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https://www.readbyqxmd.com/read/28087538/bcap-inhibits-proliferation-and-differentiation-of-myeloid-progenitors-in-the-steady-state-and-during-demand-situations
#1
Jeffrey M Duggan, Matthew B Buechler, Rebecca M Olson, Tobias M Hohl, Jessica A Hamerman
B cell adaptor for PI3-kinase (BCAP) is a signaling adaptor expressed in mature hematopoietic cells including monocytes and neutrophils. Here we investigated the role of BCAP in the homeostasis and development of these myeloid lineages. BCAP(-/-) mice had more bone marrow (BM) monocytes than WT mice, and in mixed WT:BCAP(-/-) BM chimeras, monocytes and neutrophils skewed towards BCAP(-/-) origin, showing a competitive advantage for BCAP(-/-) myeloid cells. BCAP was expressed in bone marrow hematopoietic progenitors, including LSK (Lineage(-)Sca1(+)cKit(+)), CMP (Common Myeloid Progenitor) and GMP (Granulocyte/Macrophage Progenitor) cells...
January 13, 2017: Blood
https://www.readbyqxmd.com/read/28057738/a-population-of-hematopoietic-stem-cells-derives-from-gata4-expressing-progenitors-located-in-the-placenta-and-lateral-mesoderm-of-mice
#2
Ana Cañete, Rita Carmona, Laura Ariza, Maria Jose Sanchez, Anabel Rojas, Ramon Muñoz-Chápuli
GATA transcription factors are expressed in mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at E7.5, becoming restricted to the septum transversum by E10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28052277/unknown-primary-melanoma-worldwide-survey-on-clinical-management
#3
Simone Ribero, Riccardo Pampena, Veronique Bataille, Elvira Moscarella, Luc Thomas, Pietro Quaglino, Concetta Potenza, Alexander C J Van Akkooi, Alessandro Testori, Paul Nathan, Susana Puig, Iris Zalaudek, Giuseppe Argenziano, Caterina Longo
BACKGROUND: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. OBJECTIVE: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. METHODS: A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. RESULTS: 119 physicians from 47 different countries answered the questionnaire...
January 5, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28039178/the-natural-history-and-patterns-of-metastases-from-mucosal-melanoma-an-analysis-of-706-prospectively-followed-patients
#4
B Lian, C L Cui, L Zhou, X Song, X S Zhang, D Wu, L Si, Z H Chi, X N Sheng, L L Mao, X Wang, B X Tang, X Q Yan, Y Kong, J Dai, S M Li, X Bai, N Zheng, Charles M Balch, J Guo
BACKGROUND: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. PATIENTS AND METHODS: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-beta-adrenergic-control-via-mafb-regulation
#5
Shirin Hasan, Nicholas B Johnson, Michael J Mosier, Ravi Shankar, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by beta-adrenergic stimulation leading to anemia. In mouse model of scald burn injury we observed, along with a 3-fold increase in bone marrow LSKs (lin(neg) Sca1(+)cKit(+)), the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs)...
December 28, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27980106/imatinib-spares-ckit-expressing-prostate-neuroendocrine-tumors-whereas-kills-seminal-vesicle-epithelial-stromal-tumors-targeting-pdgfr-%C3%AE
#6
Elena Jachetti, Alice Rigoni, Lucia Bongiovanni, Ivano Arioli, Laura Botti, Mariella Parenza, Valeria Cancila, Claudia Chiodoni, Fabrizio Festinese, Matteo Bellone, Regina Tardanico, Claudio Tripodo, Mario P Colombo
Prostate cancer is a leading cause of death by cancer in male worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favours prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of Imatinib in TRAMP mice...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27908352/pim1-overexpressing-ckit-cardiac-stem%C3%A2-cells-in-cardiac-regeneration-preconditioning-as-next-generation-stem-cell-therapy
#7
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
#8
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
#9
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
#10
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...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27771610/a-phase-ii-study-of-tivozanib-in-patients-with-metastatic-and-nonresectable-soft-tissue-sarcomas
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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