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https://www.readbyqxmd.com/read/28338569/case-report-immune-mediated-complete-response-in-a-patient-with-recurrent-advanced-ewing-sarcoma-ews-after-vigil-immunotherapy
#1
Maurizio Ghisoli, McCarley Rutledge, Philip J Stephens, Robert Mennel, Minal Barve, Meghan Manley, Bahram R Oliai, Kathleen M Murphy, Luisa Manning, Belen Gutierrez, Priyanka Rangadass, Ashli Walker, Zhaohui Wang, Donald Rao, Ned Adams, Gladice Wallraven, Neil Senzer, John Nemunaitis
Ewing sarcoma is a highly resistant disease with a <10% chance of survival at 5 years after failure of frontline chemotherapy. This is a case report of an Ewing sarcoma patient with metastatic disease recurrence <2 years after standard chemotherapy/radiation who achieved a durable and sustained complete response after 2 series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control...
March 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28253931/zika-virus-infection-of-cellular-components-of-the-blood-retinal-barriers-implications-for-viral-associated-congenital-ocular-disease
#2
Tracoyia Roach, Donald J Alcendor
BACKGROUND: Ocular abnormalities present in microcephalic infants with presumed Zika virus (ZIKV) congenital disease includes focal pigment mottling of the retina, chorioretinal atrophy, optic nerve abnormalities, and lens dislocation. Target cells in the ocular compartment for ZIKV infectivity are unknown. The cellular response of ocular cells to ZIKV infection has not been described. Mechanisms for viral dissemination in the ocular compartment of ZIKV-infected infants and adults have not been reported...
March 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28217374/plecanatide-mediated-activation-of-guanylate-cyclase-c-suppresses-inflammation-induced-colorectal-carcinogenesis-in-apc-min-fccc-mice
#3
Wen-Chi L Chang, Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Harry S Cooper, Vaseem A Palejwala, Margie L Clapper, Kunwar Shailubhai
AIM: To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc(+/Min-FCCC) mice with dextran sodium sulfate (DSS)-induced inflammation. METHODS: Inflammation driven colorectal carcinogenesis was induced in Apc(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide (0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid, flat and indeterminate dysplasia was evaluated...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28193636/evaluation-of-jak3-biology-in-autoimmune-disease-using-a-highly-selective-irreversible-jak3-inhibitor
#4
Fiona Elwood, David Witter, Jennifer Piesvaux, Brian Kraybill, Nathan Bays, Carla Alpert, Peter Goldenblatt, Yujie Qu, Irena Ivanovska, Hyun-Hee Lee, Chi-Sung Chiu, Hao Tang, Mark E Scott, Sujal Deshmukh, Mark Zielstorff, Alan Byford, Kalyan Chakravarty, Lauren Dorosh, Alexy Rivkin, Joel Klappenbach, Bo-Sheng Pan, Ilona Kariv, Christopher Dinsmore, Deborah Slipetz, Peter Dandliker
Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012)...
February 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28125796/three-year-follow-up-of-gmcsf-bi-shrna-furin-dna-transfected-autologous-tumor-immunotherapy-vigil-in-metastatic-advanced-ewing-s-sarcoma
#5
Maurizio Ghisoli, Minal Barve, Robert Mennel, Carl Lenarsky, Staci Horvath, Gladice Wallraven, Beena O Pappen, Sam Whiting, Donald Rao, Neil Senzer, John Nemunaitis
Ewing's sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing's patients were safely treated and went on to achieve a predicted immune response (IFNγ ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing's sarcoma patients (n = 16) with a contemporaneous group of Ewing's sarcoma patients (n = 14) not treated with Vigil...
August 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27996636/immunogenicity-evaluation-of-modified-adenovirus-vaccines-expressing-porcine-circovirus-type-2-capsid-protein-in-pigs
#6
Delong Li, Dan Xu, Zhenyu Wang, Qian Du, Lingling Chang, Xiaomin Zhao, Yong Huang, Dewen Tong
Porcine circovirus type 2 (PCV2) adenovirus vaccine has been reported, but strong immune responses induced by adenovirus vector can decrease vaccine efficacy. To reduce the immunogenicity of adenovirus proteins, in previous study, we constructed the PCV2 adenovirus vaccine either modified with human cytomegalovirus first intron (Intron A) and woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to increase the expression of Cap, or coexpressed porcine tumor necrosis factor-related activate protein (CD40L) and granulocyte macrophage colony-stimulating factor (GMCSF) to improve the immunogenicity of PCV2 Cap adenovirus vaccine...
March 2017: Viral Immunology
https://www.readbyqxmd.com/read/27940088/vitamin-a-differentially-regulates-cytokine-expression-in-respiratory-epithelial-and-macrophage-cell-lines
#7
Rhiannon R Penkert, Bart G Jones, Hans Häcker, Janet F Partridge, Julia L Hurwitz
Vitamin A is an essential nutrient for the protection of children from respiratory tract disease. Supplementation with vitamin A is frequently prescribed in the clinical setting, in part to combat deficiencies among children in developing countries, and in part to treat respiratory infections in clinical trials. This vitamin influences immune responses via multiple, and sometimes seemingly contradictory mechanisms. For example, in separate reports, vitamin A was shown to decrease Th17 T-cell activity by downregulating IL-6, and to promote B cell production of IgA by upregulating IL-6...
March 2017: Cytokine
https://www.readbyqxmd.com/read/27863041/immobilized-hematopoietic-growth-factors-onto-magnetic-particles-offer-a-scalable-strategy-for-cell-therapy-manufacturing-in-suspension-cultures
#8
Matthew J Worrallo, Rebecca L L Moore, Katie E Glen, Robert J Thomas
Hematopoietic therapies require high cell dosages and precise phenotype control for clinical success; scalable manufacturing processes therefore need to be economic and controllable, in particular with respect to culture medium and growth factor (GF) strategy. The aim of this work was to demonstrate the biological function, and integration within scalable systems, of a highly controllable immobilized growth factor (iGF) approach. GFs were biotinylated and attached to streptavidin coated magnetic particles. GF concentration during biotinylation, GF-biotin ratio, and GF lysine content were shown to control iGF surface concentration and enable predictable co-presentation of multiple GF on a single bead...
February 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/27856306/enhanced-formation-of-giant-cells-in-common-variable-immunodeficiency-relation-to-granulomatous-disease
#9
Timothy H Scott-Taylor, Karen Whiting, Ruth Pettengell, David A Webster
Peripheral monocytes from patients with common variable immunodeficiency (CVID) had on average a 2 fold greater tendency to form giant cells in medium without additional cytokines. Giant cell formation was faster and 3 to 5 fold higher in most CVID cells compared to normal. Addition of IL4, GMCSF, IFNγ, TNFa and both T cell and monocyte conditioned media promoted monocyte fusion of some CVID individuals over 5 fold the normal average level, with combinations of cytokines and monokines acting synergistically...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27813377/metabolic-syndrome-and-the-seminal-cytokine-network-in-morbidly-obese-males
#10
A Pilatz, C Hudemann, J Wolf, I Halefeld, A Paradowska-Dogan, H-C Schuppe, H Hossain, Q Jiang, D Schultheiss, H Renz, W Weidner, F Wagenlehner, T Linn
Given the increasing prevalence of metabolic syndrome (MetS) in males of reproductive age, the objective of this prospective case-controlled study was to investigate the impact of subacute systemic inflammation associated with MetS on seminal cytokines and standard sperm parameters in comparison with healthy men. Between 2011 and 2014, we recruited 27 patients with MetS out of 41 obese patients screened from an internal outpatient clinic. Twenty-seven age-matched healthy controls were enrolled from 54 men requesting vasectomy in a urological outpatient clinic...
January 2017: Andrology
https://www.readbyqxmd.com/read/27788572/gm-csf-grown-bone-marrow-derived-cells-are-composed-of-phenotypically-different-dendritic-cells-and-macrophages
#11
Yi Rang Na, Daun Jung, Gyo Jeong Gu, Seung Hyeok Seok
Granulocyte-macrophage colony stimulating factor (GM-CSF) has a role in inducing emergency hematopoiesis upon exposure to inflammatory stimuli. Although GM-CSF generated murine bone marrow derived cells have been widely used as macrophages or dendritic cells in research, the exact characteristics of each cell population have not yet been defined. Here we discriminated GM-CSF grown bone marrow derived macrophages (GM-BMMs) from dendritic cells (GM-BMDCs) in several criteria. After C57BL/6J mice bone marrow cell culture for 7 days with GM-CSF supplementation, two main populations were observed in the attached cells based on MHCII and F4/80 marker expressions...
October 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27708236/engineering-of-double-recombinant-vaccinia-virus-with-enhanced-oncolytic-potential-for-solid-tumor-virotherapy
#12
Galina Kochneva, Galina Sivolobova, Anastasiya Tkacheva, Antonina Grazhdantseva, Olga Troitskaya, Anna Nushtaeva, Anastasiya Tkachenko, Elena Kuligina, Vladimir Richter, Olga Koval
Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27678295/phase-ii-study-of-vigil%C3%A2-dna-engineered-immunotherapy-as-maintenance-in-advanced-stage-ovarian-cancer
#13
Jonathan Oh, Minal Barve, Carolyn M Matthews, E Colin Koon, Thomas P Heffernan, Bruce Fine, Elizabeth Grosen, Melanie K Bergman, Evelyn L Fleming, Leslie R DeMars, Loyd West, Daniel L Spitz, Howard Goodman, Kenneth C Hancock, Gladice Wallraven, Padmasini Kumar, Ernest Bognar, Luisa Manning, Beena O Pappen, Ned Adams, Neil Senzer, John Nemunaitis
OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS)...
December 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27597997/i%C3%AE%C2%BAb%C3%AE-regulates-human-monocyte-pro-inflammatory-responses-induced-by-streptococcus-pneumoniae
#14
Kruthika Sundaram, Mohd Akhlakur Rahman, Srabani Mitra, Daren L Knoell, Shireen A Woodiga, Samantha J King, Mark D Wewers
Pneumococcal lung infections represent a major cause of death worldwide. Single nucleotide polymorphisms (SNPs) in the NFKBIZ gene, encoding the transcription factor IκBζ, are associated with increased susceptibility to invasive pneumococcal disease. We hence analyzed how IκBζ might regulate inflammatory responses to pneumococcal infection. We first demonstrate that IκBζ is expressed in human blood monocytes but not in bronchial epithelial cells, in response to wild type pneumococcal strain D39. D39 transiently induced IκBζ in a dose dependent manner, with subsequent induction of downstream molecules involved in host defense...
2016: PloS One
https://www.readbyqxmd.com/read/27568862/coagulin-l-ameliorates-tlr4-induced-oxidative-damage-and-immune-response-by-regulating-mitochondria-and-nox-derived-ros
#15
Sukka Santosh Reddy, Parul Chauhan, Preeti Maurya, Deepika Saini, Prem Prakash Yadav, Manoj Kumar Barthwal
Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide...
October 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27561007/molecular-understanding-of-growth-inhibitory-effect-from-irradiated-to-bystander-tumor-cells-in-mouse-fibrosarcoma-tumor-model
#16
Sejal Desai, Nishad Srambikkal, Hansa D Yadav, Neena Shetake, Murali M S Balla, Amit Kumar, Pritha Ray, Anu Ghosh, B N Pandey
Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging...
2016: PloS One
https://www.readbyqxmd.com/read/27416040/molecular-signaling-and-dysfunction-of-the-human-reactive-enteric-glial-cell-phenotype-implications-for-gi-infection-ibd-poi-neurological-motility-and-gi-disorders
#17
Andromeda Liñán-Rico, Fabio Turco, Fernando Ochoa-Cortes, Alan Harzman, Bradley J Needleman, Razvan Arsenescu, Mahmoud Abdel-Rasoul, Paolo Fadda, Iveta Grants, Emmett Whitaker, Rosario Cuomo, Fievos L Christofi
BACKGROUND: Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the "reactive human enteric glial cell (rhEGC) phenotype" induced by inflammation, and probe its functional relevance. METHODS: Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca, and purinergic signaling by Ca/fluo-4 imaging and mechanosensitivity...
August 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27390350/bortezomib-treatment-sensitizes-oncolytic-hsv-1-treated-tumors-to-nk-cell-immunotherapy
#18
Ji Young Yoo, Alena Cristina Jaime-Ramirez, Chelsea Bolyard, Hongsheng Dai, Tejaswini Nallanagulagari, Jeffrey Wojton, Brian S Hurwitz, Theresa Relation, Tae Jin Lee, Michael T Lotze, Jun-Ge Yu, Jianying Zhang, Carlo M Croce, Jianhua Yu, Michael A Caligiuri, Matthew Old, Balveen Kaur
PURPOSE: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL DESIGN: Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27377463/a-frameshift-in-csf2rb-predominant-among-ashkenazi-jews-increases-risk-for-crohn-s-disease-and-reduces-monocyte-signaling-via-gm-csf
#19
Ling-Shiang Chuang, Nicole Villaverde, Ken Y Hui, Arthur Mortha, Adeeb Rahman, Adam P Levine, Talin Haritunians, Sok Meng Evelyn Ng, Wei Zhang, Nai-Yun Hsu, Jody-Ann Facey, Tramy Luong, Heriberto Fernandez-Hernandez, Dalin Li, Manuel Rivas, Elena R Schiff, Alexander Gusev, L Phillip Schumm, Beatrice M Bowen, Yashoda Sharma, Kaida Ning, Romain Remark, Sacha Gnjatic, Peter Legnani, James George, Bruce E Sands, Joanne M Stempak, Lisa W Datta, Seth Lipka, Seymour Katz, Adam S Cheifetz, Nir Barzilai, Nikolas Pontikos, Clara Abraham, Marla J Dubinsky, Stephan Targan, Kent Taylor, Jerome I Rotter, Ellen J Scherl, Robert J Desnick, Maria T Abreu, Hongyu Zhao, Gil Atzmon, Itsik Pe'er, Subra Kugathasan, Hakon Hakonarson, Jacob L McCauley, Todd Lencz, Ariel Darvasi, Vincent Plagnol, Mark S Silverberg, Aleixo M Muise, Steven R Brant, Mark J Daly, Anthony W Segal, Richard H Duerr, Miriam Merad, Dermot P B McGovern, Inga Peter, Judy H Cho
BACKGROUND & AIMS: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB)...
October 2016: Gastroenterology
https://www.readbyqxmd.com/read/27279017/roscovitine-ameliorates-endotoxin-induced-uveitis-through-neutrophil-apoptosis
#20
Zhao-Xin Jiang, Suo Qiu, Bing-Sheng Lou, Yao Yang, Wen-Cong Wang, Xiao-Feng Lin
Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin‑induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg)...
August 2016: Molecular Medicine Reports
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