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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#1
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29782011/a-preclinical-mouse-model-of-osteosarcoma-to-define-the-extracellular-vesicle-mediated-communication-between-tumor-and-mesenchymal-stem-cells
#2
Tonny Lagerweij, Maria Pérez-Lanzón, S Rubina Baglio
Within the tumor microenvironment, resident or recruited mesenchymal stem cells (MSCs) contribute to malignant progression in multiple cancer types. Under the influence of specific environmental signals, these adult stem cells can release paracrine mediators leading to accelerated tumor growth and metastasis. Defining the crosstalk between tumor and MSCs is of primary importance to understand the mechanisms underlying cancer progression and identify novel targets for therapeutic intervention. Cancer cells produce high amounts of extracellular vesicles (EVs), which can profoundly affect the behavior of target cells in the tumor microenvironment or at distant sites...
May 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29780391/concepts-collide-genomic-immune-and-microbial-influences-on-the-tumor-microenvironment-and-response-to-cancer-therapy
#3
REVIEW
Miles C Andrews, Alexandre Reuben, Vancheswaran Gopalakrishnan, Jennifer A Wargo
Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779068/new-insights-into-the-inflamed-tumor-immune-microenvironment-of-gastric-cancer-with-lymphoid-stroma-from-morphology-and-digital-analysis-to-gene-expression
#4
Irene Gullo, Patrícia Oliveira, Maria Athelogou, Gilza Gonçalves, Marta L Pinto, Joana Carvalho, Ana Valente, Hugo Pinheiro, Sara Andrade, Gabriela M Almeida, Ralf Huss, Kakoli Das, Patrick Tan, José C Machado, Carla Oliveira, Fátima Carneiro
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations...
May 19, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#5
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29777109/tak1-mediates-microenvironment-triggered-autocrine-signals-and-promotes-triple-negative-breast-cancer-lung-metastasis
#6
Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774083/engineered-microfluidic-bioreactor-for-examining-the-three-dimensional-breast-tumor-microenvironment
#7
Matthew Rogers, Tammy Sobolik, David K Schaffer, Philip C Samson, Andrew C Johnson, Philip Owens, Simona G Codreanu, Stacy D Sherrod, John A McLean, John P Wikswo, Ann Richmond
The interaction of cancer cells with the stromal cells and matrix in the tumor microenvironment plays a key role in progression to metastasis. A better understanding of the mechanisms underlying these interactions would aid in developing new therapeutic approaches to inhibit this progression. Here, we describe the fabrication of a simple microfluidic bioreactor capable of recapitulating the three-dimensional breast tumor microenvironment. Cancer cell spheroids, fibroblasts, and endothelial cells co-cultured in this device create a robust microenvironment suitable for studying in real time the migration of cancer cells along matrix structures laid down by fibroblasts within the 3D tumor microenvironment...
May 2018: Biomicrofluidics
https://www.readbyqxmd.com/read/29772538/targeting-fibroblast-activation-protein-in-cancer-prospects-and-caveats
#8
Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29767307/virus-vector-mediated-genetic-modification-of-brain-tumor-stromal-cells-after-intravenous-delivery
#9
Adrienn Volak, Stanley G LeRoy, Jeya Shree Natasan, David J Park, Pike See Cheah, Andreas Maus, Zachary Fitzpatrick, Eloise Hudry, Kelsey Pinkham, Sheetal Gandhi, Bradley T Hyman, Dakai Mu, Dwijit GuhaSarkar, Anat O Stemmer-Rachamimov, Miguel Sena-Esteves, Christian E Badr, Casey A Maguire
The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively...
May 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29764866/lrrc15-is-a-novel-mesenchymal-protein-and-stromal-target-for-antibody-drug-conjugates
#10
James W Purcell, Sonia G Tanlimco, Jonathan A Hickson, Melvin Fox, Mien Sho, Lisa Durkin, Tamar Uziel, Rick Powers, Kelly D Foster-Duke, Thomas McGonigal, Subashri Kumar, Josue Samayoa, Dong Zhang, Joann P Palma, Sasmita Mishra, Diane Hollenbaugh, Kurt Gish, Susan E Morgan-Lappe, Eric D Hsi, Debra T Chao
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29761075/transforming-growth-factor-%C3%AE-signaling-plays-a-pivotal-role-in-the-interplay-between-osteosarcoma-cells-and-their-microenvironment
#11
REVIEW
Franck Verrecchia, Françoise Rédini
Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, and young adults. Despite encouraging progress in therapeutic management, including the advent of multidrug chemotherapy, the survival rates have remained unchanged for more than four decades: 75% at 5 years for localized disease, but two groups of patients are still at high risk: metastatic at diagnosis (overall survival around 40% at 5 years) and/or poor responders to chemotherapy (20% at 5 years)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#12
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29754177/exosomes-function-in-tumor-immune-microenvironment
#13
Yin Huang, Keli Liu, Qing Li, Yikun Yao, Ying Wang
Immune cells and mesenchymal stem/stromal cells are the major cellular components in tumor microenvironment that actively migrate to tumor sites by sensing "signals" released from tumor cells. Together with other stromal cells, they form the soil for malignant cell progression. In the crosstalk between tumor cells and its surrounded microenvironment, exosomes exert multiple functions in shaping tumor immune responses. In tumor cells, their exosomes can lead to pro-tumor immune responses, whereas in immune cells, their derived exosomes can operate on tumor cells and regulate their ability to growth, metastasis, even reaction to chemotherapy...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29754176/micrornas-regulatory-messengers-inside-and-outside-cancer-cells
#14
Simone Anfossi, Xiao Fu, Rahul Nagvekar, George A Calin
MicroRNAs (miRNAs) are a class of short non-coding RNAs (ncRNAs) with typical sequence lengths of 19-25 nucleotides and extraordinary abilities to regulate gene expression. Because miRNAs regulate multiple important biological functions of the cell (proliferation, migration, invasion, apoptosis, differentiation, and drug resistance), their expression is highly controlled. Genetic and epigenetic alterations frequently found in cancer cells can cause aberrant expression of miRNAs and, consequently, of their target genes...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29752311/myeloid-derived-suppressor-cells-impair-b-cell-responses-in-lung-cancer-through-il-7-and-stat5
#15
Yong Wang, Cara C Schafer, Kenneth P Hough, Sultan Tousif, Steven R Duncan, John F Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S Deshane
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro-, pre-, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29750999/modeling-triple-negative-breast-cancer-heterogeneity-effects-of-stromal-macrophages-fibroblasts-and-tumor-vasculature
#16
Kerri-Ann Norton, Kideok Jin, Aleksander S Popel
A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells...
May 8, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29746265/microenvironment-signaling-driving-lymphomagenesis
#17
Léa Verdière, Frédéric Mourcin, Karin Tarte
PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment...
May 8, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29739972/cell-type-specific-expression-of-oncogenic-and-tumor-suppressive-micrornas-in-the-human-prostate-and-prostate-cancer
#18
Binod Kumar, Avi Z Rosenberg, Su Mi Choi, Karen Fox-Talbot, Angelo M De Marzo, Larisa Nonn, W Nathaniel Brennen, Luigi Marchionni, Marc K Halushka, Shawn E Lupold
MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29737600/stromal-barriers-to-nanomedicine-penetration-in-the-pancreatic-tumor-microenvironment
#19
REVIEW
Hiroyoshi Y Tanaka, Mitsunobu R Kano
Pancreatic cancer is known for its dismal prognosis despite efforts to improve therapeutic outcome. Recently, cancer nanomedicine, application of nanotechnology to cancer diagnosis and treatment, has gained interest for treatment of pancreatic cancer. The enhanced permeability and retention (EPR) effect that promotes selective accumulation of nanometer-sized molecules within tumors is the theoretical rationale of treatment. However, it is clear that EPR may be insufficient in pancreatic cancer due to stromal barriers within the tumor microenvironment (TME)...
May 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29725585/influence-of-the-tumor-microenvironment-on-cancer-cells-metabolic-reprogramming
#20
REVIEW
Victoire Gouirand, Fabienne Guillaumond, Sophie Vasseur
As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells...
2018: Frontiers in Oncology
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