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Toll like receptor 3 and cancer

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https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#1
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28778074/toll-like-receptor-expression-in-human-non-small-cell-lung-carcinoma-potential-prognostic-indicators-of-disease
#2
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...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746799/lack-of-il-6-in-the-tumor-microenvironment-augments-type-1-immunity-and-increases-the-efficacy-of-cancer-immunotherapy
#3
Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In this study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells...
July 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28742407/tlr5-polymorphisms-rs2072493-rs5744174-and-rs5744168-are-not-genetic-risk-factors-for-chronic-helicobacter-pylori-infection-in-indian-tamils
#4
Vaishnavi Goda, Megala Jayaraman, Rekha Loganathan, Mehnaz Nazeer, Mohammed Ali, Premkumar Karunakaran, Panneer Devaraju
The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is on the rise in India, and the genetic factors influencing the increased susceptibility in Indian population remain obscure. Toll-like receptors (TLRs) play a major role in innate immune system and genetic polymorphisms affecting their function were reported to enhance the risk for H. pylori infection. Seventy-seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168 polymorphisms within TLR5 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping techniques...
August 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28717003/surface-toll-like-receptor-3-expression-in-metastatic-intestinal-epithelial-cells-induces-inflammatory-cytokine-production-and-promotes-invasiveness
#5
Marit Bugge, Bjarte Bergstrom, Oda Kamilla Eide, Helene Solli, Ingrid F Kjønstad, Jørgen Stenvik, Terje Espevik, Nadra J Nilsen
Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28713897/expression-of-irak%C3%A2-3-is-associated-with-colitis%C3%A2-associated-tumorigenesis-in-mice
#6
Dingting Xu, Hanyun Zhang, Xiaoying Wang, Yan Chen
Interleukin‑1 receptor‑associated kinase‑3 (IRAK‑3) is a negative regulator in Toll‑like receptor (TLR) pathways. The present study investigated the importance of IRAK‑3 in a mouse model of chemically‑induced colitis‑associated tumorigenesis. The colitis‑associated tumorigenesis was induced in ICR mice by the administration of 1,2‑dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS), termed the DMH + DSS group. In the DSS group, mice were administered with DSS; in the DMH group, mice were injected with DMH; in the control group, mice were injected with physiological saline...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28706484/alantolactone-improves-prolonged-exposure-of-interleukin-6-induced-skeletal-muscle-inflammation-associated-glucose-intolerance-and-insulin-resistance
#7
Minjee Kim, Kwangho Song, Yeong Shik Kim
The pro-inflammatory cytokine, Interleukin-6 (IL-6), has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28704679/ph-sensitive-polymer-modified-liposome-based-immunity-inducing-system-effects-of-inclusion-of-cationic-lipid-and-cpg-dna
#8
Yuta Yoshizaki, Eiji Yuba, Naoki Sakaguchi, Kazunori Koiwai, Atsushi Harada, Kenji Kono
Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects...
July 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28700533/cd103-dendritic-cell-function-is-altered-in-the-colons-of-patients-with-ulcerative-colitis
#9
Hiroshi Matsuno, Hisako Kayama, Junichi Nishimura, Yuki Sekido, Hideki Osawa, Soumik Barman, Takayuki Ogino, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Motoi Uchino, Hiroki Ikeuchi, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Tsunekazu Mizushima
BACKGROUND: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). METHODS: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24)...
July 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28654888/mek-inhibition-enhances-efficacy-of-bacillus-calmette-gu%C3%A3-rin-on-bladder-cancer-cells-by-reducing-release-of-toll-like-receptor-2-activated-antimicrobial-peptides
#10
Young Mi Whang, Su Bin Jin, Serk In Park, In Ho Chang
Bacillus Calmette-Guérin (BCG) is one of the standard treatment options for non-muscle-invasive bladder cancer. The details of the biological defense mechanisms against BCG remain unclear. Here, we investigated whether BCG-induced release of antimicrobial peptides (AMPs; e.g., human β-defensin-2, -3, and cathelicidin) is involved with mitogen-activated protein kinase (MAPK) pathways, and investigated the enhanced anticancer effect of BCG through the down-regulation of Toll-like receptors (TLRs) and MAPK pathways in bladder cancer cells...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28626766/involvement-of-the-toll-like-receptor-nitric-oxide-signaling-pathway-in-the-pathogenesis-of-cervical-cancer-caused-by-high-risk-human-papillomavirus-infection
#11
Jie Li, Heping Rao, Chang'e Jin, Jinrong Liu
Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28598999/lymphatic-endothelial-progenitors-originate-from-plastic-myeloid-cells-activated-by-toll-like-receptor-4
#12
Lisa D Volk-Draper, Kelly L Hall, Andrew C Wilber, Sophia Ran
BACKGROUND: Myeloid-derived lymphatic endothelial cells (M-LECP) are induced by inflammation and play an important role in adult lymphangiogenesis. However, the mechanisms driving M-LECP differentiation are currently unclear. We previously showed that activation of Toll-like receptor-4 (TLR4) induces myeloid-lymphatic transition (MLT) of immortalized mouse myeloid cells. Here the goals were to assess the potential of different TLR4 ligands to induce pro-lymphatic reprogramming in human and mouse primary myeloid cells and to identify transcriptional changes regulating this process...
2017: PloS One
https://www.readbyqxmd.com/read/28564605/a-tlr3-specific-adjuvant-relieves-innate-resistance-to-pd-l1-blockade-without-cytokine-toxicity-in-tumor-vaccine-immunotherapy
#13
Yohei Takeda, Keisuke Kataoka, Junya Yamagishi, Seishi Ogawa, Tsukasa Seya, Misako Matsumoto
Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28545586/disulfide-high-mobility-group-box-1-causes-bladder-pain-through-bladder-toll-like-receptor-4
#14
Fei Ma, Dimitrios E Kouzoukas, Katherine L Meyer-Siegler, Karin N Westlund, David E Hunt, Pedro L Vera
BACKGROUND: Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain...
May 25, 2017: BMC Physiology
https://www.readbyqxmd.com/read/28537730/discovery-of-small-molecules-as-multi-toll-like-receptor-agonists-with-proinflammatory-and-anticancer-activities
#15
Lei Zhang, Varun Dewan, Hang Yin
Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Subsequent structural optimization and counterscreening of other TLRs produced the first small molecule 17e (CU-CPT17e) capable of simultaneously activating TLRs 3, 8, and 9. Biochemical studies demonstrated that 17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells...
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28533225/multi-functional-effects-of-a-small-molecule-stat3-inhibitor-on-nash-and-hcc-in-mice
#16
Kwang Hwa Jung, Wonbeak Yoo, Heather L Stevenson, Dipti Deshpande, Hong Shen, Mihai Gagea, Suk-Young Yoo, Jing Wang, Thomas Kris Eckols, Uddalak Bharadwaj, David J Tweardy, Laura Beretta
The incidence of hepatocellular carcinoma (HCC) is increasing in the United States and liver cancer is the second leading cause of cancer-related mortality worldwide. Non-alcoholic steatohepatitis (NASH) is becoming an important risk for HCC and most patients with HCC have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat HCC in the context of NASH and cirrhosis are urgently needed. <br /><br />Experimental Design: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in HCC tumors...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#17
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/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
#18
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/28454924/dual-effect-of-silymarin-on-experimental-non-alcoholic-steatohepatitis-induced-by-irinotecan
#19
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...
July 15, 2017: Toxicology and Applied Pharmacology
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
#20
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...
May 22, 2017: ChemMedChem
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