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https://www.readbyqxmd.com/read/28722316/the-mincle-ligand-trehalose-dibehenate-differentially-modulates-m1-like-and-m2-like-macrophage-phenotype-and-function-via-syk-signaling
#1
Kristel Kodar, Jacquie L Harper, Melanie J McConnell, Mattie S M Timmer, Bridget L Stocker
INTRODUCTION: Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied. METHODS: qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle(-/-) mice...
July 19, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28721818/eurycoma-longifolia-a-potential-phytomedicine-for-the-treatment-of-cancer-evidence-of-p53-mediated-apoptosis-in-cancerous-cells
#2
Hnin Ei Thu, Zahid Hussain, Isa Naina Mohamed, Ahmad Nazrun Shuid
BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, anti-malarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent anti-proliferative and anticancer efficacy against various types of human cancers. OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells...
July 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#3
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28720518/nanoparticle-based-hyperthermia-a-local-treatment-modulating-the-tumor-extracellular-matrix
#4
Jelena Kolosnjaj-Tabi, Iris Marangon, Alba Nicolas-Boluda, Amanda Brun, Florence Gazeau
The structural complexity and physical properties of the tumor microenvironment negatively affect the penetration and efficiency of conventional anticancer drugs. While previously underestimated, the tumor microenvironment now becomes a potential target for cancer treatment. This microenvironment can be modulated either systemically by pharmacological means, or locally, through physical effects mediated by certain nanoparticles. Some of them, such as magnetic, plasmonic or carbon-based nanoparticles, can generate heat on demand in a spatially and temporally controlled manner...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28718413/intrinsic-molecular-processes-impact-on-mutagenesis
#5
REVIEW
Byungho Lim, Jihyeob Mun, Seon-Young Kim
Mutations provide resources for genome evolution by generating genetic variability. In addition, mutations act as a driving force leading to disease pathogenesis, and thus have important implications for disease diagnosis, prognosis, and treatment. Understanding the mechanisms underlying how mutations occur is therefore of prime importance for elucidating evolutionary and pathogenic processes. Recent genomics studies have revealed that mutations occur non-randomly across the human genome. In particular, the distribution of mutations is highly associated with intrinsic molecular processes including transcription, chromatin organization, DNA replication timing, and DNA repair...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#6
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716144/macrophage-type-2-differentiation-in-a-patient-with-laryngeal-squamous-cell-carcinoma-and-metastatic-prostate-adenocarcinoma-to-the-cervical-lymph-nodes
#7
Michael C Topf, Madalina Tuluc, Larry A Harshyne, Adam Luginbuhl
BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#8
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28706280/radiation-induced-changes-in-the-glycome-of-endothelial-cells-with-functional-consequences
#9
Cyprien Jaillet, Willy Morelle, Marie-Christine Slomianny, Vincent Paget, Georges Tarlet, Valérie Buard, Sonia Selbonne, Fanny Caffin, Emilie Rannou, Pierre Martinez, Agnès François, François Foulquier, Fabrice Allain, Fabien Milliat, Olivier Guipaud
As it is altered by ionizing radiation, the vascular network is considered as a prime target in limiting normal tissue damage and improving tumor control in radiation therapy. Irradiation activates endothelial cells which then participate in the recruitment of circulating cells, especially by overexpressing cell adhesion molecules, but also by other as yet unknown mechanisms. Since protein glycosylation is an important determinant of cell adhesion, we hypothesized that radiation could alter the glycosylation pattern of endothelial cells and thereby impact adhesion of circulating cells...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28688697/dose-dependent-enhancement-of-t-lymphocyte-priming-and-ctl-lysis-following-ionizing-radiation-in-an-engineered-model-of-oral-cancer
#10
Megan Morisada, Ellen C Moore, Rachel Hodge, Jay Friedman, Harrison A Cash, James W Hodge, James B Mitchell, Clint T Allen
OBJECTIVES: Determine if direct tumor cell cytotoxicity, antigen release, and susceptibility to T-lymphocyte killing following radiation treatment is dose-dependent. MATERIALS AND METHODS: Mouse oral cancer cells were engineered to express full-length ovalbumin as a model antigen. Tumor antigen release with uptake and cross presentation of antigen by antigen presenting cells with subsequent priming and expansion of antigen-specific T-lymphocytes following radiation was modeled in vitro and in vivo...
August 2017: Oral Oncology
https://www.readbyqxmd.com/read/28687535/endothelial-nf-%C3%AE%C2%BAb-blockade-abrogates-anca-induced-gn
#11
Mira Choi, Adrian Schreiber, Claudia Eulenberg-Gustavus, Claus Scheidereit, Jan Kamps, Ralph Kettritz
ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB-dependent tumor necrosis factor α (TNF-α)...
July 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28680749/tumor-priming-converts-nk-cells-to-memory-like-nk-cells
#12
Marina Pal, Lisa Schwab, Anastasiya Yermakova, Emily M Mace, Rainer Claus, Ann-Christin Krahl, Jeanette Woiterski, Udo F Hartwig, Jordan S Orange, Rupert Handgretinger, Maya C André
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680744/intratumoral-delivery-of-tumor-antigen-loaded-dc-and-tumor-primed-cd4-t-cells-combined-with-agonist-%C3%AE-gitr-mab-promotes-durable-cd8-t-cell-dependent-antitumor-immunity
#13
Zuqiang Liu, Xingxing Hao, Yi Zhang, Jiying Zhang, Cara D Carey, Louis D Falo, Walter J Storkus, Zhaoyang You
The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4(+) T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28676241/age-dependent-sexual-dimorphism-in-susceptibility-to-develop-chronic-pain-in-the-rat
#14
Luiz F Ferrari, Dioneia Araldi, Paul Green, Jon D Levine
Neonatal pain has been suggested to contribute to the development and/or persistence of adult pain. Observations from animal models have shown that neonatal inflammation produces long-term changes in sensory neuron function, which can affect the susceptibility of adults to develop persistent pain. We used a preclinical model of transition to chronic pain, hyperalgesic priming, in which a previous inflammatory stimulus triggers a long-lasting increase in responsiveness to pro-algesic mediators, prototypically prostaglandin E2 (PGE2), to investigate if post-natal age influences susceptibility of adult rats to develop chronic pain...
July 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/28675904/in-vivo-lipopolysaccharide-tolerance-recruits-cd11b-macrophages-to-the-liver-with-enhanced-bactericidal-activity-and-low-tumor-necrosis-factor-releasing-capability-resulting-in-drastic-resistance-to-lethal-septicemia
#15
Manabu Kinoshita, Hiromi Miyazaki, Hiroyuki Nakashima, Masahiro Nakashima, Makoto Nishikawa, Takuya Ishikiriyama, Shoichiro Kato, Keiichi Iwaya, Sadayuki Hiroi, Nariyoshi Shinomiya, Shuhji Seki
OBJECTIVES: In vivo lipopolysaccharide (LPS) tolerance on bacterial infection was investigated, focusing on liver macrophages. METHODS: LPS tolerance was induced by intraperitoneal injections with 5 μg/kg of LPS for 3 consecutive days, and then mice were intravenously infected with Escherichia coli. RESULTS: All LPS-primed mice survived lethal bacterial infection. Drastic enhancement of bactericidal activity of liver macrophages strongly contributed to bacterial clearance...
July 5, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28675654/bioinformatory-assisted-analysis-of-next-generation-sequencing-data-for-precision-medicine-in-pancreatic-cancer
#16
Linnéa Malgerud, Johan Lindberg, Valtteri Wirta, Maria Gustafsson-Liljefors, Masoud Karimi, Carlos Fernández Moro, Katrin Stecker, Alexander Picker, Carolin Huelsewig, Martin Stein, Regina Bohnert, Marco Del Chiaro, Stephan L Haas, Rainer L Heuchel, Johan Permert, Markus J Maeurer, Stephan Brock, Caroline S Verbeke, Lars Engstrand, David B Jackson, Henrik Grönberg, J-Matthias Löhr
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#17
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28671563/dose-dependent-responses-of-i3c-and-dim-on-t-cell-activation-in-the-human-t-lymphocyte-jurkat-cell-line
#18
Man Liu, Rumana Yasmeen, Naomi K Fukagawa, Liangli Yu, Young S Kim, Thomas T Y Wang
Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are bioactive metabolites of a glucosinolate, glucobrassicin, found in cruciferous vegetables. Both I3C and DIM have been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways. However, results from these studies remain inconclusive since they lack thorough evaluation of these bioactives' physiological versus pharmacological effects. In the present study, we investigated I3C and DIM's dose-dependent effects on cytokines production in human T lymphocytes Jurkat cell line (Clone E6-1)...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28666115/ifn%C3%AE-dependent-tissue-immune-homeostasis-is-co-opted-in-the-tumor-microenvironment
#19
Christopher J Nirschl, Mayte Suárez-Fariñas, Benjamin Izar, Sanjay Prakadan, Ruth Dannenfelser, Itay Tirosh, Yong Liu, Qian Zhu, K Sanjana P Devi, Shaina L Carroll, David Chau, Melika Rezaee, Tae-Gyun Kim, Ruiqi Huang, Judilyn Fuentes-Duculan, George X Song-Zhao, Nicholas Gulati, Michelle A Lowes, Sandra L King, Francisco J Quintana, Young-Suk Lee, James G Krueger, Kavita Y Sarin, Charles H Yoon, Levi Garraway, Aviv Regev, Alex K Shalek, Olga Troyanskaya, Niroshana Anandasabapathy
Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28664876/scaling-up-of-a-heparg-progenitor-cell-based-bioartificial-liver-optimization-for-clinical-application-and-transport
#20
Martien van Wenum, Philipp Treskes, Chung-Yin Tang, Esmee J Coppens, Koen Jansen, Erik J Hendriks, Sandrine Camus, Thomas M van Gulik, Robert A F M Chamuleau, Ruurdtje Hoekstra
A new generation of bioartificial livers, based on differentiated proliferative hepatocyte sources, has been developed. Several practicable and regulatory demands have to be addressed before these can be clinically evaluated. We identified three main hurdles: (1) expansion and preservation of the biocomponent, (2) development of scaled-up culture conditions and (3) transport of the device to the bedside. In this study we address these three issues for the HepaRG-progenitor cell line-loaded AMC-Bioartificial Liver...
June 30, 2017: Biofabrication
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