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Charles David James – One of the best experts on this subject based on the ideXlab platform.

  • p08 01 tumor cell subpopulation changes during intracranial glioblastoma patient derived xenograft recurrence following radiation temozolomide or combination therapy
    Neuro-oncology, 2017
    Co-Authors: Atique U. Ahmed, Craig Horbinski, Roger Stupp, Maciej S. Lesniak, Charles David James

    Abstract:

    AbstractWe’ve established a model for recurrent GBM by treating mice bearing previously untreated, luciferase-modified, intracranial GBM PDX, with radiation (RT) (2 Gy/day, M-F), temozolomide (TMZ) only (10 mg/kg/day, M-F), or concurrent RT/TMZ. PDX respond to treatment by showing a reduced rate of increase in tumor bioluminescence (RT only), or decreased tumor bioluminescence (TMZ only or RT/TMZ), but with eventual tumor growth requiring Animal Euthanasia at 5.5 (RT only), 26.5 (TMZ only), or 38 (RT/TMZ) days beyond the median survival of untreated control Animal subjects. All survival extensions are significant relative to untreated control mice (p<0.05). To examine the effects of treatment on tumor cell subpopulations in intracranial PDX, we employed flow cytometric analyses of human leukocyte antigen (HLA) positive GBM cells, using a panel of markers (CD133, CD15, ABCG2, SOX2, EZH2, HIF1A, MGMT, and H3K27me3). RT alone did not cause a significant enrichment for any specific subpopulation, as identified using the markers indicated above. In contrast, PDX exposed to TMZ monotherapy or RT/TMZ combination therapy showed enrichment for CD133+HIF1A+ cells (p<0.005). PDX treated with RT/TMZ were also enriched for CD133+CD15+, and additionally showed enrichment for CD133+SOX2+ and CD133+EZH2+ cells (p<0.005 for each). Perhaps not so surprisingly, recurrent tumors that had been treated with TMZ or RT/TMZ showed increased cellular positivity for MGMT (Control 0.78% vs. TMZ 3.4% p<0.005 and RT/TMZ 4.3% p<0.0005), though, paradoxically, these tumors also showed increased cellular positivity for EZH2 (Control 0.38% vs. TMZ 3.0% p=ns and RT/TMZ 7.8% p<0.0005) and a product of EZH2 activity, H3K27me3 (Control 0.55% vs. TMZ 18.2% p<0.0005 and RT/TMZ 4.3% p=ns), which is associated with transcriptional suppression. Corresponding immunohistochemical analysis is ongoing, with results to be presented at the meeting. In total, our data indicate that, in recurrent tumors, cell subpopulation selection/enrichment depends on the type of therapy administered, which should, in turn, influence the selection of salvage therapy for treating recurrent GBM. Supported by NIH grants NS095642 and NS096376.

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  • P08.01 Tumor cell subpopulation changes during intracranial glioblastoma patient derived xenograft recurrence following radiation, temozolomide, or combination therapy
    Neuro-Oncology, 2017
    Co-Authors: Atique U. Ahmed, Craig Horbinski, Roger Stupp, Maciej S. Lesniak, Charles David James

    Abstract:

    AbstractWe’ve established a model for recurrent GBM by treating mice bearing previously untreated, luciferase-modified, intracranial GBM PDX, with radiation (RT) (2 Gy/day, M-F), temozolomide (TMZ) only (10 mg/kg/day, M-F), or concurrent RT/TMZ. PDX respond to treatment by showing a reduced rate of increase in tumor bioluminescence (RT only), or decreased tumor bioluminescence (TMZ only or RT/TMZ), but with eventual tumor growth requiring Animal Euthanasia at 5.5 (RT only), 26.5 (TMZ only), or 38 (RT/TMZ) days beyond the median survival of untreated control Animal subjects. All survival extensions are significant relative to untreated control mice (p

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Catherine Ghezzi – One of the best experts on this subject based on the ideXlab platform.

  • Sympathetic cardiac function in early sepsis: Noninvasive evaluation with [123I]-meta-iodobenzylguanidine (123I-MIBG) in vivo SPECT imaging
    Journal of Nuclear Cardiology, 2018
    Co-Authors: Romain Clerc, Alexis Broisat, Pascale Perret, Daniel Fagret, Laurent Riou, Sophia Doll, Audrey Soubies, Marie-dominique Desruet, Carole Schwebel, Catherine Ghezzi

    Abstract:

    BACKGROUND: Sympathetic system abnormalities have been reported in sepsis-related cardiac dysfunction. The present study aimed at evaluating the potential of the norepinephrine radiolabeled analogue [123I]-meta-iodobenzylguanidine (123I-MIBG) for the noninvasive assessment of modifications in cardiac sympathetic activity occurring in lipopolysaccharide (LPS)-induced experimental acute sepsis by single-photon emission computed tomographic imaging (SPECT). METHODS AND RESULTS: Sepsis was induced in male Wistar rats by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide (n = 16), whereas control Animals (n = 7) were injected with vehicle (NaCl 0.9%). Echocardiography in LPS-injected Animals (n = 8) demonstrated systolic and diastolic cardiac dysfunction. 123I-MIBG was injected 1 hour after LPS or vehicle administration (n = 8 and 7, respectively), and in vivo SPECT imaging was performed early and late (20 and 180 minutes) after tracer injection prior to Animal Euthanasia and ex vivo assessment of 123I-MIBG biodistribution. Global and 17-segment SPECT image analysis indicated that early 123I-MIBG activity was not affected by LPS treatment, whereas late cardiac tracer activity was significantly decreased in LPS-treated Animals. Consequently, the cardiac washout of 123I-MIBG was significantly higher in LPS-treated (63.3% ± 4.0%) than that in control Animals (56.7% ± 5.8%) (P < .05). CONCLUSION: Sepsis-induced modifications in cardiac sympathetic nervous system activity were evidenced by noninvasive in vivo 123I-MIBG SPECT imaging.

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  • Periaortic Brown Adipose Tissue as a Major Determinant of [18F]-Fluorodeoxyglucose Vascular Uptake in Atherosclerosis-Prone, ApoE−/− Mice
    PLoS ONE, 2014
    Co-Authors: Jakub Toczek, Alexis Broisat, Pascale Perret, M.-d. Desruet, Daniel Fagret, Laurent Riou, Catherine Ghezzi

    Abstract:

    BACKGROUND [18F]-fluorodeoxyglucose (FDG) has been suggested for the clinical and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG uptake in brown adipose tissue (BAT) has been observed both in humans and mice. The objective of the present study was to investigate the influence of periaortic BAT on apolipoprotein E-deficient (apoE-/-) mouse atherosclerotic lesion imaging with FDG. METHODS ApoE-/- mice (36 ± 2 weeks-old) were injected with FDG (12 ± 2 MBq). Control Animals (Group A, n = 7) were injected conscious and kept awake at room temperature (24°C) throughout the accumulation period. In order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n = 6) Animals were injected under anaesthesia at 37°C and Group C Animals were additionally pre-treated with propranolol. PET/CT acquisitions were performed prior to Animal Euthanasia and ex vivo analysis of FDG biodistribution. RESULTS Autoradiographic imaging indicated higher FDG uptake in atherosclerotic lesions than in the normal aortic wall (all groups, P

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Atique U. Ahmed – One of the best experts on this subject based on the ideXlab platform.

  • p08 01 tumor cell subpopulation changes during intracranial glioblastoma patient derived xenograft recurrence following radiation temozolomide or combination therapy
    Neuro-oncology, 2017
    Co-Authors: Atique U. Ahmed, Craig Horbinski, Roger Stupp, Maciej S. Lesniak, Charles David James

    Abstract:

    AbstractWe’ve established a model for recurrent GBM by treating mice bearing previously untreated, luciferase-modified, intracranial GBM PDX, with radiation (RT) (2 Gy/day, M-F), temozolomide (TMZ) only (10 mg/kg/day, M-F), or concurrent RT/TMZ. PDX respond to treatment by showing a reduced rate of increase in tumor bioluminescence (RT only), or decreased tumor bioluminescence (TMZ only or RT/TMZ), but with eventual tumor growth requiring Animal Euthanasia at 5.5 (RT only), 26.5 (TMZ only), or 38 (RT/TMZ) days beyond the median survival of untreated control Animal subjects. All survival extensions are significant relative to untreated control mice (p<0.05). To examine the effects of treatment on tumor cell subpopulations in intracranial PDX, we employed flow cytometric analyses of human leukocyte antigen (HLA) positive GBM cells, using a panel of markers (CD133, CD15, ABCG2, SOX2, EZH2, HIF1A, MGMT, and H3K27me3). RT alone did not cause a significant enrichment for any specific subpopulation, as identified using the markers indicated above. In contrast, PDX exposed to TMZ monotherapy or RT/TMZ combination therapy showed enrichment for CD133+HIF1A+ cells (p<0.005). PDX treated with RT/TMZ were also enriched for CD133+CD15+, and additionally showed enrichment for CD133+SOX2+ and CD133+EZH2+ cells (p<0.005 for each). Perhaps not so surprisingly, recurrent tumors that had been treated with TMZ or RT/TMZ showed increased cellular positivity for MGMT (Control 0.78% vs. TMZ 3.4% p<0.005 and RT/TMZ 4.3% p<0.0005), though, paradoxically, these tumors also showed increased cellular positivity for EZH2 (Control 0.38% vs. TMZ 3.0% p=ns and RT/TMZ 7.8% p<0.0005) and a product of EZH2 activity, H3K27me3 (Control 0.55% vs. TMZ 18.2% p<0.0005 and RT/TMZ 4.3% p=ns), which is associated with transcriptional suppression. Corresponding immunohistochemical analysis is ongoing, with results to be presented at the meeting. In total, our data indicate that, in recurrent tumors, cell subpopulation selection/enrichment depends on the type of therapy administered, which should, in turn, influence the selection of salvage therapy for treating recurrent GBM. Supported by NIH grants NS095642 and NS096376.

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  • P08.01 Tumor cell subpopulation changes during intracranial glioblastoma patient derived xenograft recurrence following radiation, temozolomide, or combination therapy
    Neuro-Oncology, 2017
    Co-Authors: Atique U. Ahmed, Craig Horbinski, Roger Stupp, Maciej S. Lesniak, Charles David James

    Abstract:

    AbstractWe’ve established a model for recurrent GBM by treating mice bearing previously untreated, luciferase-modified, intracranial GBM PDX, with radiation (RT) (2 Gy/day, M-F), temozolomide (TMZ) only (10 mg/kg/day, M-F), or concurrent RT/TMZ. PDX respond to treatment by showing a reduced rate of increase in tumor bioluminescence (RT only), or decreased tumor bioluminescence (TMZ only or RT/TMZ), but with eventual tumor growth requiring Animal Euthanasia at 5.5 (RT only), 26.5 (TMZ only), or 38 (RT/TMZ) days beyond the median survival of untreated control Animal subjects. All survival extensions are significant relative to untreated control mice (p

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