has never been investigated. The purpose of our study was to analyse CDH13 gene and protein levels in large sets of healthy and cancer prostate tissue specimens and evaluate CDH13 effects on the sensitivity of prostate cancer cells to chemotherapy...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28137643/mlf1-is-a-proapoptotic-antagonist-of-hop-complex-mediated-survival
#8
Yi Sun, Jyh-Rong Chao, Wu Xu, Alan Pourpak, Kelli Boyd, Simon Moshiach, Guo-Yan Qi, Amina Fu, Hua-Rong Shao, Stanley Pounds, Stephan W Morris
In the HAX1/HtrA2-OMI/PARL (HOP) mitochondrial protein complex, anti-apoptotic signals are generated by cleavage and activation of the serine protease HtrA2/OMI by the rhomboid protease PARL upon recruitment of both proteases to inner mitochondrial membrane protein HAX1 (HS1-associated protein X-1). Here we report the negative regulation of the HOP complex by human leukemia-associated myeloid leukemia factor 1 (MLF1). We demonstrate that MLF1 physically and functionally associates with HAX1 and HtrA2. Increased interaction of MLF1 with HAX1 and HtrA2 displaces HtrA2 from the HOP complex and inhibits HtrA2 cleavage and activation, resulting in the apoptotic cell death...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28135253/alternative-pathway-for-the-development-of-v%C3%AE-14-nkt-cells-directly-from-cd4-cd8-thymocytes-that-bypasses-the-cd4-cd8-stage
#9
Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi
Although invariant Vα14(+) natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28129978/synthesis-and-biological-evaluation-of-2-alkoxycarbonylallyl-esters-as-potential-anticancer-agents
#10
Conor T Ronayne, Lucas N Solano, Grady L Nelson, Erica A Lueth, Skyler L Hubbard, Tanner J Schumacher, Zachary S Gardner, Sravan K Jonnalagadda, Shirisha Gurrapu, Jon Holy, Venkatram R Mereddy
The reaction of carboxylic acids with Baylis-Hillman reaction derived α-bromomethyl acrylic esters readily provide 2-(alkoxycarbonyl)allyl esters in good to excellent yields. These functionalized allyl esters have been evaluated for their cell proliferation inhibition properties against breast cancer (MDA-MB-231 and 4T1) and pancreatic cancer (MIAPaCa-2) cell lines to explore their potential as anticancer agents. Several of the synthesized derivatives exhibit good potency against all three cancer cell lines...
January 17, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28128277/primary-cutaneous-aggressive-epidermotropic-cytotoxic-t-cell-lymphomas-reappraisal-of-a-provisional-entity-in-the-2016-who-classification-of-cutaneous-lymphomas
#11
Joan Guitart, M Estela Martinez-Escala, Antonio Subtil, Madeleine Duvic, Melissa P Pulitzer, Elise A Olsen, Ellen Kim, Alain H Rook, Sara S Samimi, Gary S Wood, Michael Girardi, Jacqueline Junkins-Hopkins, Doina S Ivan, M Angelica Selim, Kimberly A Sable, Pooja Virmani, Laura B Pincus, Michael T Tetzlaff, Jinah Kim, Youn H Kim
Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement...
January 27, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28126732/effects-of-n-acetyl-seryl-asparyl-lysyl-proline-on-blood-pressure-renal-damage-and-mortality-in-systemic-lupus-erythematosus
#12
Pablo Nakagawa, Juan X Masjoan-Juncos, Heba Basha, Branislava Janic, Morel E Worou, Tang-Dong Liao, Cesar A Romero, Edward L Peterson, Oscar A Carretero
Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE-Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac-SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE-Hyp, Ac-SDKP prevents hypertension and renal damage by modulating T cells...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#13
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28062540/adiponectin-association-with-t-cadherin-protects-against-neointima-proliferation-and-atherosclerosis
#14
Yuya Fujishima, Norikazu Maeda, Keisuke Matsuda, Shigeki Masuda, Takuya Mori, Shiro Fukuda, Ryohei Sekimoto, Masaya Yamaoka, Yoshinari Obata, Shunbun Kita, Hitoshi Nishizawa, Tohru Funahashi, Barbara Ranscht, Iichiro Shimomura
Adiponectin, an adipocyte-derived protein abundant in the circulation, is thought to be protective against atherosclerosis. However, it is not fully understood how the association of adiponectin with vascular cells and its antiatherogenic effect are connected. In this study, T-cadherin was essential for accumulation of adiponectin in the neointima and atherosclerotic plaque lesions, and the adiponectin-T-cadherin association protected against vascular injury. In the apolipoprotein E-knockout (ApoE-KO) mice, adiponectin, and T-cadherin colocalized on endothelial cells and synthetic smooth muscle cells in the aortic intima...
January 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28060545/safety-and-immunogenicity-of-adenovirus-35-tb-vaccine-candidate-in-adults-with-active-or-previous-tb-a-randomized-trial
#15
Richard N van Zyl-Smit, Aliasgar Esmail, Mary E Bateman, Rodney Dawson, Jonathan Goldin, Eva van Rikxoort, Macaya Douoguih, Maria Grazia Pau, Jerald C Sadoff, J Bruce McClain, Margaret Ann Snowden, Jacqueline Benko, David A Hokey, Kathryn Tucker Rutkowski, Andrew Graves, Barbara Shepherd, Sadritdin Ishmukhamedov, Benjamin M N Kagina, Brian Abel, Willem A Hanekom, Thomas J Scriba, Eric D Bateman
RATIONALE: Administration of tuberculosis vaccines in participants with previous or current pulmonary tuberculosis may have the potential for causing harmful post-vaccination immunological (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored tuberculosis candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary tuberculosis...
January 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28052400/programmed-death-1-ligand-1-and-2-expression-in-cutaneous-squamous-cell-carcinoma-and-their-relationship-with-tumor-infiltrating-dendritic-cells
#16
Qingqing Jiao, Cuiping Liu, Wenzhong Li, Wei Li, Fuming Fang, Qihong Qian, Xueguang Zhang
The Programmed Death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are costimulatory molecules that contribute to the negative regulation of T-lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumor infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyze PD-L1 and PD-L2 expression and dendritic cells (DCs) infiltration in tumor tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a, and CD83 in 61 CSCC tissues...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28043488/development-of-the-food-supplement-nyaditum-resae-as-a-new-tool-to-reduce-the-risk-of-tuberculosis-development
#17
Nestani Tukvadze, Paula Cardona, Sergo Vashakidze, Natalia Shubladze, Zaza Avaliani, Cris Vilaplana, Pere-Joan Cardona
Nyaditum resae (NR) is a galenic preparation of heat-killed Mycobacterium manresensis (hkMn). This is a new species that belongs to the Mycobacterium fortuitum complex, and it is present in drinking water-thus, regulatorily speaking, it is considered a food supplement. Preclinical studies in the murine model of active tuberculosis (TB) in the C3HeB/FeJ strain have demonstrated that daily administration of NR containing 10(3)-10(6)hkMn for 14days was able to stop the progression toward active TB [1]. The mechanism of action was linked to the induction of low dose tolerance and was related to the increase of Tuberculin Purified Protein Derivative (PPD) memory-specific Tregs (CD4(+)CD25(+)CD39(+) cells) after ex vivo incubation of splenocytes for 7days...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28040323/environmental-factor-and-inflammation-driven-alteration-of-the-total-peripheral-t-cell-compartment-in-granulomatosis-with-polyangiitis
#18
Anja Kerstein, Silke Schüler, Otávio Cabral-Marques, Juliane Fazio, Robert Häsler, Antje Müller, Silke Pitann, Frank Moosig, Sebastian Klapa, Christian Haas, Dieter Kabelitz, Gabriela Riemekasten, Steffen Wolters, Peter Lamprecht
Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far. In granulomatosis with polyangiitis (GPA), a prototypical autoimmune disorder of unknown aetiology, we performed for the first time a combined approach using phenotyping, transcriptome and functional analyses of T-cell populations to evaluate triggers of memory T-cell expansion...
December 28, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28035433/development-of-t-cells-carrying-two-complementary-chimeric-antigen-receptors-against-glypican-3-and-asialoglycoprotein-receptor-1-for-the-treatment-of-hepatocellular-carcinoma
#19
Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li
Adoptive immunotherapy leveraging chimeric antigen receptor-modified T (CAR-T) cells holds great promise for the treatment of cancer. However, tumor-associated antigens often have low expression levels in normal tissues, which can cause on-target, off-tumor toxicity. Recently, we reported that GPC3-targeted CAR-T cells could eradicate hepatocellular carcinoma (HCC) xenografts in mice. However, it remains unknown whether on-target, off-tumor toxicity can occur. Therefore, we proposed that dual-targeted CAR-T cells co-expressing glypican-3 (GPC3) and asialoglycoprotein receptor 1 (ASGR1) (a liver tissue-specific protein)-targeted CARs featuring CD3ζ and 28BB (containing both CD28 and 4-1BB signaling domains), respectively, may have reduced on-target, off-tumor toxicity...
December 29, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28018346/low-double-negative-cd3-cd4-cd8-t-cells-are-associated-with-incomplete-restoration-of-cd4-t-cells-and-higher-immune-activation-in-hiv-1-immunological-non-responders
#20
Xiaofan Lu, Bin Su, Huan Xia, Xin Zhang, Zhiying Liu, Yunxia Ji, Zixuan Yang, Lili Dai, Luzia M Mayr, Christiane Moog, Hao Wu, Xiaojie Huang, Tong Zhang
Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3(+)CD4(-)CD8(-) T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4(+) T cell count...
2016: Frontiers in Immunology
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