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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/29234590/an-integrative-analysis-of-dna-methylation-in-osteosarcoma
#1
Jie Xu, Deng Li, Zhiqing Cai, Yingbin Zhang, Yulin Huang, Baohua Su, Ruofan Ma
Background: The study aimed to analyze aberrantly methylated genes, relevant pathways and transcription factors (TFs) in osteosarcoma (OS) development. Methods: Based on the DNA methylation microarray data GSE36002 that were downloaded from GEO database, the differentially methylated genes in promoter regions were identified between OS and normal samples. Pathway and function enrichment analyses of differentially methylated genes was performed. Subsequently, protein-protein interaction (PPI) network was constructed, followed by identification of cancer-associated differentially methylated genes and significant differentially methylated TFs...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29230065/the-toll-like-receptor-2-6-agonist-fsl-1-lipopeptide-therapeutically-mitigates-acute-radiation-syndrome
#2
Cathryn J Kurkjian, Hao Guo, Nathan D Montgomery, Ning Cheng, Hong Yuan, Joseph R Merrill, Gregory D Sempowski, W June Brickey, Jenny P-Y Ting
Risks of radiation exposure from nuclear incidents and cancer radiotherapy are undeniable realities. These dangers urgently compel the development of agents for ameliorating radiation-induced injuries. Biologic pathways mediated by myeloid differentiation primary response gene 88 (MyD88), the common adaptor for toll-like receptor (TLR) and Interleukin-1 receptor signaling, are critical for radioprotection. Treating with agonists prior to radiation enhances survival by activating TLR signaling, whereas radiomitigating TLR-activating therapeutics given after exposure are less defined...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228714/unique-expression-signatures-of-circular-rnas-in-response-to-dna-tumor-virus-sv40-infection
#3
Jiandong Shi, Ningzhu Hu, Jianfang Li, Zhaoping Zeng, Ling Mo, Jing Sun, Meini Wu, Yunzhang Hu
Circular RNAs (circRNAs), identified as a class of widely expressed endogenous regulatory RNAs, are involved in diverse physiological and pathological processes. However, their role in viral pathogenesis and cellular antiviral response remains unexplored. In this study, a potent DNA tumor virus, simian virus 40 (SV40), was used as a model to investigate the viral influences on cellular circRNA transcriptome. Using RNA-seq, 15,241 putative circRNAs were identified de novo from 5,057 parental genes in monkey kidney-derived Vero cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228698/osteopontin-is-involved-in-tlr4-pathway-contributing-to-ovarian-cancer-cell-proliferation-and-metastasis
#4
Cong Xu, Hua Li, Miao Yin, Tao Yang, Liguo An, Guiwen Yang
Tumor cell proliferation and metastasis are critical for tumor progression and lead to death of cancer patients. TLR4 is a member of the toll-like receptor (TLR) family, which promotes tumor growth, metastasis and immune escape. Osteopontin (OPN), a phosphorylated glycoprotein extensively expressed in multiple cell-types, plays important roles in tumorigenesis, metastasis and infiltration, and participates in signal transduction of innate immunity. However, it is unclear whether TLR4 has any relationship with OPN...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225688/repurposing-drugs-in-oncology-redo-chloroquine-and-hydroxychloroquine-as-anti-cancer-agents
#5
Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis, Gauthier Bouche
Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29209564/leukotriene-b4-receptor-1-mediated-host-response-shapes-gut-microbiota-and-controls-colon-tumor-progression
#6
Venkatakrishna R Jala, Paramahamsa Maturu, Sobha R Bodduluri, Elangovan Krishnan, Steven Mathis, Krishnaprasad Subbarao, Min Wang, Alfred B Jenson, Mary L Proctor, Eric C Rouchka, Rob Knight, Bodduluri Haribabu
Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29207919/enhancement-of-natural-killer-activity-and-ifn-%C3%AE-production-in-an-il-12-dependent-manner-by-a-brassica-rapa-l
#7
Kana Yamamoto, Kanon Furuya, Kazuki Yamada, Fuka Takahashi, Chisato Hamajima, Sachi Tanaka
Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ...
December 6, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29207048/tlr4-promotes-the-expression-of-hif-1%C3%AE-by-triggering-reactive-oxygen-species-in-cervical-cancer-cells-in%C3%A2-vitro-implications-for-therapeutic-intervention
#8
Xiao Yang, Gan Tao Chen, Yan Qing Wang, Shu Xian, Li Zhang, Shao Ming Zhu, Feng Pan, Yan Xiang Cheng
The present study investigated the mechanism underlying Toll-like receptor 4 (TLR4)-mediated stimulation of hypoxia-inducible factor-1α (HIF-1α) activity and its association with reactive oxygen species (ROS) in cervical cancer cells. SiHa cells were cultured and randomized to control, lipopolysaccharide (LPS), methyl-β-cyclodextrin (MβCD)+LPS, ammonium pyrrolidinedithiocarbamate (PDTC)+LPS, ST2825+LPS and small interfering (si) RNA TLR4+LPS treatment groups. Cell proliferation was quantified using an MTT assay, cell cloning was performed using soft agar colony formation and HIF-1α expression was detected by immunocytochemical staining and western blot analyses...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206292/microrna-6869-5p-acts-as-a-tumor-suppressor-via-targeting-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-in-colorectal-cancer
#9
Shushan Yan, Zengfang Wang, Quanhong Duan, Changcheng Wang, Donghua Xu
Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play important roles in the development and progression of colorectal cancer (CRC). However, little is known about the role of a newly identified miRNA, miR-6869-5p, in CRC. We aim to investigate the modifying effects and underlying mechanisms of miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples from patients with CRC. The prediction of targets of miR-6869-5p in databases of targetscan, microRNA...
December 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29198126/effect-of-lipopolysaccharide-on-toll-like-receptor-4-signals-in-mouse-cancer-cells
#10
N Dana, S H Javanmard, G Vaseghi
BACKGROUND: Recent findings showed that activated TLR signals on cancer cells might promote cancer progression. This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on mouse melanoma and breast cancer cell proliferation and their TLR4 signalling. METHODS: Mouse melanoma cell line (B16F10) and breast cancer cell line (4T1) were taken as models. They were treated with LPS (0, 1.25, 2.5, 5, 7.5, 10 µg/ml) for 4, 16, 24, 48 h and MTT assay was done...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29196874/upregulation-of-spinal-voltage-dependent-anion-channel-1-contributes-to-bone-cancer-pain-hypersensitivity-in-rats
#11
Xiangpeng Kong, Jinrong Wei, Diyu Wang, Xiaoju Zhu, Youlang Zhou, Shusheng Wang, Guang-Yin Xu, Guo-Qin Jiang
Voltage-dependent anion channel 1 (VDAC1) is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2-5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4 (TLR4)...
December 1, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29190881/toll-like-receptor-expression-in-human-non-small-cell-lung-carcinoma-potential-prognostic-indicators-of-disease
#12
Alison K Bauer, Brad L Upham, Elizabeth A Rondini, Meredith A Tennis, Kalpana Velmuragan, David Wiese
Introduction: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. Results: Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190690/development-of-effective-tumor-immunotherapy-using-a-novel-dendritic-cell-targeting-toll-like-receptor-ligand
#13
Nadeeka H De Silva, Takashi Akazawa, Viskam Wijewardana, Norimitsu Inoue, Maremichi Oyamada, Atsuko Ohta, Yuki Tachibana, Daluthgamage Patsy H Wijesekera, Mitsuru Kuwamura, Yasuko Nishizawa, Kazuyuki Itoh, Takeshi Izawa, Shingo Hatoya, Tetsuya Hasegawa, Jyoji Yamate, Toshio Inaba, Kikuya Sugiura
Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers...
2017: PloS One
https://www.readbyqxmd.com/read/29187284/jq1-a-bet-inhibitor-controls-tlr4-induced-il-10-production-in-regulatory-b-cells-by-brd4-nf-%C3%AE%C2%BAb-axis
#14
Min Bum Lee, JunHo Lee, Seong Hwi Hong, Jueng Soo You, Seung Taek Nam, Hyun Woo Kim, Young Hwan Park, Dajeong Lee, Keun Young Min, Yeong-Min Park, Young Mi Kim, Hyuk Soon Kim, Wahn Soo Choi
Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells...
November 29, 2017: BMB Reports
https://www.readbyqxmd.com/read/29181007/interplay-between-natural-killer-cells-and-anti-her2-antibodies-perspectives-for-breast-cancer-immunotherapy
#15
REVIEW
Aura Muntasell, Mariona Cabo, Sonia Servitja, Ignasi Tusquets, María Martínez-García, Ana Rovira, Federico Rojo, Joan Albanell, Miguel López-Botet
Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29180626/mitochondrial-dynamics-controls-anti-tumour-innate-immunity-by-regulating-chip-irf1-axis-stability
#16
Zhengjun Gao, Yiyuan Li, Fei Wang, Tao Huang, Keqi Fan, Yu Zhang, Jiangyan Zhong, Qian Cao, Tong Chao, Junling Jia, Shuo Yang, Long Zhang, Yichuan Xiao, Ji-Yong Zhou, Xin-Hua Feng, Jin Jin
Macrophages, dendritic cells and other innate immune cells are involved in inflammation and host defense against infection. Metabolic shifts in mitochondrial dynamics may be involved in Toll-like receptor agonist-mediated inflammatory responses and immune cell polarization. However, whether the mitochondrial morphology in myeloid immune cells affects anti-tumor immunity is unclear. Here we show that FAM73b, a mitochondrial outer membrane protein, has a pivotal function in Toll-like receptor-regulated mitochondrial morphology switching from fusion to fission...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29179462/toll-like-receptor-5-gene-polymorphism-is-associated-with-breast-cancer-susceptibility
#17
Chen Shuang, Yuan Weiguang, Fu Zhenkun, Huang Yike, Yang Jiankun, Xue Jing, Liu Xinghan, Li Yue, Li Dalin
Toll-like receptor 5 (TLR5) plays a fundamental role in immune responses. Recent findings suggest the TLR5 expression level affects cancer progression and development. In the present study, our examination of 256 breast carcinomas specimens revealed that TLR5 is overexpressed in breast carcinomas, and that TLR5 overexpression correlated with lymph node metastasis and cancer grade (p<0.01). In a case-control study, we also analyzed associations between TLR5 single nucleotide polymorphisms (SNPs) and breast cancer risk...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29177268/advanced-manufacturing-of-microdisk-vaccines-for-uniform-control-of-material-properties-and-immune-cell-function
#18
Qin Zeng, Peipei Zhang, Xiangbin Zeng, Lisa H Tostanoski, Christopher M Jewell
The continued challenges facing vaccines in infectious disease and cancer highlight a need for better control over the features of vaccines and the responses they generate. Biomaterials offer unique advantages to achieve this goal through features such as controlled release and co-delivery of antigens and adjuvants. However, many synthesis strategies lead to particles with heterogeneity in diameter, shape, loading level, or other properties. In contrast, advanced manufacturing techniques allow precision control of material properties at the micro- and nano-scale...
November 27, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29174504/intravesical-immunomodulatory-imiquimod-enhances-bacillus-calmette-gu%C3%A3-rin-downregulation-of-nonmuscle-invasive-bladder-cancer
#19
Juliana A Camargo, Gabriela R Passos, Karen L Ferrari, Athanase Billis, Mário J A Saad, Leonardo O Reis
BACKGROUND: The Toll-like receptor (TLR)2/4 agonist bacillus Calmette-Guérin (BCG), although not failure proof, has been the most efficient immunomodulatory treatment of immunogenic nonmuscle-invasive bladder cancer (NMIBC) for > 40 years. We investigated the role of the immunomodulatory molecule TLR7 agonist imiquimod through the BCG key receptors TLR2/4 and the main downstream molecules of the mammalian target of rapamycin pathway in NMIBC treatment. MATERIALS AND METHODS: A total of 40 Fischer-344 rats, 7 weeks old, received 4 doses of 1...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29172458/transiently-thermoresponsive-acetal-polymers-for-safe-and-effective-administration-of-amphotericin-b-as-vaccine-adjuvant
#20
Simon Van Herck, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens, Xavier Saelens, Bruno G De Geest
The quest for new potent and safe adjuvants to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, Amphotericin B (AmpB) - an FDA-approved anti-fungal drug - has recently been discovered to possess TLR triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant...
November 26, 2017: Bioconjugate Chemistry
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