Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children
Abstract Background Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to
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| Veröffentlicht in: | The Journal of surgical research 2014-03, Vol.187 (1), p.197-201 |
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| creator | Reismann, Marc, PhD Ghaffarpour, Nader, MD Luvall, Ethel, MSc Jirmo, Adan C., PhD Winqvist, Ola, PhD Radtke, Josephine, MD Wester, Tomas, PhD Claesson, Gösta, PhD |
| description | Abstract Background Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to |
| doi_str_mv | 10.1016/j.jss.2013.09.037 |
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However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4–dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. Methods Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05. Results The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y ( P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. Conclusions Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2013.09.037</identifier><identifier>PMID: 24215906</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antineoplastic Agents - therapeutic use ; Child, Preschool ; Children ; Drug Monitoring - methods ; Female ; Flow Cytometry ; Humans ; Infant ; Ligands ; Lipopolysaccharides - pharmacology ; Lymphatic Abnormalities - metabolism ; Lymphatic Abnormalities - therapy ; Lymphatic malformation ; Male ; Monocytes - drug effects ; Monocytes - physiology ; OK-432 ; Picibanil - therapeutic use ; Predictive Value of Tests ; Sclerotherapy ; Sclerotherapy - methods ; Surgery ; Toll-like receptor ; Toll-Like Receptor 4 - metabolism ; Toll-Like Receptor 7 - metabolism ; Up-Regulation - drug effects</subject><ispartof>The Journal of surgical research, 2014-03, Vol.187 (1), p.197-201</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-5d2619f675e001b2211c867f9b5cc0ec2007d9613eb64545972c29428cf826a33</citedby><cites>FETCH-LOGICAL-c446t-5d2619f675e001b2211c867f9b5cc0ec2007d9613eb64545972c29428cf826a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022480413009104$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24215906$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:128393501$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Reismann, Marc, PhD</creatorcontrib><creatorcontrib>Ghaffarpour, Nader, MD</creatorcontrib><creatorcontrib>Luvall, Ethel, MSc</creatorcontrib><creatorcontrib>Jirmo, Adan C., PhD</creatorcontrib><creatorcontrib>Winqvist, Ola, PhD</creatorcontrib><creatorcontrib>Radtke, Josephine, MD</creatorcontrib><creatorcontrib>Wester, Tomas, PhD</creatorcontrib><creatorcontrib>Claesson, Gösta, PhD</creatorcontrib><title>Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4–dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. Methods Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05. Results The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y ( P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. Conclusions Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Drug Monitoring - methods</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Infant</subject><subject>Ligands</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lymphatic Abnormalities - metabolism</subject><subject>Lymphatic Abnormalities - therapy</subject><subject>Lymphatic malformation</subject><subject>Male</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - physiology</subject><subject>OK-432</subject><subject>Picibanil - therapeutic use</subject><subject>Predictive Value of Tests</subject><subject>Sclerotherapy</subject><subject>Sclerotherapy - methods</subject><subject>Surgery</subject><subject>Toll-like receptor</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-Like Receptor 7 - metabolism</subject><subject>Up-Regulation - drug effects</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk9v1DAQxS0EokvhA3BBPnJJGDt2EgsJCZW_olIPlLOVOBOts04c7KQl4svj1S49cODk8ei9J838hpCXDHIGrHwz5EOMOQdW5KByKKpHZMdAyawuq-Ix2QFwnokaxAV5FuMA6a-q4im54IIzqaDckd8ftqkZraG33rnM2QPSgAbnxQeKv-aAMVo_0VR01iyR-nUxfkTqexqNw-CXPYZm3mifDG4b532zpLSxcakxptpPkd7bZU9vvmWi4NRO1Oyt6wJOz8mTvnERX5zfS_Lj08fbqy_Z9c3nr1fvrzMjRLlksuMlU31ZSQRgLeeMmTRgr1ppDKDhAFWnSlZgWwoppKq44Urw2vQ1L5uiuCTZKTfe47y2eg52bMKmfWP1uXVIFWrJZQUy6V-f9HPwP1eMix5tNOhcM6Ffo2ZCKSY553WSspPUBB9jwP4hnIE-MtKDToz0kZEGpROj5Hl1jl_bEbsHx18oSfD2JMC0lDuLQUdjcTIJQWKz6M7b_8a_-8dtnJ2sadwBN4yDX8OUtq2ZjlyD_n48kuONsAJAMRDFH0JQt_4</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>Reismann, Marc, PhD</creator><creator>Ghaffarpour, Nader, MD</creator><creator>Luvall, Ethel, MSc</creator><creator>Jirmo, Adan C., PhD</creator><creator>Winqvist, Ola, PhD</creator><creator>Radtke, Josephine, MD</creator><creator>Wester, Tomas, PhD</creator><creator>Claesson, Gösta, PhD</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><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20140301</creationdate><title>Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children</title><author>Reismann, Marc, PhD ; Ghaffarpour, Nader, MD ; Luvall, Ethel, MSc ; Jirmo, Adan C., PhD ; Winqvist, Ola, PhD ; Radtke, Josephine, MD ; Wester, Tomas, PhD ; Claesson, Gösta, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-5d2619f675e001b2211c867f9b5cc0ec2007d9613eb64545972c29428cf826a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antineoplastic Agents - therapeutic use</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Drug Monitoring - methods</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Infant</topic><topic>Ligands</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Lymphatic Abnormalities - metabolism</topic><topic>Lymphatic Abnormalities - therapy</topic><topic>Lymphatic malformation</topic><topic>Male</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - physiology</topic><topic>OK-432</topic><topic>Picibanil - therapeutic use</topic><topic>Predictive Value of Tests</topic><topic>Sclerotherapy</topic><topic>Sclerotherapy - methods</topic><topic>Surgery</topic><topic>Toll-like receptor</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-Like Receptor 7 - metabolism</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reismann, Marc, PhD</creatorcontrib><creatorcontrib>Ghaffarpour, Nader, MD</creatorcontrib><creatorcontrib>Luvall, Ethel, MSc</creatorcontrib><creatorcontrib>Jirmo, Adan C., PhD</creatorcontrib><creatorcontrib>Winqvist, Ola, PhD</creatorcontrib><creatorcontrib>Radtke, Josephine, MD</creatorcontrib><creatorcontrib>Wester, Tomas, PhD</creatorcontrib><creatorcontrib>Claesson, Gösta, PhD</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><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reismann, Marc, PhD</au><au>Ghaffarpour, Nader, MD</au><au>Luvall, Ethel, MSc</au><au>Jirmo, Adan C., PhD</au><au>Winqvist, Ola, PhD</au><au>Radtke, Josephine, MD</au><au>Wester, Tomas, PhD</au><au>Claesson, Gösta, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>187</volume><issue>1</issue><spage>197</spage><epage>201</epage><pages>197-201</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4–dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. Methods Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05. Results The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y ( P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. Conclusions Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24215906</pmid><doi>10.1016/j.jss.2013.09.037</doi><tpages>5</tpages></addata></record> |
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| subjects | Antineoplastic Agents - therapeutic use Child, Preschool Children Drug Monitoring - methods Female Flow Cytometry Humans Infant Ligands Lipopolysaccharides - pharmacology Lymphatic Abnormalities - metabolism Lymphatic Abnormalities - therapy Lymphatic malformation Male Monocytes - drug effects Monocytes - physiology OK-432 Picibanil - therapeutic use Predictive Value of Tests Sclerotherapy Sclerotherapy - methods Surgery Toll-like receptor Toll-Like Receptor 4 - metabolism Toll-Like Receptor 7 - metabolism Up-Regulation - drug effects |
| title | Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children |
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