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Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease Rahavi, Seyed M.; Aletaha, Maryam; Farrokhi, Ali; Lorentzian, Amanda; Lange, Philipp F.; Maxwell, Chris; Lim, Chinten James; Reid, Gregor S. D.
Abstract
High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow, liver, and CNS, to achieve a cure. While preclinical modeling is a powerful tool for the development of novel cancer therapies, the lack of widely available models of metastatic neuroblastoma represents a significant barrier to the development of effective treatment strategies. To address this need, we report a novel luciferase-expressing derivative of the widely used Th-MYCN mouse. While our model recapitulates the non-metastatic neuroblastoma development seen in the parental transgenic strain, transplantation of primary tumor cells from disease-bearing mice enables longitudinal monitoring of neuroblastoma growth at distinct sites in immune-deficient or immune-competent recipients. The transplanted tumors retain GD2 expression through many rounds of serial transplantation and are sensitive to GD2-targeted immune therapy. With more diverse tissue localization than is seen with human cell line-derived xenografts, this novel model for high-risk neuroblastoma could contribute to the optimization of immune-based treatments for this deadly disease.
Item Metadata
Title |
Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease
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Creator | |
Contributor | |
Publisher |
Multidisciplinary Digital Publishing Institute
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Date Issued |
2023-07-28
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Description |
High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow, liver, and CNS, to achieve a cure. While preclinical modeling is a powerful tool for the development of novel cancer therapies, the lack of widely available models of metastatic neuroblastoma represents a significant barrier to the development of effective treatment strategies. To address this need, we report a novel luciferase-expressing derivative of the widely used Th-MYCN mouse. While our model recapitulates the non-metastatic neuroblastoma development seen in the parental transgenic strain, transplantation of primary tumor cells from disease-bearing mice enables longitudinal monitoring of neuroblastoma growth at distinct sites in immune-deficient or immune-competent recipients. The transplanted tumors retain GD2 expression through many rounds of serial transplantation and are sensitive to GD2-targeted immune therapy. With more diverse tissue localization than is seen with human cell line-derived xenografts, this novel model for high-risk neuroblastoma could contribute to the optimization of immune-based treatments for this deadly disease.
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Subject | |
Genre | |
Type | |
Language |
eng
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Date Available |
2023-08-25
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Provider |
Vancouver : University of British Columbia Library
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Rights |
CC BY 4.0
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DOI |
10.14288/1.0435589
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URI | |
Affiliation | |
Citation |
International Journal of Molecular Sciences 24 (15): 12071 (2023)
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Publisher DOI |
10.3390/ijms241512071
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty; Researcher
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
CC BY 4.0