Cargando…
Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()()
Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)–infected human lymphocytes...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487305/ https://www.ncbi.nlm.nih.gov/pubmed/28658648 http://dx.doi.org/10.1016/j.neo.2017.04.007 |
_version_ | 1783246431916654592 |
---|---|
author | Butler, Kristina A. Hou, Xiaonan Becker, Marc A. Zanfagnin, Valentina Enderica-Gonzalez, Sergio Visscher, Daniel Kalli, Kimberly R. Tienchaianada, Piyawan Haluska, Paul Weroha, S. John |
author_facet | Butler, Kristina A. Hou, Xiaonan Becker, Marc A. Zanfagnin, Valentina Enderica-Gonzalez, Sergio Visscher, Daniel Kalli, Kimberly R. Tienchaianada, Piyawan Haluska, Paul Weroha, S. John |
author_sort | Butler, Kristina A. |
collection | PubMed |
description | Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab) to 5.6% (n = 160 with rituximab), and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth. |
format | Online Article Text |
id | pubmed-5487305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54873052017-07-12 Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() Butler, Kristina A. Hou, Xiaonan Becker, Marc A. Zanfagnin, Valentina Enderica-Gonzalez, Sergio Visscher, Daniel Kalli, Kimberly R. Tienchaianada, Piyawan Haluska, Paul Weroha, S. John Neoplasia Original article Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab) to 5.6% (n = 160 with rituximab), and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth. Neoplasia Press 2017-06-26 /pmc/articles/PMC5487305/ /pubmed/28658648 http://dx.doi.org/10.1016/j.neo.2017.04.007 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Butler, Kristina A. Hou, Xiaonan Becker, Marc A. Zanfagnin, Valentina Enderica-Gonzalez, Sergio Visscher, Daniel Kalli, Kimberly R. Tienchaianada, Piyawan Haluska, Paul Weroha, S. John Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title | Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title_full | Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title_fullStr | Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title_full_unstemmed | Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title_short | Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts()() |
title_sort | prevention of human lymphoproliferative tumor formation in ovarian cancer patient-derived xenografts()() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487305/ https://www.ncbi.nlm.nih.gov/pubmed/28658648 http://dx.doi.org/10.1016/j.neo.2017.04.007 |
work_keys_str_mv | AT butlerkristinaa preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT houxiaonan preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT beckermarca preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT zanfagninvalentina preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT endericagonzalezsergio preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT visscherdaniel preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT kallikimberlyr preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT tienchaianadapiyawan preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT haluskapaul preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts AT werohasjohn preventionofhumanlymphoproliferativetumorformationinovariancancerpatientderivedxenografts |