The Experts below are selected from a list of 154872 Experts worldwide ranked by ideXlab platform
David C James - One of the best experts on this subject based on the ideXlab platform.
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identification of molecular characteristics correlated with glioblastoma sensitivity to egfr kinase inhibition through use of an intracranial xenograft Test Panel
Molecular Cancer Therapeutics, 2007Co-Authors: Jann N Sarkaria, Lin Yang, Brett L Carlson, Mark A Schroeder, Gaspar J Kitange, Patrick T Grogan, Evanthia Galanis, Caterina Giannini, Eduard B Dinca, David C JamesAbstract:In the current study, we examined a Panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR. [Mol Cancer Ther 2007;6(3):1167–74]
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identification of molecular characteristics correlated with glioblastoma sensitivity to egfr kinase inhibition through use of an intracranial xenograft Test Panel
Molecular Cancer Therapeutics, 2007Co-Authors: Jann N Sarkaria, Lin Yang, Brett L Carlson, Mark A Schroeder, Gaspar J Kitange, Patrick T Grogan, Evanthia Galanis, Caterina Giannini, Eduard B Dinca, David C JamesAbstract:In the current study, we examined a Panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR.
Alison Fellgett - One of the best experts on this subject based on the ideXlab platform.
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molecular markers for tolerance of european ash fraxinus excelsior to dieback disease identified using associative transcriptomics
Scientific Reports, 2016Co-Authors: Andrea L Harper, Lenka Havlickova, Fiona Fraser, Martin Trick, Lene Rostgaard Nielsen, Lea Vig Mckinney, Lihong Wang, Yi Li, Alison FellgettAbstract:Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity Panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a Test Panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback.
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molecular markers for tolerance of european ash fraxinus excelsior to dieback disease identified using associative transcriptomics
Scientific Reports, 2016Co-Authors: Andrea L Harper, Lenka Havlickova, Fiona Fraser, Martin Trick, Lene Rostgaard Nielsen, Lea Vig Mckinney, Lihong Wang, Yi Li, Alison FellgettAbstract:Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity Panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a Test Panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback.
Soma Mohammed - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a von willebrand factor three Test Panel and chemiluminescent based assay system for identification of and therapy monitoring in von willebrand disease
Thrombosis Research, 2016Co-Authors: Emmanuel J Favaloro, Soma MohammedAbstract:Abstract von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing of VWD has important management implications and requires a wide range of Tests, including VWF antigen (VWF:Ag) and various activities, involving differential identification of qualitative vs quantitative VWF defects. We have assessed a new hemostasis instrument, the chemiluminescent assay based ACL AcuStar™, and an associated HemosIL AcuStar three Test Panel comprising VWF:Ag, VWF ristocetin cofactor (VWF:RCo) and VWF collagen binding (VWF:CB) (Instrumentation Laboratory, Bedford, Ma. USA) for ability to identify VWD, to help provisionally type VWD, and for potential use in therapy monitoring. This Test system was compared to previously evaluated and validated Test systems including VWF:RCo on CS-5100 and BCS analyzers, the new Siemens INNOVANCE assay (VWF Ac) on CS-5100, and VWF:Ag and VWF:CB assays performed by automated ELISA. We employed a large total sample Test set (n = 535) comprising plasma and platelet-lysate samples from individuals with and without VWD, some on treatment, normal plasmas, and normal and pathological controls. We also evaluated desmopressin (DDAVP) responsiveness, plus differential sensitivity to reduction in high molecular weight (HMW) VWF. The chemiluminescent Test Panel (VWF:Ag, VWF:RCo, VWF:CB) showed good comparability to similar assays performed by alternate methods, and broadly similar data for identification of VWD, provisional VWD type identification, DDAVP and VWD therapy, and HMW VWF sensitivity, although some notable differences were evident. The chemiluminescent system showed best low level VWF sensitivity, and lowest inter-assay variability, compared to all other systems. In conclusion, we have validated theACL AcuStar and the chemiluminescent HemosIL AcuStar VWF Test Panel for use in VWD diagnostics, and have identified some favorable characteristics that may improve the future diagnosis of VWD.
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evaluation of a von willebrand factor three Test Panel and chemiluminescent based assay system for identification of and therapy monitoring in von willebrand disease
Thrombosis Research, 2016Co-Authors: Emmanuel J Favaloro, Soma MohammedAbstract:von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing of VWD has important management implications and requires a wide range of Tests, including VWF antigen (VWF:Ag) and various activities, involving differential identification of qualitative vs quantitative VWF defects. We have assessed a new hemostasis instrument, the chemiluminescent assay based ACL AcuStar™, and an associated HemosIL AcuStar three Test Panel comprising VWF:Ag, VWF ristocetin cofactor (VWF:RCo) and VWF collagen binding (VWF:CB) (Instrumentation Laboratory, Bedford, Ma. USA) for ability to identify VWD, to help provisionally type VWD, and for potential use in therapy monitoring. This Test system was compared to previously evaluated and validated Test systems including VWF:RCo on CS-5100 and BCS analyzers, the new Siemens INNOVANCE assay (VWF Ac) on CS-5100, and VWF:Ag and VWF:CB assays performed by automated ELISA. We employed a large total sample Test set (n=535) comprising plasma and platelet-lysate samples from individuals with and without VWD, some on treatment, normal plasmas, and normal and pathological controls. We also evaluated desmopressin (DDAVP) responsiveness, plus differential sensitivity to reduction in high molecular weight (HMW) VWF. The chemiluminescent Test Panel (VWF:Ag, VWF:RCo, VWF:CB) showed good comparability to similar assays performed by alternate methods, and broadly similar data for identification of VWD, provisional VWD type identification, DDAVP and VWD therapy, and HMW VWF sensitivity, although some notable differences were evident. The chemiluminescent system showed best low level VWF sensitivity, and lowest inter-assay variability, compared to all other systems. In conclusion, we have validated theACL AcuStar and the chemiluminescent HemosIL AcuStar VWF Test Panel for use in VWD diagnostics, and have identified some favorable characteristics that may improve the future diagnosis of VWD.
Fiona Fraser - One of the best experts on this subject based on the ideXlab platform.
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molecular markers for tolerance of european ash fraxinus excelsior to dieback disease identified using associative transcriptomics
Scientific Reports, 2016Co-Authors: Andrea L Harper, Lenka Havlickova, Fiona Fraser, Martin Trick, Lene Rostgaard Nielsen, Lea Vig Mckinney, Lihong Wang, Yi Li, Alison FellgettAbstract:Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity Panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a Test Panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback.
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molecular markers for tolerance of european ash fraxinus excelsior to dieback disease identified using associative transcriptomics
Scientific Reports, 2016Co-Authors: Andrea L Harper, Lenka Havlickova, Fiona Fraser, Martin Trick, Lene Rostgaard Nielsen, Lea Vig Mckinney, Lihong Wang, Yi Li, Alison FellgettAbstract:Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity Panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a Test Panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback.
Lin Yang - One of the best experts on this subject based on the ideXlab platform.
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pten loss does not predict for response to rad001 everolimus in a glioblastoma orthotopic xenograft Test Panel
Clinical Cancer Research, 2008Co-Authors: Lin Yang, Michelle J Clarke, Brett L Carlson, Ann C Mladek, Mark A Schroeder, Paul A Decker, Gaspar J Kitange, Patrick T Grogan, Jennie M Goble, Joon H UhmAbstract:Purpose: Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). Experimental Design: To Test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Results: Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. Conclusion: These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme.
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identification of molecular characteristics correlated with glioblastoma sensitivity to egfr kinase inhibition through use of an intracranial xenograft Test Panel
Molecular Cancer Therapeutics, 2007Co-Authors: Jann N Sarkaria, Lin Yang, Brett L Carlson, Mark A Schroeder, Gaspar J Kitange, Patrick T Grogan, Evanthia Galanis, Caterina Giannini, Eduard B Dinca, David C JamesAbstract:In the current study, we examined a Panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR. [Mol Cancer Ther 2007;6(3):1167–74]
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identification of molecular characteristics correlated with glioblastoma sensitivity to egfr kinase inhibition through use of an intracranial xenograft Test Panel
Molecular Cancer Therapeutics, 2007Co-Authors: Jann N Sarkaria, Lin Yang, Brett L Carlson, Mark A Schroeder, Gaspar J Kitange, Patrick T Grogan, Evanthia Galanis, Caterina Giannini, Eduard B Dinca, David C JamesAbstract:In the current study, we examined a Panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR.
