EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus
Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the...
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| Veröffentlicht in: | Gastrointestinal endoscopy 2017-07, Vol.86 (1), p.219-228 |
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| creator | Jun, Eun Jung, PhD Park, Jung-Hoon, PhD Tsauo, Jiaywei, MD Yang, Su-Geun, PhD Kim, Dae-Kee, PhD Kim, Kun Yung, MD Kim, Min Tae, MS Yoon, Sung-Hwan, BS Lim, Young Je, BS Song, Ho-Young, MD |
| description | Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. Methods Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. Results SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01). Conclusions EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus. |
| doi_str_mv | 10.1016/j.gie.2017.01.013 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1863219781</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0016510717300305</els_id><sourcerecordid>1863219781</sourcerecordid><originalsourceid>FETCH-LOGICAL-c408t-64da1dbef88144bf58535a4c5fe1ca0fa26de010b714af5de9a93940be23c93d3</originalsourceid><addsrcrecordid>eNp9kU-L1EAQxRtR3HH0A3iRPnrYjFXpJJ0gCLKsf2DBg4rHptOpzPZMppPt6izstzdhVg8ehIKqw3sP6veEeI2wQ8Dq3WG397TLAfUOcBn1RGwQGp1VWjdPxQYWUVYi6AvxgvkAAHWu8Lm4yGtUumyqjbi7_pVpbPSltEFal_y9D9ngjySPPlgmWUofbn3r0xgvJc_TFImZWO6jDfNgkx-DTJ55Jmn7RFFyopDkNFhHp_XyQUabJPE43dr9zC_Fs94OTK8e91b8_HT94-pLdvPt89erjzeZK6BOWVV0FruW-rrGomj7si5VaQtX9oTOQm_zqiNAaDUWti87amyjmgJaypVrVKe24u05d4rj3UyczMmzo2GwgcaZDdaVypfPFxRbgWepiyNzpN5M0Z9sfDAIZiVtDmYhbVbSBnAZtXjePMbP7Ym6v44_aBfB-7OAlifvPUXDzlNw1PlILplu9P-N__CP2w0-eGeHIz0QH8Y5hoWeQcO5AfN9rXptGrUCUFCq35SNpAY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1863219781</pqid></control><display><type>article</type><title>EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Jun, Eun Jung, PhD ; Park, Jung-Hoon, PhD ; Tsauo, Jiaywei, MD ; Yang, Su-Geun, PhD ; Kim, Dae-Kee, PhD ; Kim, Kun Yung, MD ; Kim, Min Tae, MS ; Yoon, Sung-Hwan, BS ; Lim, Young Je, BS ; Song, Ho-Young, MD</creator><creatorcontrib>Jun, Eun Jung, PhD ; Park, Jung-Hoon, PhD ; Tsauo, Jiaywei, MD ; Yang, Su-Geun, PhD ; Kim, Dae-Kee, PhD ; Kim, Kun Yung, MD ; Kim, Min Tae, MS ; Yoon, Sung-Hwan, BS ; Lim, Young Je, BS ; Song, Ho-Young, MD</creatorcontrib><description>Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. Methods Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. Results SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01). Conclusions EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.</description><identifier>ISSN: 0016-5107</identifier><identifier>EISSN: 1097-6779</identifier><identifier>DOI: 10.1016/j.gie.2017.01.013</identifier><identifier>PMID: 28137596</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actins - metabolism ; Aniline Compounds - pharmacology ; Animals ; Cadherins - metabolism ; Esophagus - diagnostic imaging ; Esophagus - drug effects ; Esophagus - metabolism ; Esophagus - pathology ; Fibronectins - metabolism ; Gastroenterology and Hepatology ; Granulation Tissue - diagnostic imaging ; Granulation Tissue - drug effects ; Granulation Tissue - metabolism ; Granulation Tissue - pathology ; Male ; Nerve Tissue Proteins - metabolism ; Phosphorylation ; Protein Kinase Inhibitors - pharmacology ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Radiography ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta - antagonists & inhibitors ; Self Expandable Metallic Stents - adverse effects ; Smad3 Protein - metabolism ; Transforming Growth Factor beta1 - metabolism ; Triazoles - pharmacology</subject><ispartof>Gastrointestinal endoscopy, 2017-07, Vol.86 (1), p.219-228</ispartof><rights>American Society for Gastrointestinal Endoscopy</rights><rights>2017 American Society for Gastrointestinal Endoscopy</rights><rights>Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-64da1dbef88144bf58535a4c5fe1ca0fa26de010b714af5de9a93940be23c93d3</citedby><cites>FETCH-LOGICAL-c408t-64da1dbef88144bf58535a4c5fe1ca0fa26de010b714af5de9a93940be23c93d3</cites><orcidid>0000-0002-6131-851X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0016510717300305$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28137596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jun, Eun Jung, PhD</creatorcontrib><creatorcontrib>Park, Jung-Hoon, PhD</creatorcontrib><creatorcontrib>Tsauo, Jiaywei, MD</creatorcontrib><creatorcontrib>Yang, Su-Geun, PhD</creatorcontrib><creatorcontrib>Kim, Dae-Kee, PhD</creatorcontrib><creatorcontrib>Kim, Kun Yung, MD</creatorcontrib><creatorcontrib>Kim, Min Tae, MS</creatorcontrib><creatorcontrib>Yoon, Sung-Hwan, BS</creatorcontrib><creatorcontrib>Lim, Young Je, BS</creatorcontrib><creatorcontrib>Song, Ho-Young, MD</creatorcontrib><title>EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus</title><title>Gastrointestinal endoscopy</title><addtitle>Gastrointest Endosc</addtitle><description>Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. Methods Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. Results SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01). Conclusions EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.</description><subject>Actins - metabolism</subject><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Cadherins - metabolism</subject><subject>Esophagus - diagnostic imaging</subject><subject>Esophagus - drug effects</subject><subject>Esophagus - metabolism</subject><subject>Esophagus - pathology</subject><subject>Fibronectins - metabolism</subject><subject>Gastroenterology and Hepatology</subject><subject>Granulation Tissue - diagnostic imaging</subject><subject>Granulation Tissue - drug effects</subject><subject>Granulation Tissue - metabolism</subject><subject>Granulation Tissue - pathology</subject><subject>Male</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Radiography</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Transforming Growth Factor-beta Type I</subject><subject>Receptors, Transforming Growth Factor beta - antagonists & inhibitors</subject><subject>Self Expandable Metallic Stents - adverse effects</subject><subject>Smad3 Protein - metabolism</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Triazoles - pharmacology</subject><issn>0016-5107</issn><issn>1097-6779</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-L1EAQxRtR3HH0A3iRPnrYjFXpJJ0gCLKsf2DBg4rHptOpzPZMppPt6izstzdhVg8ehIKqw3sP6veEeI2wQ8Dq3WG397TLAfUOcBn1RGwQGp1VWjdPxQYWUVYi6AvxgvkAAHWu8Lm4yGtUumyqjbi7_pVpbPSltEFal_y9D9ngjySPPlgmWUofbn3r0xgvJc_TFImZWO6jDfNgkx-DTJ55Jmn7RFFyopDkNFhHp_XyQUabJPE43dr9zC_Fs94OTK8e91b8_HT94-pLdvPt89erjzeZK6BOWVV0FruW-rrGomj7si5VaQtX9oTOQm_zqiNAaDUWti87amyjmgJaypVrVKe24u05d4rj3UyczMmzo2GwgcaZDdaVypfPFxRbgWepiyNzpN5M0Z9sfDAIZiVtDmYhbVbSBnAZtXjePMbP7Ym6v44_aBfB-7OAlifvPUXDzlNw1PlILplu9P-N__CP2w0-eGeHIz0QH8Y5hoWeQcO5AfN9rXptGrUCUFCq35SNpAY</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Jun, Eun Jung, PhD</creator><creator>Park, Jung-Hoon, PhD</creator><creator>Tsauo, Jiaywei, MD</creator><creator>Yang, Su-Geun, PhD</creator><creator>Kim, Dae-Kee, PhD</creator><creator>Kim, Kun Yung, MD</creator><creator>Kim, Min Tae, MS</creator><creator>Yoon, Sung-Hwan, BS</creator><creator>Lim, Young Je, BS</creator><creator>Song, Ho-Young, MD</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6131-851X</orcidid></search><sort><creationdate>20170701</creationdate><title>EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus</title><author>Jun, Eun Jung, PhD ; Park, Jung-Hoon, PhD ; Tsauo, Jiaywei, MD ; Yang, Su-Geun, PhD ; Kim, Dae-Kee, PhD ; Kim, Kun Yung, MD ; Kim, Min Tae, MS ; Yoon, Sung-Hwan, BS ; Lim, Young Je, BS ; Song, Ho-Young, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-64da1dbef88144bf58535a4c5fe1ca0fa26de010b714af5de9a93940be23c93d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Actins - metabolism</topic><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Cadherins - metabolism</topic><topic>Esophagus - diagnostic imaging</topic><topic>Esophagus - drug effects</topic><topic>Esophagus - metabolism</topic><topic>Esophagus - pathology</topic><topic>Fibronectins - metabolism</topic><topic>Gastroenterology and Hepatology</topic><topic>Granulation Tissue - diagnostic imaging</topic><topic>Granulation Tissue - drug effects</topic><topic>Granulation Tissue - metabolism</topic><topic>Granulation Tissue - pathology</topic><topic>Male</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Radiography</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Transforming Growth Factor-beta Type I</topic><topic>Receptors, Transforming Growth Factor beta - antagonists & inhibitors</topic><topic>Self Expandable Metallic Stents - adverse effects</topic><topic>Smad3 Protein - metabolism</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Triazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jun, Eun Jung, PhD</creatorcontrib><creatorcontrib>Park, Jung-Hoon, PhD</creatorcontrib><creatorcontrib>Tsauo, Jiaywei, MD</creatorcontrib><creatorcontrib>Yang, Su-Geun, PhD</creatorcontrib><creatorcontrib>Kim, Dae-Kee, PhD</creatorcontrib><creatorcontrib>Kim, Kun Yung, MD</creatorcontrib><creatorcontrib>Kim, Min Tae, MS</creatorcontrib><creatorcontrib>Yoon, Sung-Hwan, BS</creatorcontrib><creatorcontrib>Lim, Young Je, BS</creatorcontrib><creatorcontrib>Song, Ho-Young, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gastrointestinal endoscopy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jun, Eun Jung, PhD</au><au>Park, Jung-Hoon, PhD</au><au>Tsauo, Jiaywei, MD</au><au>Yang, Su-Geun, PhD</au><au>Kim, Dae-Kee, PhD</au><au>Kim, Kun Yung, MD</au><au>Kim, Min Tae, MS</au><au>Yoon, Sung-Hwan, BS</au><au>Lim, Young Je, BS</au><au>Song, Ho-Young, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus</atitle><jtitle>Gastrointestinal endoscopy</jtitle><addtitle>Gastrointest Endosc</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>86</volume><issue>1</issue><spage>219</spage><epage>228</epage><pages>219-228</pages><issn>0016-5107</issn><eissn>1097-6779</eissn><abstract>Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. Methods Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. Results SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01). Conclusions EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28137596</pmid><doi>10.1016/j.gie.2017.01.013</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-6131-851X</orcidid></addata></record> |
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| subjects | Actins - metabolism Aniline Compounds - pharmacology Animals Cadherins - metabolism Esophagus - diagnostic imaging Esophagus - drug effects Esophagus - metabolism Esophagus - pathology Fibronectins - metabolism Gastroenterology and Hepatology Granulation Tissue - diagnostic imaging Granulation Tissue - drug effects Granulation Tissue - metabolism Granulation Tissue - pathology Male Nerve Tissue Proteins - metabolism Phosphorylation Protein Kinase Inhibitors - pharmacology Protein-Serine-Threonine Kinases - antagonists & inhibitors Radiography Rats Rats, Sprague-Dawley Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta - antagonists & inhibitors Self Expandable Metallic Stents - adverse effects Smad3 Protein - metabolism Transforming Growth Factor beta1 - metabolism Triazoles - pharmacology |
| title | EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus |
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