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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/28332554/fucoidan-induces-toll-like-receptor-4-regulated-reactive-oxygen-species-and-promotes-endoplasmic-reticulum-stress-mediated-apoptosis-in-lung-cancer
#1
Hsien-Yeh Hsu, Tung-Yi Lin, Mei-Kuang Lu, Pei-Ju Leng, Shu-Ming Tsao, Yu-Chung Wu
Fucoidan, a sulfated polysaccharide extracted from brown algae, exhibits anti-cancer activity. However, the effects and mechanism of fucoidan-induced apoptosis via endoplasmic reticulum (ER) stress is unclear. In this study, we demonstrated that fucoidan prevents tumorigenesis and reduces tumor size in LLC1-xenograft male C57BL/6 mice. Fucoidan induces an ER stress response by activating the PERK-ATF4-CHOP pathway, resulting in apoptotic cell death in vitro and in vivo. Furthermore, ATF4 knockdown abolishes fucoidan-induced CHOP expression and rescues cell viability...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327944/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
#2
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 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...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326931/overexpression-of-suppressor-of-cytokine-signaling-3-in-dorsal-root-ganglion-attenuates-cancer-induced-pain-in-rats
#3
Jinrong Wei, Meng Li, Dieyu Wang, Hongyan Zhu, Xiangpeng Kong, Shusheng Wang, You-Lang Zhou, Zhong Ju, Guang-Yin Xu, Guo-Qin Jiang
Background Cancer-induced pain (CIP) is one of the most severe types of chronic pain with which clinical treatment remains challenging and the involved mechanisms are largely unknown. Suppressor of cytokine signaling 3 (SOCS3) is an important intracellular protein and provides a classical negative feedback loop, thus involving in a wide variety of processes including inflammation and nociception. However, the role of SOCS3 pathway in CIP is poorly understood. The present study was designed to investigate the role of SOCS3 in dorsal root ganglion (DRG) in the development of CIP...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28323577/mitigation-of-radiation-induced-epithelial-damage-by-the-tlr5-agonist-entolimod-in-a-mouse-model-of-fractionated-head-and-neck-irradiation
#4
Ilia A Toshkov, Anatoli S Gleiberman, Vadim L Mett, Alan D Hutson, Anurag K Singh, Andrei V Gudkov, Lyudmila G Burdelya
Radiation treatment of head and neck cancer frequently causes severe collateral damage to normal tissues including mouth mucosa, salivary glands and skin. This toxicity limits the radiation dose that can be delivered and affects the patient's quality of life. Previous studies in mice and nonhuman primates showed that entolimod, a toll-like receptor 5 (TLR5) agonist derived from bacterial flagellin, effectively reduced radiation damage to hematopoietic and gastrointestinal tissues in both total-body and local irradiation scenarios, with no protection of tumors...
March 21, 2017: Radiation Research
https://www.readbyqxmd.com/read/28322156/recent-findings-on-the-application-of-toll-like-receptors-agonists-in-cancer-therapy
#5
Martina Mikulandra, Jasminka Pavelic, Tanja Matijevic Glavan
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs are Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28300057/combined-toll-like-receptor-3-7-9-deficiency-on-host-cells-results-in-t-cell-dependent-control-of-tumour-growth
#6
Johanna C Klein, Katrin Moses, Gennadiy Zelinskyy, Simon Sody, Jan Buer, Stephan Lang, Iris Helfrich, Ulf Dittmer, Carsten J Kirschning, Sven Brandau
Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28296893/hnrnp-i-regulates-neonatal-immune-adaptation-and-prevents-colitis-and-colorectal-cancer
#7
Zhigang Jin, Feng Liang, Jing Yang, Wenyan Mei
The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses. During the neonatal stage, the intestinal epithelium is under immune repression, allowing the transition for newborns from a relatively sterile intra-uterine environment to one that is rich in foreign antigens. The mechanism underlying such immune repression remains largely unclear, but involves downregulation of IRAK1 (interleukin-1 receptor-associated kinase), an essential component of toll-like receptor-mediated NF-κB signaling...
March 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28296189/tlr4-promotes-breast-cancer-metastasis-via-akt-gsk3%C3%AE-%C3%AE-catenin-pathway-upon-lps-stimulation
#8
Jun Li, Jing Yin, Wenzhi Shen, Ruifang Gao, Yanhua Liu, Yanan Chen, Xiru Li, Chenghu Liu, Rong Xiang, Na Luo
Bacteria/virus-induced chronic inflammation is involved in both tumor initiation and tumor progression. Toll-like receptor 4 (TLR4) has been implicated in the development of several types of cancer. In this study, we explored the impact of TLR4 activation by lipopolysaccharide (LPS) on breast cancer metastasis and associated signaling molecules. We first examined TLR4 expression levels in breast tissue using a human breast tissue microarray and breast cell lines. We then studied the role of TLR4 activation by LPS stimulation in breast cancer metastasis using both in vitro and in vivo models...
March 14, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#9
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286864/in-vivo-expansion-of-melanoma-specific-t-cells-using-microneedle-arrays-coated-with-immune-polyelectrolyte-multilayers
#10
Qin Zeng, Joshua M Gammon, Lisa H Tostanoski, Yu-Chieh Chiu, Christopher M Jewell
Microneedles (MNs) are micron-scale polymeric or metallic structures that offer distinct advantages for vaccines by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. These advantages, along with recent studies showing therapeutic benefits achieved using traditional intradermal injections in human cancer patients, suggest MN delivery might enhance cancer vaccines and immunotherapies. We recently developed a new class of polyelectrolyte multilayers based on the self-assembly of model peptide antigens and molecular toll-like receptor agonists (TLRa) into ultrathin, conformal coatings...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28286503/wnt-tlr-dialog-in-neuroinflammation-relevance-in-alzheimer-s-disease
#11
REVIEW
Juan M Zolezzi, Nibaldo C Inestrosa
The innate immune system (IIS) represents the first line of defense against exogenous and endogenous harmful stimuli. Different types of pathogens and diverse molecules can activate the IIS via a ligand-receptor mechanism. Cytokine release, recruitment of immunocompetent cells, and inflammation constitute the initial steps in an IIS-mediated response. While balanced IIS activity can resolve a harmful event, an altered response, such as deficient or persistent IIS activity, will have a critical effect on organism homeostasis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28280355/toll-like-receptor-4-as-a-predictor-of-clinical-outcomes-of-estrogen-receptor-negative-breast-cancer-in-saudi-women
#12
Abdelhabib Semlali, Maroua Jalouli, Narasimha Reddy Parine, Abdullah Al Amri, Maha Arafah, Abdulrahman Al Naeem, Sanaa Abdullah Ajaj, Mahmoud Rouabhia, Mohammad Saud Alanazi
The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28279655/nontypeable-haemophilus-influenzae-promoted-proliferation-of-kras-induced-early-adenomatous-lesions-is-completely-dependent-on-toll-like-receptor-signaling
#13
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease is a risk factor for lung cancer. COPD is characterized by chronic airway inflammation and lung infections. The airways of patients with COPD are frequently colonized with bacteria [eg, nontypeable Haemophilus influenzae (NTHi)] that cause pulmonary inflammation and exacerbations. Pulmonary adenocarcinomas are frequently associated with an activating mutation in the KRAS gene. We determined the function of Toll-like receptor (TLR) signaling on the progression of KRas-induced early adenomatous lesions in the lung...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28260512/polypurine-reverse-hoogsteen-hairpins-as-a-gene-silencing-tool-for-cancer
#14
Carlos J Ciudad, Laura Rodríguez, Xenia Villalobos, Alex J Félix, Véronica Noé
Polypurine reverse Hoogsteen (PPRH) molecules are DNA hairpins formed by two polypurine strands running in an antiparallel orientation and containing no nucleotide modifications. The two strands, linked by a pentathymidine loop, are bound through intramolecular reverse Hoogsteen bonds. Then, PPRHs can bind by Watson-Crick bonds to their corresponding polypyrimidine target in the dsDNA provoking a displacement of the polypurine strand of the duplex. We described the effect and mechanisms of action of PPRHs in cells using PPRHs designed against the template and coding strands of the dhfr gene...
March 1, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28257116/valorization-of-lipids-from-gracilaria-sp-through-lipidomics-and-decoding-of-antiproliferative-and-anti-inflammatory-activity
#15
Elisabete da Costa, Tânia Melo, Ana S P Moreira, Carina Bernardo, Luisa Helguero, Isabel Ferreira, Maria Teresa Cruz, Andreia M Rego, Pedro Domingues, Ricardo Calado, Maria H Abreu, Maria Rosário Domingues
The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC-MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS)...
March 2, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28251971/-biomarkers-of-prostate-cancer-sensitivity-to-the-sendai-virus
#16
A A Belova, A O Sosnovtseva, A V Lipatova, K M Njushko, N N Volchenko, M M Belyakov, O V Sudalenko, A A Krasheninnikov, P V Shegai, A F Sadritdinova, M S Fedorova, N V Vorobjov, B Y Alekseev, A D Kaprin, A V Kudryavtseva
Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28242239/role-of-toll-like-receptor-4-in-drug-drug-interaction-between-paclitaxel-and-irinotecan-in-vitro
#17
Pankajini Mallick, Sumit Basu, Bhagavtula Moorthy, Romi Ghose
The bacterial receptor, Toll-like receptor (TLR) 4 mediates inflammatory responses and has been linked to a broad array of diseases. TLR4 agonists are being explored as potential treatments for cancer and other diseases. We have previously shown that activation of TLR4 by lipopolysaccharide (LPS) leads to down-regulation of drug metabolizing enzymes/transporters (DMETs), and altered pharmacokinetics/pharmacodynamics (PK/PD) of drugs. These changes can increase the risk of drug-drug interactions (DDIs) in patients on multiple medications...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28241765/heterogeneity-of-toll-like-receptor-9-signaling-in-b-cell-malignancies-and-its-potential-therapeutic-application
#18
REVIEW
Ling Bai, Wei Chen, Jingtao Chen, Wei Li, Lei Zhou, Chao Niu, Wei Han, Jiuwei Cui
Toll-like receptor 9 (TLR9) is expressed in a variety of B-cell malignancies and works as a bridge between innate and adaptive immunity. CpG oligodeoxynucleotides (CpG ODNs), TLR9 agonists, are able to induce anticancer immune responses and exert direct effects against cancer cells, serving as cancer therapeutic agents. Therefore, TLR9 might be a potential therapeutic target for drug development. However, several new evidences have revealed that direct effects of TLR9 agonists on B-cell malignancies is controversial...
February 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28240761/hepatocellular-carcinoma-and-cxcr3-chemokines-a-narrative-review
#19
E Giusy, F Poupak
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3)...
January 2017: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28238855/mkp-1-negatively-regulates-lps-mediated-il-1%C3%AE-production-through-p38-activation-and-hif-1%C3%AE-expression
#20
Harvinder Talwar, Christian Bauerfeld, Mohamad Bouhamdan, Pershang Farshi, Yusen Liu, Lobelia Samavati
Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that plays a major role in inflammatory diseases as well as cancer. The inflammatory response after Toll-like receptor (TLR) 4 activation is tightly regulated through phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 preferentially dephosphorylates p38 and JNK. IL-1β is regulated through the activation of MAPK, including p38 as well as several transcription factors...
February 24, 2017: Cellular Signalling
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