The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Therese Sorlie - One of the best experts on this subject based on the ideXlab platform.
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abstract a18 the tankyrase inhibitor g007 lk inhibits small Intestine lgr5 stem cell proliferation without altering Tissue morphology
Cancer Research, 2016Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Tankyrase enzymes play crucial roles in the Wnt signaling pathway, involved in the regulation of intestinal stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers and the tankyrase inhibitor G007-LK has previously been shown to inhibit tumor growth in an APC-mutant colorectal cancer xenograft model. We have used in vivo models to address the effect of G007-LK on small Intestine Tissue homeostasis. The mice were treated for up to 3 weeks with the tankyrase inhibitor, without affecting the body mass or observed clinical condition of the mice. HE 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A18.
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abstract 3032 the effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis
Cancer Research, 2014Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA In the small Intestine the Wnt/β-catenin pathway is involved in regulation of stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers. Tankyrase enzymes play crucial roles in the regulation of the Wnt signaling pathway. Inhibition of tankyrase activity is an effective way of inhibiting Wnt/β-catenin signaling. A small molecule tankyrase inhibitor, G007-LK, was developed that inhibits tumor growth in a APC-mutant colorectal cancer xenograft model. In in vivo experiments at high doses (60 mg/kg), G007-LK treatment resulted in severe necrosis and inflammation in the small Intestine, possibly affecting the stem cells. Different cell populations in the small Intestine have been shown to have stem cell properties, including the Lgr5+ cell population located at the bottom of the crypts and the cells residing in +4 position counting from the crypt base. Both of these cell populations can give rise to all the various cell types of the small Intestine. In the current project, we have used in vivo models to address the effect of the tankyrase inhibitor, G007-LK, on small Intestine Tissue homeostasis. H&E staining of fixed Tissue sections showed no significant differences between mice treated with 10 mg/kg G007-LK or vehicle. We performed lineage tracing from the Lgr5+ stem cells of the small Intestine and observed that treatment with G007-LK reduced the number of cells traced from Lgr5+ stem cells. Immunohistochemistry (IHC) staining for the proliferation marker Ki67 showed reduced number of positive cells in the small intestinal crypts of the G007-LK- compared to vehicle-treated mice. As expected, IHC staining for β-catenin showed reduced number of positive nuclei in the G007-LK- compared to vehicle-treated mice, suggesting reduced signaling via the Wnt/β-catenin pathway. Taken together, our data show that a daily dose of the tankyrase inhibitor G007-LK (10 mg/kg), is well tolerated by mice. Administration of the tankyrase inhibitor to the mice reduces the number of lineage traced cells from the Lgr5+ stem cell population in the small Intestine, without altering the general histology of the Tissue. Citation Format: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sorlie. The effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3032. doi:10.1158/1538-7445.AM2014-3032
Jens Henrik Norum - One of the best experts on this subject based on the ideXlab platform.
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abstract a18 the tankyrase inhibitor g007 lk inhibits small Intestine lgr5 stem cell proliferation without altering Tissue morphology
Cancer Research, 2016Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Tankyrase enzymes play crucial roles in the Wnt signaling pathway, involved in the regulation of intestinal stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers and the tankyrase inhibitor G007-LK has previously been shown to inhibit tumor growth in an APC-mutant colorectal cancer xenograft model. We have used in vivo models to address the effect of G007-LK on small Intestine Tissue homeostasis. The mice were treated for up to 3 weeks with the tankyrase inhibitor, without affecting the body mass or observed clinical condition of the mice. HE 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A18.
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abstract 3032 the effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis
Cancer Research, 2014Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA In the small Intestine the Wnt/β-catenin pathway is involved in regulation of stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers. Tankyrase enzymes play crucial roles in the regulation of the Wnt signaling pathway. Inhibition of tankyrase activity is an effective way of inhibiting Wnt/β-catenin signaling. A small molecule tankyrase inhibitor, G007-LK, was developed that inhibits tumor growth in a APC-mutant colorectal cancer xenograft model. In in vivo experiments at high doses (60 mg/kg), G007-LK treatment resulted in severe necrosis and inflammation in the small Intestine, possibly affecting the stem cells. Different cell populations in the small Intestine have been shown to have stem cell properties, including the Lgr5+ cell population located at the bottom of the crypts and the cells residing in +4 position counting from the crypt base. Both of these cell populations can give rise to all the various cell types of the small Intestine. In the current project, we have used in vivo models to address the effect of the tankyrase inhibitor, G007-LK, on small Intestine Tissue homeostasis. H&E staining of fixed Tissue sections showed no significant differences between mice treated with 10 mg/kg G007-LK or vehicle. We performed lineage tracing from the Lgr5+ stem cells of the small Intestine and observed that treatment with G007-LK reduced the number of cells traced from Lgr5+ stem cells. Immunohistochemistry (IHC) staining for the proliferation marker Ki67 showed reduced number of positive cells in the small intestinal crypts of the G007-LK- compared to vehicle-treated mice. As expected, IHC staining for β-catenin showed reduced number of positive nuclei in the G007-LK- compared to vehicle-treated mice, suggesting reduced signaling via the Wnt/β-catenin pathway. Taken together, our data show that a daily dose of the tankyrase inhibitor G007-LK (10 mg/kg), is well tolerated by mice. Administration of the tankyrase inhibitor to the mice reduces the number of lineage traced cells from the Lgr5+ stem cell population in the small Intestine, without altering the general histology of the Tissue. Citation Format: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sorlie. The effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3032. doi:10.1158/1538-7445.AM2014-3032
Richard G Payne - One of the best experts on this subject based on the ideXlab platform.
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fabrication of a multi layer three dimensional scaffold with controlled porous micro architecture for application in small Intestine Tissue engineering
Cell Adhesion & Migration, 2013Co-Authors: Toyin Knight, Joydeep Basu, Elias A Rivera, Deepak Jain, Thomas E Spencer, Richard G PayneAbstract:Various methods can be employed to fabricate scaffolds with characteristics that promote cell-to-material interaction. This report examines the use of a novel technique combining compression molding with particulate leaching to create a unique multi-layered scaffold with differential porosities and pore sizes that provides a high level of control to influence cell behavior. These cell behavioral responses were primarily characterized by bridging and penetration of two cell types (epithelial and smooth muscle cells) on the scaffold in vitro. Larger pore sizes corresponded to an increase in pore penetration, and a decrease in pore bridging. In addition, smaller cells (epithelial) penetrated further into the scaffold than larger cells (smooth muscle cells). In vivo evaluation of a multi-layered scaffold was well tolerated for 75 d in a rodent model. This data shows the ability of the components of multi-layered scaffolds to influence cell behavior, and demonstrates the potential for these scaffolds to promote desired Tissue outcomes in vivo.
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regeneration of rodent small Intestine Tissue following implantation of scaffolds seeded with a novel source of smooth muscle cells
Regenerative Medicine, 2011Co-Authors: Joydeep Basu, Kim L Mihalko, Richard G Payne, Elias A Rivera, Toyin Knight, Christopher W Genheimer, Kelly I Guthrie, Namrata Sangha, Manuel J Jayo, Deepak JainAbstract:Aims: To apply an organ regeneration platform technology of autologous smooth muscle cell/biomaterial combination products, previously demonstrated to be successful for urinary Tissue regeneration, to the regeneration of the small Intestine. Materials & methods: Patch and tubular constructs were implanted in rodent small Intestines and histologically evaluated over a time course for evidence of regeneration of the laminarly organized neo-mucosa and muscle layers. Results: Laminarly organized neo-mucosa and muscle layer bundles are demonstrated as early as 8 weeks postimplantation. Conclusion: An organ regeneration technology platform of autologous smooth muscle cell/biomaterial combination products can be extended to the regeneration of the small Intestine.
Deepak Jain - One of the best experts on this subject based on the ideXlab platform.
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fabrication of a multi layer three dimensional scaffold with controlled porous micro architecture for application in small Intestine Tissue engineering
Cell Adhesion & Migration, 2013Co-Authors: Toyin Knight, Joydeep Basu, Elias A Rivera, Deepak Jain, Thomas E Spencer, Richard G PayneAbstract:Various methods can be employed to fabricate scaffolds with characteristics that promote cell-to-material interaction. This report examines the use of a novel technique combining compression molding with particulate leaching to create a unique multi-layered scaffold with differential porosities and pore sizes that provides a high level of control to influence cell behavior. These cell behavioral responses were primarily characterized by bridging and penetration of two cell types (epithelial and smooth muscle cells) on the scaffold in vitro. Larger pore sizes corresponded to an increase in pore penetration, and a decrease in pore bridging. In addition, smaller cells (epithelial) penetrated further into the scaffold than larger cells (smooth muscle cells). In vivo evaluation of a multi-layered scaffold was well tolerated for 75 d in a rodent model. This data shows the ability of the components of multi-layered scaffolds to influence cell behavior, and demonstrates the potential for these scaffolds to promote desired Tissue outcomes in vivo.
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regeneration of rodent small Intestine Tissue following implantation of scaffolds seeded with a novel source of smooth muscle cells
Regenerative Medicine, 2011Co-Authors: Joydeep Basu, Kim L Mihalko, Richard G Payne, Elias A Rivera, Toyin Knight, Christopher W Genheimer, Kelly I Guthrie, Namrata Sangha, Manuel J Jayo, Deepak JainAbstract:Aims: To apply an organ regeneration platform technology of autologous smooth muscle cell/biomaterial combination products, previously demonstrated to be successful for urinary Tissue regeneration, to the regeneration of the small Intestine. Materials & methods: Patch and tubular constructs were implanted in rodent small Intestines and histologically evaluated over a time course for evidence of regeneration of the laminarly organized neo-mucosa and muscle layers. Results: Laminarly organized neo-mucosa and muscle layer bundles are demonstrated as early as 8 weeks postimplantation. Conclusion: An organ regeneration technology platform of autologous smooth muscle cell/biomaterial combination products can be extended to the regeneration of the small Intestine.
Andreas Brech - One of the best experts on this subject based on the ideXlab platform.
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abstract a18 the tankyrase inhibitor g007 lk inhibits small Intestine lgr5 stem cell proliferation without altering Tissue morphology
Cancer Research, 2016Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Tankyrase enzymes play crucial roles in the Wnt signaling pathway, involved in the regulation of intestinal stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers and the tankyrase inhibitor G007-LK has previously been shown to inhibit tumor growth in an APC-mutant colorectal cancer xenograft model. We have used in vivo models to address the effect of G007-LK on small Intestine Tissue homeostasis. The mice were treated for up to 3 weeks with the tankyrase inhibitor, without affecting the body mass or observed clinical condition of the mice. HE 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A18.
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abstract 3032 the effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis
Cancer Research, 2014Co-Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese SorlieAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA In the small Intestine the Wnt/β-catenin pathway is involved in regulation of stem cells and Tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers. Tankyrase enzymes play crucial roles in the regulation of the Wnt signaling pathway. Inhibition of tankyrase activity is an effective way of inhibiting Wnt/β-catenin signaling. A small molecule tankyrase inhibitor, G007-LK, was developed that inhibits tumor growth in a APC-mutant colorectal cancer xenograft model. In in vivo experiments at high doses (60 mg/kg), G007-LK treatment resulted in severe necrosis and inflammation in the small Intestine, possibly affecting the stem cells. Different cell populations in the small Intestine have been shown to have stem cell properties, including the Lgr5+ cell population located at the bottom of the crypts and the cells residing in +4 position counting from the crypt base. Both of these cell populations can give rise to all the various cell types of the small Intestine. In the current project, we have used in vivo models to address the effect of the tankyrase inhibitor, G007-LK, on small Intestine Tissue homeostasis. H&E staining of fixed Tissue sections showed no significant differences between mice treated with 10 mg/kg G007-LK or vehicle. We performed lineage tracing from the Lgr5+ stem cells of the small Intestine and observed that treatment with G007-LK reduced the number of cells traced from Lgr5+ stem cells. Immunohistochemistry (IHC) staining for the proliferation marker Ki67 showed reduced number of positive cells in the small intestinal crypts of the G007-LK- compared to vehicle-treated mice. As expected, IHC staining for β-catenin showed reduced number of positive nuclei in the G007-LK- compared to vehicle-treated mice, suggesting reduced signaling via the Wnt/β-catenin pathway. Taken together, our data show that a daily dose of the tankyrase inhibitor G007-LK (10 mg/kg), is well tolerated by mice. Administration of the tankyrase inhibitor to the mice reduces the number of lineage traced cells from the Lgr5+ stem cell population in the small Intestine, without altering the general histology of the Tissue. Citation Format: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sorlie. The effect of a tankyrase inhibitor on the small Intestine Tissue homeostasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3032. doi:10.1158/1538-7445.AM2014-3032
