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Georg Bauer - One of the best experts on this subject based on the ideXlab platform.
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low dose irradiation of nonTransformed Cells stimulates the selective removal of precancerous Cells via interCellular induction of apoptosis
Cancer Research, 2007Co-Authors: Daniel I Portess, Georg Bauer, Mark A Hill, Peter OneillAbstract:An important stage in tumorigenesis is the ability of a precancerous Cell to escape natural anticancer signals imposed on it by neighboring Cells and its microenvironment. We have previously characterized a system of interCellular induction of apoptosis whereby nonTransformed Cells selectively remove Transformed Cells from coculture via cytokine and reactive oxygen/nitrogen species (ROS/RNS) signaling. We report that irradiation of nonTransformed Cells with low doses of either high linear energy transfer (LET) α-particles or low-LET γ-rays leads to stimulation of interCellular induction of apoptosis. The use of scavengers and inhibitors confirms the involvement of ROS/RNS signaling and of the importance of Transformed Cell NADPH oxidase in the selectivity of the system. Doses as low as 2-mGy γ-rays and 0.29-mGy α-particles were sufficient to produce an observable increase in Transformed Cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for γ-rays and 25 mGy for α-particles). The use of transforming growth factor-β (TGF-β) neutralizing antibody confirms a role for the cytokine in the radiation-induced signaling. The system may represent a natural anticancer mechanism stimulated by extremely low doses of ionizing radiation. [Cancer Res 2007;67(3):1246–53]
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Transformed Cell-derived reactive oxygen species support and inhibit nitric oxide-mediated apoptosis induction
International Journal of Oncology, 2002Co-Authors: Kathrin Haberstroh, Stefanie Heigold, Georg BauerAbstract:Nitric oxide has been recently shown to require interaction with extraCellular superoxide anions and subsequent peroxynitrite formation for selective apoptosis induction in Transformed fibroblasts. In addition to foster NO-mediated apoptosis, Transformed target Cell-derived reactive oxygen species (ROS) also exhibit a marked inhibitory effect directed against NO-mediated apoptosis. This inhibition can be abrogated by catalase and can be augmented by hydrogen peroxide generation through glucose oxidase. Therefore, Transformed fibroblasts at high density seem to inhibit NO-mediated apoptosis through hydrogen peroxide formation. Inhibition of NO-mediated apoptosis can be explained by the interaction of hydrogen peroxide with NO, resulting in the generation of hydroxyl radicals. As hydrogen peroxide as well as NO represent far ranging species, hydroxyl radical generation occurs more likely distant from the Cell membrane and therefore does not have an apoptosis-inducing effect on the Cells. In total, this reaction is rather blunting apoptosis induction mediated by NO. The interaction of hydrogen peroxide with NO may have consequences for the control of Transformed Cells by NO-utilizing natural antitumor systems.
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Signaling and proapoptotic functions of Transformed Cell-derived reactive oxygen species.
Prostaglandins leukotrienes and essential fatty acids, 2002Co-Authors: Georg BauerAbstract:Abstract Transformed fibroblasts generate extraCellular superoxide anions through the recently identified membrane-associated NADPH oxidase. These Cell-derived superoxide anions exhibit signaling functions such as regulation of proliferation and maintenance of the Transformed state. Their dismutation product hydrogen peroxide regulates the intraCellular level of catalase, whose activity has been observed to be upregulated in certain Transformed Cells. After glutathione depletion, Transformed Cell-derived reactive oxygen species (ROS) exhibit apoptosis-inducing potential through the metal-catalyzed Haber–Weiss reaction. Moreover, Transformed Cell-derived ROS represent key elements for selective and efficient apoptosis induction by natural antitumor systems (such as fibroblasts, granulocytes and macrophages). These effector Cells release peroxidase, which utilizes target Cell-derived hydrogen peroxide for HOCl synthesis. In a second step, HOCl interacts with target Cell-derived superoxide anions and forms apoptosis-inducing hydroxyl radicals. In a parallel signaling pathway, effector Cell-derived NO interacts with target Cell-derived superoxide anions and generates the apoptosis inducer peroxynitrite. Therefore, Transformed Cell-derived ROS determine Transformed Cells as selective targets for induction of apoptosis by these effector systems. It is therefore proposed that Transformed Cell derived ROS interact with associated Cells to exhibit directed and specific signaling functions, some of which are beneficial and some of which can become detrimental to Transformed Cells.
Y H Tan - One of the best experts on this subject based on the ideXlab platform.
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activation and association of stat3 with src in v src Transformed Cell lines
Molecular and Cellular Biology, 1996Co-Authors: Xinmin Cao, A H N Tay, Graeme R Guy, Y H TanAbstract:STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of Cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic Cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated Cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-Transformed Cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 Cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.
Sushil Kumar - One of the best experts on this subject based on the ideXlab platform.
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diethyl maleate inhibits mca tpa Transformed Cell growth via modulation of gsh mapk and cancer pathways
Chemico-Biological Interactions, 2014Co-Authors: Shivam Priya, Akanksha Nigam, Preeti Bajpai, Sushil KumarAbstract:Abstract Murine or human cancer Cells have high glutathione levels. Depletion of the elevated GSH inhibits proliferation of cancer Cells. Molecular basis for this observation is little understood. In an attempt to find out the underlying mechanism, we reproduced these effects in Transformed C3H10T1/2 and BALB/c 3T3 Cells using diethyl maleate and studied cytogenomic changes in the whole mouse genome using spotted 8 × 60K arrays. Transformed Cells revealed an increase in GSH levels. GSH depletion by DEM inhibited the growth of Transformed Cells. The non-cytotoxic dose of DEM (0.25 mM) resulted in GSH depletion, ROS generation, Cell cycle arrest, apoptosis, decrease in anchorage independent growth, gene expression changes and activation of all three members of the MAPK family. Increase in intraCellular GSH levels by GSHe countered the effect of DEM. These results support the physiological importance of GSH in regulation of gene expression for Transformed Cell growth restraint. This study is of interest in not only understanding the molecular biology of the Transformed Cells, but also in identifying new targets for development of gene therapy together with the chemotherapy.
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Diethyl maleate inhibits MCA+TPA Transformed Cell growth via modulation of GSH, MAPK, and cancer pathways.
Chemico-biological interactions, 2014Co-Authors: Shivam Priya, Akanksha Nigam, Preeti Bajpai, Sushil KumarAbstract:Abstract Murine or human cancer Cells have high glutathione levels. Depletion of the elevated GSH inhibits proliferation of cancer Cells. Molecular basis for this observation is little understood. In an attempt to find out the underlying mechanism, we reproduced these effects in Transformed C3H10T1/2 and BALB/c 3T3 Cells using diethyl maleate and studied cytogenomic changes in the whole mouse genome using spotted 8 × 60K arrays. Transformed Cells revealed an increase in GSH levels. GSH depletion by DEM inhibited the growth of Transformed Cells. The non-cytotoxic dose of DEM (0.25 mM) resulted in GSH depletion, ROS generation, Cell cycle arrest, apoptosis, decrease in anchorage independent growth, gene expression changes and activation of all three members of the MAPK family. Increase in intraCellular GSH levels by GSHe countered the effect of DEM. These results support the physiological importance of GSH in regulation of gene expression for Transformed Cell growth restraint. This study is of interest in not only understanding the molecular biology of the Transformed Cells, but also in identifying new targets for development of gene therapy together with the chemotherapy.
Shivam Priya - One of the best experts on this subject based on the ideXlab platform.
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diethyl maleate inhibits mca tpa Transformed Cell growth via modulation of gsh mapk and cancer pathways
Chemico-Biological Interactions, 2014Co-Authors: Shivam Priya, Akanksha Nigam, Preeti Bajpai, Sushil KumarAbstract:Abstract Murine or human cancer Cells have high glutathione levels. Depletion of the elevated GSH inhibits proliferation of cancer Cells. Molecular basis for this observation is little understood. In an attempt to find out the underlying mechanism, we reproduced these effects in Transformed C3H10T1/2 and BALB/c 3T3 Cells using diethyl maleate and studied cytogenomic changes in the whole mouse genome using spotted 8 × 60K arrays. Transformed Cells revealed an increase in GSH levels. GSH depletion by DEM inhibited the growth of Transformed Cells. The non-cytotoxic dose of DEM (0.25 mM) resulted in GSH depletion, ROS generation, Cell cycle arrest, apoptosis, decrease in anchorage independent growth, gene expression changes and activation of all three members of the MAPK family. Increase in intraCellular GSH levels by GSHe countered the effect of DEM. These results support the physiological importance of GSH in regulation of gene expression for Transformed Cell growth restraint. This study is of interest in not only understanding the molecular biology of the Transformed Cells, but also in identifying new targets for development of gene therapy together with the chemotherapy.
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Diethyl maleate inhibits MCA+TPA Transformed Cell growth via modulation of GSH, MAPK, and cancer pathways.
Chemico-biological interactions, 2014Co-Authors: Shivam Priya, Akanksha Nigam, Preeti Bajpai, Sushil KumarAbstract:Abstract Murine or human cancer Cells have high glutathione levels. Depletion of the elevated GSH inhibits proliferation of cancer Cells. Molecular basis for this observation is little understood. In an attempt to find out the underlying mechanism, we reproduced these effects in Transformed C3H10T1/2 and BALB/c 3T3 Cells using diethyl maleate and studied cytogenomic changes in the whole mouse genome using spotted 8 × 60K arrays. Transformed Cells revealed an increase in GSH levels. GSH depletion by DEM inhibited the growth of Transformed Cells. The non-cytotoxic dose of DEM (0.25 mM) resulted in GSH depletion, ROS generation, Cell cycle arrest, apoptosis, decrease in anchorage independent growth, gene expression changes and activation of all three members of the MAPK family. Increase in intraCellular GSH levels by GSHe countered the effect of DEM. These results support the physiological importance of GSH in regulation of gene expression for Transformed Cell growth restraint. This study is of interest in not only understanding the molecular biology of the Transformed Cells, but also in identifying new targets for development of gene therapy together with the chemotherapy.
Xinmin Cao - One of the best experts on this subject based on the ideXlab platform.
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activation and association of stat3 with src in v src Transformed Cell lines
Molecular and Cellular Biology, 1996Co-Authors: Xinmin Cao, A H N Tay, Graeme R Guy, Y H TanAbstract:STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of Cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic Cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated Cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-Transformed Cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 Cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.
