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https://www.readbyqxmd.com/read/28343267/tumor-associated-macrophages-and-regulatory-t-cells-infiltration-and-the-clinical-outcome-in-colorectal-cancer
#1
Dariusz Waniczek, Zbigniew Lorenc, Mirosław Śnietura, Mariusz Wesecki, Agnieszka Kopec, Małgorzata Muc-Wierzgoń
The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68(+)/iNOS(-) and Tregs CD8(+)/FoxP3(+) in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases)...
March 25, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#2
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28342759/activation-of-epithelial-stat1-by-interleukin-28-controls-mucosal-healing-in-mice-with-colitis-and-is-increased-in-mucosa-of-patients-with-inflammatory-bowel-disease
#3
Mircea T Chiriac, Barbara Buchen, Alexandra Wandersee, Gheorghe Hundorfean, Claudia Günther, Yvonne Bourjau, Sean E Doyle, Benjamin Frey, Arif B Ekici, Christian Büttner, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Jürgen Siebler, Markus F Neurath
BACKGROUND & AIMS: We investigated the roles of interleukin 28A (also called IL28A or interferon lambda 2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. METHODS: Colitis was induced in C57BL/6JCrl mice (controls), mice with intestinal epithelial cell-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon lambda receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-)...
March 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#4
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28339124/gliadin-reactive-t-cells-in-italian-children-from-preventcd-cohort-at-high-risk-for-celiac-disease
#5
Alessandra Camarca, Renata Auricchio, Stefania Picascia, Olga Fierro, Mariantonia Maglio, Erasmo Miele, Basilio Malamisura, Luigi Greco, Riccardo Troncone, Carmen Gianfrani
BACKGROUND: Newborns at high risk for celiac disease (CD) were recruited in Italy in the context of the PreventCD Study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T cell reactivity to gliadin at the first clinical and/or serological signs of CD. METHODS: Gliadin-reactive T cell lines were generated from intestinal biopsies of 19 HLA-DQ2 or HLA-DQ8 positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls...
March 24, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28339085/integrated-analysis-of-mrna-and-mirna-expression-profiles-in-pancreatic-ductal-adenocarcinoma
#6
Hongwei Sun, Liang Zhao, Kehua Pan, Zhao Zhang, Mengtao Zhou, Guoquan Cao
In the present study, to investigate the potential molecular mechanism of pancreatic ductal adenocarcinoma (PDAC), mRNA and miRNA expression profiles were integrated for systematic analysis. Results showed that a total of 76 common differentially expressed genes (DEGs) were identified from 2 mRNA expression profiles that contained 39 tumor and 15 normal samples. Notably, the tumor and normal samples were able to be clearly classified into 4 groups based on the DEGs. mRNA‑miRNA regulation network analysis indicated that 22 out of the 76 DEGs including MUC4, RRM2 and CCL2 are regulated by 5 reported miRNAs...
March 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28338671/regulatory-b-cell-myeloma-cell-interaction-confers-immunosuppression-and-promotes-their-survival-in-the-bone-marrow-milieu
#7
L Zhang, Y-T Tai, M Ho, L Xing, D Chauhan, A Gang, L Qiu, K C Anderson
No abstract text is available yet for this article.
March 24, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28338207/evaluation-of-failed-immunotherapy-among-patients-with-negative-apla-recurrent-spontaneous-abortion-by-serum-anticardiolipin-antibodies-and-mononuclear-cell-of-tim-1
#8
J Li, D Xu, H-L Li
OBJECTIVE: The present study is aimed to analyze the expression of serum anticardiolipin antibody (ACA) and mononuclear cells of Tim-1 among the patients with negative anti paternal lymphocyte antibody (APLA) recurrent spontaneous abortion conducted by lymphocyte immunotherapy resulting in failure. PATIENTS AND METHODS: 58 patients with negative APLA recurrent spontaneous abortion (RSA) who was diagnosed for the first time and received lymphocyte immunotherapy in our hospital were selected continuously...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28338007/human-immunodeficiency-virus-type-1-myeloid-derived-suppressor-cells-inhibit-cytomegalovirus-inflammation-through-interleukin-27-and-b7-h4
#9
Ankita Garg, Rodney Trout, Stephen A Spector
HIV/CMV co-infected persons despite prolonged viral suppression often experience persistent immune activation, have an increased frequency of myeloid derived suppressor cells (MDSC) and are at increased risk for cardiovascular disease. We examined how HIV MDSC control CD4(+) T cell IFNγ response to a CMVpp65 peptide pool (CMVpp65). We show that HIV/CMV co-infected persons with virologic suppression and recovered CD4(+) T cells compared to HIV(-)/CMV(+) controls exhibit an increase in CD4(+)CX3CR1(+)IFNγ(+) cells in response to CMVpp65; MDSC depletion further augmented CD4(+)CX3CR1(+)IFNγ(+) cells and IFNγ production...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337964/targeting-cd47-enhances-the-efficacy-of-anti-pd-1-and-ctla-4-in-esophageal-squamous-cell-cancer-preclinical-model
#10
Hua Tao, Pudong Qian, Feijiang Wang, Hongliang Yu, Yesong Guo
Esophageal squamous cell cancer is a highly aggressive cancer with dismal five-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presenting of the immune system. Via interacting with signal regulatory protein-alpha expressed in antigen presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APCs dependent antigen presenting. Overxpression of CD47 was found in various cancer types. However, its role in esophageal squamous cell cancer is not clear yet...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28337881/indoleamine-2-3-dioxygenase-and-regulatory-t-cells-in-intestinal-mucosa-in-children-with-inflammatory-bowel-disease
#11
K Sznurkowska, A Żawrocki, J Sznurkowski, E Iżycka-Świeszewska, P Landowski, A Szlagatys-Sidorkiewicz, K Plata-Nazar, B Kamińska
Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337254/amp-activated-protein-kinase-and-energy-balance-in-breast-cancer
#12
REVIEW
Hong Zhao, Yelda C Orhan, Xiaoming Zha, Ecem Esencan, Robert T Chatterton, Serdar E Bulun
Cancer growth and metastasis depends on the availability of energy. Energy-sensing systems are critical in maintaining a balance between the energy supply and utilization of energy for tumor growth. A central regulator in this process is AMP-activated protein kinase (AMPK). In times of energy deficit, AMPK is allosterically modified by the binding of increased levels of AMP and ADP, making it a target of specific AMPK kinases (AMPKKs). AMPK signaling prompts cells to produce energy at the expense of growth and motility, opposing the actions of insulin and growth factors...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337197/hypofractionated-irradiation-has-immune-stimulatory-potential-and-induces-a-timely-restricted-infiltration-of-immune-cells-in-colon-cancer-tumors
#13
Benjamin Frey, Michael Rückert, Julia Weber, Xaver Mayr, Anja Derer, Michael Lotter, Christoph Bert, Franz Rödel, Rainer Fietkau, Udo S Gaipl
In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28336371/novel-adaptive-and-innate-immunity-targets-in-hypertension
#14
REVIEW
Justine M Abais-Battad, John Henry Dasinger, Daniel J Fehrenbach, David L Mattson
Hypertension is a worldwide epidemic and global health concern as it is a major risk factor for the development of cardiovascular diseases. A relationship between the immune system and its contributing role to the pathogenesis of hypertension has been long established, but substantial advancements within the last few years have dissected specific causal molecular mechanisms. This review will briefly examine these recent studies exploring the involvement of either innate or adaptive immunity pathways. Such pathways to be discussed include innate immunity factors such as antigen presenting cells and pattern recognition receptors, adaptive immune elements including T and B lymphocytes, and more specifically, the emerging role of T regulatory cells, as well as the potential of cytokines and chemokines to serve as signaling messengers connecting innate and adaptive immunity...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336310/regulatory-role-of-ccl5-rs2280789-and-cxcl10-rs56061981-gene-polymorphisms-on-intracellular-ccl5-and-cxcl10-expression-in-pulmonary-tuberculosis
#15
Brijendra Singh, Selvaraj Anbalagan, Paramasivam Selvaraj
Genetic variations in chemokine genes influence the chemoattractive properties of T cells which may be associated with outcome of infections. In present study, we have investigated the regulatory role played by In1.1T/C (rs2280789) polymorphism of CCL5 and -135G/A (rs56061981) polymorphism of CXCL10 gene on intracellular CCL5 and CXCL10 expression in T cells. Whole blood cell cultures were stimulated with culture filtrate antigen (CFA) and infected with live M. tuberculosis were used for intracellular CCL5 and CXCL10 expression using flow cytometry...
March 21, 2017: Human Immunology
https://www.readbyqxmd.com/read/28335009/open-chromatin-profiling-of-human-postmortem-brain-infers-functional-roles-for-non-coding-schizophrenia-loci
#16
John F Fullard, Claudia Giambartolomei, Mads E Hauberg, Ke Xu, Georgios Voloudakis, Zhiping Shao, Christopher Bare, Joel T Dudley, Manuel Mattheisen, Nikolaos K Robakis, Vahram Haroutunian, Panos Roussos
Open chromatin provides access to DNA binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS)...
March 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#17
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#18
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333899/-stem-progenitor-cells-in-diseases-of-the-respiratory-tract
#19
EDITORIAL
Tadeusz Płusa
Stem cells (SCs - stem cells) are characterized by plasticity and the ability to differentiate into other cell types. They are obtained from bone marrow, peripheral blood and cord blood. Mesenchymal stem cells (MSCs) shows a broad immunomodulating, increases the number of regulatory T cells (Treg), modifies the activity of T cells, dendritic cells and NK (natural killer). Direct impact on reducing the release of proinflammatory cytokines and increased release of proinflammatory cytokines. Within the respiratory tract has a number of resident stem and progenitor cells referred to as L-MSCs (lung mesenchymal stem cells) whose presence was confirmed by markers as defined in the trachea, epithelial cells and alveolar...
March 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#20
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
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