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T cell proliferation

Elisabeth Salzer, Deniz Cagdas, Miroslav Hons, Emily M Mace, Wojciech Garncarz, Özlem Yüce Petronczki, René Platzer, Laurène Pfajfer, Ivan Bilic, Sol A Ban, Katharina L Willmann, Malini Mukherjee, Verena Supper, Hsiang Ting Hsu, Pinaki P Banerjee, Papiya Sinha, Fabienne McClanahan, Gerhard J Zlabinger, Winfried F Pickl, John G Gribben, Hannes Stockinger, Keiryn L Bennett, Johannes B Huppa, Loïc Dupré, Özden Sanal, Ulrich Jäger, Michael Sixt, Ilhan Tezcan, Jordan S Orange, Kaan Boztug
RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1...
October 24, 2016: Nature Immunology
Zhihong Hu, L Jeffrey Medeiros, Zi Chen, Weina Chen, Shaoying Li, Sergej N Konoplev, Xinyan Lu, Lan V Pham, Ken H Young, Wei Wang, Shimin Hu
MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy...
October 21, 2016: American Journal of Surgical Pathology
Michael S Samuel, Nicola Rath, Siti F Masre, Sarah T Boyle, David A Greenhalgh, Marina Kochetkova, Sheila Bryson, David Stevenson, Michael F Olson
The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER)...
October 24, 2016: Genesis: the Journal of Genetics and Development
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Antigona Ulndreaj, Apostolia Tzekou, Andrea J Mothe, Ahad Siddiqui, Rachel Dragas, Charles Tator, Emina Torlakovic, Michael Fehlings
The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system (CNS), but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery...
October 24, 2016: Journal of Neurotrauma
H van Andel, K A Kocemba, A de Haan-Kramer, C H Mellink, M Piwowar, A Broijl, M van Duin, P Sonneveld, M M Maurice, M J Kersten, M Spaargaren, S T Pals
Deletion or mutation of the gene encoding the deubiquitinating enzyme CYLD is a common genomic aberration in multiple myeloma (MM). However, the functional consequence of CYLD loss and the mechanism underlying its putative role as a tumor suppressor gene in the pathogenesis of MM has not been established. Here, we show that CYLD expression is highly variable in myeloma cell lines and primary MMs and that low CYLD expression is associated with disease progression from monoclonal gammopathy of undetermined significance to MM, and with poor overall and progression free-survival of MM patients...
October 24, 2016: Oncogene
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
T Zhong, Y Men, L Lu, T Geng, J Zhou, A Mitsuhashi, M Shozu, N J Maihle, G G Carmichael, H S Taylor, Y Huang
The molecular mechanisms underlying the antineoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). Exposing cancer cells to metformin leads to hypermethylation of tumor-promoting pathway genes and concomitant inhibition of cell proliferation. Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH...
October 24, 2016: Oncogene
Yayun Jiang, Ting Wang, Jinshu Wang, Jing Xia, Liyao Gou, Mengyao Liu, Yan Zhang
Objective To investigate the effect of overexpressed inhibitor of β-catenin and T cell factor (ICAT) on the proliferation and migration of human cervical cancer Caski cells. Methods Caski cells were transfected with ICAT recombinant adenovirus (AdICAT). The levels of ICAT mRNA and protein were detected by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively. Effect of ICAT overexpression on proliferation, cell cycle and migration in Caski cells was respectively evaluated by MTT assay, flow cytometry and Transwell(TM) migration assays...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Lei Wang, Na Peng, Xiaoyan Hu, Wentao Liang, Kai Liang, Guizhu Peng
Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10(6)/mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs)...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Chun Chen, Zenghong Lu, Jie Yang, Weichao Hao, Yujuan Qin, Huiyan Wang, Congying Xie, Raoying Xie
MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay...
October 24, 2016: Cancer Medicine
M E Cielesh, B M McGrath, C J Scott, S T Norman, C P Stephen
Kisspeptin is a neuropeptide involved in the hypothalamic regulation of reproduction in many species. Recent studies have revealed kisspeptin within the ovaries of rats, Siberian hamsters and humans, indicating a local role in reproduction. However, the role of kisspeptin in the ovary is poorly understood in the bitch. This study investigated the presence and location of kisspeptin protein (KISS1) and kisspeptin receptors (KISS1R) in the canine ovary during different stages of the reproductive cycle (pre-pubertal, anoestrus and cycling) by means of immunohistochemical staining...
October 23, 2016: Reproduction in Domestic Animals, Zuchthygiene
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
J Cvetkovic, L Sofronic-Milosavljevicj, N Ilic, M Gnjatovic, I Nagano, A Gruden-Movsesijan
Excretory-secretory antigens (ES L1) of Trichinella spiralis muscle larvae can induce the semi-matured status of rat dendritic cells (DCs). This may at least partly be the consequence of transient activation of extracellular signal-regulated kinases 1/2 (ERK1/2). Here we investigated the potential of several components of ES L1 (native fraction containing 45, 49 and 53 kDa proteins and recombinant Tsp53, representing one of the constituents of this fraction) to demonstrate previously observed effects of ES L1 on DCs in vitro, characterized by establishment of a particular phenotype (very low MHC II expression, moderate CD86 expression and significant ICAM-1 expression) and functional properties (low production of pro-inflammatory cytokine IL-12p70, and high production of IL-10 and TGF-β)...
October 20, 2016: International Journal for Parasitology
Dongxiao Wang, Wanxian Luo, Ge Wen, Li Yang, Shaofu Hong, Shiyu Zhang, Jianxin Diao, Jianguo Wang, Hongqin Wei, Yingjia Li, Ying Wang
We have fabricated a negative-charged nanoparticle (Heparin-Folate-Tat-Taxol NP, H-F-Tat-T NP) with dual ligands, tumor targeting ligand folate and cell-penetrating peptide Tat, to deliver taxol presenting great anticancer activity for sensitive cancer cells, while it fails to overcome multidrug resistance (MDR) in MCF-7/T cells (taxol-resistant breast cancer cells). Ultrasound (US) can increase the sensitivity of positive-charged NPs thereby making it possible to reverse MDR through inducing NPs' drug release...
January 2017: Ultrasonics Sonochemistry
Taofeek K Owonikoko, Mukesh Kumar, Shu Yang, Alice O Kamphorst, Rathi N Pillai, Rama Akondy, Vivek Nautiyal, Monica S Chatwal, Wendy M Book, Anurag Sahu, Gabriel L Sica, Rafi Ahmed, Suresh S Ramalingam
INTRODUCTION: The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities. MATERIALS AND METHODS: The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples...
October 22, 2016: Cancer Immunology, Immunotherapy: CII
Jens Zierle, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: Teriflunomide, an inhibitor of pyrimidine synthesis and thus proliferation of activated T and B lymphocytes, is successfully used for treatment of inflammatory disease. Teriflunomide has further been shown to trigger apoptosis of tumor cells and has thus been considered for the treatment of malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the cell membrane with translocation of phosphatidylserine to the erythrocyte surface...
October 24, 2016: Cellular Physiology and Biochemistry
Gabriele Picco, Consalvo Petti, Francesco Sassi, Katia Grillone, Giorgia Migliardi, Teresa Rossi, Claudio Isella, Federica Di Nicolantonio, Ivana Sarotto, Anna Sapino, Alberto Bardelli, Livio Trusolino, Andrea Bertotti, Enzo Medico
BACKGROUND: The NEDD8 conjugation pathway modulates the ubiquitination and activity of a wide range of intracellular proteins, and its blockade by pevonedistat is emerging as a promising therapeutic approach in various cancer settings. However, systematic characterization of pevonedistat efficacy in specific tumor types and definition of response predictors are still missing. METHODS: We investigated in vitro sensitivity to pevonedistat in 122 colorectal cancer (CRC) cell lines by an ATP-based proliferation assay and evaluated apoptosis and DNA content by flow cytometry...
February 2017: Journal of the National Cancer Institute
Orna Gera, Efrat Shavit-Stein, Doron Bushi, Sagi Harnof, Marina Ben Shimon, Ronen Weiss, Valery Golderman, Amir Dori, Nicola Maggio, Kate Finegold, Joab Chapman
Thrombin and activated protein C (aPC) bound to the endothelial protein C receptor (EPCR) both activate protease-activated receptor 1 (PAR1) generating either harmful or protective signaling respectively. In the present study we examined the localization of PAR-1 and EPCR and thrombin activity in Schwann glial cells of normal and crushed peripheral nerve and in Schwannoma cell lines. In the sciatic crush model nerves were excised 1 hour, 1, 4, and 7 days after the injury. Schwannoma cell lines produced high levels of prothrombin which is converted to active thrombin and expressed both EPCR and PAR-1 which co-localized...
October 19, 2016: Neuroscience
Wei Peng
G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks...
October 19, 2016: Experimental Neurology
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