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https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#1
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28522600/frontline-science-nasal-epithelial-gm-csf-contributes-to-tlr5-mediated-modulation-of-airway-dendritic-cells-and-subsequent-iga-response
#2
Yuan Cao, Ejuan Zhang, Jingyi Yang, Yi Yang, Jie Yu, Yang Xiao, Wei Li, Dihan Zhou, Yaoming Li, Bali Zhao, Hu Yan, Mengji Lu, Maohua Zhong, Huimin Yan
Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. However, the molecular mechanism leading to modulation and the response by flagellin-activated NECs remain unknown. We aimed to identify the soluble mediator(s) from flagellin-activated NECs that modulate the functions of airway dendritic cells (DCs) and enhance subsequent IgA response...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522366/a-level-set-method-for-multiple-sclerosis-lesion-segmentation
#3
Yue Zhao, Shuxu Guo, Min Luo, Xue Shi, Michel Bilello, Shaoxiang Zhang, Chunming Li
In this paper, we present a level set method for multiple sclerosis (MS) lesion segmentation from FLAIR Images in the presence of intensity inhomogeneities. We use a three-phase level set formulation of segmentation and bias field estimation to segment MS lesions and normal tissue region (including GM and WM) and CSF and the background from FLAIR images. To save computational load, we derive a two-phase formulation from the original multi-phase level set formulation to segment the MS lesions and normal tissue regions...
May 15, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28515356/licensing-delineates-helper-and-effector-nk-cell-subsets-during-viral-infection
#4
Anthony E Zamora, Ethan G Aguilar, Can M Sungur, Lam T Khuat, Cordelia Dunai, G Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R Blazar, Dan L Longo, Jeffrey M Venstrom, Nicole Baumgarth, William J Murphy
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514019/does-dust-associated-pulmonary-alveolar-proteinosis-represent-an-autoimmune-disorder
#5
Bilge Uzmezoglu, Cebrail Simsek, Sevtap Gulgosteren, Berna E Gebesoglu
The role of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the development of secondary pulmonary alveolar proteinosis (PAP) in patients exposed to occupational and environmental dust remains unclear. Herein, we describe two cases of secondary PAP who had GM-CSF antibodies and absence of STAT5 phosphorylation index, suggestive of a potential relationship between the appearance of GM-CSF antibodies and environmental dust exposure. However, whether the presence of GM-CSF antibodies is a part of the pathological process or represents an epiphenomenon is currently unknown...
June 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28513595/hiv-2-infection-is-associated-with-preserved-galt-homeostasis-and-epithelial-integrity-despite-ongoing-mucosal-viral-replication
#6
S M Fernandes, A R Pires, P Matoso, C Ferreira, H Nunes-Cabaço, L Correia, E Valadas, J Poças, P Pacheco, H Veiga-Fernandes, R B Foxall, A E Sousa
The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28512190/hematopoietic-origin-of-langerhans-cell-histiocytosis-and-erdheim-chester-disease-in-adults
#7
Paul Milne, Venetia Bigley, Chris M Bacon, Antoine Néel, Naomi McGovern, Simon Bomken, Muzlifah Haniffa, Eli L Diamond, Benjamin H Durham, Johannes Visser, David Hunt, Harsha Gunawardena, Mac Macheta, Kenneth L McClain, Carl Allen, Omar Abdel-Wahab, Matthew Collin
Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL...
May 16, 2017: Blood
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#8
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507543/long-term-monocyte-dysfunction-after-sepsis-in-humanized-mice-is-related-to-persisted-activation-of-macrophage-colony-stimulation-factor-m-csf-and-demethylation-of-pu-1-and-it-can-be-reversed-by-blocking-m-csf-in-vitro-or-by-transplanting-na%C3%A3-ve-autologous
#9
Natalia Lapko, Mateusz Zawadka, Jacek Polosak, George S Worthen, Gwenn Danet-Desnoyers, Monika Puzianowska-Kuźnicka, Krzysztof Laudanski
The duration of post-sepsis long-term immune suppression is poorly understood. Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several acute conditions, but it is unclear for how long MO aberrancy post-sepsis can persist. Interestingly, the positive feedback loop sustaining secretion of macrophage-colony stimulation factor (M-CSF) can persist even after resolution of sepsis and significantly alters performance of MO...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28506023/optimization-method-of-mri-scan-parameters-of-a-double-inversion-recovery-sequence-using-a-t1-map-and-a-developed-analysis-algorithm
#10
Norio Hayashi, Kazuma Yarita, Kozue Sakata, Shunichi Motegi, Hiroyuki Nagase, Kouichi Ujita, Akio Ogura, Toshihiro Ogura, Takehiro Shimada, Yoshito Tsushima
BACKGROUND: Optimizing scan parameters for double inversion recovery (DIR) sequences remains difficult. OBJECTIVE: To evaluate a new method for optimizing DIR sequence scan parameters using T1 mapping and a newly developed analysis algorithm. METHODS: Twelve healthy volunteers underwent T1 mapping and DIR magnetic resonance imaging. The following steps were used for image optimization including: 1) measurement of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) T1 values to create a T1 map; 2) calculation of optimized scan parameters by using a developed analysis algorithm; 3) performance assessment of DIR magnetic resonance imaging by using the calculated optimized imaging parameters...
May 6, 2017: Journal of X-ray Science and Technology
https://www.readbyqxmd.com/read/28505356/distinct-th1-and-th2-cellular-responses-associated-with-malaria-protection-and-risk-in-rts-s-as01e-vaccinees
#11
Gemma Moncunill, Maxmillian Mpina, Augusto J Nhabomba, Ruth Aguilar, Aintzane Ayestaran, Héctor Sanz, Joseph J Campo, Chenjerai Jairoce, Diana Barrios, Yan Dong, Núria Díez-Padrisa, José F Fernandes, Salim Abdulla, Jahit Sacarlal, Nana A Williams, Jaroslaw Harezlak, Benjamin Mordmüller, Selidji T Agnandji, John J Aponte, Claudia Daubenberger, Clarissa Valim, Carlota Dobaño
Background.: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods.: We performed a matched case-control study nested within the multicenter African RTS,S/AS01E Phase III trial...
May 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28500302/different-polyubiquitinated-bodies-in-human-dendritic-cells-il-4-causes-pacs-during-differentiation-while-lps-or-ifn%C3%AE-induces-dalis-during-maturation
#12
Daniela Montagna, Patrizia Sommi, Vittorio Necchi, Agostina Vitali, Enrica Montini, Ilaria Turin, Daniela Ferraro, Vittorio Ricci, Enrico Solcia
Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic structures (PaCS) and dendritic cell (DC) aggresome-like induced structures (DALIS), were analyzed by electron microscopy, immunocytochemistry, immunoblotting, and flow cytometry in DC obtained from human blood monocytes incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNα (IFN-DC), or GM-CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich cytoplasmic areas of differentiating IL4-DC...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498437/autocrine-expression-of-the-epidermal-growth-factor-receptor-ligand-heparin-binding-egf-like-growth-factor-in-cervical-cancer
#13
Marlies Schrevel, E Michelle Osse, Frans A Prins, J Baptist M Z Trimbos, Gert Jan Fleuren, Arko Gorter, Ekaterina S Jordanova
In cervical cancer, the epidermal growth factor receptor (EGFR) is overexpressed in 70-90% of the cases and has been associated with poor prognosis. EGFR-based therapy is currently being explored in cervical cancer. We investigated which EGFR ligand is primarily expressed in cervical cancer and which cell type functions as the major source of this ligand. We hypothesized that macrophages are the main source of EGFR ligands and that a paracrine loop between tumor cells and macrophages is responsible for ligand expression...
May 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#14
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#15
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28493367/granulocyte-macrophage-colony-stimulating-factor-a-potent-adjuvant-for-polarization-to-th-17-pattern-an-experience-on-hiv-1-vaccine-model
#16
Mehdi Mahdavi, Amir Hossein Tajik, Massoumeh Ebtekar, Roghieh Rahimi, Mohammad Mehdi Adibzadeh, Hamid Reza Moozarmpour, Mohammad Sadegh Beikverdi, Soophie Olfat, Zuhair Mohammad Hassan, Mohammad Choopani, Morteza Kameli, Christine Hartoonian
Cytokines are mediators for polarization of immune response in vaccines. Studies show that co-immunization of DNA vaccines with granulocyte-macrophage colony-stimulating factor (GM-CSF) can increase immune responses. Here, experimental mice were immunized with HIV-1tat/pol/gag/env DNA vaccine with GM-CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL-4, IFN-γ, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN-γ cytokines, but CTL response was tiny increased...
May 11, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28491903/dimethyl-fumarate-alters-b-cell-memory-and-cytokine-production-in-ms-patients
#17
Matthew D Smith, Kyle A Martin, Peter A Calabresi, Pavan Bhargava
We evaluated the effect of dimethyl fumarate (DMF) treatment on B-cell memory and cytokine production in 18 patients with relapsing remitting multiple sclerosis (RRMS) using peripheral blood mononuclear cells obtained prior to and at 6 months post-DMF initiation. We noted a decline in the absolute B-cell number with DMF treatment, with a preferential depletion of memory B cells and a concurrent increase in naïve B cells. We noted significant reductions in GM-CSF, TNF-α, and IL-6 producing B cells with DMF treatment...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28489417/a-semiquantitative-ct-grading-system-for-evaluating-therapeutic-response-in-pulmonary-alveolar-proteinosis
#18
Sayoko Tokura, Masanori Akira, Tomohisa Okuma, Ryushi Tazawa, Toru Arai, Chikatoshi Sugimoto, Akiko Matsumuro, Masaki Hirose, Toshinori Takada, Koh Nakata, Haruyuki Ishii, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Yoshikazu Inoue
RATIONALE: A useful semi-quantitative method of using CT images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. OBJECTIVES: The purpose of this study was to establish a semi-quantitative method for evaluating therapeutic response in PAP. METHODS: CT scans obtained within one month before and after the therapy from 32 patients with PAP who participated in a multicenter phase 2 trial of GM-CSF inhalation therapy were evaluated by two chest radiologists independently...
May 10, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28489415/hepatic-steatosis-accompanies-pulmonary-alveolar-proteinosis
#19
Alan N Hunt, Anagha Malur, Tual Monfort, Pavlos Lagoudakis, Sumeet Mahajan, Anthony D Postle, Mary Jane Thomassen
Maintenance of tissue-specific organ lipid compositions characterises mammalian lipid homeostasis. Lung and liver synthesise mixed phosphatidylcholine (PC) molecular species subsequently "tailored" for function. Lungs progressively enrich disaturated PC (DSPC) directed to lamellar body (LB) surfactant stores prior to secretion. Liver accumulates polyunsaturated PC directed to VLDL assembly and secretion, or triglyceride stores. In each tissue, selective PC species enrichment mechanisms lie at the heart of effective homeostasis...
May 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28488248/response-to-treatment-with-tnf%C3%AE-inhibitors-in-rheumatoid-arthritis-is-associated-with-high-levels-of-gm-csf-and-gm-csf-t-lymphocytes
#20
Jonas Bystrom, Felix I Clanchy, Taher E Taher, Mohammed M Al-Bogami, Hawzheen A Muhammad, Saba Alzabin, Pamela Mangat, Ali S Jawad, Richard O Williams, Rizgar A Mageed
Biologic TNFα inhibitors are a mainstay treatment option for patients with rheumatoid arthritis (RA) refractory to other treatment options. However, many patients either do not respond or relapse after initially responding to these agents. This study was carried out to identify biomarkers that can distinguish responder from non-responder patients before the initiation of treatment. The level of cytokines in plasma and those produced by ex vivo T cells, B cells and monocytes in 97 RA patients treated with biologic TNFα inhibitors was measured before treatment and after 1 and 3 months of treatment by multiplex analyses...
May 9, 2017: Clinical Reviews in Allergy & Immunology
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