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Michael G Kharas

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https://www.readbyqxmd.com/read/29351846/dual-strategies-for-argonaute2-mediated-biogenesis-of-erythroid-mirnas-underlie-conserved-requirements-for-slicing-in-mammals
#1
David Jee, Jr-Shiuan Yang, Sun-Mi Park, D'Juan T Farmer, Jiayu Wen, Timothy Chou, Arthur Chow, Michael T McManus, Michael G Kharas, Eric C Lai
While Slicer activity of Argonaute is central to RNAi, conserved roles of slicing in endogenous regulatory biology are less clear, especially in mammals. Biogenesis of erythroid Dicer-independent mir-451 involves Ago2 catalysis, but mir-451-KO mice do not phenocopy Ago2 catalytic-dead (Ago2-CD) mice, suggesting other needs for slicing. Here, we reveal mir-486 as another dominant erythroid miRNA with atypical biogenesis. While it is Dicer dependent, it requires slicing to eliminate its star strand. Thus, in Ago2-CD conditions, miR-486-5p is functionally inactive due to duplex arrest...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29317678/peptidomimetic-blockade-of-myb-in-acute-myeloid-leukemia
#2
Kavitha Ramaswamy, Lauren Forbes, Gerard Minuesa, Tatyana Gindin, Fiona Brown, Michael G Kharas, Andrei V Krivtsov, Scott A Armstrong, Eric Still, Elisa de Stanchina, Birgit Knoechel, Richard Koche, Alex Kentsis
Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/28920958/the-n-6-methyladenosine-m-6-a-forming-enzyme-mettl3-controls-myeloid-differentiation-of-normal-hematopoietic-and-leukemia-cells
#3
Ly P Vu, Brian F Pickering, Yuanming Cheng, Sara Zaccara, Diu Nguyen, Gerard Minuesa, Timothy Chou, Arthur Chow, Yogesh Saletore, Matthew MacKay, Jessica Schulman, Christopher Famulare, Minal Patel, Virginia M Klimek, Francine E Garrett-Bakelman, Ari Melnick, Martin Carroll, Christopher E Mason, Samie R Jaffrey, Michael G Kharas
N6 -methyladenosine (m6 A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m6 A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m6 A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/28718412/stem-cells-cancer-and-musashi-in-blood-and-guts
#4
REVIEW
Michael G Kharas, Christopher J Lengner
The mammalian MSI family of RNA-binding proteins (RBPs) have important roles as oncoproteins in an array of tumor types, including leukemias, glioblastomas, and pancreatic, breast, lung, and colorectal cancers. The mammalian Msi genes, Msi1 and Msi2, have been most thoroughly investigated in two highly proliferative tissues prone to oncogenic transformation: the hematopoietic lineage and the intestinal epithelium. Despite their vast phenotypic differences, MSI proteins appear to have an analogous role in governing the stem cell compartment in both of these tissues, potentially providing a paradigm for a broader understanding of MSI function and oncogenic activities...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28684528/epigenetically-aberrant-stroma-in-mds-propagates-disease-via-wnt-%C3%AE-catenin-activation
#5
Tushar D Bhagat, Si Chen, Matthias Bartenstein, A Trevor Barlowe, Dagny Von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Iaonnis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafullla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Yeung, Kira Gritsman, Peter Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John M Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc H G P Raaijmakers, H Joachim Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28630930/real-time-quantitative-analysis-of-metabolic-flux-in-live-cells-using-a-hyperpolarized-micromagnetic-resonance-spectrometer
#6
Sangmoo Jeong, Roozbeh Eskandari, Sun Mi Park, Julio Alvarez, Sui Seng Tee, Ralph Weissleder, Michael G Kharas, Hakho Lee, Kayvan R Keshari
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28569734/ablation-of-pi3k-blocks-bcr-abl-leukemogenesis-in-mice-and-a-dual-pi3k-mtor-inhibitor-prevents-expansion-of-human-bcr-abl-leukemia-cells
#7
Michael G Kharas, Matthew R Janes, Vanessa M Scarfone, Michael B Lilly, Zachary A Knight, Kevan M Shokat, David A Fruman
No abstract text is available yet for this article.
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28449828/hypertension-canada-s-2017-guidelines-for-diagnosis-risk-assessment-prevention-and-treatment-of-hypertension-in-adults
#8
Alexander A Leung, Stella S Daskalopoulou, Kaberi Dasgupta, Kerry McBrien, Sonia Butalia, Kelly B Zarnke, Kara Nerenberg, Kevin C Harris, Meranda Nakhla, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Guy Tremblay, Donna McLean, Karen C Tran, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, G V Ramesh Prasad, Steven E Gryn, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Praveena Sivapalan, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman R C Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Gregory Kline, Lawrence A Leiter, Charlotte Jones, Anne-Marie Côté, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Ross T Tsuyuki, Swapnil Hiremath, Denis Drouin, Kim L Lavoie, Pavel Hamet, Jean C Grégoire, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Scott A Lear, Gregory Moullec, Milan Gupta, Laura A Magee, Alexander G Logan, Janis Dionne, Anne Fournier, Geneviève Benoit, Janusz Feber, Luc Poirier, Raj S Padwal, Doreen M Rabi
Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg...
May 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#9
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28215825/stage-specific-human-induced-pluripotent-stem-cells-map-the-progression-of-myeloid-transformation-to-transplantable-leukemia
#10
Andriana G Kotini, Chan-Jung Chang, Arthur Chow, Han Yuan, Tzu-Chieh Ho, Tiansu Wang, Shailee Vora, Alexander Solovyov, Chrystel Husser, Malgorzata Olszewska, Julie Teruya-Feldstein, Deepak Perumal, Virginia M Klimek, Alexandros Spyridonidis, Raajit K Rampal, Lewis Silverman, E Premkumar Reddy, Elli Papaemmanuil, Samir Parekh, Benjamin D Greenbaum, Christina S Leslie, Michael G Kharas, Eirini P Papapetrou
Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28081722/emerging-links-between-m-6-a-and-misregulated-mrna-methylation-in-cancer
#11
Samie R Jaffrey, Michael G Kharas
N (6)-methyladenosine (m(6)A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cellular differentiation and pluripotency. Recent studies are pointing to a role for the RNA methylation program in cancer self-renewal and cell fate, making this a new and promising therapeutic avenue for investigation.
January 12, 2017: Genome Medicine
https://www.readbyqxmd.com/read/27799368/msi-rna-binding-proteins-control-reserve-intestinal-stem-cell-quiescence
#12
Maryam Yousefi, Ning Li, Angela Nakauka-Ddamba, Shan Wang, Kimberly Davidow, Jenna Schoenberger, Zhengquan Yu, Shane T Jensen, Michael G Kharas, Christopher J Lengner
Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnt(high) ISC that fuels turnover during homeostasis and a reserve, radioresistant Wnt(low/off) ISC capable of generating active Wnt(high) ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27118291/hypertension-canada-s-2016-canadian-hypertension-education-program-guidelines-for-blood-pressure-measurement-diagnosis-assessment-of-risk-prevention-and-treatment-of-hypertension
#13
Alexander A Leung, Kara Nerenberg, Stella S Daskalopoulou, Kerry McBrien, Kelly B Zarnke, Kaberi Dasgupta, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, G V Ramesh Prasad, Marcel Lebel, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman R C Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Pierre Larochelle, Lawrence A Leiter, Charlotte Jones, Richard I Ogilvie, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Robert J Petrella, Swapnil Hiremath, Denis Drouin, Kim L Lavoie, Pavel Hamet, George Fodor, Jean C Grégoire, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Scott A Lear, Gregory Moullec, Milan Gupta, Laura A Magee, Alexander G Logan, Kevin C Harris, Janis Dionne, Anne Fournier, Geneviève Benoit, Janusz Feber, Luc Poirier, Raj S Padwal, Doreen M Rabi
Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure...
May 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/27104777/musashi-2-duels-in-myelodysplastic-syndromes
#14
EDITORIAL
Tzu-Chieh Ho, James Taggart, Michael G Kharas
No abstract text is available yet for this article.
July 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/26898884/msi2-is-required-for-maintaining-activated-myelodysplastic-syndrome-stem-cells
#15
James Taggart, Tzu-Chieh Ho, Elianna Amin, Haiming Xu, Trevor S Barlowe, Alexendar R Perez, Benjamin H Durham, Patrick Tivnan, Rachel Okabe, Arthur Chow, Ly Vu, Sun Mi Park, Camila Prieto, Christopher Famulare, Minal Patel, Christopher J Lengner, Amit Verma, Gail Roboz, Monica Guzman, Virginia M Klimek, Omar Abdel-Wahab, Christina Leslie, Stephen D Nimer, Michael G Kharas
Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia and stem cell function, but its role in MDS is unknown. Here, we demonstrate that elevated MSI2 expression correlates with poor survival in MDS. Conditional deletion of Msi2 in a mouse model of MDS results in a rapid loss of MDS haematopoietic stem and progenitor cells (HSPCs) and reverses the clinical features of MDS. Inversely, inducible overexpression of MSI2 drives myeloid disease progression...
February 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/26673327/the-msi-family-of-rna-binding-proteins-function-redundantly-as-intestinal-oncoproteins
#16
Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Fan Li, Lee Vandivier, Kimberly Parada, Dong-Hun Woo, Shan Wang, Ammar S Naqvi, Shilpa Rao, John Tobias, Ryan J Cedeno, Gerard Minuesa, Katz Y, Trevor S Barlowe, Alexander Valvezan, Sheila Shankar, Raquel P Deering, Peter S Klein, Shane T Jensen, Michael G Kharas, Brian D Gregory, Zhengquan Yu, Christopher J Lengner
Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis...
December 22, 2015: Cell Reports
https://www.readbyqxmd.com/read/26666262/integrative-genetic-analysis-of-mouse-and-human-aml-identifies-cooperating-disease-alleles
#17
Megan A Hatlen, Kanika Arora, Vladimir Vacic, Ewa A Grabowska, Willey Liao, Bridget Riley-Gillis, Dayna M Oschwald, Lan Wang, Jacob E Joergens, Alan H Shih, Franck Rapaport, Shengqing Gu, Francesca Voza, Takashi Asai, Benjamin G Neel, Michael G Kharas, Mithat Gonen, Ross L Levine, Stephen D Nimer
t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO-driven mouse models of leukemia with the mutational profiles of human AML patients...
January 11, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26011822/applying-comprehensive-environmental-assessment-to-research-planning-for-multiwalled-carbon-nanotubes-refinements-to-inform-future-stakeholder-engagement
#18
Christina M Powers, Khara Grieger, Connie A Meacham, Meredith Lassiter Gooding, Jeffrey S Gift, Geniece M Lehmann, Christine O Hendren, J Michael Davis, Lyle Burgoon
Risk assessments and risk management efforts to protect human health and the environment can benefit from early, coordinated research planning by researchers, risk assessors, and risk managers. However, approaches for engaging these and other stakeholders in research planning have not received much attention in the environmental scientific literature. The Comprehensive Environmental Assessment (CEA) approach under development by the United States Environmental Protection Agency (USEPA) is a means to manage complex information and input from diverse stakeholder perspectives on research planning that will ultimately support environmental and human health decision making...
January 2016: Integrated Environmental Assessment and Management
https://www.readbyqxmd.com/read/25936483/the-2015-canadian-hypertension-education-program-recommendations-for-blood-pressure-measurement-diagnosis-assessment-of-risk-prevention-and-treatment-of-hypertension
#19
REVIEW
Stella S Daskalopoulou, Doreen M Rabi, Kelly B Zarnke, Kaberi Dasgupta, Kara Nerenberg, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Donald W McKay, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, G V Ramesh Prasad, Marcel Lebel, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman R C Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Pierre Larochelle, Lawrence A Leiter, Charlotte Jones, Richard I Ogilvie, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Robert J Petrella, Swapnil Hiremath, James A Stone, Denis Drouin, Kim L Lavoie, Pavel Hamet, George Fodor, Jean C Grégoire, Anne Fournier, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Geneviève Benoit, Janusz Feber, Kevin C Harris, Luc Poirier, Raj S Padwal
The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended...
May 2015: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/25774828/transformation-of-the-intestinal-epithelium-by-the-msi2-rna-binding-protein
#20
Shan Wang, Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Fan Li, Kimberly Parada, Shilpa Rao, Gerard Minuesa, Yarden Katz, Brian D Gregory, Michael G Kharas, Zhengquan Yu, Christopher J Lengner
The MSI2 RNA-binding protein is a potent oncogene playing key roles in haematopoietic stem cell homeostasis and malignant haematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss-of-function abrogates colorectal cancer cell growth. MSI2 gain-of-function in the intestinal epithelium in a drug-inducible mouse model is sufficient to phenocopy many of the morphological and molecular consequences of acute loss of the APC tumour suppressor in the intestinal epithelium in a Wnt-independent manner...
March 16, 2015: Nature Communications
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