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https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#1
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#2
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28092382/a-vascularized-and-perfused-organ-on-a-chip-platform-for-large-scale-drug-screening-applications
#3
Duc T T Phan, Xiaolin Wang, Brianna M Craver, Agua Sobrino, Da Zhao, Jerry C Chen, Lilian Y N Lee, Steven C George, Abraham P Lee, Christopher C W Hughes
There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type - the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels...
January 31, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-framework-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#4
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28074274/glioma-experimental-models-and-reality
#5
REVIEW
Krissie Lenting, Roel Verhaak, Mark Ter Laan, Pieter Wesseling, William Leenders
In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in...
February 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28061981/talimogene-laherparepvec-t-vec-for-the-treatment-of-melanoma-and-other-cancers
#6
REVIEW
Claud Grigg, Zoë Blake, Robyn Gartrell, Adrian Sacher, Bret Taback, Yvonne Saenger
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28054086/3d-microvascular-model-recapitulates-the-diffuse-large-b-cell-lymphoma-tumor-microenvironment-in-vitro
#7
Robert G Mannino, Adriana N Santiago-Miranda, Pallab Pradhan, Yongzhi Qiu, Joscelyn C Mejias, Sattva S Neelapu, Krishnendu Roy, Wilbur A Lam
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ∼22 000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL...
January 31, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28042325/smart-cu-ii-aptamer-complexes-based-gold-nanoplatform-for-tumor-micro-environment-triggered-programmable-intracellular-prodrug-release-photodynamic-treatment-and-aggregation-induced-photothermal-therapy-of-hepatocellular-carcinoma
#8
Da Zhang, Aixian Zheng, Juan Li, Ming Wu, Lingjie Wu, Zuwu Wei, Naishun Liao, Xiaolong Zhang, Zhixiong Cai, Huanghao Yang, Gang Liu, Xiaolong Liu, Jingfeng Liu
This study describes smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable prodrug release, in demand photodynamic therapy and aggregation induced photothermal ablation of hepatocellular carcinoma. The nanoplatform is consist of monodispersed gold nanoparticle (GNP) that is binding to HCC cell specific targeting aptamers (TLS11a) through Au-S bond; the aptamer is labeled with Ce6 at the 5'end and coordinated with Cu(II) through (GA)10 repeating bases to load AQ4N at the 3' end...
2017: Theranostics
https://www.readbyqxmd.com/read/28034806/targeting-the-extracellular-matrix-of-ovarian-cancer-using-functionalized-drug-loaded-lyophilisomes
#9
Sophieke C H A van der Steen, René Raavé, Sjoerd Langerak, Laurens van Houdt, Sander M J van Duijnhoven, Sanne A M van Lith, Leon F A G Massuger, Willeke F Daamen, William P Leenders, Toin H van Kuppevelt
Epithelial ovarian cancer is characterized by a high mortality rate and is in need for novel therapeutic avenues to improve patient outcome. The tumor's extracellular matrix ("stroma") offers new possibilities for targeted drug-delivery. Recently we identified highly sulfated chondroitin sulfate (CS-E) as a component abundantly present in the ovarian cancer extracellular matrix, and as an novel target for anti-cancer therapy. Here, we report on the functionalization of drug-loaded lyophilisomes (albumin-based biocapsules) to specifically target the stroma of ovarian carcinomas with the potential to eliminate cancer cells...
December 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28026951/polymer-drug-nanoparticles-combine-doxorubicin-carrier-and-heparin-bioactivity-functionalities-for-primary-and-metastatic-cancer-treatment
#10
Ling Mei, Yayuan Liu, Chunyu Xia, Yubei Zhou, Zhirong Zhang, Qin He
Here, a biocompatible amphiphilic copolymer of low molecular weight heparin (LMWH) and doxorubicin (DOX) connected by an acid-sensitive hydrazone bond for enhanced tumor treatment efficacy and safety has been designed and tested. The conjugate combines DOX delivery with LMWH antimetastatic capabilities. After the nanoparticles reach the tumor site, the acidic tumor microenvironment triggers the breakage of the hydrazone bond releasing DOX from the nanoparticles, which results in an increase in the cellular uptake and enhanced in vivo antitumor efficacy...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28017801/spatial-avascular-growth-of-tumor-in-a-homogeneous-environment
#11
Louise Viger, Fabrice Denis, Clément Draghi, Thibault Ménard, Christophe Letellier
Describing tumor growth is a key issue in oncology for correctly understanding the underlying mechanisms leading to deleterious cancers. In order to take into account the micro-environment in tumor growth, we used a model describing - at the tissue level - the interactions between host (non malignant), effector immune and tumor cells to simulate the evolution of cancer. The spatial growth is described by a Laplacian operator for the diffusion of tumor cells. We investigated how the evolution of the tumor diameter is related to the dynamics (periodic or chaotic oscillations, stable singular points) underlying the interactions between the different populations of cells in proliferation sites...
December 23, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28003476/efficient-dna-binding-of-nf-%C3%AE%C2%BAb-requires-the-chaperone-like-function-of-npm1
#12
Jianhuang Lin, Mitsuyasu Kato, Kyosuke Nagata, Mitsuru Okuwaki
NPM1/nucleophosmin is frequently overexpressed in various tumors, although the oncogenic role of NPM1 remains unclear. Here we revealed the link between NPM1 and nuclear factor-κB (NF-κB), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-κB-mediated transcription of selected target genes by decreasing the recruitment of NF-κB p65 to the gene promoters. NPM1 is directly associated with the DNA binding domain of p65 to enhance its DNA binding activity without being a part of the DNA-NF-κB complex...
December 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27987733/optimizing-structural-and-mechanical-properties-of-cryogel-scaffolds-for-use-in-prostate-cancer-cell-culturing
#13
A Cecilia, A Baecker, E Hamann, A Rack, T van de Kamp, F J Gruhl, R Hofmann, J Moosmann, S Hahn, J Kashef, S Bauer, T Farago, L Helfen, T Baumbach
Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate...
February 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/27976373/tumour-associated-macrophage-mediated-survival-of-myeloma-cells-through-stat3-activation
#14
Nathan De Beule, Kim De Veirman, Ken Maes, Elke De Bruyne, Eline Menu, Karine Breckpot, Hendrik De Raeve, Rian Van Rampelbergh, Jo A Van Ginderachter, Rik Schots, Els Van Valckenborgh, Karin Vanderkerken
Overcoming drug resistance is one of the greatest challenges in the treatment of multiple myeloma (MM). The interaction of myeloma cells with the bone marrow (BM) microenvironment is a major factor contributing to drug resistance. Tumour-associated macrophages (TAMs) with different polarization states constitute an important component of this microenvironment. Previous studies have revealed a role of TAMs in MM cell survival and drug resistance; however, the impact of macrophage polarization (anti-tumoural 'M1' versus pro-tumoural 'M2'-like phenotype) in this process has not yet been described...
December 15, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27903981/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#15
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27853646/hepatocellular-carcinoma-is-accelerated-by-nash-involving-m2-macrophage-polarization-mediated-by-hif-1%C3%AE-induced-il-10
#16
Aditya Ambade, Abhishek Satishchandran, Banishree Saha, Benedek Gyongyosi, Patrick Lowe, Karen Kodys, Donna Catalano, Gyongyi Szabo
Obesity-related inflammation promotes cancer development. Tissue resident macrophages affect tumor progression and the tumor micro-environment favors polarization into alternatively activated macrophages (M2) that facilitate tumor invasiveness. Here, we dissected the role of western diet-induced NASH in inducing macrophage polarization in a carcinogen initiated model of hepatocellular carcinoma (HCC). Adult C57BL/6 male mice received diethyl nitrosamine (DEN) followed by 24 weeks of high fat-high cholesterol-high sugar diet (HF-HC-HSD)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27846403/magnetic-hyperthermia-enhances-cell-toxicity-with-respect-to-exogenous-heating
#17
Beatriz Sanz, M Pilar Calatayud, Teobaldo E Torres, Mónica L Fanarraga, M Ricardo Ibarra, Gerardo F Goya
Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures...
November 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/27834402/macrophages-form-functional-vascular-mimicry-channels-in-vivo
#18
Faith H Barnett, Mauricio Rosenfeld, Malcolm Wood, William B Kiosses, Yoshihiko Usui, Valentina Marchetti, Edith Aguilar, Martin Friedlander
Macrophages, key cells of the innate immune system, are known to support angiogenesis but are not believed to directly form vessel walls. Here we show that macrophages structurally form primitive, NON-ENDOTHELIAL "vessels" or vascular mimicry (VM) channels in both tumor and angiogenesis in vivo models. These channels are functionally connected to the systemic vasculature as they are perfused by intravenously injected dye. Since both models share hypoxic micro-environments, we hypothesized that hypoxia may be an important mediator of VM formation...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825375/binding-of-galectin-1-to-breast-cancer-cells-mcf7-induces-apoptosis-and-inhibition-of-proliferation-in-vitro-in-a-2d-and-3d-cell-culture-model
#19
Pamina Geiger, Barbara Mayer, Irmi Wiest, Sandra Schulze, Udo Jeschke, Tobias Weissenbacher
BACKGROUND: Galectin-1 (gal-1) belongs to the family of β-galactoside-binding proteins which primarily recognizes the Galβ1-4GlcNAc sequences of oligosaccharides associated with several cell surface glycoconjugates. The lectin recognizes correspondent glycoepitopes on human breast cancer cells. Galectin-1 is expressed both in normal and malignant tissues. Lymphatic organs naturally possessing high rates of apoptotic cells, express high levels of Galectin-1. Furthermore galectin-1 can initiate T cell apoptosis...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27801609/persistence-to-anti-cancer-treatments-in-the-stationary-to-proliferating-transition
#20
Sivan Pearl Mizrahi, Orit Gefen, Itamar Simon, Nathalie Q Balaban
The heterogeneous responses of clonal cancer cells to treatment is understood to be caused by several factors, including stochasticity, cell-cycle dynamics, and different micro-environments. In a tumor, cancer cells may encounter fluctuating conditions and transit from a stationary culture to a proliferating state, for example this may occur following treatment. Here, we undertake a quantitative evaluation of the response of single cancerous lymphoblasts (L1210 cells) to various treatments administered during this transition...
December 16, 2016: Cell Cycle
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