Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a...
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| Veröffentlicht in: | Cancer research and treatment 2017-10, Vol.49 (4), p.915-926 |
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| creator | Heo, Eun Jin Cho, Young Jae Cho, William Chi Hong, Ji Eun Jeon, Hye-Kyung Oh, Doo-Yi Choi, Yoon-La Song, Sang Yong Choi, Jung-Joo Bae, Duk-Soo Lee, Yoo-Young Choi, Chel Hun Kim, Tae-Joong Park, Woong-Yang Kim, Byoung-Gie Lee, Jeong-Won |
| description | Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC. |
| doi_str_mv | 10.4143/crt.2016.322 |
| format | Article |
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We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.</description><identifier>EISSN: 2005-9256</identifier><identifier>DOI: 10.4143/crt.2016.322</identifier><identifier>PMID: 28052650</identifier><language>eng</language><publisher>Korea (South)</publisher><subject>Adult ; Animals ; Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor ; Biopsy ; Carboplatin - pharmacology ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Drug Evaluation, Preclinical ; ErbB Receptors - antagonists & inhibitors ; ErbB Receptors - metabolism ; Female ; Genomic Instability ; Heterografts ; Humans ; Mice ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial - drug therapy ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - pathology ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Paclitaxel - pharmacology ; Translational Medical Research ; Xenograft Model Antitumor Assays</subject><ispartof>Cancer research and treatment, 2017-10, Vol.49 (4), p.915-926</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28052650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heo, Eun Jin</creatorcontrib><creatorcontrib>Cho, Young Jae</creatorcontrib><creatorcontrib>Cho, William Chi</creatorcontrib><creatorcontrib>Hong, Ji Eun</creatorcontrib><creatorcontrib>Jeon, Hye-Kyung</creatorcontrib><creatorcontrib>Oh, Doo-Yi</creatorcontrib><creatorcontrib>Choi, Yoon-La</creatorcontrib><creatorcontrib>Song, Sang Yong</creatorcontrib><creatorcontrib>Choi, Jung-Joo</creatorcontrib><creatorcontrib>Bae, Duk-Soo</creatorcontrib><creatorcontrib>Lee, Yoo-Young</creatorcontrib><creatorcontrib>Choi, Chel Hun</creatorcontrib><creatorcontrib>Kim, Tae-Joong</creatorcontrib><creatorcontrib>Park, Woong-Yang</creatorcontrib><creatorcontrib>Kim, Byoung-Gie</creatorcontrib><creatorcontrib>Lee, Jeong-Won</creatorcontrib><title>Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies</title><title>Cancer research and treatment</title><addtitle>Cancer Res Treat</addtitle><description>Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.</description><subject>Adult</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomarkers, Tumor</subject><subject>Biopsy</subject><subject>Carboplatin - pharmacology</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>ErbB Receptors - antagonists & inhibitors</subject><subject>ErbB Receptors - metabolism</subject><subject>Female</subject><subject>Genomic Instability</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Molecular Targeted Therapy</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Neoplasms, Glandular and Epithelial - drug therapy</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Paclitaxel - pharmacology</subject><subject>Translational Medical Research</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2005-9256</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEtLw0AUhQdBbK3uXMss3aTeeWaylFofUGlBC-7CZHKjI2kSZyYF_70F6-oszsfH4RByxWAumRS3LqQ5B6bngvMTMuUAKiu40hNyHuMXgJYiZ2dkwg0orhVMyXZjk8cuZfcY_B5r-o5d_xFsk-hLX2Mbad_Q5eDTJ7betnS9t8Hbji5s5zDQpg90E9C1vvPuUL-msfYYL8hpY9uIl8ecke3D8m3xlK3Wj8-Lu1U2MMlSphAgZ1g5xiRwkx8GAq9AOqZN3gjNmyKvCs1rqAyrpAOpwRSgKlfkTBguZuTmzzuE_nvEmMqdjw7b1nbYj7FkRqm8YGDMAb0-omO1w7ocgt_Z8FP-XyF-ASrfXEU</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Heo, Eun Jin</creator><creator>Cho, Young Jae</creator><creator>Cho, William Chi</creator><creator>Hong, Ji Eun</creator><creator>Jeon, Hye-Kyung</creator><creator>Oh, Doo-Yi</creator><creator>Choi, Yoon-La</creator><creator>Song, Sang Yong</creator><creator>Choi, Jung-Joo</creator><creator>Bae, Duk-Soo</creator><creator>Lee, Yoo-Young</creator><creator>Choi, Chel Hun</creator><creator>Kim, Tae-Joong</creator><creator>Park, Woong-Yang</creator><creator>Kim, Byoung-Gie</creator><creator>Lee, Jeong-Won</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201710</creationdate><title>Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies</title><author>Heo, Eun Jin ; Cho, Young Jae ; Cho, William Chi ; Hong, Ji Eun ; Jeon, Hye-Kyung ; Oh, Doo-Yi ; Choi, Yoon-La ; Song, Sang Yong ; Choi, Jung-Joo ; Bae, Duk-Soo ; Lee, Yoo-Young ; Choi, Chel Hun ; Kim, Tae-Joong ; Park, Woong-Yang ; Kim, Byoung-Gie ; Lee, Jeong-Won</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p141t-5e0071ebc114028700602b04c1687f362f97b962d0b81b4c04608905bc9713823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomarkers, Tumor</topic><topic>Biopsy</topic><topic>Carboplatin - pharmacology</topic><topic>Carcinoma, Ovarian Epithelial</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>ErbB Receptors - antagonists & inhibitors</topic><topic>ErbB Receptors - metabolism</topic><topic>Female</topic><topic>Genomic Instability</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Molecular Targeted Therapy</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Neoplasms, Glandular and Epithelial - drug therapy</topic><topic>Neoplasms, Glandular and Epithelial - genetics</topic><topic>Neoplasms, Glandular and Epithelial - pathology</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Paclitaxel - pharmacology</topic><topic>Translational Medical Research</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heo, Eun Jin</creatorcontrib><creatorcontrib>Cho, Young Jae</creatorcontrib><creatorcontrib>Cho, William Chi</creatorcontrib><creatorcontrib>Hong, Ji Eun</creatorcontrib><creatorcontrib>Jeon, Hye-Kyung</creatorcontrib><creatorcontrib>Oh, Doo-Yi</creatorcontrib><creatorcontrib>Choi, Yoon-La</creatorcontrib><creatorcontrib>Song, Sang Yong</creatorcontrib><creatorcontrib>Choi, Jung-Joo</creatorcontrib><creatorcontrib>Bae, Duk-Soo</creatorcontrib><creatorcontrib>Lee, Yoo-Young</creatorcontrib><creatorcontrib>Choi, Chel Hun</creatorcontrib><creatorcontrib>Kim, Tae-Joong</creatorcontrib><creatorcontrib>Park, Woong-Yang</creatorcontrib><creatorcontrib>Kim, Byoung-Gie</creatorcontrib><creatorcontrib>Lee, Jeong-Won</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heo, Eun Jin</au><au>Cho, Young Jae</au><au>Cho, William Chi</au><au>Hong, Ji Eun</au><au>Jeon, Hye-Kyung</au><au>Oh, Doo-Yi</au><au>Choi, Yoon-La</au><au>Song, Sang Yong</au><au>Choi, Jung-Joo</au><au>Bae, Duk-Soo</au><au>Lee, Yoo-Young</au><au>Choi, Chel Hun</au><au>Kim, Tae-Joong</au><au>Park, Woong-Yang</au><au>Kim, Byoung-Gie</au><au>Lee, Jeong-Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies</atitle><jtitle>Cancer research and treatment</jtitle><addtitle>Cancer Res Treat</addtitle><date>2017-10</date><risdate>2017</risdate><volume>49</volume><issue>4</issue><spage>915</spage><epage>926</epage><pages>915-926</pages><eissn>2005-9256</eissn><abstract>Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.</abstract><cop>Korea (South)</cop><pmid>28052650</pmid><doi>10.4143/crt.2016.322</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animals Antineoplastic Agents - therapeutic use Biomarkers, Tumor Biopsy Carboplatin - pharmacology Carcinoma, Ovarian Epithelial Disease Models, Animal Drug Evaluation, Preclinical ErbB Receptors - antagonists & inhibitors ErbB Receptors - metabolism Female Genomic Instability Heterografts Humans Mice Middle Aged Molecular Targeted Therapy Neoplasm Grading Neoplasm Staging Neoplasms, Glandular and Epithelial - drug therapy Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - pathology Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Paclitaxel - pharmacology Translational Medical Research Xenograft Model Antitumor Assays |
| title | Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies |
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