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https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#1
Radhashree Maitra, Titto Augustine, Yitzchak Dayan, Carol Chandy, Matthew Coffey, Sanjay Goel
New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#2
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28418096/expression-of-toll-like-receptors-in-t-lymphocytes-stimulated-with-n-3-oxododecanoyl-l-homoserine-lactone-from-pseudomonas-aeruginosa
#3
Lei Bao, Jialin Yu, Haiying Zhong, Daochao Huang, Qi Lu
The establishment of chronic Pseudomonas aeruginosa infections is correlated with the disturbance of the host immune system. The P. aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential to modulate the host immune system. The immune system recognizes pathogens via toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in monocytes. However, the role of T cells in P. aeruginosa infection has not been delineated. In order to understand this activity, we examined whether 3-O-C12-HSL has an effect on the immune function and the expression of TLRs in T lymphocytes...
April 18, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28413476/the-mechanism-of-human-%C3%AE-defensin-3-in-mrsa-induced-infection-of-implant-drug-resistant-bacteria-biofilm-in-the-mouse-tibial-bone-marrow
#4
Chen Zhu, Ni-Rong Bao, Shuo Chen, Jian-Ning Zhao
The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group)...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28413475/evaluation-of-the-role-of-human-%C3%AE-defensin-3-in-modulation-of-immunity-and-inflammatory-response-after-knee-replacement
#5
Jiguang Jia, Hao Peng, Sen Chen
The present study investigated the value of human β-defensin 3 (HBD-3) in adjusting the immunity and inflammatory response of T lymphocytes in the body after knee replacement. Sixty-four cases of knee replacement patients were successively selected and randomly divided into the control group and the observation group each with 32 cases. Once a day, for 7 days, patients in the control group were injected with placebo saline solution in the articular cavity. Levels of Th1 and/Th2, interleukin (IL)-2 and IL-10, tumor necrosis factor (TNF)-α, toll-like receptor (TLR)-4, and alkaline phosphatase (ALP) were compared one month later, and implant infection rates were compared within 1-year follow-up...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28408332/molecular-cloning-structural-modeling-and-expression-analysis-of-myd88-and-irak4-of-golden-pompano-trachinotus-ovatus
#6
Zhitao Qi, Baobao Sun, Qihuan Zhang, Fancui Meng, Qiaoqing Xu, Youchuan Wei, Qian Gao
MyD88 and IRAK4 are important components of TLR signaling pathways. However, information about MyD88 and IRAK4 is vacant in golden pompano (Trachinotus ovatus), a marine teleost with great commercial value. Thus, in this study the full lengths of trMyD88 and trIRAK4 were cloned from golden pompano using RT-PCR and RACE-PCR methods. trMyD88 was 1213 bp in length, encoding a putative protein of 288 amino acids (aa), consisting of a 99 aa of death domain at its N-terminal and a 137 aa of the TIR domain at its C-terminal...
April 10, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28402971/implicating-receptor-activator-of-nf-%C3%AE%C2%BAb-rank-rank-ligand-signalling-in-microglial-responses-to-toll-like-receptor-stimuli
#7
Anton Kichev, Pascale Eede, Pierre Gressens, Claire Thornton, Henrik Hagberg
Inflammation in the perinatal brain caused by maternal or intrauterine fetal infection is now well established as an important contributor to the development of perinatal brain injury. Exposure to inflammatory products can impair perinatal brain development and act as a risk factor for neurological dysfunction, cognitive disorders, cerebral palsy, or preterm birth. Pre-exposure to inflammation significantly exacerbates brain injury caused by hypoxic/ischaemic insult. Tumour necrosis factor (TNF) is a family of cytokines largely involved in inflammation signalling...
April 13, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28400218/outcomes-of-the-japanese-multicenter-viabahn-trial-of-endovascular-stent-grafting-for-superficial-femoral-artery-lesions
#8
Takao Ohki, Kimihiko Kichikawa, Hiroyoshi Yokoi, Masaaki Uematsu, Terutoshi Yamaoka, Koji Maeda, Yuji Kanaoka
OBJECTIVE: The objective of this study was to assess 1-year safety, efficacy, and invasiveness outcomes of endovascular stent grafting of symptomatic long lesions (≥10 cm) in the superficial femoral artery (SFA) as a substitute for above-knee open bypass surgery. METHODS: This prospective, multicenter (15 hospitals) study assessed heparin-coated stent grafts for the treatment of long SFA lesions in Japanese subjects with peripheral arterial disease. Inclusion criteria were Rutherford category 2 to 5 symptoms (grade 5 without active infection), ankle-brachial index ≤0...
April 8, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28396322/camp-elevating-capacity-of-the-adenylate-cyclase-toxin-hemolysin-is-sufficient-for-lung-infection-but-not-for-full-virulence-of-bordetella-pertussis
#9
Karolina Skopova, Barbora Tomalova, Ivan Kanchev, Pavel Rossmann, Martina Svedova, Irena Adkins, Ilona Bibova, Jakub Tomala, Jiri Masin, Nicole Guiso, Radim Osicka, Radislav Sedlacek, Marek Kovar, Peter Sebo
The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cAMP, a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes...
April 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28392361/dexmedetomidine-confers-neuroprotection-against-transient-global-cerebral-ischemia-reperfusion-injury-in-rats-by-inhibiting-inflammation-through-inactivation-of-the-tlr-4-nf-%C3%AE%C2%BAb-pathway
#10
Eugene Kim, Hyun-Chang Kim, Seungmi Lee, Ho-Geol Ryu, Yong-Hee Park, Jun Hyun Kim, Young-Jin Lim, Hee-Pyoung Park
Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotection from cerebral ischemia/reperfusion injury. We determined whether the anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment; Group C underwent transient global ischemia (10min); Group D received DXM 30min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30min before ischemia; and Group RD received resatorvid and DXM 30min before ischemia...
April 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28388966/vaccination-with-poly-ic-lc-and-peptide-pulsed-autologous-dendritic-cells-in-patients-with-pancreatic-cancer
#11
Shikhar Mehrotra, Carolyn D Britten, Steve Chin, Elizabeth Garrett-Mayer, Colleen A Cloud, Mingli Li, Gina Scurti, Mohamed L Salem, Michelle H Nelson, Melanie B Thomas, Chrystal M Paulos, Andres M Salazar, Michael I Nishimura, Mark P Rubinstein, Zihai Li, David J Cole
BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from the peripheral blood of HLA-A2(+) patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin (SRV...
April 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28373780/drug-eluting-stents-or-balloon-angioplasty-for-drug-eluting-stent-associated-restenosis-an-observational-follow-up-study-of-first-time-versus-repeated-restenosis
#12
Mohamed Aboel-Kassem F Abdelmegid, Tarek A N Ahmed, Masashi Kato, Kenji Ando, Takenori Domei, Masashi Iwabuchi, Masakiyo Nobuyoshi
BACKGROUND: The treatment of patients with repeated drug-eluting stent-in stent restenosis (DES-ISR) remains a challenge and a burdensome clinical problem. METHODS: Over a 3-year period, 130 lesions in 123 patients who underwent target lesion revascularization (TLR) for DES restenosis were included in the study. They were classified into two main groups: the first group having first-time DES-ISR (n = 84), and the second group having rerestenosis of DES-treated DES-ISR (n = 39)...
April 2017: Journal of the Saudi Heart Association
https://www.readbyqxmd.com/read/28373665/polyfunctional-natural-killer-cells-with-a-low-activation-profile-in-response-to-toll-like-receptor-3-activation-in-hiv-1-exposed-seronegative-subjects
#13
Josenilson F Lima, Luanda M S Oliveira, Nátalli Z Pereira, Alberto J S Duarte, Maria N Sato
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371137/proanthocyanidin-protects-against-cisplatin-induced-oxidative-liver-damage-through-inhibition-of-inflammation-and-nf-%C3%AE%C2%BA%C3%AE-tlr-4-pathway
#14
Nagla A El-Shitany, Basma Eid
Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS...
March 29, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28365415/immediate-and-short-term-performance-of-a-novel-sirolimus-coated-balloon-during-complex-percutaneous-coronary-interventions-the-fatebenefratelli-sirolimus-coated-balloon-fasico-registry
#15
Bernardo Cortese, Gaetano di Palma, Roberto A Latini, Mostafa Elwany, Pedro Silva Orrego, Romano G Seregni
BACKGROUND AND PURPOSES: Drug-coated balloons (DCB) currently represent an alternative to drug-eluting stents (DES) for the treatment of in-stent restenosis and they are also variably used for small coronary vessel and bifurcation lesion management. All DCB variably elute paclitaxel as an anti-proliferative drug. The first sirolimus coated balloon (SCB) received the CE mark in 2016, but its clinical performance has not been shown yet. METHODS AND RESULTS: FASICO in an all-comer registry of the first consecutive patients with at least one lesion treated with SCB between March and July 2016 at the first European centre that used this device...
March 25, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28363496/therapeutic-progenitor-cell-application-for-tissue-regeneration-analyzing-the-impact-of-toll-like-receptor-signaling-on-c-kit-cell-migration-following-ischemia-reperfusion-injury-in-vivo
#16
Peter Donndorf, Saifullah Abubaker, Brigitte Vollmar, Christian Rimmbach, Gustav Steinhoff, Alexander Kaminski
OBJECTIVES: Toll-like-receptor (TLR) mediated immune response has been shown to regulate myocardial damage following cardiac ischemia-reperfusion (IR). It has not been described conclusively so far whether migration of therapeutically applied progenitor cells following an IR event depends on TLR-signaling. METHODS: In vivo migratory capacity murine c-kit(+) cells following IR injury was quantified by intravital fluorescence microscopy, utilizing the mouse cremaster muscle model and analyzing early (rolling) and late (adhesion) c-kit(+) cell interaction with the local endothelium...
March 29, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28359672/cloning-and-expression-analysis-of-a-toll-like-receptor-21-tlr21-gene-from-turbot-scophthalmus-maximus
#17
Song Li, Guanjie Wang, Dahai Liu, Qiuming Liu, Guobin Hu
Toll-like receptor 21 (TLR21) is a non-mammalian TLR recognizing unmethylated CpG DNA and considered as a functional homolog of mammalian TLR9. In the present study, a TLR21 gene was cloned from turbot, Scophthalmus maximus, its immune responsive expression was subsequently studied in vivo. The turbot (Sm)TLR21 gene is an intronless gene with a length of 3527 bp and encodes a peptide of 984 amino acids. The deduced protein possesses a signal peptide sequence, a leucine-rich repeat (LRR) domain composed of 16 LRR motifs, a transmembrane (TM) region and a Toll/interleukin-1 receptor (TIR) domain...
March 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28351310/one-year-outcomes-of-the-paclitaxel-eluting-self-expanding-stentys-stent-system-in-the-treatment-of-infrapopliteal-lesions-in-patients-with-critical-limb-ischemias
#18
Marc Bosiers, Joren Callaert, Koen Keirse, Jeroen M H Hendriks, Patrick Peeters, Jürgen Verbist, Lieven Maene, Roel Beelen, Koen Deloose
PURPOSE: To investigate the efficacy of the paclitaxel-coated, self-expanding, nitinol Stentys Stent System in tibioperoneal lesions ≤50 mm long. METHODS: The prospective, single-arm, multicenter PES-BTK-70 trial ( ClinicalTrials.gov identifier NCT01630070) evaluated the safety and efficacy of the coronary Stentys Stent System in the treatment of a stenotic or occlusive lesion ≤50 mm long in the tibioperoneal arteries of patients with critical limb ischemia (CLI)...
March 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28351204/results-from-the-visibility-iliac-study
#19
John H Rundback, Patrick Peeters, Jon C George, Michael R Jaff, Peter L Faries
PURPOSE: To evaluate the safety and effectiveness of primary stenting of the common (CIA) or external iliac artery (EIA) using the Visi-Pro Balloon-Expandable Peripheral Stent System for treatment of stenotic, restenotic, or occluded lesions. METHODS: Between 2011 and 2012, 75 patients (mean age 64.2±8.9 years; 46 men) with Rutherford category 2-4 ischemia and atherosclerotic lesions ≤10 cm in length underwent iliac artery stenting at 17 centers in the United States and Europe...
February 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28350104/induction-of-galectin-1-by-tlr-dependent-pi3k-activation-enhances-epithelial-mesenchymal-transition-of-metastatic-ovarian-cancer-cells
#20
Ga Bin Park, Yoon Hee Chung, Daejin Kim
The expression of different toll-like receptors (TLRs) on tumor cells has been associated with disease aggressiveness, treatment resistance, and poor prognosis. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is considered critical for cancer cell survival and proliferation. Thus, we investigated the effect of TLR-stimulated PI3K activation on the epithelial-to-mesenchymal transition (EMT) of primary (Caov-3) and metastatic (SK‑OV‑3) epithelial ovarian cancer cell lines in this study. TLR engagement with various ligands promoted the expression of class IA PI3K (p110α, p110β, and p110δ) and increased the expression of mesenchymal markers (N-cadherin, Slug, Vimentin, Snail, α-SMA, and TCF) in SK‑OV‑3 cells...
March 27, 2017: Oncology Reports
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