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https://www.readbyqxmd.com/read/29774608/virion-like-membrane-breaking-nanoparticles-with-tumor-activated-cell-and-tissue-dual-penetration-conquer-impermeable-cancer
#1
Xiao Zhang, Xianghui Xu, Yachao Li, Cheng Hu, Zhijun Zhang, Zhongwei Gu
Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure...
May 17, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29774034/targeting-vegf-vegfr-to-modulate-antitumor-immunity
#2
REVIEW
Ju Yang, Jing Yan, Baorui Liu
In addition to the crucial role in promoting the growth of tumor vessels, vascular endothelial growth factor (VEGF) is also immunosuppressive. VEGF can inhibit the function of T cells, increase the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and hinder the differentiation and activation of dendritic cells (DCs). Recent studies have investigated the role of antiangiogenic agents in antitumor immunity, especially in recent 3 years. Therefore, it is necessary to update the role of targeting VEGF/VEGFR in antitumor immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772024/use-of-human-amniotic-epithelial-cells-in-mouse-models-of-bleomycin-induced-lung-fibrosis-a-systematic-review-and-meta-analysis
#3
Fang He, Aiting Zhou, Shuo Feng
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use...
2018: PloS One
https://www.readbyqxmd.com/read/29771487/cancer-cell-membrane-coated-adjuvant-nanoparticles-with-mannose-modification-for-effective-anticancer-vaccination
#4
Rong Yang, Jun Xu, Ligeng Xu, Xiaoqi Sun, Qian Chen, Yuhuan Zhao, Rui Peng, Zhuang Liu
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membrane modified by mannose. Poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles are firstly loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens...
May 17, 2018: ACS Nano
https://www.readbyqxmd.com/read/29765110/mast-cells-contribute-to-enterovirus-71-infection-induced-pulmonary-edema-in-neonatal-mice
#5
Yuefei Jin, Chao Zhang, Hui Wang, Guangyuan Zhou, Xiangpeng Wang, Rongguang Zhang, Shuaiyin Chen, Jingchao Ren, Lu Chen, Dejian Dang, Peng Zhang, Yuanlin Xi, Weidong Wu, Weiguo Zhang, Guangcai Duan
Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs...
May 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29764863/extracorporeal-photochemotherapy-drives-monocyte-to-dendritic-cell-maturation-to-induce-anti-cancer-immunity
#6
Alessandra Ventura, Aaron Vassall, Eve Robinson, Renata Filler, Douglas Hanlon, Katrina Meeth, Harib Ezaldein, Michael Girardi, Olga Sobolev, Marcus W Bosenberg, Richard L Edelson
Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#7
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29760696/podosomes-but-not-the-maturation-status-determine-the-protease-dependent-3d-migration-in-human-dendritic-cells
#8
Céline Cougoule, Claire Lastrucci, Romain Guiet, Rémi Mascarau, Etienne Meunier, Geanncarlo Lugo-Villarino, Olivier Neyrolles, Renaud Poincloux, Isabelle Maridonneau-Parini
Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo , or in collagen matrices in vitro ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755954/immune-response-generated-with-the-administration-of-autologous-dendritic-cells-pulsed-with-an-allogenic-tumoral-cell-lines-lysate-in-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#9
Daniel Benitez-Ribas, Raquel Cabezón, Georgina Flórez-Grau, Mari Carmen Molero, Patricia Puerta, Antonio Guillen, Sonia Paco, Angel M Carcaboso, Vicente Santa-Maria Lopez, Ofelia Cruz, Carmen de Torres, Noelia Salvador, Manel Juan, Jaume Mora, Andres Morales La Madrid
Background and objective: Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29755693/exosomes-in-melanoma-a-role-in-tumor-progression-metastasis-and-impaired-immune-system-activity
#10
REVIEW
Marco Tucci, Francesco Mannavola, Anna Passarelli, Luigia Stefania Stucci, Mauro Cives, Franco Silvestris
Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755681/dendritic-cell-activation-enhances-anti-pd-1-mediated-immunotherapy-against-glioblastoma
#11
Tomas Garzon-Muvdi, Debebe Theodros, Andrew S Luksik, Russell Maxwell, Eileen Kim, Christopher M Jackson, Zineb Belcaid, Sudipto Ganguly, Betty Tyler, Henry Brem, Drew M Pardoll, Michael Lim
Introduction: The glioblastoma (GBM) immune microenvironment is highly suppressive as it targets and hinders multiple components of the immune system. Checkpoint blockade (CB) is being evaluated for GBM patients. However, biomarker analyses suggest that CB monotherapy may be effective only in a small fraction of GBM patients. We hypothesized that activation of antigen presentation would increase the therapeutic response to PD-1 blockade. Results: We show that activating DCs through TLR3 agonists enhances the anti-tumor immune response to CB and increases survival in GBM...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#12
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754770/skewing-effect-of-sulprostone-on-dendritic-cell-maturation-compared-with-dinoprostone
#13
Jenny Bulgarelli, Laura Fiammenghi, Serena Cassan, Anna Maria Granato, Massimiliano Petrini, Elena Pancisi, Valentina Soldati, Francesco De Rosa, Laura Ridolfi, Angela Riccobon, Massimo Guidoboni
BACKGROUND: Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails. METHODS: We evaluated the feasibility of dinoprostone (PGE2 ) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine...
May 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29752722/a-new-cancer-immunotherapy-via-simultaneous-dc-mobilization-and-dc-targeted-ido-gene-silencing-using-an-immune-stimulatory-nanosystem
#14
Yujuan Zhang, Jiamin Fu, Yanmei Shi, Shanshan Peng, Ying Cai, Xuelin Zhan, Na Song, Yanling Liu, Zhigang Wang, Yanrong Yu, Yifan Wang, Qiaofa Shi, Yingyuan Fu, Keng Yuan, Nanjin Zhou, Rakesh Joshi, Thomas E Ichim, Weiping Min
The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In this study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752315/formation-of-immune-complexes-with-a-tetanus-derived-b-cell-epitope-boosts-human-t-cell-responses-to-covalently-linked-peptides-in-an-ex-vivo-blood-loop-system
#15
Erika A K Fletcher, Wendy van Maren, Robert Cordfunke, Jasper Dinkelaar, Jeroen D C Codee, Gijs van der Marel, Cornelis J M Melief, Ferry Ossendorp, Jan Wouter Drijfhout, Sara M Mangsbo
Enhancing T cell responses against both viral and tumor Ags requires efficient costimulation and directed delivery of peptide Ags into APCs. Long peptide vaccines are considered favorable vaccine moieties from a clinical perspective, as they can harbor more than one immunogenic epitope enabling treatment of a broader target population. In addition, longer peptides are not extracellularly loaded on MHC class I; rather, they require intracellular processing and will thereby be presented to T cells mainly by professional APCs, thereby avoiding the risk of tolerance induction...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29748373/slan-monocytes-and-macrophages-mediate-cd20-dependent-b-cell-lymphoma-elimination-via-adcc-and-adcp
#16
William Vermi, Alessandra Micheletti, Giulia Finotti, Cristina Tecchio, Federica Calzetti, Sara Costa, Mattia Bugatti, Stefano Calza, Claudio Agostinelli, Stefano Pileri, Piera Balzarini, Alessandra Tucci, Giuseppe Rossi, Lara Furlani, Giuseppe Todeschini, Alberto Zamò, Fabio Facchetti, Luisa Lorenzi, Silvia Lonardi, Marco A Cassatella
Terminal tissue differentiation and function of slan+ monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan+ monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan+ cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan+ cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extra-nodal, forms...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29748013/loss-of-c-ebp-%C3%AE-lip-drives-cisplatin-resistance-in-malignant-pleural-mesothelioma
#17
Joanna Kopecka, Iris C Salaroglio, Luisella Righi, Roberta Libener, Sara Orecchia, Federica Grosso, Vladan Milosevic, Preeta Ananthanarayanan, Luisa Ricci, Enrica Capelletto, Monica Pradotto, Francesca Napoli, Massimo Di Maio, Silvia Novello, Menachem Rubinstein, Giorgio V Scagliotti, Chiara Riganti
OBJECTIVES: Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: We investigated if LIP levels can predict the clinical response to cisplatin and survival of MPM patients receiving cisplatin-based chemotherapy...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29744371/proteomic-identification-of-heat-shock-induced-danger-signals-in-a-melanoma-cell-lysate-used-in-dendritic-cell-based-cancer-immunotherapy
#18
Fermín E González, Alexey Chernobrovkin, Cristián Pereda, Tamara García-Salum, Andrés Tittarelli, Mercedes N López, Flavio Salazar-Onfray, Roman A Zubarev
Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29739853/mycobacterium-tuberculosis-ppe60-antigen-drives-th1-th17-responses-via-toll-like-receptor-2-dependent-maturation-of-dendritic-cells
#19
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86, and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738228/enhanced-tumor-retention-effect-by-click-chemistry-for-improved-cancer-immunochemotherapy
#20
Ling Mei, Yayuan Liu, Jingdong Rao, Xian Tang, Man Li, Zhirong Zhang, Qin He
Due to the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce reticuloendothelial system uptake and to maximize the enhanced permeability and retention effect. Herein, we demonstrated that Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues...
May 8, 2018: ACS Applied Materials & Interfaces
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