3篇
您的检索式：作者名="Jeremy Shaw"
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| 1 | Development of Hepatocellular Carcinoma in a Murine Model of Nonalcoholic Steatohepatitis Induced by Use of a High-Fat/Fructose Diet and Sedentary Lifestyle显示文摘 | Joanna K. Dowman Laurence J. Hopkins Gary M. Reynolds Nikolaos Nikolaou Matthew J. Armstrong Jean C. Shaw Diarmaid D. Houlihan Patricia F. Lalor Jeremy W. Tomlinson Stefan G. Hübscher Philip N. Newsome | 2014 | The American Journal of Pathology2014，，： | 1 |
| 2 | STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia显示文摘The pathogenesis of chronic lymphocytic leukemia(CLL)is poorly understood and it remains incurable with current therapies.We have previously shown that nanoliposomal C6-ceramide(CNL)is an effective therapy in an in vivo murine model of CLL.However,the key signaling pathways mediating CNL-induced cell death in CLL remains unknown.We hypothesized that CNL targets STAT3,a critical regulator of hematopoietic biology.We observed that CNL treatment reduced phosphorylated STAT3 at both Y705 and S727 residues in CLL cell lines and patient cells.This,in turn,reduced STAT3 transcriptional activity and expression of critical STAT3-dependent survival factors like Mcl-1 and survivin.The effect of CNL on STAT3 was further confirmed ex vivo as shown by reduced STAT3 phosphorylation in xenograft tumors obtained from mice treated with CNL.CNL suppressed STAT3 phosphorylation at Y705 and S727 through reduction in BTK activity and MEK1/2 kinase/PKC activities,respectively.Moreover,a synergistic reduction in CLL cell viability was observed on co-treatment with CNL and the BTK inhibitor,ibrutinib.Expression of an oncogenic form of STAT3 conferred partial resistance to CNL,providing confirmation that STAT3 mediates CNL-induced cell death.Taken together,these findings provide the first body of evidence demonstrating ceramide regulation of STAT3 phosphorylation.These results are also the first to demonstrate an effect of ceramide on BTK,a critical kinase mediating the B-cell receptor signaling in CLL cells and suggest a novel and synergistic combination of CNL and BTK inhibitors for CLL treatment. | Ushma A Doshi Jeremy Shaw Todd E Fox David F Claxton Thomas P Loughran Mark Kester | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 0 |
| 3 | Unintended consequences of rangeland conservation structures显示文摘By the 1930's vast areas of the western US were severely degraded by overgrazing and erosion.In response,Congress authorized conservation work including the construction of erosion control and water storage,distribution,and conveyance structures.Thousands of structures such as check dams,water spreaders,and contour berms were built during the 1930s and 40s to control water and sediment in an attempt to restore degraded rangelands.However,across most of the western US,these soil and water conservation measures were implemented without the benefit of local hydrologic data or technical design guidance.Many of the established conservation practices had been developed for humid regions and were untested for use in semiarid areas that are characterized by highly variable rainfall and flash floods.As a result,many structures proved ineffective and were subsequently abandoned.Even in cases where structures were effective,many never received maintenance after their initial construction.Although structurally compromised,abandoned and unmaintained structures continue to alter surface runoff patterns and can greatly exacerbate erosion.Four sites in Arizona,USA were selected to charac-terize the multi-decadal impacts of conservation structures.Breaches have formed in 100%of contour berms(n=67)while 96%of water spreader berms(n=26)were compromised.Localized failures in these structures has created concentrated flow paths that reorganized routing of runoff and sediment thus transforming sheetflow regimes to concentrated flow regimes.This study emphasizes the unin-tended legacy impacts of soil and water conservation structures and highlights their role as a potential constraint on contemporary resource management. | Mary H.Nichols Jeremy R Shaw William K.Brandau | 2021 | International Soil and Water Conservation Research2021，9，1： | 0 |
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