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TLR lung cancer

Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
Anna Pomerenke, Simon R Lea, Sarah Herrick, Mark A Lindsay, Dave Singh
PURPOSE: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD). They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers. METHODS: We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Priyanka Khare, Anjali Bose, Poonam Singh, Sandhya Singh, Saleem Javed, Swatantra Kumar Jain, Om Singh, Rahul Pal
Human chorionic gonadotropin (hCG), a hormone essential for pregnancy, is also ectopically expressed by a variety of cancers and is associated with poor prognosis; molecular mechanisms which may contribute to tumor progression remain ill-defined. Exogenous hCG enhanced the viability of human colorectal and lung cancer cells and promoted the growth of syngeneic tumors in mice. It induced the synthesis of VEGF, IL-8, matrix metalloprotease (MMP)-2 and MMP-9, and increased invasiveness in an MMP-dependent manner...
May 6, 2016: Molecular Carcinogenesis
Xiaoxia Li, Shihua Wang, Rongjia Zhu, Hongling Li, Qin Han, Robert Chunhua Zhao
BACKGROUND: In tumor microenvironment, a continuous cross-talk between cancer cells and other cellular components is required to sustain tumor progression. Accumulating evidence suggests that exosomes, a novel way of cell communication, play an important role in such cross-talk. Exosomes could facilitate the direct intercellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells. Since mesenchymal stem cells (MSCs) can be attracted to tumor sites and become an important component of the tumor microenvironment, there is an urgent need to reveal the effect of tumor exosomes on MSCs and to further explore the underlying molecular mechanisms...
2016: Journal of Hematology & Oncology
Selvi Ramasamy, Borja Saez, Subhankar Mukhopadhyay, Daching Ding, Alwiya M Ahmed, Xi Chen, Ferdinando Pucci, Rae'e Yamin, Jianfeng Wang, Mikael J Pittet, Cassandra M Kelleher, David T Scadden, David A Sweetser
Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a variety of DNA-binding transcription factors and has been implicated in many cellular functions; however, physiological studies are limited. Tle1-deficient (Tle1(Δ/Δ)) mice, although grossly normal at birth, exhibit skin defects, lung hypoplasia, severe runting, poor body condition, and early mortality. Tle1(Δ/Δ) mice display a chronic inflammatory phenotype with increased expression of inflammatory cytokines and chemokines in the skin, lung, and intestine and increased circulatory IL-6 and G-CSF, along with a hematopoietic shift toward granulocyte macrophage progenitor and myeloid cells...
February 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Pramod Kumar Gupta, Devavrat Tripathi, Savita Kulkarni, M G R Rajan
Chronic infections of Mycobacterium tuberculosis (MTB) cause oxidative stress, TLR activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. Epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. In present study, we have shown for the first time that MTB infection in human monocytic cell line (THP-1) enhances invasion and induces EMT characteristics in lung adenocarcinoma cell line (A549) during co-culture...
February 2016: Cellular Immunology
Pini Matzner, Liat Sorski, Lee Shaashua, Ely Elbaz, Hagar Lavon, Rivka Melamed, Ella Rosenne, Neta Gotlieb, Amit Benbenishty, Steve G Reed, Shamgar Ben-Eliyahu
The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of cancer metastases-the major cause of cancer related death. However, immune-stimulatory approach has not been used perioperatively given several contraindications to surgery...
April 1, 2016: International Journal of Cancer. Journal International du Cancer
Hulyam Kurt, Cansu Ozbayer, Aysegul Bayramoglu, Hasan Veysi Gunes, İrfan Degirmenci, Kevser Setenay Oner, Muzaffer Metintas
Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor (TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with NcoI and HinfI then visualized...
February 2016: Inflammation
Renata Ursu, Sophie Taillibert, Claire Banissi, Eric Vicaut, Olivier Bailon, Emilie Le Rhun, Jean-Sebastien Guillamo, Dimitri Psimaras, Annick Tibi, Adama Sacko, Athina Marantidou, Catherine Belin, Antoine F Carpentier
TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3-6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28...
September 2015: Cancer Science
Chiara Storti, Valentino Le Noci, Michele Sommariva, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Intratumoral delivery of drugs, enabling increased local concentrations in the tumor microenvironment, might be superior to systemic administration in promoting antitumor activity and minimizing the systemic side effects of some drugs. Unfortunately, not all human cancers are amenable to drug injection into the tumor site. Lung cancers are candidate tumors for taking advantage of local delivery, being accessible via the endobronchial space by aerosol administration. Inhalation of aerosolized drugs is a promising option in the management of lung diseases and currently represents the standard treatment for asthma and chronic obstructive pulmonary disease...
2015: Current Cancer Drug Targets
Araceli García-Castro, Manuela Zonca, Douglas Florindo-Pinheiro, Carla E Carvalho-Pinto, Alex Cordero, Burgo Gutiérrez del Fernando, Aránzazu García-Grande, Santos Mañes, Michael Hahne, Eva González-Suárez, Lourdes Planelles
APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL...
May 2015: Carcinogenesis
Barbara Behm, Pietro Di Fazio, Patrick Michl, Daniel Neureiter, Ralf Kemmerling, Eckhart Georg Hahn, Deike Strobel, Thomas Gress, Detlef Schuppan, Thaddaeus Till Wissniowski
INTRODUCTION: Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma. METHODS: Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days...
January 2016: Gut
Tatsuya Ando, Hiroyasu Ito, Yuko Arioka, Hideyuki Ogiso, Mitsuru Seishima
α-galactosylceramide (GalCer), which is a natural killer T (NKT) cell ligand, has been reported to exert therapeutic effects against cancer in humans and mice. Toll-like receptor (TLR) agonists systemically or locally boost antitumor efficacy in mouse cancer models. In our previous study, the co-administration of GalCer and a TLR agonist synergistically enhanced interferon-γ (IFN-γ) production in mouse splenocytes in vitro and in vivo. The increased IFN-γ production promoted a tumor antigen-specific Th1 response...
February 2015: Oncology Reports
Anahit Ghochikyan, Alexey Pichugin, Alexander Bagaev, Arpine Davtyan, Armine Hovakimyan, Amir Tukhvatulin, Hayk Davtyan, Dmitry Shcheblyakov, Denis Logunov, Marina Chulkina, Anastasia Savilova, Dmitry Trofimov, Edward L Nelson, Michael G Agadjanyan, Ravshan I Ataullakhanov
BACKGROUND: Previously we demonstrated that the resection of primary 4T1 tumors only slightly prolongs mouse survival, but importantly, creates a "window of opportunity" with attenuated suppressor cell and increased activated T cell populations. This suggests that additional activation of the immune system by immunostimulatory agents during this period may enhance anti-tumor immunity and potentially eradicate micro-metastatic disease in this stringent model. We hypothesized that the immunostimulator Immunomax®, which is comprised of a plant-derived polysaccharide, is non-toxic in humans and stimulates immune defense during the infectious diseases treatment, may have also anti-tumor activity and be beneficial in the adjuvant setting when endogenous anti-tumor responses are present and during the "window of opportunity" in post-resection metastatic breast cancer model...
2014: Journal of Translational Medicine
Brett P Gross, Amaraporn Wongrakpanich, Meghan B Francis, Aliasger K Salem, Lyse A Norian
Metastatic breast cancer is currently incurable, and available therapies are associated with severe toxicities. Induction of protective anti-tumor immunity is a promising therapeutic approach for disseminated breast cancer, as immune responses are (i) systemic; (ii) antigen-specific; and (iii) capable of generating long-lived "memory" populations that protect against future tumor recurrences. Pursuant with this approach, we have developed a novel heterologous prime/boost vaccination regimen that reduces spontaneous lung metastases in mice with established murine 4T1 adenocarcinoma breast tumors...
November 2014: AAPS Journal
Shu Zhao, Yifan Zhang, Qingyuan Zhang, Fen Wang, Dekai Zhang
Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex...
2014: Frontiers in Immunology
Simon C Chow, Stephen D Gowing, Jonathan J Cools-Lartigue, Crystal B Chen, Julie Berube, Hee-Won Yoon, Carlos H F Chan, Mathieu C Rousseau, France Bourdeau, Betty Giannias, Lucie Roussel, Salman T Qureshi, Simon Rousseau, Lorenzo E Ferri
Surgery is required for the curative treatment of lung cancer but is associated with high rates of postoperative pneumonias predominantly caused by gram negative bacteria. Recent evidence suggests that these severe infectious complications may decrease long term survival after hospital discharge via cancer recurrence, but the mechanism is unclear. Lung cancer cells have recently been demonstrated to express Toll-like receptors (TLR) that mediate pathogen recognition. We hypothesized that incubation of non-small cell lung cancer (NSCLC) cells with heat-inactivated Escherichia coli can augment cancer cell adhesion, migration and metastasis via TLR4 signaling...
March 15, 2015: International Journal of Cancer. Journal International du Cancer
Saradiya Chatterjee, Lucile Crozet, Diane Damotte, Kristina Iribarren, Catherine Schramm, Marco Alifano, Audrey Lupo, Julien Cherfils-Vicini, Jeremy Goc, Sandrine Katsahian, Mohammad Younes, Marie Caroline Dieu-Nosjean, Wolf Herman Fridman, Catherine Sautès-Fridman, Isabelle Cremer
Toll-like receptors (TLR) recognize pathogen molecules and danger-associated signals that stimulate inflammatory processes. TLRs have been studied mainly in antigen-presenting cells, where they exert important immune regulatory functions, but they are also expressed by epithelial tumor cells, where they have been implicated in tumor progression. In this study, we demonstrate that the injection of TLR7 agonist in NOD/SCID mice, in C57BL/6 wild-type, and TLR7-deficient mice grafted with lung adenocarcinoma tumor cells leads to increased tumor progression and chemotherapeutic resistance...
September 15, 2014: Cancer Research
Pankaj Baral, Sanjay Batra, Rachel L Zemans, Gregory P Downey, Samithamby Jeyaseelan
Lower respiratory tract infections caused by bacteria are a major cause of death in humans irrespective of sex, race, or geography. Indeed, accumulated data indicate greater mortality and morbidity due to these infections than cancer, malaria, or HIV infection. Successful recognition of, followed by an appropriate response to, bacterial pathogens in the lungs is crucial for effective pulmonary host defense. Although the early recruitment and activation of neutrophils in the lungs is key in the response against invading microbial pathogens, other sentinels, such as alveolar macrophages, epithelial cells, dendritic cells, and CD4(+) T cells, also contribute to the elimination of the bacterial burden...
October 1, 2014: American Journal of Respiratory and Critical Care Medicine
Zhenzhen Zhan, Xuefeng Xie, Hao Cao, Xiaohui Zhou, Xu Dong Zhang, Huimin Fan, Zhongmin Liu
Autophagy contributes to the pathogenesis of cancer, whereas toll-like receptors (TLRs) also play an important role in cancer development and immune escape. However, little is known about the potential interaction between TLR signaling and autophagy in cancer cells. Here we show that autophagy induced by TLR4 or TLR3 activation enhances various cytokine productions through promoting TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) ubiquitination and thus facilitates migration and invasion of lung cancer cells...
February 2014: Autophagy
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