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toll like receptors and lymphoma

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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28153771/b-cell-function-gene-mutations-in-diffuse-large-b-cell-lymphoma-a-retrospective-cohort-study
#2
Peng-Peng Xu, Hui-Juan Zhong, Yao-Hui Huang, Xiao-Dong Gao, Xia Zhao, Yang Shen, Shu Cheng, Jin-Yan Huang, Sai-Juan Chen, Li Wang, Wei-Li Zhao
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous subtype of non-Hodgkin lymphoma. In addition to clinical and immunophenotypic characteristics, recurrent gene mutations have recently been identified in patients with DLBCL using next-generation sequencing technologies. The aim of this study is to investigate the clinical relevance of B-cell function gene mutations in DLBCL. Clinical analysis was performed on 680 Chinese DLBCL patients (146 non-CR and 534 CR cases) treated with six cycles of 21-day R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), alone or followed by two additional doses of rituximab consolidation on patients' own intention...
January 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28147336/dual-inhibition-of-histone-deacetylases-and-phosphoinositide-3-kinase-enhances-therapeutic-activity-against-b-cell-lymphoma
#3
Patrizia Mondello, Enrico Derenzini, Zahra Asgari, John Philip, Elliott J Brea, Venkatraman Seshan, Ronald C Hendrickson, Elisa de Stanchina, David A Scheinberg, Anas Younes
Phosphoinositide 3-kinase (PI3K) and Myc are known to cooperate in promoting the survival and growth of a variety of B-cell lymphomas. While currently there are no small molecule inhibitors of Myc protein, histone deacetylase (HDAC) inhibitors have been shown to reduce levels of Myc protein by suppressing its transcription. We assessed the efficacy of CUDC-907, a new rationally designed dual inhibitor of PI3K and HDACs, in a panel of lymphoma cell lines. CUDC-907 treatment resulted in a dose- and time-dependent growth inhibition and cell death of DLBCL cell lines, irrespective of the cell of origin...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#4
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#5
Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang
Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28099084/mechanisms-and-new-strategies-for-primary-sj%C3%A3-gren-s-syndrome
#6
Clio P Mavragani
Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28054376/toll-like-receptor-tlr-7-expression-in-mycosis-fungoides-and-psoriasis-a-case-control-study
#7
A M El Tawdy, I M Amin, R M Abdel Hay, A S Hassan, Z S Gad, L A Rashed
BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions...
January 5, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27980783/plasmodium-chabaudi-infection-induces-aid-expression-in-transitional-and-marginal-zone-b-cells
#8
Joel R Wilmore, Alexander C Maue, Rosemary Rochford
INTRODUCTION: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus and repeated malaria infections. A defining feature of eBL is the translocation of the c-myc oncogene to the control of the immunoglobulin promoter. Activation-induced cytidine deaminase (AID) has been shown to be critical for this translocation. Malaria infection induces AID in germinal center B cells, but whether malaria infection more broadly affects AID activation in extrafollicular B cells is unknown...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27757307/cd1b-autoreactive-t-cells-recognize-phospholipid-antigens-and-contribute-to-antitumor-immunity-against-a-cd1b-t-cell-lymphoma
#9
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27668411/synergy-of-interleukin-10-and-toll-like-receptor-9-signalling-in-b-cell-proliferation-implications-for-lymphoma-pathogenesis
#10
Maren Feist, Judith Kemper, Franziska Taruttis, Thorsten Rehberg, Julia C Engelmann, Wolfram Gronwald, Michael Hummel, Rainer Spang, Dieter Kube
A network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, α-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27622045/a-novel-tlr7-agonist-reverses-nk-cell-anergy-and-cures-rma-s-lymphoma-bearing-mice
#11
Gabriela Maria Wiedemann, Severin Johannes Jacobi, Michael Chaloupka, Angelina Krächan, Svetlana Hamm, Stefan Strobl, Roland Baumgartner, Simon Rothenfusser, Peter Duewell, Stefan Endres, Sebastian Kobold
Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated immune suppression. Due to dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need for TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, a novel small molecule agonist for TLR7, is a potent type-1 interferon inducer, comparable to the reference TLR7 agonist resiquimod, yet with lower induction of proinflammatory cytokines...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27602749/toll-like-receptors-targeting-technology-for-the-treatment-of-lymphoma
#12
Maria Batool, Muhammad Ayaz Anwar, Sangdun Choi
The crucial role of Toll-like Receptors (TLRs) in innate and adaptive immune systems is well discussed in the literature. In cancer, TLRs act as a double-edged sword that can promote or suppress tumor growth. Areas covered: In this article, the authors uncover the potential role of TLRs in lymphomas, which are cancers related to the lymphatic system and blood cells. TLRs are de facto inflammation-inducing receptors that can either worsen disease or ameliorate lymphoma treatment. From this perspective, the usage of TLRs to modulate the immune system toward lymphoma regression is desirable...
November 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27503954/conformational-dynamics-of-cancer-associated-myd88-tir-domain-mutant-l252p-l265p-allosterically-tilts-the-landscape-toward-homo-dimerization
#13
Chendi Zhan, Ruxi Qi, Guanghong Wei, Emine Guven-Maiorov, Ruth Nussinov, Buyong Ma
MyD88 is an essential adaptor protein, which mediates the signaling of the toll-like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation has been identified in diffuse large B-cell lymphoma. The identification of this mutation has been a major advance in the diagnosis of patients with aldenstrom macroglobulinemia and related lymphoid neoplasms. Here we used computational methods to characterize the conformational effects of the mutation. Our molecular dynamics simulations revealed that the mutation allosterically quenched the global conformational dynamics of the toll/IL-1R (TIR) domain, and readjusted its salt bridges and dynamic community network...
September 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27503123/c-cbl-mediated-ubiquitination-of-irf3-negatively-regulates-ifn-%C3%AE-production-and-cellular-antiviral-response
#14
Xibao Zhao, Huihui Zhu, Juan Yu, Hongrui Li, Jiafeng Ge, Weilin Chen
Induction of type I interferon is a fundamental cellular response to viral infection. Interferon regulatory factor 3 (IRF3) plays an essential role in Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) mediated induction of type I interferon and host antiviral responses. However, posttranslational regulation of IRF3 remains to be fully understood. In this study, we identified E3 ubiquitin ligase Casitas B-lineage lymphoma (c-Cbl) as a negative regulator for IRF3 protein stability and IFN-β signal pathway...
November 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27491692/nf-%C3%AE%C2%BAb-activation-in-chronic-lymphocytic-leukemia-a-point-of-convergence-of-external-triggers-and-intrinsic-lesions
#15
Larry Mansouri, Nikos Papakonstantinou, Stavroula Ntoufa, Kostas Stamatopoulos, Richard Rosenquist
The nuclear factor-κB (NF-κB) pathway is constitutively activated in chronic lymphocytic leukemia (CLL) patients, and hence plays a major role in disease development and evolution. In contrast to many other mature B-cell lymphomas, only a few recurrently mutated genes involved in canonical or non-canonical NF-κB activation have been identified in CLL (i.e. BIRC3, MYD88 and NFKBIE mutations) and often at a low frequency. On the other hand, CLL B cells seem 'addicted' to the tumor microenvironment for their survival and proliferation, which is primarily mediated by interaction through a number of cell surface receptors, e...
August 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27469333/peli1-expression-is-correlated-with-myc-and-bcl6-expression-and-associated-with-poor-prognosis-in-diffuse-large-b-cell-lymphoma
#16
Ji-Young Choe, Mira Park, Ji Yun Yun, Hee Young Na, Heounjeong Go, Hyun-Jung Kim, Sohee Oh, Ji Eun Kim
PELI is a family of E3 ubiquitin ligases that regulate protein activity through a post-translational modification, ubiquitination. While PELI1 has been found to play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NF-kB pathway, the role of PELI1 in oncogenesis has not been the subject of much investigation. We aimed to explore PELI1 expression in various malignant lymphomas and identify clinicopathologic significance. Immunohistochemistry for PELI1 was performed on a total of 502 cases, including 406 B-cell, 76 T or NK-cell, and 20 Hodgkin lymphomas...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27458005/inhibiting-tlr9-and-other-unc93b1-dependent-tlrs-paradoxically-increases-accumulation-of-myd88l265p-plasmablasts-in-vivo
#17
James Q Wang, Bruce Beutler, Christopher C Goodnow, Keisuke Horikawa
The MYD88(L265P) mutation is found in 2% to 10% of chronic lymphocytic leukemia, 29% of activated B-cell type diffuse large B-cell lymphoma and 90% of Waldenström macroglobulinemia, making it conceptually attractive to treat these malignancies with inhibitors of endosomal Toll-like receptors (TLR9, TLR7) that activate MYD88. Here we show that genetic inhibition of endosomal TLRs has the opposite effect on accumulation of MYD88(L265P) B cells in vitro and in vivo. Activated mature B cells from wild-type, Unc93b1(3d/3d)-mutant, or Tlr9-deficient mice were transduced with retrovirus encoding MYD88(L265P) and analyzed either in vitro or after transplantation into Rag1(-/-) recipient mice...
September 22, 2016: Blood
https://www.readbyqxmd.com/read/27402288/toll-like-receptors-signaling-a-complex-network-for-nf-%C3%AE%C2%BAb-activation-in-b-cell-lymphoid-malignancies
#18
Stavroula Ntoufa, Maria Giovanna Vilia, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio
Malignancies of mature B cells are quite distinctive in originating from well-differentiated cells. Hence, it is not paradoxical that, similar to their normal counterparts, most mature B cell lymphoma subtypes are critically dependent on microenvironmental cues. Such external signals are sensed by various receptors present on the malignant cells, including the Toll-like receptors (TLRs), eliciting a range of cellular responses, including proliferation but also anergy and apoptosis, often with disease-specific patterns...
August 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27354597/enhanced-tlr4-expression-on-colon-cancer-cells-after-chemotherapy-promotes-cell-survival-and-epithelial-mesenchymal-transition-through-phosphorylation-of-gsk3%C3%AE
#19
Yoon Hee Chung, Daejin Kim
BACKGROUND: Phosphorylation of glycogen synthase kinase 3β (GSK3β) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3β with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3β activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post-chemotherapy cancer cells. MATERIALS AND METHODS: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting...
July 2016: Anticancer Research
https://www.readbyqxmd.com/read/27320593/protective-effect-of-eupatilin-pretreatment-against-hepatic-ischemia-reperfusion-injury-in-mice
#20
H M Lee, H J Jang, S S Kim, H J Kim, S Y Lee, M Y Oh, H C Kwan, D S Jang, D W Eom
BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice. MATERIALS AND METHODS: Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours...
May 2016: Transplantation Proceedings
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