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| 1 | Effects of insulin and pathway inhibitors on the PI3K-Akt- mTOR phosphorylation profile in acute myeloid leukemia cells显示文摘The phosphatidylinositol 3-kinase(PI3K)-Akt-mechanistic target of rapamycin(mTOR)pathway is constitutively activated in human acute myeloid leukemia(AML)cells and is regarded as a possible therapeutic target.Insulin is an agonist of this pathway and a growth factor for AML cells.We characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive patients.The overall results showed that insulin significantly increased the phosphorylation of all investigated mediators.However,insulin effects on the pathway activation profile varied among patients,and increased phosphorylation in all mediators was observed only in a minority of patients;in other patients,insulin had divergent effects.Global gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation,transcriptional regulation,RNA metabolism,and cellular metabolism.Strong insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic inhibitors.PI3K,Akt,and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin,although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 phosphorylation.For Akt inhibition,the phosphorylation of upstream mediators was generally increased or unaltered.In contrast,mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 phosphorylation.In conclusion,the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets,and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting. | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Elise Aasebø Maria Hernandez-Valladares Karen Marie Hagen Kristin Paulsen Rye Frode SBerven Frode Selheim Håkon Reikvam Øystein Bruserud | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 4 |
| 2 | Clinical evaluation of a chemiluminescence immunoassay for determination of immunoglobulin G avidity to human cytomegalovirus显示文摘 | MARIA GR GIOVANNA G | 2004 | Clinical and Diagnostic Laboratory Immunology2004，11，： | 1 |
| 3 | FOXP3 Expression in Hepatitis C Virus–Specific CD4 + T Cells During Acute Hepatitis C显示文摘 | Malte H.J. Heeg Axel Ulsenheimer Norbert H. Grüner Reinhart Zachoval Maria–Christina Jung J. Tilman Gerlach Bijan Raziorrouh Winfried Schraut Sophia Horster Teresa Kauke Michael Spannagl Helmut M. Diepolder | 2009 | Gastroenterology2009，，4： | 1 |
| 4 | Isoenzymes detect variation in populations of Triatoma brasiliensis ( Hemiptera: Reduviidae: Triatominae) 显示文摘 | Costa J Maria GR Freitas S etal | 1997 | Memorias do instituto Oswaldo Cruz1997，92，4： | 1 |
| 5 | Quantification of human eytomegalovirus DNA in amniotic fluid of mothers of congenitally infected fetuses 显示文摘 | Maria GR Maurizio Z Milena F | 1999 | J Clin Microbiol1999，37，10： | 1 |
| 6 | Liver fibrosis and chronic viral hepatitis显示文摘 | GABRIELA GR MARIA CG | 2007 | Arch Med Res2007，38，： | 1 |
| 7 | Platelet-Derived Microvesicles: Multitalented Participants in Intercellular Communication显示文摘 | Maria Aatonen Mikaela Gr?nholm Pia Siljander | 2012 | Semin Thromb Hemost2012，，01： | 1 |
| 8 | Clinical Evaluation of a Chemiluminescence Immunoassay for Determination of Immunoglobulin G Avidity to Human Cytomegalovirus显示文摘 | Maria GR Giovanna G Giuseppe G | 2004 | Clinical and Diagnostic Laboratory Immunology2004，11，4： | 1 |
| 9 | Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns显示文摘 | Heike Allgayer Rudolf Babic Klaus Uwe Grützner Bianca C. M. Beyer Anwar Tarabichi Friedrich Wilhelm Schildberg Markus Maria Heiss | 1998 | Clinical and Experimental Metastasis1998，，1： | 1 |
| 10 | EGFR targeting drugs in the treatment of head and neck squamous cell carcinoma显示文摘 | Maria Sundvall Anna Karrila Janne Nordberg Reidar Gré nman Klaus Elenius | 2010 | Expert Opinion on Emerging Drugs2010，，： | 1 |
| 11 | Development and evaluation of standardized protocol to prevent nasoenteral tube obstruction in cardiac patients requiring enteral nutrition with restricted fluid volumes显示文摘 | Claudia ST Matsuba Maria GR De Gutiérrez Iveth Y Whitaker | 2007 | Journal of Clinical Nursing2007，，10： | 1 |
| 12 | Downregulation of organic cation transporter 1 (SLC22A1) is associatedwith tumor progression and reduced patient survival in human cholangiocellularcarcinoma显示文摘 | Anja Lautem Michael Heise Andreas Gr?sel Maria Hoppe?Lotichius Nina Weiler Daniel Foltys Johanna Knapstein J?rn Schattenberg Arno Schad Anca Zimmermann Gerd Otto Hauke Lang Peter Galle Marcus Schuchmann Tim Zimmermann | 2013 | International Journal of Oncology2013，，4： | 1 |
| 13 | Silva Determination of calcium, magnesium and zinc in lubricating oils by flame atomic absorption spectrometry using a three-component solution显示文摘 | Ariane VZ Alexandre de J Maria GR | 2010 | Talanta2010，83，2： | 1 |
| 14 | FOXP3 Expression in Hepatitis C Virus–Specific CD4 + T Cells During Acute Hepatitis C显示文摘 | Malte H.J. Heeg Axel Ulsenheimer Norbert H. Grüner Reinhart Zachoval Maria–Christina Jung J. Tilman Gerlach Bijan Raziorrouh Winfried Schraut Sophia Horster Teresa Kauke Michael Spannagl Helmut M. Diepolder | 2009 | Gastroenterology2009，，4： | 1 |
| 15 | Type 1 T regulatory cells显示文摘 | Maria GR Rosa B Claudio B | 2001 | Immunol Rev2001，182，1： | 1 |
| 16 | The role of different subsets of T regulatory cells in controlling autoimmunity显示文摘 | Maria GR Megan KL | 2000 | Current Opinion in Immunology2000，12，： | 1 |
| 17 | Human cytomegalovirus UL131A-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes显示文摘 | HAHN G MARIA GR MARCO P | 2004 | J Virol2004，78，10： | 1 |
| 18 | Isolation and characterization of physicochemical and material properties of arabinoxylans from barley husks显示文摘 | Anders H?ije Maria Gr?ndahl Kristoffer T?mmeraas Paul Gatenholm | 2005 | Carbohydrate Polymers2005，，3： | 1 |
| 19 | Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns显示文摘 | Heike Allgayer Rudolf Babic Klaus Uwe Grützner Bianca C. M. Beyer Anwar Tarabichi Friedrich Wilhelm Schildberg Markus Maria Heiss | 1998 | Clinical and Experimental Metastasis1998，，1： | 1 |
| 20 | Molecular analysis of Vibrio cholerae O1, 0139, non -O1, and non -0139 Strains:Clinical and environmental isolates显示文摘 | DV Singh Maria H Matte GR Matte | 2001 | Appl Environ Microbiol2001，67，2： | 1 |
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