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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
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)...
September 24, 2016: Gynecologic Oncology
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
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
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
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
Ji Young Yoo, Alena C Jaime-Ramirez, Chelsea Bolyard, Hongsheng Dai, Tejaswini Nallanagulagari, Jeffrey Wojton, Brian Hurwitz, Theresa Relation, Jun-Ge Yu, Tae Jin Lee, Michael T Lotze, Jianying Zhang, Carlo M Croce, Jianhua Yu, Michael A Caligiuri, Matthew Old, Balveen Kaur
BACKGROUND: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV) expressing GMCSF are currently FDA-approved. While proteasome blockade can increase oHSV replication, immunological 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 Killier (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...
July 7, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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
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
Simona Bramante, Anniina Koski, Ilkka Liikanen, Lotta Vassilev, Minna Oksanen, Mikko Siurala, Raita Heiskanen, Tiina Hakonen, Timo Joensuu, Anna Kanerva, Sari Pesonen, Akseli Hemminki
Breast cancer is a heterogeneous disease, characterized by several distinct biological subtypes, among which triple-negative breast cancer (TNBC) is one associated with a poor prognosis. Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules to boost virus triggered antitumoral immune responses. Cyclophosphamide (CP) is a chemotherapy drug that is associated with cytotoxicity and immunosuppression at higher doses, whereas immunostimulatory and anti-angiogenic properties are observed at low continuous dosage...
February 2016: Oncoimmunology
Susweta Das Mitra, Bibek Ranjan Shome, Bhuvana Mani, D Velu, Apala Banerjee, Kiran Bankar, Sankar Kumar Ghosh, Sandip Santra, K P Suresh, Habibur Rahman
Streptococcus uberis causing mastitis is a growing challenge to the dairy industry. Molecular, epidemiological and population structure studies have revealed clonal diversity among the infecting strains. In this study, mouse intramammary infection model was used to uncover the host immune response to two epidemiologically important live strains of S. uberis (SU1and SU2) obtained from subclinical case of mastitis possessing specific and unique multi locus sequence types (ST), pulsed field gel electrophoresis (PFGE) pulsotypes and virulence profiles...
July 10, 2016: Gene
Delong Li, Yong Huang, Qian Du, Zhenyu Wang, Lingling Chang, Xiaomin Zhao, Dewen Tong
Porcine circovirus 2 (PCV2) capsid protein (Cap) is the major structural protein that is responsible for neutralizing antibodies development and protective immunity, thus it is usually used to develop vaccines against porcine circovirus-associated disease (PCVAD). Porcine CD40 ligand (CD40L) and granulocyte-macrophage colony-stimulating factor (GMCSF) have positive immunostimulatory effects on immunocytes and have been applied in vaccine efficacy improvement as attractive adjuvant cytokines, respectively. However, whether these two cytokines can produce synergistic effect in vaccines still need to be further studied...
April 2016: Viral Immunology
Tuuli Ranki, Sari Pesonen, Akseli Hemminki, Kaarina Partanen, Kalevi Kairemo, Tuomo Alanko, Johan Lundin, Nina Linder, Riku Turkki, Ari Ristimäki, Elke Jäger, Julia Karbach, Claudia Wahle, Matti Kankainen, Charlotta Backman, Mikael von Euler, Elina Haavisto, Tiina Hakonen, Raita Heiskanen, Magnus Jaderberg, Juuso Juhila, Petri Priha, Laura Suoranta, Lotta Vassilev, Antti Vuolanto, Timo Joensuu
BACKGROUND: We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. Further, the response rate and overall survival were evaluated as well as preliminary evidence of disease control...
2016: Journal for Immunotherapy of Cancer
Lin Quan, Hua He
The aim of the current study was to investigate whether olopatadine and naphazoline hydrochloride reduce allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF. An allergic conjunctivitis mouse model was established using histamine or an antigen (ovalbumin), following which mice were treated with 1% olopatadine solution and/or 0.2 mg/ml of naphazoline hydrochloride. Histamine or antigen‑induced conjunctival vascular hyperpermeability was examined and the levels of inflammatory factors, cytokines, IgE, GMCSF and NGF were analyzed using ELISA in antigen‑induced conjunctival vascular hyperpermeability mice...
April 2016: Molecular Medicine Reports
Marie-Pier Tétreault, Daniel Weinblatt, Jody Dyan Ciolino, Andres J Klein-Szanto, Bridget K Sackey, Christina Twyman-Saint Victor, Tatiana Karakasheva, Valerie Teal, Jonathan P Katz
BACKGROUND & AIMS: IκB kinase-β (IKKβ) mediates activation of the nuclear factor-κB, which regulates immune and inflammatory responses. Although nuclear factor-κB is activated in cells from patients with inflammatory diseases or cancer, little is known about its roles in the development and progression of esophageal diseases. We investigated whether mice that express an activated form of IKKβ in the esophageal epithelia develop esophageal disorders. METHODS: We generated ED-L2-Cre/Rosa26-IKK2caSFL mice, in which the ED-L2 promoter activates expression of Cre in the esophageal epithelia, leading to expression of a constitutively active form of IKKβ (IKKβca) in epithelial cells but not in inflammatory cells or the surrounding stroma (IKKβca mice)...
June 2016: Gastroenterology
Qian Wen, Wenjing Xiong, Jianchun He, Shimeng Zhang, Xialin Du, Sudong Liu, Juanjuan Wang, Mingqian Zhou, Li Ma
BACKGROUND: Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study. METHODS: The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR...
2016: Journal of Translational Medicine
Lili Deng, Jun Fan, Mingming Guo, Biao Huang
Targeted oncolytic vaccinia viruses are being developed as a novel strategy in cancer therapy. Arming vaccinia viruses with immunostimulatory cytokines can enhance antitumor efficacy. Such engineered oncolytic viruses, like JX-594, a Wyeth strain vaccinia virus modified with human granulocyte-macrophage colony-stimulating factor (GM-CSF), have shown promising results and have proceeded rapidly in clinical trials. However, the oncolytic potential of the Chinese vaccine strain Tian Tan (VTT) has not been explored...
March 28, 2016: Cancer Letters
Ashish Ranjan Sharma, Garima Sharma, Sang-Soo Lee, Chiranjib Chakraborty
Rheumatoid arthritis (RA) is an inflammatory disease that primarily affects joints. This autoimmune disease pathogenesis is related to cytokine signaling. In this review, we have described the existence of various microRNAs (miRNAs) involved in regulation of major protein cascades of cytokine signaling associated with RA. Moreover, we have tried to portray the role of various miRNAs in different cytokines such as TNF-α, IL-1, IL-6, IL-10, IL-17, IL-18, IL-21, and granulocyte macrophage colony-stimulating factor (GMCSF)...
May 2016: Medicinal Research Reviews
Y Nakamura, R Suzuki, T Mizuno, K Abe, S Chiba, Y Horii, J Tsuboi, S Ito, W Obara, T Tanita, H Kanno, K Yamauchi
BACKGROUND: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. OBJECTIVE: We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. METHODS: In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations...
September 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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