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https://www.readbyqxmd.com/read/27908352/pim1-overexpressing-ckit-cardiac-stem%C3%A2-cells-in-cardiac-regeneration-preconditioning-as-next-generation-stem-cell-therapy
#1
EDITORIAL
Rabea Hinkel
No abstract text is available yet for this article.
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27908351/pim1-kinase-overexpression-enhances-ckit-cardiac-stem-cell-cardiac-repair-following-myocardial-infarction-in-swine
#2
Shathiyah Kulandavelu, Vasileios Karantalis, Julia Fritsch, Konstantinos E Hatzistergos, Viky Y Loescher, Frederic McCall, Bo Wang, Luiza Bagno, Samuel Golpanian, Ariel Wolf, Justin Grenet, Adam Williams, Aaron Kupin, Aaron Rosenfeld, Sadia Mohsin, Mark A Sussman, Azorides Morales, Wayne Balkan, Joshua M Hare
BACKGROUND: Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit(+) cardiac stem cells (CSCs) enhances their cardioreparative properties. OBJECTIVES: The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI). METHODS: Human cardiac stem cells (hCSCs, n = 10), hckit(+) CSCs overexpressing Pim1 (Pim1(+); n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27845396/first-steps-to-define-murine-amniotic-fluid-stem-cell-microenvironment
#3
E Bertin, M Piccoli, C Franzin, G Spiro, S Donà, A Dedja, F Schiavi, E Taschin, P Bonaldo, P Braghetta, P De Coppi, M Pozzobon
Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit(+) cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit(+) cells present both in the amniotic fluid and in the amnion...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27793944/imatinib-induced-gastrointestinal-vascular-ectasia-in-a-patient-with-advanced-gist-case-report-and-literature-review
#4
Mahmoud Abu-Amna, Halim Awadie, Gil Bar-Sela
BACKGROUND: Imatinib is generally well tolerated in the treatment of advanced gastrointestinal stromal tumors (GIST). Gastrointestinal vascular ectasia (GIVE) and gastric antral vascular ectasia (GAVE), while rare, are significant under-reported complications of imatinib therapy. CASE REPORT: We present one patient with GIVE complicating imatinib therapy with a literature review of this rare side-effect. RESULTS: A 68-year-old woman was diagnosed with advanced GIST, wild-type CKIT...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27771610/a-phase-ii-study-of-tivozanib-in-patients-with-metastatic-and-nonresectable-soft-tissue-sarcomas
#5
M Agulnik, R L B Costa, M Milhem, A W Rademaker, B C Prunder, D Daniels, B T Rhodes, C Humphreys, S Abbinanti, L Nye, R Cehic, A Polish, C Vintilescu, T McFarland, K Skubitz, S Robinson, S Okuno, B A Van Tine
BACKGROUND: Soft tissue sarcomas (STSs) overexpress vascular endothelial growth factors (VEGF) and VEGF-receptors (VEGFR) activation have been associated with tumor aggressiveness. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFRα/β and cKIT. The primary endpoint of this study was progression free survival (PFS) rate at 16 weeks. Secondary end points were overall survival (OS), response rate, safety and correlative studies...
October 22, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27764183/morphological-and-molecular-characterization-of-human-dermal-lymphatic-collectors
#6
Viktoria Hasselhof, Anastasia Sperling, Kerstin Buttler, Philipp Ströbel, Jürgen Becker, Thiha Aung, Gunther Felmerer, Jörg Wilting
Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1)...
2016: PloS One
https://www.readbyqxmd.com/read/27746675/src-tyrosine-kinase-regulates-the-stem-cell-factor-induced-breakdown-of-the-blood-retinal-barrier
#7
Ji-Eun Im, Sun-Hwa Song, Wonhee Suh
PURPOSE: Stem cell factor (SCF) has been recently acknowledged as a novel endothelial permeability factor. However, the mechanisms by which SCF-induced activation of the SCF cognate receptor, cKit, enhances endothelial permeability have not been fully elucidated. This study aimed to investigate the role of Src in SCF-induced breakdown of the blood-retinal barrier (BRB). METHODS: In vitro endothelial permeability and in vivo retinal vascular permeability assays were performed to investigate the role of Src in SCF-induced breakdown of the BRB...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27733321/human-hepatocytes-loaded-in-3d-bioprinting-generate-mini-liver
#8
Cheng Zhong, Hai-Yang Xie, Lin Zhou, Xiao Xu, Shu-Sen Zheng
BACKGROUND: Because of an increasing discrepancy between the number of potential liver graft recipients and the number of organs available, scientists are trying to create artificial liver to mimic normal liver function and therefore, to support the patient's liver when in dysfunction. 3D printing technique meets this purpose. The present study was to test the feasibility of 3D hydrogel scaffolds for liver engineering. METHODS: We fabricated 3D hydrogel scaffolds with a bioprinter...
October 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27688303/mesenchymal-stem-cells-drive-cardiac-stem-cell-chemotaxis-proliferation-and-phenotype-via-cxcr4-and-ckit-signaling
#9
EDITORIAL
Kenneth Michael Fish
No abstract text is available yet for this article.
September 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27660467/sunitinib-the-antiangiogenic-effects-and-beyond
#10
REVIEW
Zhonglin Hao, Ibrahim Sadek
As a multitargeted kinase inhibitor, sunitinib has carved its way into demonstrating itself as a most effective tyrosine kinase inhibitor in the treatment of metastatic renal cell carcinoma. Mechanistically, sunitinib inhibits multiple receptor tyrosine kinases, especially those involved in angiogenesis, that is, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and proto-oncogene cKIT. Sunitinib has also been implicated in enhancing cancer invasiveness and metastasis. Mechanisms of resistance are poorly understood, but both intrinsic and acquired mechanisms are thought to be involved...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27614029/contribution-of-mast-cells-to-injury-mechanisms-in-a-mouse-model-of-pediatric-traumatic-brain-injury
#11
Raffaella Moretti, Vibol Chhor, Donatella Bettati, Elena Banino, Silvana De Lucia, Tifenn Le Charpentier, Sophie Lebon, Leslie Schwendimann, Julien Pansiot, Sowmyalakshmi Rasika, Vincent Degos, Luigi Titomanlio, Pierre Gressens, Bobbi Fleiss
The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than injuries to the adult brain. Understanding this developmental sensitivity is critical because children under 4 years of age of sustain TBI more frequently than any other age group. One of the first events after TBI is the infiltration and degranulation of mast cells (MCs) in the brain, releasing a range of immunomodulatory substances; inhibition of these cells is neuroprotective in other types of neonatal brain injury...
December 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27605552/combined-targeting-of-bcl-2-and-bcr-abl-tyrosine-kinase-eradicates-chronic-myeloid-leukemia-stem-cells
#12
Bing Z Carter, Po Yee Mak, Hong Mu, Hongsheng Zhou, Duncan H Mak, Wendy Schober, Joel D Leverson, Bin Zhang, Ravi Bhatia, Xuelin Huang, Jorge Cortes, Hagop Kantarjian, Marina Konopleva, Michael Andreeff
BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin(-)Sca-1(+)cKit(+) cells of inducible CML in mice, as determined by CyTOF mass cytometry...
September 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27581136/cml-mouse-model-generated-from-leukemia-stem-cells
#13
Yiguo Hu
Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a high number of well-differentiated neutrophils in peripheral blood and myeloid cells in bone marrow (BM). CML is derived from the hematopoietic stem cells (HSCs) with the Philadelphia chromosome (Ph(+), t(9;22)-(q34;q11)), resulting in generating a fusion oncogene, BCR/ABL1. HSCs with Ph(+) are defined as leukemia stem cells (LSCs), a subpopulation cell at the apex of hierarchies in leukemia cells and responsible for the disease continuous propagation...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27556889/clinical-pharmacology-drug-drug-interactions-and-safety-of-pazopanib-a-review
#14
Pascaline Boudou-Rouquette, Camille Tlemsani, Benoit Blanchet, Olivier Huillard, Anne Jouinot, Jennifer Arrondeau, Audrey Thomas-Schoemann, Michel Vidal, Jérôme Alexandre, François Goldwasser
In the past decade, treatment options for metastatic renal cell carcinoma and soft-tissue sarcoma have expanded. Pazopanib was discovered during the screening of compounds that suppressed vascular endothelial growth factor receptor-2 (VEGFR-2). As other tyrosine kinase inhibitors (TKI), pazopanib is not totally specific for one target since it also inhibits stem-cell factor receptor (cKIT), platelet-derived growth factor receptors (PDGFRα, β), VEGFR-1 and -3. Areas covered: Clinical pharmacology, drug-drug interactions and safety data published on pazopanib, between January 2006 and April 2016, are reviewed...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27545040/discovery-of-n-1-4-3-3-6-7-dimethoxyquinolin-3-yl-oxy-phenyl-ureido-2-trifluoromethyl-phenyl-piperidin-4-yl-methyl-propionamide-chmfl-kit-8140-as-a-highly-potent-type-ii-inhibitor-capable-of-inhibiting-the-t670i-gatekeeper-mutant-of-ckit-kinase
#15
Binhua Li, Aoli Wang, Juan Liu, Ziping Qi, Xiaochuan Liu, Kailin Yu, Hong Wu, Cheng Chen, Chen Hu, Wenchao Wang, Jiaxin Wu, Zhenquan Hu, Ling Ye, Fengming Zou, Feiyang Liu, Beilei Wang, Li Wang, Tao Ren, Shaojuan Zhang, Mingfeng Bai, Shanchun Zhang, Jing Liu, Qingsong Liu
cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited both cKIT wt (IC50 = 33 nM) and cKIT gatekeeper T670I mutant (IC50 = 99 nM). Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM)...
September 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27539289/receptor-for-advanced-glycation-end-products-mediated-signaling-impairs-the-maintenance-of-bone-marrow-mesenchymal-stromal-cells-in-diabetic-model-mice
#16
Eriko Aikawa, Ryo Fujita, Maiko Asai, Yasufumi Kaneda, Katsuto Tamai
Bone marrow mesenchymal stromal cells (BM-MSCs) have been demonstrated to contribute to tissue regeneration. However, chronic pathological conditions, such as diabetes and aging, can result in a decreased number and/or quality of BM-MSCs. We therefore investigated the maintenance mechanism of BM-MSCs by studying signaling through the receptor for advanced glycation end products (RAGE), which is thought to be activated under various pathological conditions. The abundance of endogenous BM-MSCs decreased in a type 2 diabetes mellitus (DM2) model, as determined by performing colony-forming unit (CFU) assays...
November 15, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27461939/acute-catecholamine-exposure-causes-reversible-myocyte-injury-without-cardiac-regeneration
#17
Markus Wallner, Jason M Duran, Sadia Mohsin, Constantine D Troupes, Davy Vanhoutte, Giulia Borghetti, Ronald J Vagnozzi, Polina Gross, Daohai Yu, Danielle M Trappanese, Hajime Kubo, Amir Toib, Thomas E Sharp, Shavonn C Harper, Michael A Volkert, Timothy Starosta, Eric A Feldsott, Remus M Berretta, Tao Wang, Mary F Barbe, Jeffrey D Molkentin, Steven R Houser
RATIONALE: Catecholamines increase cardiac contractility, but exposure to high concentrations or prolonged exposures can cause cardiac injury. A recent study demonstrated that a single subcutaneous injection of isoproterenol (ISO; 200 mg/kg) in mice causes acute myocyte death (8%-10%) with complete cardiac repair within a month. Cardiac regeneration was via endogenous cKit(+) cardiac stem cell-mediated new myocyte formation. OBJECTIVE: Our goal was to validate this simple injury/regeneration system and use it to study the biology of newly forming adult cardiac myocytes...
September 16, 2016: Circulation Research
https://www.readbyqxmd.com/read/27278627/male-specific-colon-motility-dysfunction-in-the-tasht-mouse-line
#18
A M Touré, B Charrier, N Pilon
BACKGROUND: In Hirschsprung disease (HSCR), the absence of myenteric neural ganglia in the distal bowel prevents motility and thereby causes functional intestinal obstruction. Although surgical resection of the aganglionic segment allows HSCR children to survive this condition, a number of patients still suffer from impaired motility despite having myenteric ganglia in their postoperative distal bowel. Such phenomenon is also observed in patients suffering from other enteric neuropathies and, in both cases, colonic dysmotility is believed to result from abnormalities of myenteric ganglia and/or associated interstitial cells of Cajal (ICC)...
October 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27188595/impaired-mobilization-of-vascular-reparative-bone-marrow-cells-in-streptozotocin-induced-diabetes-but-not-in-leptin-receptor-deficient-db-db-mice
#19
Goutham Vasam, Shrinidh Joshi, Yagna P R Jarajapu
Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27174098/c-myb-regulates-proliferation-and-differentiation-of-adventitial-sca1-vascular-smooth-muscle-cell-progenitors-by-transactivation-of-myocardin
#20
Eric A Shikatani, Mark Chandy, Rickvinder Besla, Cedric C Li, Abdul Momen, Omar El-Mounayri, Clinton S Robbins, Mansoor Husain
OBJECTIVE: Vascular smooth muscle cells (VSMCs) are believed to dedifferentiate and proliferate in response to vessel injury. Recently, adventitial progenitor cells were implicated as a source of VSMCs involved in vessel remodeling. c-Myb is a transcription factor known to regulate VSMC proliferation in vivo and differentiation of VSMCs from mouse embryonic stem cell-derived progenitors in vitro. However, the role of c-Myb in regulating specific adult vascular progenitor cell populations was not known...
July 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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