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https://www.readbyqxmd.com/read/28302670/modelling-pulmonary-microthrombosis-coupled-to-metastasis-distinct-effects-of-thrombogenesis-on-tumorigenesis
#1
Colin E Evans, Asis Palazon, Jingwei Sim, Petros A Tyrakis, Alice Prodger, Xiao Lu, Saria Chan, Pär-Ola Bendahl, Mattias Belting, Love Von Euler, Helene Rundqvist, Randall S Johnson, Cristina Branco
Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumor cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we model the effect of microvascular occlusion in metastatic efficiency, by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumor cell injection...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28287120/optimizing-non-invasive-radiofrequency-hyperthermia-treatment-for-improving-drug-delivery-in-4t1-mouse-breast-cancer-model
#2
Matthew J Ware, Martyna Krzykawska-Serda, Jason Chak-Shing Ho, Jared Newton, Sarah Suki, Justin Law, Lam Nguyen, Vazrik Keshishian, Maciej Serda, Kimberly Taylor, Steven A Curley, Stuart J Corr
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257435/idelalisib-and-caffeine-reduce-suppression-of-t-cell-responses-mediated-by-activated-chronic-lymphocytic-leukemia-cells
#3
Barry D Hock, Sean A MacPherson, Judith L McKenzie
Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28255126/-regulatory-effect-of-exosome-on-cell-apoptosis
#4
Xin Li, Zuocheng Yang
Exosome, a nano-grade biological membrane structure, is secreted by multiple cells, widely distributing in saliva, plasma, milk and other body fluid. It can directly and indirectly take part in the biological information transcription between the receptor cells and their micro-environment. Recent studies have demonstrated that exosomes play pivotal roles in the occurrence and development of viral infectious diseases, tumors and other cell apoptosis related diseases via regulating the apoptosis in various ways...
February 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#5
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro Enrizues-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander Ra Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche-construction adaptive strategies that remained stable in culture: (1) Invasive cells that produce an acidic environment via upregulated aerobic glycolysis, and (2) Non-invasive cells that were angiogenic and metabolically near-normal...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28219197/-down-regulation-of-mir-146b-5p-promotes-malignant-transformation-of-fusion-cells-after-co-culture-of-macrophages-with-glioma-stem-cells-in-vitro
#6
H H Cai, H Y Wang, H R Liu, Y J Sheng, D G Xi, Y P Xue, X L Dai, A D Wang, Q Huang, J Dong
Objective: To observe mutual interactions between macrophages(Mφ) and glioma stem cells (GSCs)in dual-color tracing model in vitro, to identify the biological characteristics of fusion cells in multiple levels, and to analysis the relevant molecular mechanisms. Methods: Red fluorescent protein(RFP) gene was stably transfected into human GSCs cell line SU4. Mφ cells were obtained from Balb/c nude mice with enhanced green fluorescent protein (EGFP) expression. Then two cells were co-cultured in dual-color tracing platform...
February 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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
#7
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 16, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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 a 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...
April 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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