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https://www.readbyqxmd.com/read/29453454/a-microvascularized-tumor-mimetic-platform-for-assessing-anti-cancer-drug-efficacy
#1
Shantanu Pradhan, Ashley M Smith, Charles J Garson, Iman Hassani, Wen J Seeto, Kapil Pant, Robert D Arnold, Balabhaskar Prabhakarpandian, Elizabeth A Lipke
Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29451855/in-vivo-labeling-by-cd73-marks-multipotent-stromal-cells-and-highlights-endothelial-heterogeneity-in-the-bone-marrow-niche
#2
Martin Breitbach, Kenichi Kimura, Tiago C Luis, Christopher J Fuegemann, Petter S Woll, Michael Hesse, Raffaella Facchini, Sarah Rieck, Katarzyna Jobin, Julia Reinhardt, Osamu Ohneda, Daniela Wenzel, Caroline Geisen, Christian Kurts, Wolfgang Kastenmüller, Michael Hölzel, Sten E W Jacobsen, Bernd K Fleischmann
Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP + MSCs in various organs. In vivo, EGFP + mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP + cells exhibited a perivascular distribution pattern. EGFP + cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential...
February 1, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29449267/single-cell-transcriptome-analyses-reveal-endothelial-cell-heterogeneity-in-tumors-and-changes-following-anti-angiogenic-treatment
#3
Qi Zhao, Alexandra Eichten, Asma A Parveen, Christina Adler, Ying Huang, Wei Wang, Yueming Ding, Alexander Adler, Thomas Nevins, Min Ni, Yi Wei, Gavin Thurston
Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here we characterized by single cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling...
February 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29444818/sox7-promotes-high-grade-glioma-by-increasing-vegfr2-mediated-vascular-abnormality
#4
Il-Kug Kim, Kangsan Kim, Eunhyeong Lee, Dong Sun Oh, Chan Soon Park, Seongyeol Park, Jee Myung Yang, Ju-Hee Kim, Hyung-Seok Kim, David T Shima, Jeong Hoon Kim, Seok Ho Hong, Young Hyun Cho, Young Hoon Kim, Jong Bae Park, Gou Young Koh, Young Seok Ju, Heung Kyu Lee, Seungjoo Lee, Injune Kim
High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs...
February 14, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29444773/lung-function-inflammation-and-endothelin-1-in-congenital-heart-disease-associated-pulmonary-arterial-hypertension
#5
Andrew Low, Sarah George, Luke Howard, Nicholas Bell, Ann Millar, Robert M R Tulloh
BACKGROUND: Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls. METHODS AND RESULTS: Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls...
February 14, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29438884/sprouting-angiogenesis-induces-significant-mechanical-heterogeneities-and-ecm-stiffening-across-length-scales-in-fibrin-hydrogels
#6
Benjamin A Juliar, Mark T Keating, Yen P Kong, Elliot L Botvinick, Andrew J Putnam
Matrix stiffness is a well-established instructive cue in two-dimensional cell cultures. Its roles in morphogenesis in 3-dimensional (3D) cultures, and the converse effects of cells on the mechanics of their surrounding microenvironment, have been more elusive given the absence of suitable methods to quantify stiffness on a length-scale relevant for individual cell-extracellular matrix (ECM) interactions. In this study, we applied traditional bulk rheology and laser tweezers-based active microrheology to probe mechanics across length scales during the complex multicellular process of capillary morphogenesis in 3D, and further characterized the relative contributions of neovessels and supportive stromal cells to dynamic changes in stiffness over time...
February 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29430386/tumor-microenvironment-heterogeneity-challenges-and-opportunities
#7
F Runa, S Hamalian, K Meade, P Shisgal, P C Gray, J A Kelber
The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers...
December 2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29426834/value-of-circulating-cytokine-profiling-during-submaximal-exercise-testing-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome
#8
Kegan J Moneghetti, Mehdi Skhiri, Kévin Contrepois, Yukari Kobayashi, Holden Maecker, Mark Davis, Michael Snyder, Francois Haddad, Jose G Montoya
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous syndrome in which patients often experience severe fatigue and malaise following exertion. Immune and cardiovascular dysfunction have been postulated to play a role in the pathophysiology. We therefore, examined whether cytokine profiling or cardiovascular testing following exercise would differentiate patients with ME/CFS. Twenty-four ME/CFS patients were matched to 24 sedentary controls and underwent cardiovascular and circulating immune profiling...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29421553/hacking-macrophage-associated-immunosuppression-for-regulating-glioblastoma-angiogenesis
#9
Xin Cui, Renee-Tyler Tan Morales, Weiyi Qian, Haoyu Wang, Jean-Pierre Gagner, Igor Dolgalev, Dimitris Placantonakis, David Zagzag, Luisa Cimmino, Matija Snuderl, Raymond H W Lam, Weiqiang Chen
Glioblastoma (GBM) is the most lethal primary adult brain tumor and its pathology is hallmarked by distorted neovascularization, diffuse tumor-associated macrophage infiltration, and potent immunosuppression. Reconstituting organotypic tumor angiogenesis models with biomimetic cell heterogeneity and interactions, pro-/anti-inflammatory milieu and extracellular matrix (ECM) mechanics is critical for preclinical anti-angiogenic therapeutic screening. However, current in vitro systems do not accurately mirror in vivo human brain tumor microenvironment...
February 2, 2018: Biomaterials
https://www.readbyqxmd.com/read/29420858/endothelial-notch-activation-reshapes-the-angiocrine-of-sinusoidal-endothelia-to-aggravate-liver-fibrosis-and-blunt-regeneration
#10
Juan-Li Duan, Bai Ruan, Xian-Chun Yan, Liang Liang, Ping Song, Zi-Yan Yang, Yuan Liu, Ke-Feng Dou, Hua Han, Lin Wang
Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch signaling was activated by inducible EC-specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC-associated genes and increased continuous EC-associated genes, suggesting LSEC dedifferentiation...
February 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29417261/the-ratio-of-adscs-to-hsc-progenitors-in-adipose-tissue-derived-svf-may-provide-the-key-to-predict-the-outcome-of-stem-cell-therapy
#11
Mehmet Okyay Kilinc, Antonio Santidrian, Ivelina Minev, Robert Toth, Dobrin Draganov, Duong Nguyen, Elliot Lander, Mark Berman, Boris Minev, Aladar A Szalay
BACKGROUND: Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer...
February 7, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29415653/xanthine-oxidase-inhibitors-for-prevention-of-cardiovascular-events-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#12
Markus Bredemeier, Lediane Moreira Lopes, Matheus Augusto Eisenreich, Sheila Hickmann, Guilherme Kopik Bongiorno, Rui d'Avila, André Luis Bittencourt Morsch, Fernando da Silva Stein, Guilherme Gomes Dias Campos
BACKGROUND: Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI...
February 7, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29409057/endothelial-shear-stress-5-years-after-implantation-of-a-coronary-bioresorbable-scaffold
#13
Vikas Thondapu, Erhan Tenekecioglu, Eric K W Poon, Carlos Collet, Ryo Torii, Christos V Bourantas, Cheng Chin, Yohei Sotomi, Hans Jonker, Jouke Dijkstra, Eve Revalor, Frank Gijsen, Yoshinobu Onuma, Andrew Ooi, Peter Barlis, Patrick W Serruys
Aims: As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results: Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography...
February 2, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29406779/at-the-root-defining-and-halting-progression-of-early-chronic-obstructive-pulmonary-disease
#14
Fernando J Martinez, MeiLan K Han, James P Allinson, R Graham Barr, Richard C Boucher, Peter Calverley, Bartolome R Celli, Stephanie A Christenson, Ronald G Crystal, Malin Fagerås, Christine M Freeman, Lars Groenke, Eric A Hoffman, Mehmet Kesimer, Konstantinos Kostikas, Robert Paine Iii, Shahin Rafii, Stephen I Rennard, Leopoldo N Segal, Renat Shaykhiev, Christopher Stevenson, Ruth Tal-Singer, Jørgen Vestbo, Prescott G Woodruff, Jeffrey L Curtis, Jadwiga A Wedzicha
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with varying presentations and progression, but limited disease-modifying therapies. Trajectories of lung function decline in COPD differ significantly between individuals, with differences detectable in young adulthood. "Early disease" (initial manifestations in young individuals) should be distinguished from "late mild disease" (disease of mild severity in older individuals potentially present for decades). For research purposes, we propose an operational definition of early COPD: ever-smokers (≥10 pack-years) younger than 50 years with any of these abnormalities: (1) FEV1/FVC< lower limit of normal; (2) compatible CT abnormalities (airway abnormality and/or emphysema); or (3) FEV1 decline (≥60 mL/year)...
February 6, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29401716/do-coffee-polyphenols-have-a-preventive-action-on-metabolic-syndrome-associated-endothelial-dysfunctions-an-assessment-of-the-current-evidence
#15
REVIEW
Kazuo Yamagata
Epidemiologic studies from several countries have found that mortality rates associated with the metabolic syndrome are inversely associated with coffee consumption. Metabolic syndrome can lead to arteriosclerosis by endothelial dysfunction, and increases the risk for myocardial and cerebral infarction. Accordingly, it is important to understand the possible protective effects of coffee against components of the metabolic syndrome, including vascular endothelial function impairment, obesity and diabetes. Coffee contains many components, including caffeine, chlorogenic acid, diterpenes and trigonelline...
February 4, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29396703/immunologic-milieu-of-mature-t-cell-and-nk-cell-lymphomas-implications-for-therapy
#16
REVIEW
Eric Tse, Yok-Lam Kwong
PURPOSE OF THE REVIEW: T-cells and natural killer (NK) cells share the same ontogeny, and lymphomas derived from them are clinically diverse, occurring in nodal and extranodal sites. In addition to inherent properties of these lymphomas, their microenvironment also impacts on pathogenesis and response to therapy. An understanding of the milieu of T-cell and NK cell lymphomas has important implications on treatment. RECENT FINDINGS: Components of the microenvironment include tumour-associated macrophages (TAM), non-neoplastic T-cells and B-cells, eosinophils, dendritic cells, endothelial cells and blood vessels...
February 2, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29395658/dermal-fibroblasts-a-heterogeneous-population-with-regulatory-function-in-wound-healing
#17
REVIEW
Anna Stunova, Lucie Vistejnova
Dermal fibroblasts, which make up the major cell type in the dermis, have, historically, been considered to be relatively 'passive' cells which are responsible for the synthesis and remodeling of extracellular matrix proteins. However, the dermal fibroblast population is composed of heterogeneous and distinct cell types, and it has been established that, under the stress conditions of healing wound environments, dermal fibroblasts participate in the regulation of ongoing inflammation and cell proliferation by secreting a variety of signaling molecules that modulate the functions of immune cells, keratinocyte, endothelial cells and mast cells via both direct cell to cell communication and autocrine and paracrine interactions...
January 29, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29393169/hereditary-and-acquired-angioedema-heterogeneity-of-pathogenesis-and-clinical-phenotypes
#18
Maria Bova, Giulia De Feo, Roberta Parente, Tiziana De Pasquale, Carmela Gravante, Stefano Pucci, Eustachio Nettis, Massimo Triggiani
Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system...
January 26, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29393024/axitinib-cabozantinib-everolimus-nivolumab-sunitinib-and-best-supportive-care-in-previously-treated-renal-cell-carcinoma-a-systematic-review-and-economic-evaluation
#19
Steve J Edwards, Victoria Wakefield, Peter Cain, Charlotta Karner, Kayleigh Kew, Mariana Bacelar, Natalie Masento, Fatima Salih
BACKGROUND: Several therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta®, Pfizer Inc., NY, USA), cabozantinib (Cabometyx®, Ipsen, Slough, UK), everolimus (Afinitor®, Novartis, Basel, Switzerland), nivolumab (Opdivo®, Bristol-Myers Squibb, NY, USA), sunitinib (Sutent®, Pfizer, Inc...
January 2018: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/29392712/avian-coronary-endothelium-is-a-mosaic-of-sinus-venosus-and-ventricle-derived-endothelial-cells-in-a-region-specific-manner
#20
Tatsuya Kamimura, Toshiyuki Yamagishi, Yuji Nakajima
The origin of coronary endothelial cells (ECs) has been investigated in avian species, and the results showed that the coronary ECs originate from the proepicardial organ (PEO) and developing epicardium. Genetic approaches in mouse models showed that the major source of coronary ECs is the sinus venosus endothelium or ventricular endocardium. To clarify and reconcile the differences between avian and mouse species, we examined the source of coronary ECs in avian embryonic hearts. Using an enhanced green fluorescent protein-Tol2 system and fluorescent dye labeling, four types of quail-chick chimeras were made and quail-specific endothelial marker (QH1) immunohistochemistry was performed...
February 2, 2018: Development, Growth & Differentiation
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