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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 | Visual function in 6 to 7 year-old children born extremely preterm: a populationbased study显示文摘 | Haugen OH Nepstad L Standal OA | 2012 | Acta Ophthalmol2012，90，5： | 1 |
| 3 | Amazon drought and its implications for forest flammability and tree growth : a basin-wide analysis 显示文摘 | NEPSTAD D LEFEBVRE P SILVA U L D | 2004 | Global Change Biology2004，10，： | 1 |
| 4 | Vertical patterns of soil water uptake by plants in a primary forest and an abandoned pasture in the eastern Amazon:An isotopic approach显示文摘 | Moreira M Z Sternberg L S L Nepstad D C | 2000 | Plant and Soil2000，222，： | 1 |
| 5 | Effects of an exper imental drought on soil emissions of carbon dioxide, meth ane,nitrous oxide, and nitric oxide in a moist tropical forest 显示文摘 | Davidson E A Ishida F Y Nepstad D C | 2004 | Global Change Biology2004，10，： | 1 |
| 6 | The role of deep roots in the hydrological and carbon cycles of Amazonian forests and pastures 显示文摘 | Nepstad D C de Carvalho C R Davidson E A | 1994 | Nature1994，372，6507： | 1 |
| 7 | The end of deforestation in the brazilian amazon显示文摘 | Nepstad D Soares-Filho B S Merry F | 2009 | Science2009，326，5958： | 1 |
| 8 | The role of deep roots in the hydrological and carbon cycles of Amazonian forests and pastures显示文摘 | NEPSTAD D C de CARVALHO C R DAVIDSON E A | 1994 | Nature1994，372，： | 1 |
| 9 | Contribution of vines to the evapotranspiration of a secondary forest in eastern Amazonia 显示文摘 | Restore T G Nepstad D C | 2001 | Plant and Soil2001，236，2： | 1 |
| 10 | Vertical patterns of soil water uptake by plants in a primary forest and an abandoned pasture in the Eastern Amazon: an isotopic approach显示文摘 | Moreira M Z Steinberg L D L Nepstad D C | 2000 | Plant and Soil2000，222，： | 1 |
| 11 | The role of deep roots in the hydrological and carbon cycles of Amazonian forests and pastures显示文摘 | Nepstad DC de Carvalho CR Davidson EA | 1994 | Nature1994，372，： | 1 |
| 12 | The Potential EcologicalCosts and Co-Benefits of REDD:A Critical Review and Case Study fromthe Amazon Region显示文摘 | STICKLER C M NEPSTAD D C COE M T | 2009 | Global Change Biology2009，15，： | 1 |
| 13 | Deep soil moisture storage and transpiration in forests and pastures of seasonallydry amazonia显示文摘 | Jipp P H Nepstad D C Cassel D K | 1998 | Climatic Change1998，39，23： | 1 |
| 14 | Effects of an experimental drought and recovery on soil emission of carbon dioxide,methane,nitrous oxide,and nitric oxide in a moist tropical forest显示文摘 | Davidson E A Nepstad D C Ishida F Y | 2008 | Global Change Biology2008，14，： | 1 |
| 15 | Nonviolent Resistance in the Arab Spring:The Critical Role of Military-Opposition Alliances显示文摘 | Sharon Erickson Nepstad | | 0，，04： | 1 |
| 16 | Modeling conservation in the Amazon Basin显示文摘 | Soares-Filo Garcia R A Nepstad D C | 2006 | Nature2006，440，5： | 1 |
| 17 | Drought effects on litter fall, wood production and belowground carbon cycling in an Amazon forest: results of a through fall reduction experiment 显示文摘 | Brando P M Nepstad D C Davidson E A | 2008 | Philosophical Transactions of the Royal Society B: Biological Sciences2008，363，1498： | 1 |
| 18 | Rainfall exclusion in an eastern Amazonian forest alters soil water movement and depth of water uptake 显示文摘 | Romero-Sahos H Sternberg L S L Moreira M Z Nepstad D C | 2005 | American Journal of Botany2005，92，3： | 1 |
| 19 | Increased an- tileukemic effects in human acute myeloid leukemia by com- bining HSPT0 and HSP90 inhihitors显示文摘 | Reikvam H Nepstad I Sulen A | 2013 | Expert Opin In- vestig Drugs2013，22，5： | 1 |
| 20 | Mutiny and Nonviolence in the Arab Spring:Exploring Military Defections and Loyalty in Egypt,Bahrain,and Syria显示文摘 | Sharon Erickson Nepstad | | 0，，03： | 1 |
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