The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Bror Morein - One of the best experts on this subject based on the ideXlab platform.
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the nanoparticulate quillaja saponin kgi exerts anti proliferative effects by down regulation of cell cycle molecules in u937 and hl 60 human leukemia cells
Leukemia & Lymphoma, 2014Co-Authors: Saideh Berenjian, Manuchehr Abedivalugerdi, Moustapha Hassan, Sadia Hassan, Bror MoreinAbstract:Cancer cells are characterized by uncontrolled replication involving loss of control of cyclin dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, which is a nanoparticle with a Quillaja saponin as an active molecule. By the use of RNA array analysis and confirmation at the protein level, we show that KGI affects myeloid leukemia cells (in particular, the U937 Monoblast cancer cell) by the following mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down-regulation of key molecules at check points between G1/S and G2/M phases, (C) reduction of thymidine kinase activity, followed by (D) exit to differentiation and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukemic cells by interfering with the cell cycle process.
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p0012 the nanoparticle quillaja saponin kgi exerts anti proliferative effects by down regulation of cell cycle molecules in u937 and hl 60 human leukaemia cells
European Journal of Cancer, 2014Co-Authors: Saideh Berenjian, Manuchehr Abedivalugerdi, Moustapha Hassan, Bashir S Hassan, Bror MoreinAbstract:Background Cancer cells are characterised by uncontrolled replication involving loss of control of cyclin-dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, a nanoparticle with a Quillaja saponin as an active molecule. Methods By the use of RNA array analysis and confirmation at the protein level, we studied the effects of KGI on myeloid leukaemia cells. Findings KGI affects myeloid leukaemia cells (particularly the U937 Monoblast cancer cell) by the following mechanisms: ceasing cell replication via proteasome degradation; down-regulation of key molecules at check points between G 1 /S and G 2 /M phases; reduction of thymidine kinase activity; followed by exit to differentiation and production of IL-8, eventually leading to apoptosis. Leukaemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Interpretation Our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukaemic cells by interfering with the cell cycle process.
Saideh Berenjian - One of the best experts on this subject based on the ideXlab platform.
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the nanoparticulate quillaja saponin kgi exerts anti proliferative effects by down regulation of cell cycle molecules in u937 and hl 60 human leukemia cells
Leukemia & Lymphoma, 2014Co-Authors: Saideh Berenjian, Manuchehr Abedivalugerdi, Moustapha Hassan, Sadia Hassan, Bror MoreinAbstract:Cancer cells are characterized by uncontrolled replication involving loss of control of cyclin dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, which is a nanoparticle with a Quillaja saponin as an active molecule. By the use of RNA array analysis and confirmation at the protein level, we show that KGI affects myeloid leukemia cells (in particular, the U937 Monoblast cancer cell) by the following mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down-regulation of key molecules at check points between G1/S and G2/M phases, (C) reduction of thymidine kinase activity, followed by (D) exit to differentiation and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukemic cells by interfering with the cell cycle process.
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p0012 the nanoparticle quillaja saponin kgi exerts anti proliferative effects by down regulation of cell cycle molecules in u937 and hl 60 human leukaemia cells
European Journal of Cancer, 2014Co-Authors: Saideh Berenjian, Manuchehr Abedivalugerdi, Moustapha Hassan, Bashir S Hassan, Bror MoreinAbstract:Background Cancer cells are characterised by uncontrolled replication involving loss of control of cyclin-dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, a nanoparticle with a Quillaja saponin as an active molecule. Methods By the use of RNA array analysis and confirmation at the protein level, we studied the effects of KGI on myeloid leukaemia cells. Findings KGI affects myeloid leukaemia cells (particularly the U937 Monoblast cancer cell) by the following mechanisms: ceasing cell replication via proteasome degradation; down-regulation of key molecules at check points between G 1 /S and G 2 /M phases; reduction of thymidine kinase activity; followed by exit to differentiation and production of IL-8, eventually leading to apoptosis. Leukaemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Interpretation Our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukaemic cells by interfering with the cell cycle process.
Shinobu Imajohohmi - One of the best experts on this subject based on the ideXlab platform.
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monocytic differentiation modulates apoptotic response to cytotoxic anti fas antibody and tumor necrosis factor alpha in human Monoblast u937 cells
Journal of Leukocyte Biology, 1996Co-Authors: Hidehiko Kikuchi, Ryoko Iizuka, Shinji Sugiyama, Gotetsu Gon, Hiroyuki Mori, Masaaki Arai, Kiyohisa Mizumoto, Shinobu ImajohohmiAbstract:Interferon-gamma (IFN-gamma), vitamin D3 (VD), and retinoic acid (RA) induce differentiation of human Monoblastic leukemia U937 cells to macrophage-like cells with potential superoxide anion-generating activity upon further stimulation. Here we report that U937 cells thus differentiated show various responses to apoptotic induction with a cytotoxic anti-Fas antibody and tumor necrosis factor (TNF). VD-or RA-treated U937 cells acquired resistance against Fas- or TNF receptor (TNFR)-mediated apoptosis, whereas apoptotic cell death was accelerated in IFN-gamma-treated cells. By flow cytometric analyses, no decrease in expression of surface Fas antigen or p55 TNFR was observed in differentiated U937 cells. Cell surface expression of CD11b was seen only when differentiation was induced with VD or RA but not with IFN-gamma. The growth of VD- or RA-treated cells was retarded but IFN-gamma-treated cells were prolific. These findings suggest that the differentiation state differs with the inducer and that the cellular response to apoptotic induction is closely related to the state including the cell cycle.
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activation and possible involvement of calpain a calcium activated cysteine protease in down regulation of apoptosis of human Monoblast u937 cells
Cell Death & Differentiation, 1995Co-Authors: Hidehiko Kikuchi, Shinobu ImajohohmiAbstract:An active form of calpain mu, a low-Ca(2+)-requiring intracellular cysteine protease, was detected using a cleavage site-directed antibody in apoptotic human Monoblast U937 cells treated with tumor necrosis factor-alpha and interferon-gamma. Membrane-permeable calpain inhibitors accelerated apoptosis of U937 cells thus induced and suppressed the activation of procalpain. These findings suggest that calpain down-regulates apoptosis by shutting off the intracellular signals for cell death.
Hironobu Sasano - One of the best experts on this subject based on the ideXlab platform.
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progesterone metabolism in human leukemic Monoblast u937 cells
Endocrine Journal, 2002Co-Authors: Takashi Suzuki, Barbara A. Murry, Andrew D. Darnel, Hironobu SasanoAbstract:Progesterone markedly inhibitis the functions of human macrophages and T lymphocytes, and acts as an immunosuppressant during pregnancy. It is important to examine progesterone metabolites to understand the overall bioactive properties of this sex steroid. However, progesterone metabolism has not been examined in human immune cells. The human leukemic Monoblast U937 cell line exhibits monocytic lineage and provides a valuable model to analyze monocyte-macrophage differentiation. Therefore, in this study, we analyzed progesterone metabolism in U937 cells by thin-layer chromatography. Progesterone was metabolized to 5α-pregnan-3β,6α-diol-20-one via 5α-dihydroprogesterone and 5α-pregnan-3β-ol-20-one, and 5α-pregnan-3β,20α-diol was also detected as a final metabolic product via 20α-dihydroprogesterone and 5α-pregnan-20α-ol-3-one. 5α-reduction (5α-reductase type 1) and 20α-reduction were involved in the first step of metabolism. To identify the enzyme responsible for the 20α-reduction, we screened an U937 cDNA library, and obtained a clone (1.2 kb), which was identical to the human hepatic bile acid-binding protein or 20α-hydroxysteroid dehydrogenase (20α-HSD). 293 cells transfected with this cDNA demonstrated marked 20α-reduction of progesterone to 20αDHP, but 20α-oxidative, 3α-HSD or 17β-HSD activity was found to be negligible. In experimental animals, the importance of 20α-HSD has been reported to be involved in the protection of immune cells from the toxic effects of progesterone. Therefore, our present data suggest that 20α-HSD plays an important role in the reguation of progesterone actions in human immune cells.
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Progesterone metabolism in human leukemic Monoblast U937 cells.
Endocrine journal, 2002Co-Authors: Takashi Suzuki, Barbara A. Murry, Andrew D. Darnel, Hironobu SasanoAbstract:Progesterone markedly inhibits the functions of human macrophages and T lymphocytes, and acts as an immunosuppressant during pregnancy. It is important to examine progesterone metabolites to understand the overall bioactive properties of this sex steroid. However, progesterone metabolism has not been examined in human immune cells. The human leukemic Monoblast U937 cell line exhibits monocytic lineage and provides a valuable model to analyze monocyte-macrophage differentiation. Therefore, in this study, we analyzed progesterone metabolism in U937 cells by thin-layer chromatography. Progesterone was metabolized to 5alpha-pregnan-3beta,6alpha-diol-20-one via 5alpha-dihydroprogesterone and 5alpha-pregnan-3beta-ol-20-one, and 5alpha-pregnan-3beta,20alpha-diol was also detected as a final metabolic product via 20alpha-dihydroprogesterone and 5alpha-pregnan-20alpha-ol-3-one. 5alpha-reduction (5alpha-reductase type 1) and 20alpha-reduction were involved in the first step of metabolism. To identify the enzyme responsible for the 20alpha-reduction, we screened an U937 cDNA library, and obtained a clone (1.2 kb), which was identical to the human hepatic bile acid-binding protein or 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD). 293 cells transfected with this cDNA demonstrated marked 20alpha-reduction of progesterone to 20alphaDHP, but 20alpha-oxidative, 3alpha-HSD or 17beta-HSD activity was found to be negligible. In experimental animals, the importance of 20alpha-HSD has been reported to be involved in the protection of immune cells from the toxic effects of progesterone. Therefore, our present data suggest that 20alpha-HSD plays an important role in the regulation of progesterone actions in human immune cells.
Grant M Hatch - One of the best experts on this subject based on the ideXlab platform.
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complex expression pattern of the barth syndrome gene product tafazzin in human cell lines and murine tissues
Biochemistry and Cell Biology, 2004Co-Authors: Biao Lu, Marguerite R Kelher, Tal M Lewin, Rosalind A. Coleman, Patrick C. Choy, Grant M HatchAbstract:Tafazzins, a group of proteins that are defective in patients with Barth syndrome, are produced by alternate splicing of the gene G4.5 or TAZ. RT-PCR and transcription-coupled in vitro translation analysis were undertaken to determine the expression of alternatively spliced TAZ mRNA in mouse tissues and human cell lines. Only two tafazzin transcripts, both lacking exon 5, were expressed in murine tissues, whereas four tafazzin transcripts, all lacking exon 5, were observed in human umbilical vein vascular endothelial cells and U937 human Monoblasts indicating a species-specific difference in the expression of TAZ mRNAs in mouse and humans. Only TAZ lacking exon 5 was expressed in murine heart. Differentiation of U937 human Monoblasts into macrophages did not alter expression of the tafazzin transcripts indicating that TAZ expression is independent of monocyte differentiation. Cloning and in vitro expression of both murine and human tafazzin cDNA revealed two prominent protein bands that corresponded to th...
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complex expression pattern of the barth syndrome gene product tafazzin in human cell lines and murine tissues
Biochemistry and Cell Biology, 2004Co-Authors: Marguerite R Kelher, Tal M Lewin, Rosalind A. Coleman, Patrick C. Choy, Douglas P Lee, Grant M HatchAbstract:Tafazzins, a group of proteins that are defective in patients with Barth syndrome, are produced by alternate splicing of the gene G4.5 or TAZ. RT-PCR and transcription-coupled in vitro translation analysis were undertaken to determine the expression of alternatively spliced TAZ mRNA in mouse tissues and human cell lines. Only two tafazzin transcripts, both lacking exon 5, were expressed in murine tissues, whereas four tafazzin transcripts, all lacking exon 5, were observed in human umbilical vein vascular endothelial cells and U937 human Monoblasts indicating a species-specific difference in the expression of TAZ mRNAs in mouse and humans. Only TAZ lacking exon 5 was expressed in murine heart. Differentiation of U937 human Monoblasts into macrophages did not alter expression of the tafazzin transcripts indicating that TAZ expression is independent of monocyte differentiation. Cloning and in vitro expression of both murine and human tafazzin cDNA revealed two prominent protein bands that corresponded to the expected sizes of alternative translation. A novel fifth motif, identified as critical for the glycerolphosphate acyltransferase family, was observed in human tafazzin. The presence of a mutation in this region in Barth syndrome patients indicates that this motif is essential for tafazzin function.