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Immune modulatory agents

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https://www.readbyqxmd.com/read/29774034/targeting-vegf-vegfr-to-modulate-antitumor-immunity
#1
REVIEW
Ju Yang, Jing Yan, Baorui Liu
In addition to the crucial role in promoting the growth of tumor vessels, vascular endothelial growth factor (VEGF) is also immunosuppressive. VEGF can inhibit the function of T cells, increase the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and hinder the differentiation and activation of dendritic cells (DCs). Recent studies have investigated the role of antiangiogenic agents in antitumor immunity, especially in recent 3 years. Therefore, it is necessary to update the role of targeting VEGF/VEGFR in antitumor immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760047/nanoparticles-that-reshape-the-tumor-milieu-create-a-therapeutic-window-for-effective-t-cell-therapy-in-solid-malignancies
#2
Fan Zhang, Sirkka B Stephan, Chibawanye I Ene, Tyrel T Smith, Eric C Holland, Matthias T Stephan
A major obstacle to the success rate of chimeric antigen receptor (CAR-) T cell therapy against solid tumors is the microenvironment antagonistic to T cells that solid tumors create. Conventional checkpoint blockade can silence lymphocyte anti-survival pathways activated by tumors, but because they are systemic, these treatments disrupt immune homeostasis and induce autoimmune side effects. Thus, new technologies are required to remodel the tumor milieu without causing systemic toxicities. Here we demonstrate that targeted nanocarriers that deliver a combination of immune-modulatory agents can remove pro-tumor cell populations and simultaneously stimulate anti-tumor effector cells...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29738529/identifying-novel-strategies-for-treating-human-hair-loss-disorders-cyclosporine-a-suppresses-the-wnt-inhibitor-sfrp1-in-the-dermal-papilla-of-human-scalp-hair-follicles
#3
Nathan J Hawkshaw, Jonathan A Hardman, Iain S Haslam, Asim Shahmalak, Amos Gilhar, Xinhong Lim, Ralf Paus
Hair growth disorders often carry a major psychological burden. Therefore, more effective human hair growth-modulatory agents urgently need to be developed. Here, we used the hypertrichosis-inducing immunosuppressant, Cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting molecular targets. Through microarray analysis we identified the Wnt inhibitor, secreted frizzled related protein 1 (SFRP1), as being down-regulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo...
May 2018: PLoS Biology
https://www.readbyqxmd.com/read/29705791/biliary-tract-cancer-implicated-immune-mediated-pathways-and-their-associated-potential-targets
#4
Noor-Ul-Ain Tariq, Arndt Vogel, Mairead G McNamara, Juan W Valle
There is a well-established link between biliary tract cancers (BTC) and chronic inflammatory conditions such as primary sclerosing cholangitis, chronic cholecystitis, chronic cholelithiasis, liver fluke-associated infestations, and chronic viral hepatic infections. These associated risk factors highlight the potential for development of immune-modulatory agents in this poor-prognostic disease group with limited treatment options. Clinical trials have evaluated the role of immune cells, inflammatory biomarkers, vaccines, cytokines, adoptive cell therapy, and immune checkpoint inhibitors in patients with BTC...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29691472/production-and-delivery-of-helicobacter-pylori-napa-in-lactococcus-lactis-and-its-protective-efficacy-and-immune-modulatory-activity
#5
Xiaoyan Peng, Rongguang Zhang, Guangcai Duan, Chen Wang, Nan Sun, Linghan Zhang, Shuaiyin Chen, Qingtang Fan, Yuanlin Xi
Helicobacter pylori neutrophil-activating protein A subunit (NapA) has been identified as a virulence factor, a protective antigen and a potent immunomodulator. NapA shows unique application potentials for anti-H. pylori vaccines and treatment strategies of certain allergic diseases and carcinomas. However, appropriate production and utilization modes of NapA still remain uncertain to date. This work has established a novel efficient production and utilization mode of NapA by using L. lactis as an expression host and delivery vector, and demonstrated immune protective efficacy and immune modulatory activity of the engineered L...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670611/advances-in-biomarker-guided-therapy-for-pediatric-and-adult-onset-neuroinflammatory-disorders-targeting-chemokines-cytokines
#6
REVIEW
Michael R Pranzatelli
The concept and recognized components of "neuroinflammation" are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron-glia interactions and other mechanisms affecting neurotransmission. They issue the "help me" cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29623180/pembrolizumab-and-its-role-in-relapsed-refractory-classical-hodgkin-s-lymphoma-evidence-to-date-and-clinical-utility
#7
REVIEW
Polina Shindiapina, Lapo Alinari
Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy...
April 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29589540/-lactoferrin-and-peptide-derivatives-antimicrobial-agents-with-potential-use-in-nonspecific-immunity-modulation
#8
Maria Elisa Drago-Serrano, Rafael Campos-Rodriguez, Julio Cesar Carrero, Mireya de la Garza
Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, pro- and anti-inflammatory cytokines, and reactive oxygen species...
March 27, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29528247/managing-the-side-effects-of-multiple-sclerosis-therapy-pharmacotherapy-options-for-patients
#9
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...
April 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29496049/sting-activation-enhances-cetuximab-mediated-nk-cell-activation-and-dc-maturation-and-correlates-with-hpv-status-in-head-and-neck-cancer
#10
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
https://www.readbyqxmd.com/read/29487979/the-multi-receptor-inhibitor-axitinib-reverses-tumor-induced-immunosuppression-and-potentiates-treatment-with-immune-modulatory-antibodies-in-preclinical-murine-models
#11
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...
May 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29473532/the-promising-pharmacological-effects-and-therapeutic-medicinal-applications-of-punica-granatum-l-pomegranate-as-a-functional-food-in-humans-and-animals
#12
Muhammad Saeed, Muhammad Naveed, Jannat BiBi, Asghar Ali Kamboh, Muhammad Asif Arain, Qurban Ali Shah, Mahmoud Alagawany, Mohamed Ezzat Abd El-Hack, Mervat A. Abdel-Latif, Mohd. Iqbal Yatoo, Ruchi Tiwari, Sandip Chakraborty, 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
https://www.readbyqxmd.com/read/29358273/ciap1-2-traf2-shp-1-src-myd88-complex-regulates-lipopolysaccharide-induced-il-27-production-through-nf-%C3%AE%C2%BAb-activation-in-human-macrophages
#13
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...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351079/syphacia-muris-infection-in-rats-attenuates-colorectal-carcinogenesis-through-oxidative-stress-and-gene-expression-alterations-implications-for-modulatory-effects-by-bryostatin-1
#14
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
https://www.readbyqxmd.com/read/29299156/inhibition-of-pi4k-iii%C3%AE-radiosensitizes-in-human-tumor-xenograft-and-immune-competent-syngeneic-murine-tumor-model
#15
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
https://www.readbyqxmd.com/read/29222299/management-of-multiple-myeloma-in-the-relapsed-refractory-patient
#16
REVIEW
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
https://www.readbyqxmd.com/read/29210175/site-specific-and-endothelial-mediated-dysfunction-of-the-alveolar-capillary-barrier-in-response-to-lipopolysaccharides
#17
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
https://www.readbyqxmd.com/read/29163520/the-injury-related-activation-of-hedgehog-signaling-pathway-modulates-the-repair-associated-inflammation-in-liver-fibrosis
#18
REVIEW
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
https://www.readbyqxmd.com/read/29066299/%C3%AE-elemene-attenuates-macrophage-activation-and-proinflammatory-factor-production-via-crosstalk-with-wnt-%C3%AE-catenin-signaling-pathway
#19
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...
January 2018: Fitoterapia
https://www.readbyqxmd.com/read/29054949/metachronous-solitary-plasmacytoma
#20
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
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