Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins
Summary Context First‐line therapy for thyrotropin‐secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2‐preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximate...
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| Veröffentlicht in: | Clinical endocrinology (Oxford) 2012-03, Vol.76 (3), p.407-414 |
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| creator | Gatto, Federico Barbieri, Federica Gatti, Monica Wurth, Roberto Schulz, Stefan Ravetti, Jean-Louis Zona, Gianluigi Culler, Michael D. Saveanu, Alexandru Giusti, Massimo Minuto, Francesco Hofland, Leo J. Ferone, Diego Florio, Tullio |
| description | Summary
Context First‐line therapy for thyrotropin‐secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2‐preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%.
Objective We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long‐acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM‐23A760 and BIM‐23A387.
Results All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long‐term treatment was observed in only two patients, showing a high sst5/sst2 ratio. Patient 2, characterized by high expression of sst2 and sst1 and a relative lower expression of sst5, experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM‐23A760 caused the highest antiproliferative effect among those tested. Combined treatment with octreotide and cabergoline displayed an additive effect of magnitude comparable to that of the other chimeric compound (BIM‐23A387). Octreotide resistance was confirmed in cells isolated from the nonresponder patient, although it could be overcome by treatment with the chimeric compounds.
Conclusions A high sst5/sst2 ratio might be predictive of a positive outcome to long‐term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D2 receptor targeting might be considered as a potential tool to improve the response rate in octreotide‐resistant tumours. |
| doi_str_mv | 10.1111/j.1365-2265.2011.04200.x |
| format | Article |
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Context First‐line therapy for thyrotropin‐secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2‐preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%.
Objective We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long‐acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM‐23A760 and BIM‐23A387.
Results All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long‐term treatment was observed in only two patients, showing a high sst5/sst2 ratio. Patient 2, characterized by high expression of sst2 and sst1 and a relative lower expression of sst5, experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM‐23A760 caused the highest antiproliferative effect among those tested. Combined treatment with octreotide and cabergoline displayed an additive effect of magnitude comparable to that of the other chimeric compound (BIM‐23A387). Octreotide resistance was confirmed in cells isolated from the nonresponder patient, although it could be overcome by treatment with the chimeric compounds.
Conclusions A high sst5/sst2 ratio might be predictive of a positive outcome to long‐term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D2 receptor targeting might be considered as a potential tool to improve the response rate in octreotide‐resistant tumours.</description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1111/j.1365-2265.2011.04200.x</identifier><identifier>PMID: 21848909</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adenoma - drug therapy ; Adenoma - genetics ; Adenoma - metabolism ; Adult ; Biological and medical sciences ; Cabergoline ; Cell Proliferation - drug effects ; Dopamine ; Dopamine - analogs & derivatives ; Dopamine - pharmacology ; Dopamine - therapeutic use ; Dopamine Agonists - pharmacology ; Dopamine Agonists - therapeutic use ; Drug Synergism ; Endocrinopathies ; Ergolines - pharmacology ; Ergolines - therapeutic use ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; Humans ; Immunohistochemistry ; Male ; Medical sciences ; Octreotide - pharmacology ; Octreotide - therapeutic use ; Patients ; Pituitary gland ; Pituitary Neoplasms - drug therapy ; Pituitary Neoplasms - genetics ; Pituitary Neoplasms - metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - metabolism ; Receptors, Somatostatin - genetics ; Receptors, Somatostatin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Somatostatin - analogs & derivatives ; Somatostatin - pharmacology ; Somatostatin - therapeutic use ; Thyrotropin - blood ; Thyrotropin - metabolism ; Thyroxine - blood ; Treatment Outcome ; Triiodothyronine - blood ; Tumor Cells, Cultured ; Vertebrates: endocrinology</subject><ispartof>Clinical endocrinology (Oxford), 2012-03, Vol.76 (3), p.407-414</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><rights>2012 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4640-c73223b27ecdfbd2c2ce1eea37a27482d5a4ceb94c166f474155e0144f3bd5a83</citedby><cites>FETCH-LOGICAL-c4640-c73223b27ecdfbd2c2ce1eea37a27482d5a4ceb94c166f474155e0144f3bd5a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2265.2011.04200.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2265.2011.04200.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,45565,45566</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25502352$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21848909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gatto, Federico</creatorcontrib><creatorcontrib>Barbieri, Federica</creatorcontrib><creatorcontrib>Gatti, Monica</creatorcontrib><creatorcontrib>Wurth, Roberto</creatorcontrib><creatorcontrib>Schulz, Stefan</creatorcontrib><creatorcontrib>Ravetti, Jean-Louis</creatorcontrib><creatorcontrib>Zona, Gianluigi</creatorcontrib><creatorcontrib>Culler, Michael D.</creatorcontrib><creatorcontrib>Saveanu, Alexandru</creatorcontrib><creatorcontrib>Giusti, Massimo</creatorcontrib><creatorcontrib>Minuto, Francesco</creatorcontrib><creatorcontrib>Hofland, Leo J.</creatorcontrib><creatorcontrib>Ferone, Diego</creatorcontrib><creatorcontrib>Florio, Tullio</creatorcontrib><title>Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description>Summary
Context First‐line therapy for thyrotropin‐secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2‐preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%.
Objective We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long‐acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM‐23A760 and BIM‐23A387.
Results All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long‐term treatment was observed in only two patients, showing a high sst5/sst2 ratio. Patient 2, characterized by high expression of sst2 and sst1 and a relative lower expression of sst5, experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM‐23A760 caused the highest antiproliferative effect among those tested. Combined treatment with octreotide and cabergoline displayed an additive effect of magnitude comparable to that of the other chimeric compound (BIM‐23A387). Octreotide resistance was confirmed in cells isolated from the nonresponder patient, although it could be overcome by treatment with the chimeric compounds.
Conclusions A high sst5/sst2 ratio might be predictive of a positive outcome to long‐term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D2 receptor targeting might be considered as a potential tool to improve the response rate in octreotide‐resistant tumours.</description><subject>Adenoma - drug therapy</subject><subject>Adenoma - genetics</subject><subject>Adenoma - metabolism</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cabergoline</subject><subject>Cell Proliferation - drug effects</subject><subject>Dopamine</subject><subject>Dopamine - analogs & derivatives</subject><subject>Dopamine - pharmacology</subject><subject>Dopamine - therapeutic use</subject><subject>Dopamine Agonists - pharmacology</subject><subject>Dopamine Agonists - therapeutic use</subject><subject>Drug Synergism</subject><subject>Endocrinopathies</subject><subject>Ergolines - pharmacology</subject><subject>Ergolines - therapeutic use</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Octreotide - pharmacology</subject><subject>Octreotide - therapeutic use</subject><subject>Patients</subject><subject>Pituitary gland</subject><subject>Pituitary Neoplasms - drug therapy</subject><subject>Pituitary Neoplasms - genetics</subject><subject>Pituitary Neoplasms - metabolism</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Receptors, Somatostatin - genetics</subject><subject>Receptors, Somatostatin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Somatostatin - analogs & derivatives</subject><subject>Somatostatin - pharmacology</subject><subject>Somatostatin - therapeutic use</subject><subject>Thyrotropin - blood</subject><subject>Thyrotropin - metabolism</subject><subject>Thyroxine - blood</subject><subject>Treatment Outcome</subject><subject>Triiodothyronine - blood</subject><subject>Tumor Cells, Cultured</subject><subject>Vertebrates: endocrinology</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi1ERZfCX0CWEMek468ke-BAl7JFrVohysfNcpxJlSUbp3aWbn9B_zZOs10kTvhiS_M849E7hFAGKYvneJUykamE80ylHBhLQXKAdPuMzPaF52QGAiCBLJOH5GUIKwBQBeQvyCFnhSzmMJ-RhxPTms4iLXG4Q-xocGszuDCYoemo6Sr6kVOPFvvBeYrb3mMIjeto5ZvfGOj117MkoPUY8RtqKuyiH4XQuy4gHdy_DU3rbjZRHFtXrjdTIbwiB7VpA77e3Ufk26fT68VZcnG1_Lz4cJFYmUlIbC44FyXP0VZ1WXHLLTJEI3LDc1nwShlpsZxLy7KslrlkSiEwKWtRxlohjsjbqW_v3W2cY9Art_FxqqCZkqqYM8azSBUTZb0LwWOte9-sjb_XDPS4Ab3SY9B6DFqPG9CPG9DbqL7ZfbAp11jtxafII_BuB5hgTVv7GH8T_nJKAReKR-79xN01Ld7_9wB6cXo5vqKfTH4TBtzufeN_6SwXudI_Lpf6y_nPJT9h3_W5-AMUxLMm</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Gatto, Federico</creator><creator>Barbieri, Federica</creator><creator>Gatti, Monica</creator><creator>Wurth, Roberto</creator><creator>Schulz, Stefan</creator><creator>Ravetti, Jean-Louis</creator><creator>Zona, Gianluigi</creator><creator>Culler, Michael D.</creator><creator>Saveanu, Alexandru</creator><creator>Giusti, Massimo</creator><creator>Minuto, Francesco</creator><creator>Hofland, Leo J.</creator><creator>Ferone, Diego</creator><creator>Florio, Tullio</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>201203</creationdate><title>Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins</title><author>Gatto, Federico ; Barbieri, Federica ; Gatti, Monica ; Wurth, Roberto ; Schulz, Stefan ; Ravetti, Jean-Louis ; Zona, Gianluigi ; Culler, Michael D. ; Saveanu, Alexandru ; Giusti, Massimo ; Minuto, Francesco ; Hofland, Leo J. ; Ferone, Diego ; Florio, Tullio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4640-c73223b27ecdfbd2c2ce1eea37a27482d5a4ceb94c166f474155e0144f3bd5a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenoma - drug therapy</topic><topic>Adenoma - genetics</topic><topic>Adenoma - metabolism</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cabergoline</topic><topic>Cell Proliferation - drug effects</topic><topic>Dopamine</topic><topic>Dopamine - analogs & derivatives</topic><topic>Dopamine - pharmacology</topic><topic>Dopamine - therapeutic use</topic><topic>Dopamine Agonists - pharmacology</topic><topic>Dopamine Agonists - therapeutic use</topic><topic>Drug Synergism</topic><topic>Endocrinopathies</topic><topic>Ergolines - pharmacology</topic><topic>Ergolines - therapeutic use</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Octreotide - pharmacology</topic><topic>Octreotide - therapeutic use</topic><topic>Patients</topic><topic>Pituitary gland</topic><topic>Pituitary Neoplasms - drug therapy</topic><topic>Pituitary Neoplasms - genetics</topic><topic>Pituitary Neoplasms - metabolism</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Receptors, Somatostatin - genetics</topic><topic>Receptors, Somatostatin - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Somatostatin - analogs & derivatives</topic><topic>Somatostatin - pharmacology</topic><topic>Somatostatin - therapeutic use</topic><topic>Thyrotropin - blood</topic><topic>Thyrotropin - metabolism</topic><topic>Thyroxine - blood</topic><topic>Treatment Outcome</topic><topic>Triiodothyronine - blood</topic><topic>Tumor Cells, Cultured</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gatto, Federico</creatorcontrib><creatorcontrib>Barbieri, Federica</creatorcontrib><creatorcontrib>Gatti, Monica</creatorcontrib><creatorcontrib>Wurth, Roberto</creatorcontrib><creatorcontrib>Schulz, Stefan</creatorcontrib><creatorcontrib>Ravetti, Jean-Louis</creatorcontrib><creatorcontrib>Zona, Gianluigi</creatorcontrib><creatorcontrib>Culler, Michael D.</creatorcontrib><creatorcontrib>Saveanu, Alexandru</creatorcontrib><creatorcontrib>Giusti, Massimo</creatorcontrib><creatorcontrib>Minuto, Francesco</creatorcontrib><creatorcontrib>Hofland, Leo J.</creatorcontrib><creatorcontrib>Ferone, Diego</creatorcontrib><creatorcontrib>Florio, Tullio</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gatto, Federico</au><au>Barbieri, Federica</au><au>Gatti, Monica</au><au>Wurth, Roberto</au><au>Schulz, Stefan</au><au>Ravetti, Jean-Louis</au><au>Zona, Gianluigi</au><au>Culler, Michael D.</au><au>Saveanu, Alexandru</au><au>Giusti, Massimo</au><au>Minuto, Francesco</au><au>Hofland, Leo J.</au><au>Ferone, Diego</au><au>Florio, Tullio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2012-03</date><risdate>2012</risdate><volume>76</volume><issue>3</issue><spage>407</spage><epage>414</epage><pages>407-414</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>Summary
Context First‐line therapy for thyrotropin‐secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2‐preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%.
Objective We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long‐acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM‐23A760 and BIM‐23A387.
Results All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long‐term treatment was observed in only two patients, showing a high sst5/sst2 ratio. Patient 2, characterized by high expression of sst2 and sst1 and a relative lower expression of sst5, experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM‐23A760 caused the highest antiproliferative effect among those tested. Combined treatment with octreotide and cabergoline displayed an additive effect of magnitude comparable to that of the other chimeric compound (BIM‐23A387). Octreotide resistance was confirmed in cells isolated from the nonresponder patient, although it could be overcome by treatment with the chimeric compounds.
Conclusions A high sst5/sst2 ratio might be predictive of a positive outcome to long‐term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D2 receptor targeting might be considered as a potential tool to improve the response rate in octreotide‐resistant tumours.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21848909</pmid><doi>10.1111/j.1365-2265.2011.04200.x</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenoma - drug therapy Adenoma - genetics Adenoma - metabolism Adult Biological and medical sciences Cabergoline Cell Proliferation - drug effects Dopamine Dopamine - analogs & derivatives Dopamine - pharmacology Dopamine - therapeutic use Dopamine Agonists - pharmacology Dopamine Agonists - therapeutic use Drug Synergism Endocrinopathies Ergolines - pharmacology Ergolines - therapeutic use Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Humans Immunohistochemistry Male Medical sciences Octreotide - pharmacology Octreotide - therapeutic use Patients Pituitary gland Pituitary Neoplasms - drug therapy Pituitary Neoplasms - genetics Pituitary Neoplasms - metabolism Protein Isoforms - genetics Protein Isoforms - metabolism Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism Receptors, Somatostatin - genetics Receptors, Somatostatin - metabolism Reverse Transcriptase Polymerase Chain Reaction Somatostatin - analogs & derivatives Somatostatin - pharmacology Somatostatin - therapeutic use Thyrotropin - blood Thyrotropin - metabolism Thyroxine - blood Treatment Outcome Triiodothyronine - blood Tumor Cells, Cultured Vertebrates: endocrinology |
| title | Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins |
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