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Yi Wang, Yao-Xin Lin, Sheng-Lin Qiao, Hong-Wei An, Yang Ma, Zeng-Ying Qiao, R P Yeshan J Rajapaksha, Hao Wang
Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects...
October 4, 2016: Biomaterials
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
Amy R Mackos, Ross Maltz, Michael T Bailey
Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli...
October 16, 2016: Hormones and Behavior
Bruno Tilocca, Maren Witzig, Markus Rodehutscord, Jana Seifert
The chicken gastrointestinal tract (GIT) harbours a complex microbial community, involved in several physiological processes such as host immunomodulation and feed digestion. For the first time, the present study analysed dietary effects on the protein inventory of the microbiome in crop and ceca of broilers. We performed quantitative label-free metaproteomics by using 1-D-gel electrophoresis coupled with LC-MS/MS to identify the structural and functional changes triggered by diets supplied with varying amount of mineral phosphorous (P) and microbial phytase (MP)...
2016: PloS One
N M Scott, J F Lauzon-Joset, A C Jones, K T Mincham, N M Troy, J Leffler, M Serralha, S L Prescott, S A Robertson, C Pasquali, A Bosco, P G Holt, D H Strickland
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza...
October 19, 2016: Mucosal Immunology
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
Joseph G Crompton, Madhusudhanan Sukumar, Nicholas P Restifo
Pharmacologic inhibitors of the serine/threonine kinase Akt, initially aimed at deranged oncogenic pathways in tumors, have recently been shown to act as immunomodulators that markedly enhance the antitumor properties of T cells. Repurposing Akt inhibitors to improve antitumor immunity may be viewed as a manifestation of a larger paradigmatic shift in which hallmark characteristics of cancer (e.g., immune evasion), rather than merely causal features (e.g., somatic mutations) can be exploited for therapeutic benefit...
2016: Oncoimmunology
Kimberly N Weaver, Michael D Kappelman, Robert S Sandler, Christopher F Martin, Wenli Chen, Kristen Anton, Millie D Long
BACKGROUND: As variation in care has previously been linked to quality, we aimed to describe variations in inflammatory bowel diseases care by gastroenterology (GI) practice setting. METHODS: We performed a cross-sectional study within the Crohn's and Colitis Foundation of America Partners and used bivariate analyses to compare patient characteristics by GI practice setting (GI-academic [GIA], GI-private, or GI-other). Regression models were used to describe the effects of provider type on steroid use, disease activity, and the quality of life...
November 2016: Inflammatory Bowel Diseases
Firas Rinawi, Amit Assa, Corina Hartman, Yael Mozer Glassberg, Vered Nachmias Friedler, Yoram Rosenbach, Ari Silbermintz, Noam Zevit, Raanan Shamir
BACKGROUND: Data describing the incidence and the risk factors for surgical interventions in pediatric Crohn's disease (CD) is inconsistent. Our aim was to describe the rates of intestinal surgery and to identify associated risk factors in a large cohort of children with CD. METHODS: Medical charts of 482 children with CD from the Schneider Pediatric Inflammatory Bowel Disease cohort who were diagnosed between 1981 and 2013 were carefully reviewed retrospectively...
October 13, 2016: Inflammatory Bowel Diseases
Angelo Sisto, Diomira Luongo, Lucia Treppiccione, Palmira De Bellis, Donato Di Venere, Paola Lavermicocca, Mauro Rossi
The most recent trend in research on probiotic bacteria aims at the exploitation of bioactive bacterial compounds that are responsible for health-promoting effects and suitable for medical applications. Therefore, the main purpose of this study was to ascertain if the immunomodulatory effects of L. paracasei strains on dendritic cells (DCs) were caused by bacterial metabolites released in the culture medium. For that reason, bacterial strains were grown in two media generally used for the culture of DCs, and the effects of culture filtrates on the maturation of DCs and cytokine production were evaluated...
October 14, 2016: Nutrients
A Mekinian, J Cohen, G Kayem, L Carbillon, P Nicaise-Roland, B Gaugler, E Darai, M Bornes, O Fain
About 1-3% of women experience early recurrent miscarriages, defined by ≥3 fetal loss before 14 weeks of gestation. About half of these recurrent early miscarriages could be related to a genetic cause. Pre-implantation genetic diagnosis is used in several European countries, but it is still prohibited in France except for couples at risk for transmission of severe genetic diseases. The immune dysregulation, and in particular allo-immune excessive response, could be responsible for fetal loss in remaining cases, although currently we lack biomarker to confirm the immune-mediated fetal loss...
October 14, 2016: La Revue de Médecine Interne
Christian L Johnson, Yorick Soeder, Marc H Dahlke
PURPOSE OF REVIEW: The current review presents an update on the existing preclinical and human experience of mesenchymal stromal cell (MSC) therapies for post-transplant immunomodulation. RECENT FINDINGS: Although results from early clinical studies have demonstrated that the application of autologous and allogeneic MSC to be both safe and feasible in a solid organ transplantation setting, for example in liver, the efficacy of MSC immunotherapy demonstrated in preclinical models has yet to be replicated in human clinical trials...
October 7, 2016: Current Opinion in Organ Transplantation
Phillip Minar, Kimberly Jackson, Yi-Ting Tsai, Michael J Rosen, Michael Northcutt, Marat Khodoun, Fred D Finkelman, Lee A Denson
BACKGROUND: We have previously shown that CD64 surface expression on circulating neutrophils is significantly elevated in children with newly diagnosed Crohn's disease (CD). Our primary aim was to investigate whether elevations in neutrophil CD64 in asymptomatic patients could be used to predict treatment failure during maintenance infliximab. METHODS: Pediatric CD subjects receiving maintenance infliximab in clinical remission (short pediatric CD activity index [shPCDAI] <15) were enrolled...
November 2016: Inflammatory Bowel Diseases
Julie A Birt, YingMeei Tan, Neelufar Mozaffarian
OBJECTIVES: To better understand the real-world characteristics and costs of Sjögren's syndrome (SS). METHODS: Analysing the MarketScan Commercial Claims database from Jan. 1, 2006 to Dec. 31, 2011, we identified 10,414 patients ≥18 years old newly diagnosed with SS. Patient characteristics, drugs (commonly used for SS), resource utilisation, and medical costs were evaluated for 12 months pre- and post-diagnosis. RESULTS: Mean age was 55 years; 90% were female...
October 7, 2016: Clinical and Experimental Rheumatology
Dana Duricova, Mathurin Fumery, Vito Annese, Peter L Lakatos, Laurent Peyrin-Biroulet, Corinne Gower-Rousseau
The incidence of Crohn's disease (CD) has been reported to increase. The aim of this review is to perform a comprehensive literature search of population-based studies focused on the natural history of paediatric-onset CD. A literature search of English and non-English language publications listed in the electronic database of MEDLINE (source PUBMED) and EMBASE from 1935 to 2016 was performed. Population-based studies or national cohorts reporting data on the short-term or long-term disease course of paediatric CD were included...
September 29, 2016: European Journal of Gastroenterology & Hepatology
Alice Lejeune, Luise Martin, Sabine Santibanez, Stephanie Thee, Alexander Gratopp, Peter Späth, Annette Mankertz, Tilmann Kallinich, Horst von Bernuth
Most non-immune individuals exposed to the highly contagious measles virus will develop measles. Complications, such as encephalitis and bacterial infections due to measles virus-induced immunomodulation, account for an acute mortality rate of approximately 0.1% (1). It has been calculated that measles-related immunomodulation may last for several years and may contribute to child mortality on a larger scale than acute measles-related mortality (2). Since humans provide the only host for the virus, and an efficient vaccine is available, it is possible to eliminate measles...
October 17, 2016: Acta Paediatrica
Gulnihal Ozcan, Emel Aykac, Yelda Kasap, Nergiz T Nemutlu, Ebru Sen, N Demet Aydinkarahaliloglu
INTRODUCTION: In Turkey, pharmacovigilance began in 1985. A fully structured adverse drug reaction (ADR)-reporting system was established with the publication of the first pharmacovigilance regulation in 2005. Subsequent regulation published in 2014 brought further improvements to the system. OBJECTIVE: In this study, we aimed to analyse the ADR-reporting pattern in the context of the first pharmacovigilance legislation in Turkey. METHODS: We analysed ADR reports submitted to the Turkish Pharmacovigilance Center (TUFAM) from 2005 to 2014 with respect to reporting rate (RR), patient characteristics, type of the ADRs, suspected drugs, source of the report and the profession of the reporter...
March 2016: Drugs—Real World Outcomes
Dan Ishihara, Laurentiu Pop, Tsuguhide Takeshima, Puneeth Iyengar, Raquibul Hannan
Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT)...
October 14, 2016: Cancer Immunology, Immunotherapy: CII
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Martin J Hoogduijn
No abstract text is available yet for this article.
October 12, 2016: Transplantation
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