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George P Studzinski - One of the best experts on this subject based on the ideXlab platform.
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the pan caspase inhibitor q vd oph has anti leukemia effects and can interact with vitamin d analogs to increase hpk1 signaling in aml cells
Leukemia Research, 2012Co-Authors: Xiangwen Chendeutsch, Andrzej Kutner, Jonathan S Harrison, George P StudzinskiAbstract:Caspase function is known to be essential for cell death by apoptosis, but it is now increasingly recognized that these proteases also play important roles in other cellular events. Here we report for the first time that inhibition of cellular caspase activity can induce Differentiation of AML blasts, and can enhance vitamin D-induced cell Differentiation of these cells. This was studied in blasts obtained from nine patients with AML and one patient with CML by ex vivo culture in the presence of Q-VD-OPh (QVD), a pan caspase inhibitor. Cell Differentiation was manifested by the expression of markers of monocytic Differentiation CD11b and CD14. Differentiation induced by 1α,25-dihydroxyvitamin D3 (1,25D) or its analogs PRI-1906 and PRI-2191 was enhanced by QVD to a varying degree, depending on the subtype of the leukemia. QVD and 1,25D-induced Differentiation was accompanied by increased signaling by Hematopoietic Progenitor Kinase 1(HPK1), and the expression of transcription factors known to be involved in monocytic Differentiation was increased. Although the magnitude and nature of these changes were not invariable, it is clear that caspase inhibitors warrant attention as components of Differentiation Therapy of leukemia, perhaps in combination with derivatives of vitamin D.
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synergistic antileukemic activity of carnosic acid rich rosemary extract and the 19 nor gemini vitamin d analogue in a mouse model of systemic acute myeloid leukemia
Oncology, 2008Co-Authors: Ayelet Shabtay, Hagar Sharabani, Zeev Barvish, Michael Kafka, Doron Amichay, Joseph Levy, Yoav Sharoni, Milan R Uskokovic, George P Studzinski, Michael DanilenkoAbstract:Objective: Differentiation Therapy with the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), is a promising approach to treatment of acute myelo
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akt pathway is activated by 1 25 dihydroxyvitamin d3 and participates in its anti apoptotic effect and cell cycle control in differentiating hl60 cells
Cell Cycle, 2006Co-Authors: Yingyu Zhang, Jing Zhang, George P StudzinskiAbstract:Differentiation Therapy for cancer is a developing treatment modality that is based on the anti-proliferative effects associated with Differentiation of the malignant cells. 1,25-dihydroxyvitamin D3 (1,25D) and its analogs are currently being evaluated clinically, alone or in combination with other agents, for treatment of several neoplastic diseases, but their usefulness as single agents may be limited by the enhancement of cell survival in some cell types exposed to 1,25D. In this study we evaluated the role of AKT signaling pathway, known to be anti-apoptotic in diverse cell types, in enhancing the survival of human leukemia HL60 cells induced to differentiate with 1,25D. We found that the phosphorylation and activity of AKT, as well as of its down-stream targets, are increased after the exposure to 1,25D. Treatment of HL60 cells with PI3K inhibitors LY294002 and Wortmannin, which decrease the activity of the AKT pathway, induced apoptosis, but this effect was reduced in cells simultaneously treated wi...
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carnosic acid potentiates the antioxidant and proDifferentiation effects of 1α 25 dihydroxyvitamin d3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium
Cancer Research, 2003Co-Authors: Michael Danilenko, Joseph Levy, Yoav Sharoni, Qing Wang, Xuening Wang, George P StudzinskiAbstract:Differentiation Therapy of cancer remains an only partially attained goal. Agents currently under active investigation include derivatives of vitamin D, modeled on its physiological hormone form, 1α,25-dihydroxyvitamin D 3 (1,25D 3 ), but the calcemic effects of these compounds preclude their use in the clinic. An approach that may obviate this problem is to combine 1,25D 3 or its derivatives with other agents that increase the antineoplastic effects of low, nontoxic concentrations of vitamin D compounds. We have recently used the plant-derived polyphenolic antioxidant, carnosic acid (CA), to demonstrate an increase in the differentiating action of 1,25D 3 on human leukemia cells under these conditions (M. Danilenko et al. , JNCI, 93: 1224–1233, 2001). We now show that treatment of HL60-G cells with either CA or 1,25D 3 alone resulted in a decrease in the intracellular levels of reactive oxygen species. Furthermore, the combination of 10 μm CA and a low concentration of 1,25D 3 (1 nm) produced an enhanced antioxidant effect, which correlated with the potentiation of monocytic Differentiation. Other plant antioxidants tested (curcumin, silibinin, and the organoselenium antioxidant ebselen) also potentiated Differentiation induced by 1,25D 3 , although alone, they had only minor differentiating effects. Differentiation induced by CA/1,25D 3 combinations was associated with increased intracellular glutathione content, whereas buthionine sulfoxime decreased both Differentiation and the cellular glutathione content. This combination also enhanced the activation of the Raf-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase mitogen-activated protein kinase module and increased the binding of the activator protein-1 (AP-1) transcription factor to its cognate DNA element in the promoter regions of vitamin D receptor gene, suggesting that the mechanism of potentiation is at least in part attributable to induction and activation of components of this mitogen-activated protein kinase pathway. Cell treatment with a high concentration of 1,25D 3 (100 nm) resulted in a substantial elevation of basal intracellular calcium concentration. In contrast, importantly for an eventual clinical application of these studies, the potentiating action of CA on Differentiation induced by a low concentration of 1,25D 3 (1 nm) was not accompanied by an elevation of basal intracellular calcium concentration. These findings suggest that combinations of CA with derivatives of vitamin D should be evaluated for use in Differentiation Therapy of myeloid leukemias.
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inhibition of p38 map kinase activity up regulates multiple map kinase pathways and potentiates 1 25 dihydroxyvitamin d3 induced Differentiation of human leukemia hl60 cells
Experimental Cell Research, 2000Co-Authors: Xuening Wang, Jie Rao, George P StudzinskiAbstract:Differentiation Therapy for neoplastic diseases has potential for supplementing existing treatment modalities but its implementation has been slow. One of the reasons is the lack of full understanding of the complexities of cellular pathways through which signals for Differentiation lead to cell maturation. This was addressed in this study using HL60 cells, a well-established model of Differentiation of neoplastic cells. SB 203580 and SB 202190, specific inhibitors of a signaling protein p38 MAP kinase, were found to markedly accelerate monocytic Differentiation of HL60 cells induced by low concentrations of 1,25-dihydroxyvitamin D(3) (1,25D(3)). Surprisingly, inhibition of p38 activity resulted in sustained enhancement of p38 phosphorylation and of its in vitro activity in the absence of the inhibitor, indicating up-regulation of the upstream components of the p38 pathway. In addition, SB 203580 or SB 202190 treatment of HL60 cells resulted in a prolonged activation of the JNK and, to a lesser extent, the ERK pathways. The data are consistent with the hypothesis that in HL60 cells an interruption of a negative feedback loop from a p38 target activates a common regulator of multiple MAPK pathways. The possibility also exists that JNK and/or ERK pathways amplify a Differentiation signal provided by 1,25D(3).
David Yannick Leger - One of the best experts on this subject based on the ideXlab platform.
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sedimentation field flow fractionation to study human erythroleukemia cell megakaryocytic Differentiation after short period diosgenin induction
Journal of Chromatography A, 2007Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Serge Battu, Jeanlouis BeneytoutAbstract:Anti-cancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. We propose a new sedimentation field flow fractionation (SdFFF) cell separation application in the field of cancer research. It concerns the study of megakaryocytic Differentiation processes after a short exposure to an inducting agent (diosgenin). Washout process and early dual SdFFF separation--removing the influence of diosgenin and decreasing the influence of undifferentiated cells--resulted in the preparation of an enriched population to study the mechanism and kinetics of megakaryocytic Differentiation. A short exposure to diosgenin was able to induce complete Differentiation leading to maximal maturation which ended naturally after 192h incubation without the influence of a secondary effect of diosgenin. The study of isolated undifferentiated cells also showed that no resistance to diosgenin was observed. This result suggested different sensitivities to Differentiation induction, and SdFFF cell separation would be of great interest to explore this phenomena.
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megakaryocyte cell sorting from diosgenin differentiated human erythroleukemia cells by sedimentation field flow fractionation
Analytical Biochemistry, 2006Co-Authors: David Yannick Leger, Bertrand Liagre, Jeanlouis Beneytout, Serge Battu, Philippe J P CardotAbstract:Anticancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 μM diosgenin, underwent megakaryocytic Differentiation. Thus, the association diosgenin/HEL could be used as a model of chemically induced cellular Differentiation and anticancer treatment. The goal of this work was to determine the capacity of sedimentation field-flow fractionation (SdFFF) to sort megakaryocytic differentiated cells. SdFFF cell sorting was associated with cellular characterization methods to calibrate specific elution profiles. As demonstrated by cell size measurement methods, cellular morphology, ploidy, and phenotype, we obtained an enriched, sterile, viable, and functional fraction of megakaryocytic cells. Thus, SdFFF is proposed as a routine method to prepare differentiated cells that will be further used to better understand the megakaryocytic Differentiation process.
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diosgenin dose dependent apoptosis and Differentiation induction in human erythroleukemia cell line and sedimentation field flow fractionation monitoring
Analytical Biochemistry, 2004Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Jeanlouis Beneytout, Serge BattuAbstract:To limit or stop cancer spreading, one of the most prevalent strategies is to induce cancer cell death. Differentiation Therapy and apoptosis induction are two ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes advantage of intrinsic properties of eluted cells (size, density, shape), we studied the capacity of SdFFF to monitor specific biophysical modifications that occurred during cellular apoptosis or Differentiation induction. Then, we used, as an in vitro cellular model of apoptosis and Differentiation, diosgenin dose-dependent induction in the polyvalent human erythroleukemia cell line. Two other chemicals were used: phorbol myristate acetate (Differentiation inducer) and staurosporine (apoptosis inducer). Our results demonstrated a correlation between SdFFF elution profile changes and induction of effective biological processes. Thus, after acquisition of a reference profile, SdFFF could be used alone to follow chemically induced biological events, suggesting many different applications such as testing series of molecules, evaluation of new cellular/biological models used in different life science fields, or sorting purified populations with the aim of better understanding mechanisms of induced cellular events.
Philippe J P Cardot - One of the best experts on this subject based on the ideXlab platform.
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sedimentation field flow fractionation to study human erythroleukemia cell megakaryocytic Differentiation after short period diosgenin induction
Journal of Chromatography A, 2007Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Serge Battu, Jeanlouis BeneytoutAbstract:Anti-cancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. We propose a new sedimentation field flow fractionation (SdFFF) cell separation application in the field of cancer research. It concerns the study of megakaryocytic Differentiation processes after a short exposure to an inducting agent (diosgenin). Washout process and early dual SdFFF separation--removing the influence of diosgenin and decreasing the influence of undifferentiated cells--resulted in the preparation of an enriched population to study the mechanism and kinetics of megakaryocytic Differentiation. A short exposure to diosgenin was able to induce complete Differentiation leading to maximal maturation which ended naturally after 192h incubation without the influence of a secondary effect of diosgenin. The study of isolated undifferentiated cells also showed that no resistance to diosgenin was observed. This result suggested different sensitivities to Differentiation induction, and SdFFF cell separation would be of great interest to explore this phenomena.
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megakaryocyte cell sorting from diosgenin differentiated human erythroleukemia cells by sedimentation field flow fractionation
Analytical Biochemistry, 2006Co-Authors: David Yannick Leger, Bertrand Liagre, Jeanlouis Beneytout, Serge Battu, Philippe J P CardotAbstract:Anticancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 μM diosgenin, underwent megakaryocytic Differentiation. Thus, the association diosgenin/HEL could be used as a model of chemically induced cellular Differentiation and anticancer treatment. The goal of this work was to determine the capacity of sedimentation field-flow fractionation (SdFFF) to sort megakaryocytic differentiated cells. SdFFF cell sorting was associated with cellular characterization methods to calibrate specific elution profiles. As demonstrated by cell size measurement methods, cellular morphology, ploidy, and phenotype, we obtained an enriched, sterile, viable, and functional fraction of megakaryocytic cells. Thus, SdFFF is proposed as a routine method to prepare differentiated cells that will be further used to better understand the megakaryocytic Differentiation process.
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diosgenin dose dependent apoptosis and Differentiation induction in human erythroleukemia cell line and sedimentation field flow fractionation monitoring
Analytical Biochemistry, 2004Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Jeanlouis Beneytout, Serge BattuAbstract:To limit or stop cancer spreading, one of the most prevalent strategies is to induce cancer cell death. Differentiation Therapy and apoptosis induction are two ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes advantage of intrinsic properties of eluted cells (size, density, shape), we studied the capacity of SdFFF to monitor specific biophysical modifications that occurred during cellular apoptosis or Differentiation induction. Then, we used, as an in vitro cellular model of apoptosis and Differentiation, diosgenin dose-dependent induction in the polyvalent human erythroleukemia cell line. Two other chemicals were used: phorbol myristate acetate (Differentiation inducer) and staurosporine (apoptosis inducer). Our results demonstrated a correlation between SdFFF elution profile changes and induction of effective biological processes. Thus, after acquisition of a reference profile, SdFFF could be used alone to follow chemically induced biological events, suggesting many different applications such as testing series of molecules, evaluation of new cellular/biological models used in different life science fields, or sorting purified populations with the aim of better understanding mechanisms of induced cellular events.
Serge Battu - One of the best experts on this subject based on the ideXlab platform.
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sedimentation field flow fractionation to study human erythroleukemia cell megakaryocytic Differentiation after short period diosgenin induction
Journal of Chromatography A, 2007Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Serge Battu, Jeanlouis BeneytoutAbstract:Anti-cancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. We propose a new sedimentation field flow fractionation (SdFFF) cell separation application in the field of cancer research. It concerns the study of megakaryocytic Differentiation processes after a short exposure to an inducting agent (diosgenin). Washout process and early dual SdFFF separation--removing the influence of diosgenin and decreasing the influence of undifferentiated cells--resulted in the preparation of an enriched population to study the mechanism and kinetics of megakaryocytic Differentiation. A short exposure to diosgenin was able to induce complete Differentiation leading to maximal maturation which ended naturally after 192h incubation without the influence of a secondary effect of diosgenin. The study of isolated undifferentiated cells also showed that no resistance to diosgenin was observed. This result suggested different sensitivities to Differentiation induction, and SdFFF cell separation would be of great interest to explore this phenomena.
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megakaryocyte cell sorting from diosgenin differentiated human erythroleukemia cells by sedimentation field flow fractionation
Analytical Biochemistry, 2006Co-Authors: David Yannick Leger, Bertrand Liagre, Jeanlouis Beneytout, Serge Battu, Philippe J P CardotAbstract:Anticancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 μM diosgenin, underwent megakaryocytic Differentiation. Thus, the association diosgenin/HEL could be used as a model of chemically induced cellular Differentiation and anticancer treatment. The goal of this work was to determine the capacity of sedimentation field-flow fractionation (SdFFF) to sort megakaryocytic differentiated cells. SdFFF cell sorting was associated with cellular characterization methods to calibrate specific elution profiles. As demonstrated by cell size measurement methods, cellular morphology, ploidy, and phenotype, we obtained an enriched, sterile, viable, and functional fraction of megakaryocytic cells. Thus, SdFFF is proposed as a routine method to prepare differentiated cells that will be further used to better understand the megakaryocytic Differentiation process.
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diosgenin dose dependent apoptosis and Differentiation induction in human erythroleukemia cell line and sedimentation field flow fractionation monitoring
Analytical Biochemistry, 2004Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Jeanlouis Beneytout, Serge BattuAbstract:To limit or stop cancer spreading, one of the most prevalent strategies is to induce cancer cell death. Differentiation Therapy and apoptosis induction are two ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes advantage of intrinsic properties of eluted cells (size, density, shape), we studied the capacity of SdFFF to monitor specific biophysical modifications that occurred during cellular apoptosis or Differentiation induction. Then, we used, as an in vitro cellular model of apoptosis and Differentiation, diosgenin dose-dependent induction in the polyvalent human erythroleukemia cell line. Two other chemicals were used: phorbol myristate acetate (Differentiation inducer) and staurosporine (apoptosis inducer). Our results demonstrated a correlation between SdFFF elution profile changes and induction of effective biological processes. Thus, after acquisition of a reference profile, SdFFF could be used alone to follow chemically induced biological events, suggesting many different applications such as testing series of molecules, evaluation of new cellular/biological models used in different life science fields, or sorting purified populations with the aim of better understanding mechanisms of induced cellular events.
Jeanlouis Beneytout - One of the best experts on this subject based on the ideXlab platform.
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sedimentation field flow fractionation to study human erythroleukemia cell megakaryocytic Differentiation after short period diosgenin induction
Journal of Chromatography A, 2007Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Serge Battu, Jeanlouis BeneytoutAbstract:Anti-cancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. We propose a new sedimentation field flow fractionation (SdFFF) cell separation application in the field of cancer research. It concerns the study of megakaryocytic Differentiation processes after a short exposure to an inducting agent (diosgenin). Washout process and early dual SdFFF separation--removing the influence of diosgenin and decreasing the influence of undifferentiated cells--resulted in the preparation of an enriched population to study the mechanism and kinetics of megakaryocytic Differentiation. A short exposure to diosgenin was able to induce complete Differentiation leading to maximal maturation which ended naturally after 192h incubation without the influence of a secondary effect of diosgenin. The study of isolated undifferentiated cells also showed that no resistance to diosgenin was observed. This result suggested different sensitivities to Differentiation induction, and SdFFF cell separation would be of great interest to explore this phenomena.
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megakaryocyte cell sorting from diosgenin differentiated human erythroleukemia cells by sedimentation field flow fractionation
Analytical Biochemistry, 2006Co-Authors: David Yannick Leger, Bertrand Liagre, Jeanlouis Beneytout, Serge Battu, Philippe J P CardotAbstract:Anticancer Differentiation Therapy could be one strategy to stop cancer cell proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 μM diosgenin, underwent megakaryocytic Differentiation. Thus, the association diosgenin/HEL could be used as a model of chemically induced cellular Differentiation and anticancer treatment. The goal of this work was to determine the capacity of sedimentation field-flow fractionation (SdFFF) to sort megakaryocytic differentiated cells. SdFFF cell sorting was associated with cellular characterization methods to calibrate specific elution profiles. As demonstrated by cell size measurement methods, cellular morphology, ploidy, and phenotype, we obtained an enriched, sterile, viable, and functional fraction of megakaryocytic cells. Thus, SdFFF is proposed as a routine method to prepare differentiated cells that will be further used to better understand the megakaryocytic Differentiation process.
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diosgenin dose dependent apoptosis and Differentiation induction in human erythroleukemia cell line and sedimentation field flow fractionation monitoring
Analytical Biochemistry, 2004Co-Authors: David Yannick Leger, Bertrand Liagre, Philippe J P Cardot, Jeanlouis Beneytout, Serge BattuAbstract:To limit or stop cancer spreading, one of the most prevalent strategies is to induce cancer cell death. Differentiation Therapy and apoptosis induction are two ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has been described as an effective tool for cell separation, respecting integrity and viability. Because SdFFF takes advantage of intrinsic properties of eluted cells (size, density, shape), we studied the capacity of SdFFF to monitor specific biophysical modifications that occurred during cellular apoptosis or Differentiation induction. Then, we used, as an in vitro cellular model of apoptosis and Differentiation, diosgenin dose-dependent induction in the polyvalent human erythroleukemia cell line. Two other chemicals were used: phorbol myristate acetate (Differentiation inducer) and staurosporine (apoptosis inducer). Our results demonstrated a correlation between SdFFF elution profile changes and induction of effective biological processes. Thus, after acquisition of a reference profile, SdFFF could be used alone to follow chemically induced biological events, suggesting many different applications such as testing series of molecules, evaluation of new cellular/biological models used in different life science fields, or sorting purified populations with the aim of better understanding mechanisms of induced cellular events.