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https://www.readbyqxmd.com/read/29767328/a-placebo-controlled-efficacy-study-of-the-intravesical-immunomodulators-tmx-101-and-tmx-202-in-an-orthotopic-bladder-cancer-rat-model
#1
Johannes Falke, Christina A Hulsbergen-van de Kaa, Roberto Maj, Egbert Oosterwijk, J Alfred Witjes
PURPOSE: TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. METHODS: Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0...
May 16, 2018: World Journal of Urology
https://www.readbyqxmd.com/read/29765617/accelerated-model-of-lupus-autoimmunity-and-vasculopathy-driven-by-toll-like-receptor-7-9-imbalance
#2
Yudong Liu, Nickie L Seto, Carmelo Carmona-Rivera, Mariana J Kaplan
Objectives: Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29755453/clec10a-is-a-specific-marker-for-human-cd1c-dendritic-cells-and-enhances-their-toll-like-receptor-7-8-induced-cytokine-secretion
#3
Lukas Heger, Silke Balk, Jennifer J Lühr, Gordon F Heidkamp, Christian H K Lehmann, Lukas Hatscher, Ariawan Purbojo, Arndt Hartmann, Fayna Garcia-Martin, Shin-Ichiro Nishimura, Robert Cesnjevar, Falk Nimmerjahn, Diana Dudziak
Dendritic cells (DCs) are major players for the induction of immune responses. Apart from plasmacytoid DCs (pDCs), human DCs can be categorized into two types of conventional DCs: CD141+ DCs (cDC1) and CD1c+ DCs (cDC2). Defining uniquely expressed surface markers on human immune cells is not only important for the identification of DC subpopulations but also a prerequisite for harnessing the DC subset-specific potential in immunomodulatory approaches, such as antibody-mediated antigen targeting. Although others identified CLEC9A as a specific endocytic receptor for CD141+ DCs, such a receptor for CD1c+ DCs has not been discovered, yet...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29747237/treponema-denticola-chymotrypsin-like-proteinase-is-present-in-early-stage-mobile-tongue-squamous-cell-carcinoma-and-related-to-the-clinicopathological-features
#4
Dyah Listyarifah, Mikko T Nieminen, Laura K Mäkinen, Caj Haglund, Daniel Grenier, Valtteri Häyry, Dan Nordström, Marcela Hernandez, Tülay Yucel-Lindberg, Taina Tervahartiala, Mari Ainola, Timo Sorsa, Jaana Hagström
BACKGROUND: Certain periodontopathogenic bacteria have been linked to cancers. Treponema denticola (Td) is associated with severe periodontitis. Chymotrypsin-like proteinase (CTLP), a major virulence factor of Td, can degrade various host proteins and peptides, and modulate inflammatory responses. However the role of Td in the tongue carcinogenesis remains unknown. This study aimed to investigate the presence of Td-CTLP in early-stage mobile tongue squamous cell carcinoma (MTSCC) and its relation to clinical and pathological characteristics...
May 10, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29698474/interferon-induced-protein-35-exacerbates-h5n1-influenza-disease-through-the-expression-of-il-12p40-homodimer
#5
Anshu P Gounder, Christine C Yokoyama, Nicholas N Jarjour, Traci L Bricker, Brian T Edelson, Adrianus C M Boon
Pro-inflammatory cytokinemia is a hallmark of highly pathogenic H5N1 influenza virus (IAV) disease yet little is known about the role of host proteins in modulating a pathogenic innate immune response. The host Interferon Induced Protein 35 (Ifi35) has been implicated in increased susceptibility to H5N1-IAV infection. Here, we show that Ifi35 deficiency leads to reduced morbidity in mouse models of highly pathogenic H5N1- and pandemic H1N1-IAV infection. Reduced weight loss in Ifi35-/- mice following H5N1-IAV challenge was associated with reduced cellular infiltration and decreased production of specific cytokines and chemokines including IL-12p40...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29686670/alum-toll-like-receptor-7-adjuvant-enhances-the-expansion-of-memory-b-cell-compartment-within-the-draining-lymph-node
#6
Hoa Thi My Vo, Barbara Christiane Baudner, Stefano Sammicheli, Matteo Iannacone, Ugo D'Oro, Diego Piccioli
Vaccination is one of the most cost-effective health interventions and, with the exception of water sanitization, no other action has had such a major effect in mortality reduction. Combined with other approaches, such as clean water, better hygiene, and health education, vaccination contributed to prevent millions of cases of deaths among children under 5 years of age. New or improved vaccines are needed to fight some vaccine-preventable diseases that are still a threat for the public health globally, as reported also in the Global Vaccine Action Plan (GVAP) endorsed by the World Health Assembly in 2012...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29679037/the-therapeutic-potential-and-molecular-mechanism-of-isoflavone-extract-against-psoriasis
#7
Hsin-Ju Li, Nan-Lin Wu, Gon-Ann Lee, Chi-Feng Hung
Psoriasis is a common inflammatory disease. It affects 1-3% of the population worldwide and is associated with increasing medical costs every year. Typical psoriatic skin lesions are reddish, thick, scaly plaques that can occur on multiple skin sites all over the body. Topical application of imiquimod (IMQ), a toll-like receptor (TLR)7 agonist and potent immune system activator, can induce and exacerbate psoriasis. Previous studies have demonstrated that isoflavone extract has an antioxidant effect which may help decrease inflammation and inflammatory pain...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670609/enhanced-replication-of-virulent-newcastle-disease-virus-in-chicken-macrophages-is-due-to-polarized-activation-of-cells-by-inhibition-of-tlr7
#8
Pingze Zhang, Zhuang Ding, Xinxin Liu, Yanyu Chen, Junjiao Li, Zhi Tao, Yidong Fei, Cong Xue, Jing Qian, Xueli Wang, Qingmei Li, Tobias Stoeger, Jianjun Chen, Yuhai Bi, Renfu Yin
Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29578170/association-of-toll-like-receptors-with-the-risk-of-oral-squamous-cell-carcinoma
#9
Si-Lian Fang, Xiang-Bo Kong, Zhao-Qiang Zhang
Aim of Study: Association of toll-like receptors (TLRs) with the risk of oral squamous cell carcinoma (OSCC) from the published reports is still conflicting. This study was conducted to evaluate the relationship between TLRs and the risk of OSCC using meta-analysis method. Materials and Methods: The association studies were identified from PubMed and Cochrane Library on April 01 2015, and eligible investigations were included and synthesized using meta-analysis method...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29569859/toll-like-receptor-7-8-activation-exacerbates-murine-experimental-autoimmune-myositis
#10
Clara Sciorati, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Dana P Ascherman, Angelo A Manfredi, Patrizia Rovere-Querini
OBJECTIVE: TLR-7/8 and Interferon (IFN)-induced genes are expressed in patients with inflammatory idiopathic myositis. Here we investigated whether their activation influences the natural history of the disease. METHODS: Experimental autoimmune myositis (EAM) was induced by injection of the amino-terminal portion of the murine Histydil t-RNA synthetase (HisRS). Disease was compared in the presence or the absence of the TLR-7/8 agonist R848 in wild-type mice and in mice that fail to express the IFNαβ receptor (IFNαβR null)...
March 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29552145/novel-tlr7-agonist-stimulates-activity-of-cik-nk-immunological-effector-cells-to-enhance-antitumor-cytotoxicity
#11
Dong Gao, Yongguang Cai, Yanyuan Chen, Wang Li, Chih-Chang Wei, Xiaoling Luo, Yuhuan Wang
Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29515583/k63-linked-polyubiquitination-on-traf6-regulates-lps-mediated-mapk-activation-cytokine-production-and-bacterial-clearance-in-toll-like-receptor-7-8-primed-murine-macrophages
#12
Jaya Talreja, Lobelia Samavati
Post viral infection bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. Despite much efforts put into the discovery of mechanisms of post viral-bacterial infections and their complications in recent years, the molecular mechanisms underlying the increased susceptibility to bacterial infection remain poorly understood. In this study, we focused on the pathways regulating immune responses in murine macrophages and modeled post viral-bacterial infections through pretreatment of bone marrow-derived macrophages (BMDMs) with a toll-like receptor (TLR) 7/8 ligand (R848) and subsequent challenge with TLR2/4 agonists to mimic bacterial infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29500135/pharmacokinetics-and-pharmacodynamics-of-intravesical-and-intravenous-tmx-101-and-tmx-202-in-a-f344-rat-model
#13
Johannes Falke, Christina A Hulsbergen-van de Kaa, Roberto Maj, Egbert Oosterwijk, Johannes Alfred Witjes
OBJECTIVES: To evaluate and compare the pharmacokinetic and pharmacodynamic properties of 2 investigational Toll-like receptor 7 agonists, TMX-101, and TMX-202 after intravenous and intravesical administration in a rat model. TLR-7 agonists are successfully used as topical treatment for various (pre)malignant skin lesions and are now under investigation as intravesical therapy for non-muscle-invasive bladder cancer. METHODS: Rats received an intravesical instillation with TMX-101, TMX-202, or vehicle...
May 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29482062/polymeric-nanoparticles-encapsulating-novel-tlr7-8-agonists-as-immunostimulatory-adjuvants-for-enhanced-cancer-immunotherapy
#14
Hyunjoon Kim, Lin Niu, Peter Larson, Tamara A Kucaba, Katherine A Murphy, Britnie R James, David M Ferguson, Thomas S Griffith, Jayanth Panyam
Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy because of their ability to directly kill tumor cells and secrete tumor suppressive cytokines. Anticancer vaccines aim to provoke tumor-specific CTL responses, which require activation of antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages. Therefore, a potent immunostimulatory adjuvant capable of activating APCs is an essential component of anticancer vaccines. In this study, we introduce novel TLR 7/8 bi-specific agonists that significantly enhance cytokine secretion compared to TLR7 mono-selective compounds...
May 2018: Biomaterials
https://www.readbyqxmd.com/read/29422777/imiquimod-inhibits-growth-and-induces-differentiation-of-myeloid-leukemia-cell-lines
#15
Eva Villamón, Javier González-Fernández, Esperanza Such, José Vicente Cervera, Daniel Gozalbo, M Luisa Gil
Background: The antitumoral effects of different Toll-like receptor (TLRs) agonists is mediated by activating immune responses to suppress tumors growth, although TLR ligands may also have a direct effect on tumoral cells. Given that TLR signaling induces hematopoietic cell differentiations this may serve as a novel differentiation therapeutic approach for AML. Methods: We investigated the effects of agonists for the ten human TLRs on the proliferation, apoptosis, cell cycle and differentiation of ten different types of myeloid leukemia cell lines (HL-60, U-937, KG-1, KG-1a, K-562, Kasumi-1, EOL-1, NB4, MOLM-13 and HEL)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29398273/the-choice-of-linker-for-conjugating-r848-to-inactivated-influenza-virus-determines-the-stimulatory-capacity-for-innate-immune-cells
#16
Marlena M Westcott, Elene A Clemens, Beth C Holbrook, S Bruce King, Martha A Alexander-Miller
Inactivated influenza vaccines are not approved for use in infants less than 6 months of age due to poor immunogenicity in that population. While the live attenuated influenza vaccine has the potential to be more immunogenic, it is not an option for infants and other vulnerable populations, including the elderly and immunocompromised individuals due to safety concerns. In an effort to improve the immunogenicity of the inactivated vaccine for use in vulnerable populations, we have used an approach of chemically crosslinking the Toll-like receptor (TLR) 7/8 agonist R848 directly to virus particles...
February 21, 2018: Vaccine
https://www.readbyqxmd.com/read/29366653/discovery-of-selective-2-4-diaminoquinazoline-toll-like-receptor-7-tlr-7-agonists
#17
Serge Pieters, David McGowan, Florence Herschke, Frederik Pauwels, Bart Stoops, Stefaan Last, Werner Embrechts, Annick Scholliers, Wendy Mostmans, Kris Van Dijck, Bertrand Van Schoubroeck, Tine Thoné, Dorien De Pooter, Gregory Fanning, Mari Luz Rosauro, Mourad Daoubi Khamlichi, Ioannis Houpis, Eric Arnoult, Tim H M Jonckers, Pierre Raboisson
The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is described. The synthesis and structure-activity relationship is presented. Structural requirements and optimization of this series toward TLR 7 selectivity afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies highlighted 48 as an orally available endogenous interferon (IFN-α) inducer in mice.
February 15, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29356269/bioresorbable-vascular-scaffold-versus-everolimus-eluting-stents-or-drug-eluting-balloon-for-the-treatment-of-coronary-in-stent-restenosis-1-year-follow-up-of-a-propensity-score-matching-comparison-the-bioresolve-isr-study
#18
Elisabetta Moscarella, Akihito Tanaka, Alfonso Ielasi, Bernardo Cortese, Sebastian Coscarelli, Maria Carmen De Angelis, Davide Piraino, Azeem Latib, Giulietta Grigis, Renatomaria Bianchi, Dario Buccheri, Paolo Calabrò, Maurizio Tespili, Pedro Silva Orrego, Antonio Colombo, Attilio Varricchio
OBJECTIVES: to compare the 1-year outcome between bioresorbable vascular scaffold (BVS), everolimus-eluting stent (EES), and drug-eluting balloon (DEB) for in-stent restenosis (ISR) treatment. BACKGROUND: BVS has been proposed as alternative for ISR treatment. To date a direct comparison between BVS and DES or DEB for ISR treatment is lacking. METHODS: We retrospectively analyzed all ISR lesions treated with BVS, DEB, and EES from January 2012 to December 2014...
January 22, 2018: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#19
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29306151/enhancement-of-immune-response-of-piglets-to-pcv-2-vaccine-by-porcine-il-2-and-fusion-il-4-6-gene-entrapped-in-chitosan-nanoparticles
#20
Yi Chen, Tingyu Song, Yong-Le Xiao, Xiaoping Wan, Luyi Yang, Jinghai Li, Guangzhi Zeng, Pengfei Fang, Ze-Zhou Wang, Rong Gao
In order to develop a novel effective immunomodulator to enhance pig resistance against post-weaning multi systemic wasting syndrome (PMWS), a recombinant plasmid co-expressing pig interleukin-2 (IL-2) and fusion interleukin-4/6 (IL-4/6) genes, designated VRIL4/6-2, was constructed and encapsulated in chitosan (CS) nanoparticles prepared by the ionotropic gelation method. Then 21-day old piglets were divided into two groups and intramuscularly injected respectively with VPIL4/6-2-CS and saline along with the porcine circovirus-2 (PCV-2) vaccine...
April 2018: Research in Veterinary Science
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