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T cell proliferation

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https://www.readbyqxmd.com/read/28822832/combined-immunodeficiency-with-ebv-positive-b-cell-lymphoma-and-epidermodysplasia-verruciformis-due-to-a-novel-homozygous-mutation-in-rasgrp1
#1
Craig D Platt, Ari J Fried, Rodrigo Hoyos-Bachiloglu, G Naheed Usmani, Birgitta Schmidt, Jennifer Whangbo, Roberto Chiarle, Janet Chou, Raif S Geha
RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4(+) T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma...
August 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28822831/ifna-as1-regulates-cd4-t-cell-activation-in-myasthenia-gravis-though-hla-drb1
#2
Mengchuan Luo, Xiaofang Liu, Huanyu Meng, Liqun Xu, Yi Li, Zhibin Li, Chang Liu, Yuebei Luo, Bo Hu, Yuanyuan Xue, Yu Liu, Zhaohui Luo, Huan Yang
Abnormal CD4(+)T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4(+) cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model...
August 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28822698/staphylococcus-aureus-from-atopic-dermatitis-skin-alters-cytokine-production-triggered-by-monocyte-derived-langerhans-cell
#3
Kazumasa Iwamoto, Masaya Moriwaki, Yoshie Niitsu, Masachika Saino, Shunsuke Takahagi, Junzo Hisatsune, Motoyuki Sugai, Michihiro Hide
BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The skin of patients with AD presents as a disbalance of the microbiome with a strong colonization by Staphylococcus aureus, which positively correlates with the severity of the disease. However, the effect of colonized S. aureus on the skin immune system has not been fully elucidated. OBJECTIVE: The aim of this study is to explore whether S. aureus isolated from AD skin is able to skew T cell responses via Langerhans cells (LC) as compared to a standard strain of S...
August 5, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28822407/-clinical-observation-on-the-effect-of-glucocorticoid-insensitivity-on-sudden-sensorineural-hearing-loss-patients
#4
J Hou, H Qi, Y H Dai, X M Wei, L Lu, J G Wang, W D She
Objective: To investigate the correlation between the proliferation inhibition effect of glucocorticoid (GC) on peripheral blood mononuclear cell (PBMC) and the pure tone average (PTA) improvement in SSNHL patients. Methods: Sixty inpatients with SSNHL were included from July 2013 to October 2015 in Nanjing Drum Tower Hospital, Medical School of Nanjing University. Peripheral venous blood was collected before receiving treatment, then the PBMC was isolated for GC proliferation inhibition. PBMCs of each patient were cultivated into 4 groups: Group A: PBMCs+ Medium; Group B: PBMCs+ Medium+ lipopolysaccharide (LPS, 1 μmol/L); Group C: PBMCs+ Medium+ LPS+ Dexamethasone; Group D: Medium...
August 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#5
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/28822225/altered-thymocyte-and-t-cell-development-in-neonatal-mice-with-hyperoxia-induced-lung-injury
#6
Sowmya Angusamy, Tamer Mansour, Mohammed Abdulmageed, Rachel Han, Brian C Schutte, John LaPres, Jack R Harkema, Said A Omar
BACKGROUND: The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. METHODS: Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation...
August 19, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28821816/an-expandable-embryonic-stem-cell-derived-purkinje-neuron-progenitor-population-that-exhibits-in-vivo-maturation-in-the-adult-mouse-cerebellum
#7
Gustavo A Higuera, Grazia Iaffaldano, Meiwand Bedar, Guy Shpak, Robin Broersen, Shashini T Munshi, Catherine Dupont, Joost Gribnau, Femke M S de Vrij, Steven A Kushner, Chris I De Zeeuw
The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821752/hybrid-nitric-oxide-donor-and-its-carrier-for-the-treatment-of-peripheral-arterial-diseases
#8
Duong Q Le, Aneetta E Kuriakose, Dat X Nguyen, Kytai T Nguyen, Suchismita Acharya
Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821558/defective-cyclin-b1-induction-in-trastuzumab-emtansine-t-dm1-acquired-resistance-in-her2-positive-breast-cancer
#9
MohammadA Sabbaghi, Gabriel Gil-Gómez, Cristina Guardia, Sonia Servitja, Oriol Arpi, Sara García-Alonso, Silvia Menéndez, Montserrat Arumi-Uria, Laia Serrano, Marta Salido, Aura Muntasell, Maria Martinez-Garcia, Sandra Zazo, Cristina Chamizo, Paula González-Alonso, Juan Madoz-Gúrpide, Pilar Eroles, Joaquin Arribas, Ignasi Tusquets, Ana Lluch, Atanasio Pandiella, Federico Rojo, Ana Rovira, Joan Albanell
Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2 positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance. <p>Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3 and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821531/cd28-and-41bb-costimulation-enhances-the-effector-function-of-cd19-specific-engager-t-cells
#10
Mireya Paulina Velasquez, Arpad Szoor, Abishek Vaidya, Aarohi Thakkar, Phuong Nguyen, Meng-Fen Wu, Hao Liu, Stephen Gottschalk
T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3zeta and CD28 or 41BB have potent antitumor activity in early phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs (engager [ENG] T cells). Since BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells...
August 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28820501/interleukin-armed-chimeric-antigen-receptor-modified-t-cells-for-cancer-immunotherapy
#11
REVIEW
Y Huang, D Li, D-Y Qin, H-F Gou, W Wei, Y-S Wang, Y-Q Wei, W Wang
Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28819429/map2k1-mutation-in-colorectal-cancer-patients-therapeutic-challenge-using-patient-derived-tumor-cell-lines
#12
J E Kim, K K Kim, S Y Kim, J Lee, S H Park, J O Park, Y S Park, H Y Lim, W K Kang, S T Kim
BACKGROUND: The MAP2K1 K57T mutation is known to be a potential mechanism of primary and secondary resistance to EGFR inhibitors in metastatic colorectal cancer (CRC) and has also been reported to promote resistance to BRAF and MEK inhibitors. It is important to overcome therapeutic resistance to EGFR inhibitors to improve the treatment outcomes of metastatic CRC. METHODS: We established patient-derived tumor cells (PDCs) from metastatic lesions that newly appeared during treatment with a BRAF inhibitor (LGX-818) plus an EGFR inhibitor (cetuximab) in a patient with BRAF-mutant CRC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819400/rapid-breast-cancer-disease-progression-following-cyclin-dependent-kinase-4-and-6-inhibitor-discontinuation
#13
Sami I Bashour, Iman Doostan, Khandan Keyomarsi, Vicente Valero, Naoto T Ueno, Powel H Brown, Jennifer K Litton, Kimberly B Koenig, Meghan Karuturi, Sausan Abouharb, Debasish Tripathy, Stacy L Moulder-Thompson, Nuhad K Ibrahim
Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819383/metformin-inhibits-tumorigenesis-and-tumor-growth-of-breast-cancer-cells-by-upregulating-mir-200c-but-downregulating-akt2-expression
#14
Jiali Zhang, Gefei Li, Yuan Chen, Lei Fang, Chen Guan, Fumao Bai, Mengni Ma, Jianxin Lyu, Qing H Meng
Background: Metformin has been reported to inhibit the growth of various types of cancers, including breast cancer. Yet the mechanisms underlying the anticancer effects of metformin are not fully understood. Growing evidence suggests that metformin's anticancer effects are mediated at least in part by modulating microRNAs, including miR-200c, which has a tumor suppressive role in breast cancer. We hypothesized that miR-200c has a role in the antitumorigenic effects of metformin on breast cancer cells. Methods: To delineate the role of miR-200c in the effects of metformin on breast cancer, plasmids containing pre-miR-200c or miR-200c inhibitor were transfected into breast cancer cell lines...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819257/cytolytic-dna-vaccine-encoding-lytic-perforin-augments-the-maturation-of-and-antigen-presentation-by-dendritic-cells-in-a-time-dependent-manner
#15
Danushka K Wijesundara, Wenbo Yu, Ben J C Quah, Preethi Eldi, John D Hayball, Kerrilyn R Diener, Ilia Voskoboinik, Eric J Gowans, Branka Grubor-Bauk
The use of cost-effective vaccines capable of inducing robust CD8(+) T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8(+) T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8(+) T cell immunity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819023/therapeutic-effects-of-xpo1-inhibition-in-thymic-epithelial-tumors
#16
Fabio Conforti, Xu Zhang, Guanhua Rao, Tommaso De Pas, Yoko Yonemori, Jose A Rodriguez, Justine N McCutcheon, Raneen Rahhal, Anna T Alberobello, Yisong Wang, Yu-Wen Zhang, Udayan Guha, Giuseppe Giaccone
Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818973/mutations-in-the-promoter-of-the-telomerase-gene-tert-contribute-to-tumorigenesis-by-a-two-step-mechanism
#17
Kunitoshi Chiba, Franziska K Lorbeer, A Hunter Shain, David T McSwiggen, Eva Schruf, Areum Oh, Jekwan Ryu, Xavier Darzacq, Boris C Bastian, Dirk Hockemeyer
TERT promoter mutations (TPMs) are the most common non-coding mutations in cancer. The timing and consequences of TPMs have not been fully established. Here we show that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance. In vitro experiments revealed that TPMs do not prevent telomere attrition, resulting in cells with critically short and unprotected telomeres. Immortalization by TPMs requires a gradual upregulation of telomerase, coinciding with telomere fusions...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818867/exploring-potential-germline-associated-roles-of-the-trim-nhl-protein-nhl-2%C3%A2-through-rnai-screening
#18
Gregory M Davis, Wai Y Low, Joshua W T Anderson, Peter R Boag
TRIM-NHL proteins are highly conserved regulators of developmental pathways in vertebrates and invertebrates. The TRIM-NHL family member, NHL-2 in Caenorhabditis elegans functions as a miRNA cofactor to regulate developmental timing. Similar regulatory roles have been reported in other model systems, with the mammalian orthologue in mice, TRIM32, contributing to muscle and neuronal cell proliferation via miRNA activity. Given the interest associated with TRIM-NHL family proteins, we aimed to further investigate the role of NHL-2 in C...
August 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28817833/fmnl2-destabilises-commd10-to-activate-nf-%C3%AE%C2%BAb-pathway-in-invasion-and-metastasis-of-colorectal-cancer
#19
S S Yang, X M Li, M Yang, X L Ren, J L Hu, X H Zhu, F F Wang, Z C Zeng, J Y Li, Z Q Cheng, W T Liao, Y Q Ding, J Guan, L Liang
BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817660/cited4-is-related-to-cardiogenic-induction-and-maintenance-of-proliferation-capacity-of-embryonic-stem-cell-derived-cardiomyocytes-during-in-vitro-cardiogenesis
#20
Junichiro Miake, Tomomi Notsu, Katsumi Higaki, Kyoko Hidaka, Takayuki Morisaki, Kazuhiro Yamamoto, Ichiro Hisatome
Cardiac progenitor cells have a limited proliferative capacity. The CREB-binding protein/p300-interacting transactivator, with the Glu/Asp-rich carboxy-terminal domain (Cited) gene family, regulates gene transcription. Increased expression of the Cited4 gene in an adult mouse is associated with exercise-induced cardiomyocyte hypertrophy and proliferation. However, the expression patterns and functional roles of the Cited4 gene during cardiogenesis are largely unknown. Therefore, in the present study, we investigated the expression patterns and functional roles of the Cited4 gene during in vitro cardiogenesis...
2017: PloS One
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