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https://www.readbyqxmd.com/read/29775615/extracellular-matrix-protein-dmp1-suppresses-osteogenic-differentiation-of-mesenchymal-stem-cells
#1
Shufan Zhang, Huixuan Wan, Peng Wang, Mengmeng Liu, Gongchen Li, Chunxue Zhang, Yao Sun
Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775390/polarization-and-distribution-of-tumor-associated-macrophages-and-cox-2-expression-in-basal-cell-carcinoma-of-the-ocular-adnexae
#2
Ute Kaiser, Karin U Loeffler, Jennifer Nadal, Frank G Holz, Martina C Herwig-Carl
PURPOSE: Basal cell carcinoma (BCC) is a locally invasive skin tumor which can be subdivided into a circumscribed nodular and an invasive fibrosing subtype. There is increasing evidence that macrophages play an important role in interacting between tumor cells and their microenvironment, thereby affecting not only the invasive potential but also the patients' prognosis. Thus, we wanted to compare these two BCC variants with regard to tumor-related inflammation, COX-2 expression, distribution and polarization of tumor-associated macrophages...
May 18, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29775280/fluorine-meets-amine-reducing-microenvironment-induced-amino-activatable-nanoprobes-for-19f-magnetic-resonance-imaging-of-bio-thiols
#3
Pingsheng Huang, Weisheng Guo, Guang Yang, Huijuan Song, Yuqing Wang, Chun Wang, Deling Kong, Weiwei Wang
19F MRI is of great significance for non-invasive imaging and detection of various diseases. However, the main obstacle in the application of 19F MRI agents stems from the unmet signal sensitivity, due to the poor water-solubility and restricted mobility of segments with high numbers of fluorine atoms. Herein, we report a kind of intracellular reducing microenvironment-induced amino-activatable 19F MRI nanoprobe, which can be used for specific imaging of bio-thiols. In principle, the nanoprobe has an initial architecture of hydrophobic core, where the trifluoromethyl-containing segments are compactly packed and 19F NMR/MRI signals are quenched ("OFF" state)...
May 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29774998/-the-expressions-and-correlations-of-il-10-cd14-and-cd68-in-laryngal-squamous-cell-carcinoma
#4
S Zhang, H Huangfu, B Q Wang, W Gao, L N Wu, Y Li, W Y Li
Objective: The aim of this study is to investigate the distribution of IL-10, CD14 and CD68 in the tumor microenvironment of LSCC with the clinicopathologic factors. Method: We detected the expressions of IL-10, CD14 and CD68 in 46 primary LSCC tumor tissues by immunohistochemistry staining and explore the relationship between them and clinicopathologic factors. Result: We found that the expressions of IL-10, CD14 and CD68 were significantly correlated with clinical stage and T stage ( P <0.01). IL-10 and CD14 were correlated with lymph node metastasis ( P <0...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29774910/design-of-rgd-atwlppr-peptide-conjugates-for-the-dual-targeting-of-%C3%AE-v-%C3%AE-3-integrin-and-neuropilin-1
#5
Fabien Thoreau, Laetitia Vanwonterghem, Maxime Henry, Jean-Luc Coll, Didier Boturyn
Targeting the tumour microenvironment is a promising strategy to detect and/or treat cancer. The design of selective compounds that co-target several receptors frequently overexpressed in solid tumours may allow a reliable and selective detection of tumours. Here we report the modular synthesis of compounds encompassing ligands of αVβ3 integrin and neuropilin-1 that are overexpressed in the tumour microenvironment. These compounds were then evaluated through cellular experiments and imaging of tumours in mice...
May 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29774654/a-photoactivatable-%C3%AE-5%C3%AE-1-specific-integrin-ligand
#6
Aranzazu Del Campo, Roshna V Nair, Aleeza Farrukh
The integrin α5β1 is overexpressed in colon, breast, ovarian, lung and brain tumors and has been identified as key component in mechanosensing. In order to study how dynamic changes of α5β1 engagement affect cellular behaviour, photoactivatable derivatives of α5β1 specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. The presence of the chromophore temporally inhibited ligand bioactivity...
May 18, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29774312/breast-cancer-prevention-current-approaches-and-future-directions
#7
REVIEW
Edward R Sauter
The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease...
April 2018: European Journal of Breast Health
https://www.readbyqxmd.com/read/29774083/engineered-microfluidic-bioreactor-for-examining-the-three-dimensional-breast-tumor-microenvironment
#8
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/29774062/-in-vivo-imaging-biomarkers-of-neuroinflammation-in-the-development-and-assessment-of-stroke-therapies-towards-clinical-translation
#9
REVIEW
Bastian Zinnhardt, Maximilian Wiesmann, Lisa Honold, Cristina Barca, Michael Schäfers, Amanda J Kiliaan, Andreas H Jacobs
Modulation of the inflammatory microenvironment after stroke opens a new avenue for the development of novel neurorestorative therapies in stroke. Understanding the spatio-temporal profile of (neuro-)inflammatory imaging biomarkers in detail thereby represents a crucial factor in the development and application of immunomodulatory therapies. The early integration of quantitative molecular imaging biomarkers in stroke drug development may provide key information about (i) early diagnosis and follow-up, (ii) spatio-temporal drug-target engagement (pharmacodynamic biomarker), (iii) differentiation of responders and non-responders in the patient cohort (inclusion/exclusion criteria; predictive biomarkers), and (iv) the mechanism of action...
2018: Theranostics
https://www.readbyqxmd.com/read/29773902/nedd9-promotes-oncogenic-signaling-a-stem-mesenchymal-gene-signature-and-aggressive-ovarian-cancer-growth-in-mice
#10
Rashid Gabbasov, Fang Xiao, Caitlin G Howe, Laura E Bickel, Shane W O'Brien, Daniel Benrubi, Thuy-Vy Do, Yan Zhou, Emmanuelle Nicolas, Kathy Q Cai, Samuel Litwin, Sachiko Seo, Erica A Golemis, Denise C Connolly
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) supports oncogenic signaling in a number of solid and hematologic tumors. Little is known about the role of NEDD9 in ovarian carcinoma (OC), but available data suggest elevated mRNA and protein expression in advanced stage high-grade cancers. We used a transgenic MISIIR-TAg mouse OC model combined with genetic ablation of Nedd9 to investigate its action in the development and progression of OC. A Nedd9-/- genotype delayed tumor growth rate, reduced incidence of ascites, and reduced expression and activation of signaling proteins including SRC, STAT3, E-cadherin, and AURKA...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#11
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773599/tgf%C3%AE-1-mediated-functional-inhibition-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#12
Stefanie Geyh, Manuel Rodríguez-Paredes, Paul Jäger, Annemarie Koch, Felix Bormann, Julian Gutekunst, Christoph Zilkens, Ulrich Germing, Guido Kobbe, Frank Lyko, Rainer Haas, Thomas Schroeder
Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#13
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773227/de1sign-of-synthetic-extracellular-matrices-for-probing-breast-cancer-cell-growth-using-robust-cyctocompatible-nucleophilic-thiol-yne-addition-chemistry
#14
Laura J Macdougall, Katherine L Wiley, April M Kloxin, Andrew P Dove
Controlled, three-dimensional (3D) cell culture systems are of growing interest for both tissue regeneration and disease, including cancer, enabling hypothesis testing about the effects of microenvironment cues on a variety of cellular processes, including aspects of disease progression. In this work, we encapsulate and culture in three dimensions different cancer cell lines in a synthetic extracellular matrix (ECM), using mild and efficient chemistry. Specifically, harnessing the nucleophilic addition of thiols to activated alkynes, we have created hydrogel-based materials with multifunctional poly(ethylene glycol) (PEG) and select biomimetic peptides...
May 7, 2018: Biomaterials
https://www.readbyqxmd.com/read/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#15
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29772694/the-nf-%C3%AE%C2%BAb-activating-pathways-in-multiple-myeloma
#16
REVIEW
Payel Roy, Uday Aditya Sarkar, Soumen Basak
Multiple myeloma(MM), an incurable plasma cell cancer, represents the second most prevalent hematological malignancy. Deregulated activity of the nuclear factor kappaB (NF-κB) family of transcription factors has been implicated in the pathogenesis of multiple myeloma. Tumor microenvironment-derived cytokines and cancer-associated genetic mutations signal through the canonical as well as the non-canonical arms to activate the NF-κB system in myeloma cells. In fact, frequent engagement of both the NF-κB pathways constitutes a distinguishing characteristic of myeloma...
May 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#17
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772648/adhesion-in-physiological-benign-and-malignant-proliferative-states-of-the-endometrium-microenvironment-and-the-clinical-big-picture
#18
REVIEW
Emily J Rutherford, Arnold D K Hill, Ann M Hopkins
Although the developments in cellular and molecular biology over the last few decades have significantly advanced our understanding of the processes and players that regulate invasive disease, many areas of uncertainty remain. This review will discuss the contribution of dysregulated cell⁻cell and cell⁻matrix adhesion to the invasion in both benign and malignant contexts. Using the endometrium as an illustrative tissue that undergoes clinically significant invasion in both contexts, the adhesion considerations in the cells ("seed") and their microenvironment ("soil") will be discussed...
May 16, 2018: Cells
https://www.readbyqxmd.com/read/29772539/spheroids-of-stem-cells-as-endochondral-templates-for-improved-bone-engineering
#19
Leandra Santos Baptista, Gabriela Soares Kronemberger, Karina Ribeiro Silva, Jose Mauro Granjeiro
Osteodegenerative disease and bone fractures lead to bone damage or loss, requiring new bone formation to replace the damaged tissues. Classical 'top-down' tissue engineering relies on seeding cell suspensions into biomaterial scaffolds, and then guiding cell fate by growth factors. However, complex tissue fabrication using this approach has important limitations. 'Bottom-up' tissue engineering has the potential to overcome the drawbacks of the top-down approach, by using 'building blocks' of cell spheroids for tissue biofabrication without a scaffold...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772538/targeting-fibroblast-activation-protein-in-cancer-prospects-and-caveats
#20
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)
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