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Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts

High engraftment rates are critical to any patient-derived xenograft (PDX) program and the loss of PDX models due to the development of lymphoproliferative tumors (LTs) is costly and inefficient. We hypothesized that routine injection of rituximab, an anti-CD20 antibody, at the time of implantation...

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Autores principales: Leiting, Jennifer L., Hernandez, Matthew C., Yang, Lin, Bergquist, John R., Ivanics, Tommy, Graham, Rondell P., Truty, Mark J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459856/
https://www.ncbi.nlm.nih.gov/pubmed/30976061
http://dx.doi.org/10.1038/s41598-019-42470-w
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author Leiting, Jennifer L.
Hernandez, Matthew C.
Yang, Lin
Bergquist, John R.
Ivanics, Tommy
Graham, Rondell P.
Truty, Mark J.
author_facet Leiting, Jennifer L.
Hernandez, Matthew C.
Yang, Lin
Bergquist, John R.
Ivanics, Tommy
Graham, Rondell P.
Truty, Mark J.
author_sort Leiting, Jennifer L.
collection PubMed
description High engraftment rates are critical to any patient-derived xenograft (PDX) program and the loss of PDX models due to the development of lymphoproliferative tumors (LTs) is costly and inefficient. We hypothesized that routine injection of rituximab, an anti-CD20 antibody, at the time of implantation would reduce the incidence of LTs. Rituximab injection was added to the standard PDX engraftment protocol. Univariate analysis and multivariate logistic regression were used to determine the significance of various factors. A total of 811 generations of PDX were implanted with 406 receiving rituximab with implantation. On multivariable analysis, rituximab was an independent factor for decreased LT formation across the entire cohort (OR 0.465, 95% CI 0.271–0.797, p = 0.005). Hepatocellular carcinomas (OR 0.319, 95% CI 0.107–0.949, p = 0.040) and cholangiocarcinomas (OR 0.185, 95% CI 0.049–0.696, p = 0.113) were the specific malignant histologic subtypes that demonstrated the greatest benefit. The frequency of LTs decreased across the entire cohort with rituximab administration and PDX tumors that are traditionally associated with higher rates of LT formation, HCCs and CCAs, appear to benefit the most from rituximab treatment. Routine use of rituximab at the time of tumor implantation may have significant programmatic benefits for laboratories that utilize PDX models.
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spelling pubmed-64598562019-04-16 Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts Leiting, Jennifer L. Hernandez, Matthew C. Yang, Lin Bergquist, John R. Ivanics, Tommy Graham, Rondell P. Truty, Mark J. Sci Rep Article High engraftment rates are critical to any patient-derived xenograft (PDX) program and the loss of PDX models due to the development of lymphoproliferative tumors (LTs) is costly and inefficient. We hypothesized that routine injection of rituximab, an anti-CD20 antibody, at the time of implantation would reduce the incidence of LTs. Rituximab injection was added to the standard PDX engraftment protocol. Univariate analysis and multivariate logistic regression were used to determine the significance of various factors. A total of 811 generations of PDX were implanted with 406 receiving rituximab with implantation. On multivariable analysis, rituximab was an independent factor for decreased LT formation across the entire cohort (OR 0.465, 95% CI 0.271–0.797, p = 0.005). Hepatocellular carcinomas (OR 0.319, 95% CI 0.107–0.949, p = 0.040) and cholangiocarcinomas (OR 0.185, 95% CI 0.049–0.696, p = 0.113) were the specific malignant histologic subtypes that demonstrated the greatest benefit. The frequency of LTs decreased across the entire cohort with rituximab administration and PDX tumors that are traditionally associated with higher rates of LT formation, HCCs and CCAs, appear to benefit the most from rituximab treatment. Routine use of rituximab at the time of tumor implantation may have significant programmatic benefits for laboratories that utilize PDX models. Nature Publishing Group UK 2019-04-11 /pmc/articles/PMC6459856/ /pubmed/30976061 http://dx.doi.org/10.1038/s41598-019-42470-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Leiting, Jennifer L.
Hernandez, Matthew C.
Yang, Lin
Bergquist, John R.
Ivanics, Tommy
Graham, Rondell P.
Truty, Mark J.
Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title_full Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title_fullStr Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title_full_unstemmed Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title_short Rituximab Decreases Lymphoproliferative Tumor Formation in Hepatopancreaticobiliary and Gastrointestinal Cancer Patient-Derived Xenografts
title_sort rituximab decreases lymphoproliferative tumor formation in hepatopancreaticobiliary and gastrointestinal cancer patient-derived xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459856/
https://www.ncbi.nlm.nih.gov/pubmed/30976061
http://dx.doi.org/10.1038/s41598-019-42470-w
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