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Immune modulatory agents

Paulus S Rommer, Uwe K Zettl
Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review...
March 12, 2018: Expert Opinion on Pharmacotherapy
Shanhong Lu, Fernando Concha-Benavente, Gulidanna Shayan, Raghvendra M Srivastava, Sandra P Gibson, Lin Wang, William E Gooding, Robert L Ferris
OBJECTIVES: The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab...
March 2018: Oral Oncology
Heinz Läubli, Philipp Müller, Lucia D'Amico, Mélanie Buchi, Abhishek S Kashyap, Alfred Zippelius
Cancer immunotherapies have significantly improved the prognosis of cancer patients. Despite the clinical success of targeting inhibitory checkpoint receptors, including PD-1 and/or CTLA-4 on T cells, only a minority of patients derive benefit from these therapies. New strategies to improve cancer immunotherapy are therefore needed. Combination therapy of checkpoint inhibitors with targeted agents has promisingly shown to increase the efficacy of immunotherapy. Here, we analyzed the immunomodulatory effects of the multi-receptor tyrosine kinase inhibitor axitinib and its efficacy in combination with immunotherapies...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
Kuldeep Dhama
BACKGROUND: Punica granatum L (pomegranate), is a shrub mostly available in the Mediterranean Sea region. The fruits have gained the substantial attention among researchers due to its promising biological activities including anti-inflammatory, antibacterial, antidiarrheal, immune modulatory, antitumor, wound healing and antifungal that have been attributed to various constituents of seeds, bark, juice, pericarp and leaf of this tree across the globe. The phenolic compounds of pomegranate have been documented to possess numbers of prophylactic and therapeutic utilities against various pathological infections as well as non-infectious disorders...
February 21, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
Aurelia Busca, Yulia Konarski, Niranjala Gajanayaka, Shifawn O'Hara, Jonathan Angel, Maya Kozlowski, Ashok Kumar
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement of IAPs in primary human cells and in particular macrophages with respect to cytokine production and innate immune responses remain largely unknown...
January 22, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Elsayed I Salim, Samar F Harras, Aisha G Abdalla, Mohmmed H Mona
Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S...
March 26, 2018: Acta Parasitologica
Younghee Park, Ji Min Park, Dan Hyo Kim, Jeanny Kwon, In Ah Kim
Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model...
December 15, 2017: Oncotarget
Pieter Sonneveld
The approach to the patient with relapsed or relapsed/refractory multiple myeloma requires a careful evaluation of the results of previous treatments, the toxicities associated with it, and an assessment of prognostic factors. The majority of patients will have received prior therapy with drug combinations, including a proteasome inhibitor and an immune-modulatory agent. It is the physician's task to choose the right moment for the start of therapy and decide with the patient which goals need to be achieved...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Harshavardhan Janga, Liam Cassidy, Fanlu Wang, Dietmar Spengler, Stefanie Oestern-Fitschen, Martin F Krause, Andreas Seekamp, Andreas Tholey, Sabine Fuchs
Infectious agents such as lipopolysaccharides (LPS) challenge the functional properties of the alveolar-capillary barrier (ACB) in the lung. In this study, we analyse the site-specific effects of LPS on the ACB and reveal the effects on the individual cell types and the ACB as a functional unit. Monocultures of H441 epithelial cells and co-cultures of H441 with endothelial cells cultured on Transwells® were treated with LPS from the apical or basolateral compartment. Barrier properties were analysed by the transepithelial electrical resistance (TEER), by transport assays, and immunostaining and assessment of tight junctional molecules at protein level...
February 2018: Journal of Cellular and Molecular Medicine
Xin Shen, Yu Peng, Hanmin Li
Liver fibrosis is a wound healing response initiated by inflammation responding for different iterative parenchymal damages caused by diverse etiologies. Immune cells, which exert their ability of either inducing injury or promoting repair, have been regarded as crucial participants in the fibrogenic response. A characteristic feature of the fibrotic microenvironment associated with chronic liver injury is aberrant activation of hedgehog (Hh) signaling pathway. Growing evidence from a number of different studies in vivo and in vitro has indicated that immune-mediated events involved in liver fibrogenesis are regulated by Hh signaling pathway...
2017: Frontiers in Immunology
Yangyi Fang, Yanhua Kang, Han Zou, Xiaxuan Cheng, Tian Xie, Liyun Shi, Hang Zhang
β-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of β-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of β-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by LPS was significantly suppressed by β-elemene in a dose-dependent manner in RAW264...
October 21, 2017: Fitoterapia
Robin Khosa, Shishir Seth, Sapna Nangia
Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell neoplasms. Progression to multiple myeloma is the most common pattern of relapse. Appearance of new lesions without any systemic disease is the most unusual pattern of relapse seen in <2% cases. We present a case of a 46-year-old female who presented with features of third and seventh cranial nerve palsy, diagnosed with solitary plasmacytoma, with no evidence of any systemic disease. As per standard recommendations, the patient received radiotherapy to the local site...
October 19, 2017: BMJ Case Reports
Letizia Mezzasoma, Matthew J Peirce, Alba Minelli, Ilaria Bellezza
Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ingrid Herskovitz, Flor E MacQuhae, Luis J Borda, Stephanie Bhagwandin, Juan A Paredes, Thais Polanco, John C Lantis, Paul J Kim, Tania J Phillips, Robert S Kirsner
INTRODUCTION: Wound care dressings have evolved over time, from bandaging to the development of occlusive dressings to negative pressure wound therapy. A novel therapeutic delivery system dressing has been cleared by the United States Food and Drug Administration. This semi occlusive wound dressing has been developed to provide local, continuous delivery of aqueous topical agents, such as therapeutics (anesthetics, antiseptics, antibiotics, steroids, topical beta-blockers, immune modulatory agents, growth factors, and fibrinolytic agents, among others), at a rate of about ¾ mL per day, thus maintaining a hydrated environment and providing topical treatment...
September 2017: Wounds: a Compendium of Clinical Research and Practice
Ioannis A Voutsadakis
   The immune system has come to the forefront of cancer therapeutics in recent years with the success of immune blockade inhibitors in a variety of cancers whose list is increasing with a quick pace. Despite the efficacy of these drugs across a significant part of the cancer spectrum, responses are still seen only in a minority of patients, that implies that most patients are refractory or promptly develop resistance to these agents. Mechanisms of this resistance are important to decipher as this knowledge may lead to the introduction of additional therapies or manipulations to modulate resistance...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
November 2017: Autoimmunity
Adam J Guess, Beth Daneault, Rongzhang Wang, Hillary Bradbury, Krista M D La Perle, James Fitch, Sheri L Hedrick, Elizabeth Hamelberg, Caroline Astbury, Peter White, Kathleen Overolt, Hemalatha Rangarajan, Rolla Abu-Arja, Steven M Devine, Satoru Otsuru, Massimo Dominici, Lynn O'Donnell, Edwin M Horwitz
Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule...
September 9, 2017: Stem Cells Translational Medicine
Tarek B Ahmad, Lei Liu, Michael Kotiw, Kirsten Benkendorff
ETHNOPHARMACOLOGICAL RELEVANCE: This review focuses on traditional and contemporary anti-inflammatory uses of mollusc-derived products summarising all the in vitro, in vivo and human clinical trials that have tested the anti-inflammatory activity of molluscan natural products. Inflammatory conditions, burns and wounds have been an ongoing concern for human health since the early era of civilisation. Many texts from ancient medicine have recorded the symptoms, signs and treatments for these conditions...
August 19, 2017: Journal of Ethnopharmacology
Uwe Pleyer, Engi Abdel-Hady Algharably, Eugen Feist, Reinhold Kreutz
Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'...
September 2017: Expert Opinion on Pharmacotherapy
Luo-Qin Fu, Ya-Li Li, Ai-Kun Fu, Yan-Ping Wu, Yuan-Yuan Wang, Sheng-Lan Hu, Wei-Fen Li
Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control)...
October 2017: Molecular Medicine Reports
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