A patient derived xenograft model of cervical cancer and cervical dysplasia
To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule. Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the re...
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| Veröffentlicht in: | PloS one 2018-10, Vol.13 (10), p.e0206539-e0206539 |
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| creator | Larmour, Luke I Cousins, Fiona L Teague, Julie A Deane, James A Jobling, Tom W Gargett, Caroline E |
| description | To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.
Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.
The overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.
The subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model. |
| doi_str_mv | 10.1371/journal.pone.0206539 |
| format | Article |
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Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.
The overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.
The subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0206539</identifier><identifier>PMID: 30365542</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenosquamous ; Analysis ; Biology and life sciences ; Biopsy ; Cancer ; Cell suspensions ; Cervical cancer ; Cervix ; Cervix dysplasia ; Dysplasia ; Family medical history ; Gene expression ; Grafts ; Gynecology ; Human papillomavirus ; Immunohistochemistry ; Invasiveness ; Medical research ; Medical screening ; Medicine and Health Sciences ; Metastasis ; Mice ; Obstetrics ; Prostate ; Squamous cell carcinoma ; Tissues ; Tumors ; Womens health ; Xenografts ; Xenotransplantation</subject><ispartof>PloS one, 2018-10, Vol.13 (10), p.e0206539-e0206539</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Larmour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Larmour et al 2018 Larmour et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-1ae2c01ed6e7d1c13a3791125389eed366c0477525a7403a1ed1e2ee3099b7763</citedby><cites>FETCH-LOGICAL-c653t-1ae2c01ed6e7d1c13a3791125389eed366c0477525a7403a1ed1e2ee3099b7763</cites><orcidid>0000-0002-3590-2077 ; 0000-0002-7146-5978</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203389/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203389/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30365542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Larmour, Luke I</creatorcontrib><creatorcontrib>Cousins, Fiona L</creatorcontrib><creatorcontrib>Teague, Julie A</creatorcontrib><creatorcontrib>Deane, James A</creatorcontrib><creatorcontrib>Jobling, Tom W</creatorcontrib><creatorcontrib>Gargett, Caroline E</creatorcontrib><title>A patient derived xenograft model of cervical cancer and cervical dysplasia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.
Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.
The overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.
The subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model.</description><subject>Adenocarcinoma</subject><subject>Adenosquamous</subject><subject>Analysis</subject><subject>Biology and life sciences</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cell suspensions</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cervix dysplasia</subject><subject>Dysplasia</subject><subject>Family medical history</subject><subject>Gene expression</subject><subject>Grafts</subject><subject>Gynecology</subject><subject>Human papillomavirus</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Medical research</subject><subject>Medical screening</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Obstetrics</subject><subject>Prostate</subject><subject>Squamous cell 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patient derived xenograft model of cervical cancer and cervical dysplasia</title><author>Larmour, Luke I ; Cousins, Fiona L ; Teague, Julie A ; Deane, James A ; Jobling, Tom W ; Gargett, Caroline E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-1ae2c01ed6e7d1c13a3791125389eed366c0477525a7403a1ed1e2ee3099b7763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma</topic><topic>Adenosquamous</topic><topic>Analysis</topic><topic>Biology and life sciences</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Cell suspensions</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Cervix dysplasia</topic><topic>Dysplasia</topic><topic>Family medical history</topic><topic>Gene expression</topic><topic>Grafts</topic><topic>Gynecology</topic><topic>Human papillomavirus</topic><topic>Immunohistochemistry</topic><topic>Invasiveness</topic><topic>Medical 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derived xenograft model of cervical cancer and cervical dysplasia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-10-26</date><risdate>2018</risdate><volume>13</volume><issue>10</issue><spage>e0206539</spage><epage>e0206539</epage><pages>e0206539-e0206539</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.
Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages. Parent and xenograft tumours were examined by immunohistochemistry for p16INK41, HPV, and CD-45. Single cell suspensions of mixed mouse and human, or human only cell populations were also transplanted.
The overall engraftment rate for the primary cervical cancer PDX model was 71.4 ±12.5% (n = 14). Tumours maintained morphological, histoarchitecture and immunohistochemical features of the parent tumour, and demonstrated invasiveness into local tissues. Single cell suspensions did not produce tumour growth in this model. Mean length of time (32.4 +/- 3.5 weeks) for the transplanted tissue to generate a tumour in the animal was similar between successive transplantations. Three of four xenografted cervical dysplasia tissues generated microscopic cystic structures resembling dysplastic cervical tissue. Normal cervical tissue (4 of 5 xenografted) also developed microscopic cervical tissue grafts.
The subrenal capsule can be used for a PDX model of human cervical cancer with a good engraftment rate and the ability to model in vivo characteristics of cervical cancer. For the first time we have demonstrated that cervical dysplasia and normal cervical tissue generated microscopic tissues in a PDX model.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30365542</pmid><doi>10.1371/journal.pone.0206539</doi><tpages>e0206539</tpages><orcidid>https://orcid.org/0000-0002-3590-2077</orcidid><orcidid>https://orcid.org/0000-0002-7146-5978</orcidid><oa>free_for_read</oa></addata></record> |
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| source | PLoS; Full-Text Journals in Chemistry (Open access); PubMed Central; Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | Adenocarcinoma Adenosquamous Analysis Biology and life sciences Biopsy Cancer Cell suspensions Cervical cancer Cervix Cervix dysplasia Dysplasia Family medical history Gene expression Grafts Gynecology Human papillomavirus Immunohistochemistry Invasiveness Medical research Medical screening Medicine and Health Sciences Metastasis Mice Obstetrics Prostate Squamous cell carcinoma Tissues Tumors Womens health Xenografts Xenotransplantation |
| title | A patient derived xenograft model of cervical cancer and cervical dysplasia |
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