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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/28521686/prothymosin-alpha-an-alarmin-and-more
#1
Pinelopi Samara, Chrysoula-Evangelia Karachaliou, Kyriaki Ioannou, Nikos E Papaioannou, Ioannis F Voutsas, Christos Zikos, Ioannis Pirmettis, Minas Papadopoulos, Hubert Kalbacher, Evangelia Livaniou, Ourania E Tsitsilonis, Wolfgang Voelter
BACKGROUND/OBJECTIVE: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed "alarmins". Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα. RESULTS: We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#2
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#3
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28497211/association-of-toll-like-receptor-gene-polymorphisms-and-its-interaction-with-hpv-infection-in-determining-the-susceptibility-of-cervical-cancer-in-chinese-han-population
#4
Ye Jin, Shuang Qiu, Na Shao, Jianhua Zheng
The aim of the study is to investigate the association of several single-nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and additional gene-gene and gene-human papillomavirus (HPV) infection interaction with cervical cancer risk. A total of 1262 participants are selected, including 420 cervical cancer patients and 842 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among five SNPs within TLR gene and HPV infection...
May 11, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28490891/no-genetic-relationship-between-tlr2-rs4696480-rs3804100-and-rs3804099-gene-polymorphisms-and-female-breast-cancer-in-saudi-populations
#5
Abdelhabib Semlali, Mikhlid Almutairi, Narasimha Reddy Parine, Abdullah Al Amri, Jilani P Shaik, Abdulrahman Al Naeem, Sana Abdulla Ajaj, Mahmoud Rouabhia, Mohammad Saud Alanazi
Breast cancer (BC) is the most common cause of cancer-related deaths among women in the Kingdom of Saudi Arabia. An association between the dysregulation of innate immunity, primarily the deregulation of Toll-like receptors (TLRs), and BC development was described a long time ago. Several studies have reported that BC risk factors appear to be related to the interaction between certain genes and exposure to various environmental factors. Here, we investigated the potential correlation of three TLR2 single-nucleotide polymorphisms (SNPs; rs3804100, rs4696480, and rs3804099) with the development of BC in female patients from Saudi Arabia...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28488351/homozygous-microdeletion-of-the-eri1-and-mfhas1-genes-in-a-patient-with-intellectual-disability-limb-abnormalities-and-cardiac-malformation
#6
Nancy Choucair, Mariam Rajab, André Mégarbané, Eliane Chouery
A male child, born from consanguineous parents and having intellectual disability, short stature, dysmorphic facial features, synpolydactyly, and cardiac malformations is reported. Chromosomal microarray analysis showed that the patient presents with an 8p23.1 homozygous deletion, containing the microRNA miR-4660, the exoribonuclease 1 (ERI1), and malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) genes. The microRNA miR-4660 has no known function. MFHAS1 is an immunomodulatory protein involved in Toll-like receptor signaling, erythropoiesis, and cancer...
May 9, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28485332/current-status-of-systemic-therapy-for-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck
#7
REVIEW
L A Jacob, T Chaudhuri, K C Lakshmaiah, K G Babu, L Dasappa, McS Babu, A H Rudresha, K N Lokesh, L K Rajeev
Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28484456/expression-of-tlr4-in-non-small-cell-lung-cancer-is-associated-with-pd-l1-and-poor-prognosis-in-patients-receiving-pulmonectomy
#8
Kaiyuan Wang, Jian Wang, Feng Wei, Ning Zhao, Fan Yang, Xiubao Ren
Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28481875/identification-of-a-tlr2-regulated-gene-signature-associated-with-tumor-cell-growth-in-gastric-cancer
#9
A C West, K Tang, H Tye, L Yu, N Deng, M Najdovska, S J Lin, J J Balic, E Okochi-Takada, P McGuirk, B Keogh, W McCormack, P S Bhathal, M Reilly, M Oshima, T Ushijima, P Tan, B J Jenkins
Toll-like receptors (TLRs) are key regulators of innate immune responses, and their dysregulation is observed in numerous inflammation-associated malignancies, including gastric cancer (GC). However, the identity of specific TLRs and their molecular targets which promote the pathogenesis of human GC is ill-defined. Here, we sought to determine the clinical utility of TLR2 in human GC. TLR2 mRNA and protein expression levels were elevated in >50% of GC patient tumors across multiple ethnicities. TLR2 was also widely expressed among human GC cell lines, and DNA microarray-based expression profiling demonstrated that the TLR2-induced growth responsiveness of human GC cells corresponded with the up-regulation of six anti-apoptotic (BCL2A1, BCL2, BIRC3, CFLAR, IER3, TNFAIP3) and down-regulation of two tumor suppressor (PDCD4, TP53INP1) genes...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28480962/human-papillomavirus-type-16-e6-oncoprotein-promotes-proliferation-and-invasion-of-non-small-cell-lung-cancer-cells-through-toll-like-receptor-3-signaling-pathway
#10
Xia Wang, Zhiqiang Zhang, Huimin Cao, Wenyi Niu, Mingying Li, Xiu'e Xi, Jing Wang
Human papillomavirus (HPV) oncoproteins play vital roles in non-small cell lung cancer (NSCLC) pathogenesis, and Toll-like receptors (TLRs) contribute to tumor progression. However, interaction between HPV oncoproteins and TLR signaling in NSCLC progression remains unclear. Thus, the aim of the study was to explore effects of HPV16 E6 oncoprotein-induced TLRs pathway on growth and invasion of NSCLC cells and to examine potential mechanisms being involved. Recombinant plasmid (pcDNA-HPV16 E6) expressing HPV16 E6 protein was constructed...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28474563/opioids-and-the-blood-brain-barrier-a-dynamic-interaction-with-consequences-on-drug-disposition-in-brain
#11
Catarina Chaves, Fernando Remião, Salvatore Cisterninoa, Xavier Declèves
Opioids are widely used in pain management whose effects are due to binding to classical opioid receptors and/or Toll-like receptors (TLR) present at the central nervous system (CNS). At the blood-brain barrier (BBB), several influx and/or efflux transporters are expressed, such as the ATP-binding cassette (ABC) P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRP, ABCC) transporters, and solute carrier transporters (SLC), and are responsible for the transport of many xenobiotics from the brain into the bloodstream or vice versa...
May 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28472619/toll-like-receptor-4-and-hepatocellular-carcinoma-a-systematic-review
#12
REVIEW
Zahra Sepehri, Zohre Kiani, Farhad Kohan, Seyed Moayed Alavian, Saeid Ghavami
INTRODUCTION: Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC...
May 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28464762/cancer-targeted-oncolytic-adenoviruses-for-modulation-of-the-immune-system
#13
Vincenzo Cerullo, Cristian Capasso, Markus Vähä-Koskela, Otto Hemminki, Akseli Hemminki
Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit...
May 2, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28456734/thermosensitive-gel-based-formulation-for-intra-tumoral-delivery-of-toll-like-receptor-7-8-dual-agonist-medi9197
#14
Amir Fakhari, Sean Nugent, James Elvecrog, John Vasilakos, Marta Corcoran, Ashenafi Tilahun, Kristen Siebenaler, Jenny Sun, J Anand Subramony, Alexander Schwarz
Toll-like receptor (TLR) agonists TLR 7/8, MEDI9197, is a, imidazoquinoline analogue that can be used for cancer immunotherapy based on its efficacy toward a variety of tumors. Systemic administration of TLR agonists results in stimulation of the immune system throughout the entire body causing undesirable side effects. To minimize these adverse events, local administration of TLR agonists including intra-tumoral (IT) delivery has been introduced. Here, a poloxamer 407 thermogel formulation for IT delivery of a TLR 7/8 dual agonist, MEDI9197, is described in which the combination of the aqueous thermogel and the ethanolic TLR 7/8 dual agonist, MEDI9197, solution leads to precipitated drug particles within the gel...
April 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28454924/dual-effect-of-silymarin-on-experimental-non-alcoholic-steatohepatitis-induced-by-irinotecan
#15
Eudmar Marcolino Assis-Júnior, Anielle Torres Melo, Venúcia Bruna Magalhães Pereira, Deysi Viviana Tenazoa Wong, Nathalia Ribeiro Pinho Sousa, Christiane Mendes Gonçalves Oliveira, Lara Raissa Cavalcante Malveira, Leonardo Silva Moreira, Marcellus Henrique Loiola Ponte Souza, Paulo Roberto Carvalho Almeida, Roberto César Pereira Lima-Júnior
Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5ml/kg i.p.), IRI (50mg/kg i.p.), SIL (150mg/kg p.o.) or IRI (50mg/kg i.p.)+(SIL 1.5, 15 or 150mg/kg p.o.) thrice/week/7weeks...
April 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28454333/a-polysaccharide-component-from-strongylocentrotus-nudus-eggs-inhibited-hepatocellular-carcinoma-in-mice-by-activating-t-lymphocytes
#16
Min Zhang, Yang Liu, Jingwen Li, Mengyun Ke, Jie Yu, Jie Dou, Hui Wang, Changlin Zhou
A component purified from Strongylocentrotus nudus eggs on a diethylaminoethyl cellulose-52 chromatography column and eluted using a NaCl solution gradient (SEP-S), is a homogeneous polysaccharide of α-D-glucan with a reduced molecular weight of 9.33×10(5) Da, compared with that of S. nudus egg polysaccharide (SEP). In an in vivo antitumor assay of histocompatibility-22 hepatocellular carcinoma in tumor-bearing mice, the inhibitory rates at SEP-S doses of 5, 10 and 20 mg/kg/day were 38.8, 50.7 and 70.3%, respectively...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#17
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28440596/immunogenicity-of-a-fully-synthetic-muc1-glycopeptide-antitumor-vaccine-enhanced-by-poly-i-c-as-a-tlr3-activating-adjuvant
#18
Markus Glaffig, Natascha Stergiou, Edgar Schmitt, Horst Kunz
Fully synthetic MUC1 glycopeptide antitumor vaccines have a precisely specified structure and induce a targeted immune response without suppression of the immune response when using an immunogenic carrier protein. However, tumor-associated aberrantly glycosylated MUC1 glycopeptides are endogenous structures, "self-antigens", that exhibit only low immunogenicity. To overcome this obstacle, a fully synthetic MUC1 glycopeptide antitumor vaccine was combined with poly(inosinic acid:cytidylic acid), poly(I:C), as a structurally defined Toll-like receptor 3 (TLR3)-activating adjuvant...
April 25, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28440494/low-dose-paclitaxel-suppresses-the-induction-of-m2%C3%A2-macrophages-in-gastric-cancer
#19
Takahisa Yamaguchi, Sachio Fushida, Yasuhiko Yamamoto, Tomoya Tsukada, Jun Kinoshita, Katsunobu Oyama, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Seiichi Munesue, Ai Harashima, Shinichi Harada, Hiroshi Yamamoto, Tetsuo Ohta
Tumor-associated macrophages of the M2 phenotype promote tumor proliferation and are associated with a poor prognosis in patients with various malignancies, including gastric cancer with peritoneal dissemination. The present study assessed whether paclitaxel (PTX) suppresses M2 macrophages, by acting as a Toll-like receptor 4 (TLR4) agonist. Macrophages derived from the THP-1 monocytic cell line and peripheral blood mononuclear cell (PBMC)-derived macrophages were cultured with gastric cancer cells in medium containing PTX, at a concentration that did not affect cell proliferation...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#20
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
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