The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform
Marie-angèle Grandbastien - One of the best experts on this subject based on the ideXlab platform.
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ltr retrotransposons handy hitchhikers of plant regulation and stress response
Biochimica et Biophysica Acta, 2015Co-Authors: Marie-angèle GrandbastienAbstract:LTR retrotransposons are major components of plant genomes. They are regulated by a diverse array of external stresses and tissue culture conditions, displaying finely tuned responses to these stimuli, mostly in the form of upregulation. Second to stress conditions and tissue culture, meristems are also permissive for LTR retrotransposon expression, suggesting that a Dedifferentiated Cell status may represent a frequent activating condition. LTR regions are highly plastic and contain regulatory motifs similar to those of Cellular genes. The activation of LTR retrotransposons results from interplay between the release of epigenetic silencing and the recruitment by LTRs of specific regulatory factors. Despite the role of LTR retrotransposons in driving plant genome diversification, convincing evidence for major mobilizations of LTR retrotransposons remains much rarer than observations of massive bursts of transcriptional upregulation. Current evidence suggests that LTR retrotransposon expression may be involved in host functional plasticity, acting as dispersed regulatory modules able to redirect stress stimuli to adjacent plant genes. This may be of crucial importance for plants that cannot escape stress, and have evolved complex and highly coordinated responses to external challenges. This article is part of a Special Issue entitled: Stress as a fundamental theme in Cell plasticity.
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LTR retrotransposons, handy hitchhikers of plant regulation and stress response
BBA - Biochimica et Biophysica Acta, 2014Co-Authors: Marie-angèle GrandbastienAbstract:LTR retrotransposons are major components of plant genomes. They are regulated by a diverse array of external stresses and tissue culture conditions, displaying finely tuned responses to these stimuli, mostly in the form of upregulation. Second to stress conditions and tissue culture, meristems are also permissive for LTR retrotransposon expression, suggesting that a Dedifferentiated Cell status may represent a frequent activating condition. LTR regions are highly plastic and contain regulatory motifs similar to those of Cellular genes. The activation of LTR retrotransposons results from interplay between the release of epigenetic silencing and the recruitement by LTRs of specific regulatory factors. Despite the role of LTR retrotransposons in driving plant genome diversification, convincing evidence for major mobilizations of LTR retrotransposons remains much rarer than observations of massive bursts of transcriptional upregulation. Current evidence suggests that LTR retrotransposon expression may be involved in host functional plasticity, acting as dispersed regulatory modules able to redirect stress stimuli to adjacent plant genes. This may be of crucial importance for plants that cannot escape stress, and have evolved complex and highly coordinated responses to external challenges. This article is part of a Special Issue entitled: Stress as a fundamental theme in Cell plasticity.
Gary A. Bulla - One of the best experts on this subject based on the ideXlab platform.
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Apoptosis of Dedifferentiated Hepatoma Cells is Independent of NF-κB Activation in Response to LPS
Bioscience Reports, 2007Co-Authors: M. Ryan Reidy, Janette Ellis, Erin A. Schmitz, David M. Kraus, Gary A. BullaAbstract:Dedifferentiated hepatoma Cells, in contrast to most other Cell types including hepatoma Cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the Dedifferentiated hepatoma Cells also exhibit a strong and prolonged NF-κB induction phenotype upon exposure to LPS, suggesting that NF-κB signaling may play a pro-survival role, as reported in several other Cell systems. To test the role of NF-κB in preventing LPS-mediated apoptosis, we examined the Dedifferentiated Cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated Cell death in the M38 Cells, yet only modestly inhibited NF-κB induction. In addition, inhibition of NF-κB translocation by infection of the M38 Cells with an adenoviral vector expressing an IκBα super-repressor did not result in LPS-mediated Cell death. These results suggest that unlike TNFα induction, the Cell survival pathway activated in response to LPS is independent of NF-κB translocation in the Dedifferentiated Cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, Cell survival pathways other than those involving NF-κB inducible gene expression or other well-known pathways appear to be involved in protecting the Dedifferentiated hepatoma variant Cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma Cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.
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Apoptosis of Dedifferentiated hepatoma Cells is independent of NF-kappaB activation in response to LPS.
Bioscience reports, 2007Co-Authors: M. Ryan Reidy, Janette Ellis, Erin A. Schmitz, David M. Kraus, Gary A. BullaAbstract:Dedifferentiated hepatoma Cells, in contrast to most other Cell types including hepatoma Cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the Dedifferentiated hepatoma Cells also exhibit a strong and prolonged NF-kappaB induction phenotype upon exposure to LPS, suggesting that NF-kappaB signaling may play a pro-survival role, as reported in several other Cell systems. To test the role of NF-kappaB in preventing LPS-mediated apoptosis, we examined the Dedifferentiated Cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated Cell death in the M38 Cells, yet only modestly inhibited NF-kappaB induction. In addition, inhibition of NF-kappaB translocation by infection of the M38 Cells with an adenoviral vector expressing an IkappaBalpha super-repressor did not result in LPS-mediated Cell death. These results suggest that unlike TNFalpha induction, the Cell survival pathway activated in response to LPS is independent of NF-kappaB translocation in the Dedifferentiated Cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, Cell survival pathways other than those involving NF-kappaB inducible gene expression or other well-known pathways appear to be involved in protecting the Dedifferentiated hepatoma variant Cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma Cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.
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Tissue-specificity of apoptosis in hepatoma-derived Cell lines
Apoptosis : an international journal on programmed cell death, 2004Co-Authors: E. K. Schmitz, D. M. Kraus, Gary A. BullaAbstract:Apoptosis is known to play a critical role in development and homeostasis in metazoans. Although apoptotic responses vary widely among Cell types, the underlying mechanisms responsible for these differences are not known. In order to understand the molecular basis for these differences, we have studied a Cell culture model comparing hepatoma Cells to Dedifferentiated Cell lines derived from them. We recently reported evidence suggesting that a common regulatory locus affects both liver-specific function and sensitivity to lipopolysaccharide (LPS)-mediated apoptosis. Here, we show that Dedifferentiated hepatoma Cells undergo apoptosis in response to multiple compounds, including sorbitol (to induce hyperosmotic shock), TNFα and the microtubule damaging agent vinblastin. In contrast, the hepatoma parental Cells fail to undergo apoptosis in response to any of the compounds tested. Further analysis of LPS-mediated Cell death found that antioxidants N-acetylcysteine and α-tocopherol partially prevented apoptosis. Lastly, evidence is presented showing that LPS-mediated Cell death of the hepatoma variant Cell lines is caspase-dependent. These results suggest that pathways dictating hepatic phenotype also affect general Cellular survival mechanisms in response to multiple agents. The Dedifferentiated Cells provide a model to examine the influence of Cell-type specific expression on apoptotic signaling.
Marcel Deckert - One of the best experts on this subject based on the ideXlab platform.
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Bad Neighborhood: Fibrotic Stroma as a New Player in Melanoma Resistance to Targeted Therapies
Cancers, 2020Co-Authors: Serena Diazzi, Sophie Tartare-deckert, Marcel DeckertAbstract:Current treatments for metastatic cutaneous melanoma include immunotherapies and drugs targeting key molecules of the mitogen-activated protein kinase (MAPK) pathway, which is often activated by BRAF driver mutations. Overall responses from patients with metastatic BRAF mutant melanoma are better with therapies combining BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. However, most patients that initially respond to therapies develop drug resistance within months. Acquired resistance to targeted therapies can be due to additional genetic alterations in melanoma Cells and to non-genetic events frequently associated with transcriptional reprogramming and a Dedifferentiated Cell state. In this second scenario, it is possible to identify pro-fibrotic responses induced by targeted therapies that contribute to the alteration of the melanoma tumor microenvironment. A close interrelationship between chronic fibrosis and cancer has been established for several malignancies including breast and pancreatic cancers. In this context, the contribution of fibrosis to drug adaptation and therapy resistance in melanoma is rapidly emerging. In this review, we summarize recent evidence underlining the hallmarks of fibrotic diseases in drug-exposed and resistant melanoma, including increased remodeling of the extraCellular matrix, enhanced actin cytoskeleton plasticity, high sensitivity to mechanical cues, and the establishment of an inflammatory microenvironment. We also discuss several potential therapeutic options for manipulating this fibrotic-like response to combat drug-resistant and invasive melanoma.
Serena Diazzi - One of the best experts on this subject based on the ideXlab platform.
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Bad Neighborhood: Fibrotic Stroma as a New Player in Melanoma Resistance to Targeted Therapies
Cancers, 2020Co-Authors: Serena Diazzi, Sophie Tartare-deckert, Marcel DeckertAbstract:Current treatments for metastatic cutaneous melanoma include immunotherapies and drugs targeting key molecules of the mitogen-activated protein kinase (MAPK) pathway, which is often activated by BRAF driver mutations. Overall responses from patients with metastatic BRAF mutant melanoma are better with therapies combining BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. However, most patients that initially respond to therapies develop drug resistance within months. Acquired resistance to targeted therapies can be due to additional genetic alterations in melanoma Cells and to non-genetic events frequently associated with transcriptional reprogramming and a Dedifferentiated Cell state. In this second scenario, it is possible to identify pro-fibrotic responses induced by targeted therapies that contribute to the alteration of the melanoma tumor microenvironment. A close interrelationship between chronic fibrosis and cancer has been established for several malignancies including breast and pancreatic cancers. In this context, the contribution of fibrosis to drug adaptation and therapy resistance in melanoma is rapidly emerging. In this review, we summarize recent evidence underlining the hallmarks of fibrotic diseases in drug-exposed and resistant melanoma, including increased remodeling of the extraCellular matrix, enhanced actin cytoskeleton plasticity, high sensitivity to mechanical cues, and the establishment of an inflammatory microenvironment. We also discuss several potential therapeutic options for manipulating this fibrotic-like response to combat drug-resistant and invasive melanoma.
M. Ryan Reidy - One of the best experts on this subject based on the ideXlab platform.
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Apoptosis of Dedifferentiated Hepatoma Cells is Independent of NF-κB Activation in Response to LPS
Bioscience Reports, 2007Co-Authors: M. Ryan Reidy, Janette Ellis, Erin A. Schmitz, David M. Kraus, Gary A. BullaAbstract:Dedifferentiated hepatoma Cells, in contrast to most other Cell types including hepatoma Cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the Dedifferentiated hepatoma Cells also exhibit a strong and prolonged NF-κB induction phenotype upon exposure to LPS, suggesting that NF-κB signaling may play a pro-survival role, as reported in several other Cell systems. To test the role of NF-κB in preventing LPS-mediated apoptosis, we examined the Dedifferentiated Cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated Cell death in the M38 Cells, yet only modestly inhibited NF-κB induction. In addition, inhibition of NF-κB translocation by infection of the M38 Cells with an adenoviral vector expressing an IκBα super-repressor did not result in LPS-mediated Cell death. These results suggest that unlike TNFα induction, the Cell survival pathway activated in response to LPS is independent of NF-κB translocation in the Dedifferentiated Cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, Cell survival pathways other than those involving NF-κB inducible gene expression or other well-known pathways appear to be involved in protecting the Dedifferentiated hepatoma variant Cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma Cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.
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Apoptosis of Dedifferentiated hepatoma Cells is independent of NF-kappaB activation in response to LPS.
Bioscience reports, 2007Co-Authors: M. Ryan Reidy, Janette Ellis, Erin A. Schmitz, David M. Kraus, Gary A. BullaAbstract:Dedifferentiated hepatoma Cells, in contrast to most other Cell types including hepatoma Cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the Dedifferentiated hepatoma Cells also exhibit a strong and prolonged NF-kappaB induction phenotype upon exposure to LPS, suggesting that NF-kappaB signaling may play a pro-survival role, as reported in several other Cell systems. To test the role of NF-kappaB in preventing LPS-mediated apoptosis, we examined the Dedifferentiated Cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated Cell death in the M38 Cells, yet only modestly inhibited NF-kappaB induction. In addition, inhibition of NF-kappaB translocation by infection of the M38 Cells with an adenoviral vector expressing an IkappaBalpha super-repressor did not result in LPS-mediated Cell death. These results suggest that unlike TNFalpha induction, the Cell survival pathway activated in response to LPS is independent of NF-kappaB translocation in the Dedifferentiated Cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, Cell survival pathways other than those involving NF-kappaB inducible gene expression or other well-known pathways appear to be involved in protecting the Dedifferentiated hepatoma variant Cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma Cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.
