Rhabdomyosarcoma xenotransplants in zebrafish embryos
Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High‐risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost‐efficient estimates of antitumor efficacy of cand...
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Veröffentlicht in: | Pediatric blood & cancer 2023-01, Vol.70 (1), p.e30053-n/a |
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description | Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High‐risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost‐efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish‐based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water‐soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof‐of‐principle experiments, chemotherapy drugs with established clinical anti‐RMS efficacy (vincristine, dactinomycin) and the mitogen‐activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross‐sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost‐effective solution for preclinical candidate drug testing. |
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High‐risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost‐efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish‐based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water‐soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof‐of‐principle experiments, chemotherapy drugs with established clinical anti‐RMS efficacy (vincristine, dactinomycin) and the mitogen‐activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross‐sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost‐effective solution for preclinical candidate drug testing.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.30053</identifier><identifier>PMID: 36317680</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; Antitumor activity ; Cell culture ; Chemotherapy ; Child ; Dactinomycin ; Danio rerio ; Drug development ; Drug screening ; Embryos ; Enzyme inhibitors ; Hematology ; Heterografts ; Humans ; Kinases ; Mammals ; Metastases ; Oncology ; Pediatrics ; Precision medicine ; Protein kinase ; Rhabdomyosarcoma ; Rhabdomyosarcoma - drug therapy ; Rhabdomyosarcoma - pathology ; Rhabdomyosarcoma, Embryonal - drug therapy ; RMS ; Tumor cells ; Vincristine ; xenograft ; Xenograft Model Antitumor Assays ; Xenografts ; Zebrafish ; zebrafish embryo</subject><ispartof>Pediatric blood & cancer, 2023-01, Vol.70 (1), p.e30053-n/a</ispartof><rights>2022 The Authors. published by Wiley Periodicals LLC.</rights><rights>2022 The Authors. 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High‐risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost‐efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish‐based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water‐soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof‐of‐principle experiments, chemotherapy drugs with established clinical anti‐RMS efficacy (vincristine, dactinomycin) and the mitogen‐activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross‐sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost‐effective solution for preclinical candidate drug testing.</description><subject>Animals</subject><subject>Antitumor activity</subject><subject>Cell culture</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Dactinomycin</subject><subject>Danio rerio</subject><subject>Drug development</subject><subject>Drug screening</subject><subject>Embryos</subject><subject>Enzyme inhibitors</subject><subject>Hematology</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Kinases</subject><subject>Mammals</subject><subject>Metastases</subject><subject>Oncology</subject><subject>Pediatrics</subject><subject>Precision medicine</subject><subject>Protein kinase</subject><subject>Rhabdomyosarcoma</subject><subject>Rhabdomyosarcoma - drug therapy</subject><subject>Rhabdomyosarcoma - pathology</subject><subject>Rhabdomyosarcoma, Embryonal - drug therapy</subject><subject>RMS</subject><subject>Tumor cells</subject><subject>Vincristine</subject><subject>xenograft</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><subject>Zebrafish</subject><subject>zebrafish embryo</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp10M1LwzAYBvAgipvTg_-AFLzooVs-mqY9uuEXDBTRc3ibJayjbWqyovOvN7NzB8HT-x5-PDw8CJ0TPCYY00lbqDHDmLMDNCQ84THHRBzuf5wP0In3q0BTzLNjNGApIyLN8BDxlyUUC1tvrAenbA3Rp27s2kHj2wqatY_KJvrShQNT-mWk68IFeoqODFRen-3uCL3d3b7OHuL50_3j7GYeK0YyFnNNE8rMAjK1rUISnjMClAqhGAA1GS2y1IBQBlRKqKGhNxCDlS5ACJazEbrqc1tn3zvt17IuvdJVaKZt5yUVjGDOCU8DvfxDV7ZzTWgXVIJJmic0C-q6V8pZ7502snVlDW4jCZbbLWXYUv5sGezFLrErar3Yy9_xApj04KOs9Ob_JPk8nfWR31PgfCE</recordid><startdate>202301</startdate><enddate>202301</enddate><creator>Siebert, Jakob</creator><creator>Schneider, Michaela</creator><creator>Reuter‐Schmitt, Daniela</creator><creator>Würtemberger, Julia</creator><creator>Neubüser, Annette</creator><creator>Driever, Wolfgang</creator><creator>Hettmer, Simone</creator><creator>Kapp, Friedrich G.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</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>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5709-8000</orcidid><orcidid>https://orcid.org/0000-0003-1709-4448</orcidid><orcidid>https://orcid.org/0000-0002-2729-6177</orcidid></search><sort><creationdate>202301</creationdate><title>Rhabdomyosarcoma xenotransplants in zebrafish embryos</title><author>Siebert, Jakob ; Schneider, Michaela ; Reuter‐Schmitt, Daniela ; Würtemberger, Julia ; Neubüser, Annette ; Driever, Wolfgang ; Hettmer, Simone ; Kapp, Friedrich G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3183-5e2423fda8c1545145931a2277c3aa2f82b86fa7cfac612f2501a1f0ceba77393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Antitumor activity</topic><topic>Cell culture</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Dactinomycin</topic><topic>Danio rerio</topic><topic>Drug development</topic><topic>Drug screening</topic><topic>Embryos</topic><topic>Enzyme inhibitors</topic><topic>Hematology</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Kinases</topic><topic>Mammals</topic><topic>Metastases</topic><topic>Oncology</topic><topic>Pediatrics</topic><topic>Precision medicine</topic><topic>Protein kinase</topic><topic>Rhabdomyosarcoma</topic><topic>Rhabdomyosarcoma - drug therapy</topic><topic>Rhabdomyosarcoma - pathology</topic><topic>Rhabdomyosarcoma, Embryonal - drug therapy</topic><topic>RMS</topic><topic>Tumor cells</topic><topic>Vincristine</topic><topic>xenograft</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><topic>Zebrafish</topic><topic>zebrafish embryo</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siebert, Jakob</creatorcontrib><creatorcontrib>Schneider, Michaela</creatorcontrib><creatorcontrib>Reuter‐Schmitt, Daniela</creatorcontrib><creatorcontrib>Würtemberger, Julia</creatorcontrib><creatorcontrib>Neubüser, Annette</creatorcontrib><creatorcontrib>Driever, Wolfgang</creatorcontrib><creatorcontrib>Hettmer, Simone</creatorcontrib><creatorcontrib>Kapp, Friedrich G.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siebert, Jakob</au><au>Schneider, Michaela</au><au>Reuter‐Schmitt, Daniela</au><au>Würtemberger, Julia</au><au>Neubüser, Annette</au><au>Driever, Wolfgang</au><au>Hettmer, Simone</au><au>Kapp, Friedrich G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rhabdomyosarcoma xenotransplants in zebrafish embryos</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2023-01</date><risdate>2023</risdate><volume>70</volume><issue>1</issue><spage>e30053</spage><epage>n/a</epage><pages>e30053-n/a</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High‐risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost‐efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish‐based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water‐soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof‐of‐principle experiments, chemotherapy drugs with established clinical anti‐RMS efficacy (vincristine, dactinomycin) and the mitogen‐activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross‐sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost‐effective solution for preclinical candidate drug testing.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36317680</pmid><doi>10.1002/pbc.30053</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5709-8000</orcidid><orcidid>https://orcid.org/0000-0003-1709-4448</orcidid><orcidid>https://orcid.org/0000-0002-2729-6177</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antitumor activity Cell culture Chemotherapy Child Dactinomycin Danio rerio Drug development Drug screening Embryos Enzyme inhibitors Hematology Heterografts Humans Kinases Mammals Metastases Oncology Pediatrics Precision medicine Protein kinase Rhabdomyosarcoma Rhabdomyosarcoma - drug therapy Rhabdomyosarcoma - pathology Rhabdomyosarcoma, Embryonal - drug therapy RMS Tumor cells Vincristine xenograft Xenograft Model Antitumor Assays Xenografts Zebrafish zebrafish embryo |
title | Rhabdomyosarcoma xenotransplants in zebrafish embryos |
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