Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish
An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited...
Ausführliche Beschreibung
Autor*in: |
Xiaolin Ai [verfasserIn] Zengpanpan Ye [verfasserIn] Chaoxin Xiao [verfasserIn] Jian Zhong [verfasserIn] Joseph J. Lancman [verfasserIn] Xuelan Chen [verfasserIn] Xiangyu Pan [verfasserIn] Yu Yang [verfasserIn] Lin Zhou [verfasserIn] Xiang Wang [verfasserIn] Huashan Shi [verfasserIn] Dongmei Zhang [verfasserIn] Yuqin Yao [verfasserIn] Dan Cao [verfasserIn] Chengjian Zhao [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Disease Models & Mechanisms - The Company of Biologists, 2011, 15(2022), 4 |
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Übergeordnetes Werk: |
volume:15 ; year:2022 ; number:4 |
Links: |
Link aufrufen |
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DOI / URN: |
10.1242/dmm.049109 |
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Katalog-ID: |
DOAJ028890485 |
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10.1242/dmm.049109 doi (DE-627)DOAJ028890485 (DE-599)DOAJ61dea9b1204249fe97e11002a8215fb4 DE-627 ger DE-627 rakwb eng RB1-214 Xiaolin Ai verfasserin aut Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. zebrafish glioblastoma heterogeneity blood–brain barrier pdx pdox Medicine R Pathology Zengpanpan Ye verfasserin aut Chaoxin Xiao verfasserin aut Jian Zhong verfasserin aut Joseph J. Lancman verfasserin aut Xuelan Chen verfasserin aut Xiangyu Pan verfasserin aut Yu Yang verfasserin aut Lin Zhou verfasserin aut Xiang Wang verfasserin aut Huashan Shi verfasserin aut Dongmei Zhang verfasserin aut Yuqin Yao verfasserin aut Dan Cao verfasserin aut Chengjian Zhao verfasserin aut In Disease Models & Mechanisms The Company of Biologists, 2011 15(2022), 4 (DE-627)578531917 (DE-600)2451104-3 17548411 nnns volume:15 year:2022 number:4 https://doi.org/10.1242/dmm.049109 kostenfrei https://doaj.org/article/61dea9b1204249fe97e11002a8215fb4 kostenfrei http://dmm.biologists.org/content/15/4/dmm049109 kostenfrei https://doaj.org/toc/1754-8403 Journal toc kostenfrei https://doaj.org/toc/1754-8411 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2022 4 |
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10.1242/dmm.049109 doi (DE-627)DOAJ028890485 (DE-599)DOAJ61dea9b1204249fe97e11002a8215fb4 DE-627 ger DE-627 rakwb eng RB1-214 Xiaolin Ai verfasserin aut Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. zebrafish glioblastoma heterogeneity blood–brain barrier pdx pdox Medicine R Pathology Zengpanpan Ye verfasserin aut Chaoxin Xiao verfasserin aut Jian Zhong verfasserin aut Joseph J. Lancman verfasserin aut Xuelan Chen verfasserin aut Xiangyu Pan verfasserin aut Yu Yang verfasserin aut Lin Zhou verfasserin aut Xiang Wang verfasserin aut Huashan Shi verfasserin aut Dongmei Zhang verfasserin aut Yuqin Yao verfasserin aut Dan Cao verfasserin aut Chengjian Zhao verfasserin aut In Disease Models & Mechanisms The Company of Biologists, 2011 15(2022), 4 (DE-627)578531917 (DE-600)2451104-3 17548411 nnns volume:15 year:2022 number:4 https://doi.org/10.1242/dmm.049109 kostenfrei https://doaj.org/article/61dea9b1204249fe97e11002a8215fb4 kostenfrei http://dmm.biologists.org/content/15/4/dmm049109 kostenfrei https://doaj.org/toc/1754-8403 Journal toc kostenfrei https://doaj.org/toc/1754-8411 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2022 4 |
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10.1242/dmm.049109 doi (DE-627)DOAJ028890485 (DE-599)DOAJ61dea9b1204249fe97e11002a8215fb4 DE-627 ger DE-627 rakwb eng RB1-214 Xiaolin Ai verfasserin aut Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. zebrafish glioblastoma heterogeneity blood–brain barrier pdx pdox Medicine R Pathology Zengpanpan Ye verfasserin aut Chaoxin Xiao verfasserin aut Jian Zhong verfasserin aut Joseph J. Lancman verfasserin aut Xuelan Chen verfasserin aut Xiangyu Pan verfasserin aut Yu Yang verfasserin aut Lin Zhou verfasserin aut Xiang Wang verfasserin aut Huashan Shi verfasserin aut Dongmei Zhang verfasserin aut Yuqin Yao verfasserin aut Dan Cao verfasserin aut Chengjian Zhao verfasserin aut In Disease Models & Mechanisms The Company of Biologists, 2011 15(2022), 4 (DE-627)578531917 (DE-600)2451104-3 17548411 nnns volume:15 year:2022 number:4 https://doi.org/10.1242/dmm.049109 kostenfrei https://doaj.org/article/61dea9b1204249fe97e11002a8215fb4 kostenfrei http://dmm.biologists.org/content/15/4/dmm049109 kostenfrei https://doaj.org/toc/1754-8403 Journal toc kostenfrei https://doaj.org/toc/1754-8411 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2022 4 |
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10.1242/dmm.049109 doi (DE-627)DOAJ028890485 (DE-599)DOAJ61dea9b1204249fe97e11002a8215fb4 DE-627 ger DE-627 rakwb eng RB1-214 Xiaolin Ai verfasserin aut Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. zebrafish glioblastoma heterogeneity blood–brain barrier pdx pdox Medicine R Pathology Zengpanpan Ye verfasserin aut Chaoxin Xiao verfasserin aut Jian Zhong verfasserin aut Joseph J. Lancman verfasserin aut Xuelan Chen verfasserin aut Xiangyu Pan verfasserin aut Yu Yang verfasserin aut Lin Zhou verfasserin aut Xiang Wang verfasserin aut Huashan Shi verfasserin aut Dongmei Zhang verfasserin aut Yuqin Yao verfasserin aut Dan Cao verfasserin aut Chengjian Zhao verfasserin aut In Disease Models & Mechanisms The Company of Biologists, 2011 15(2022), 4 (DE-627)578531917 (DE-600)2451104-3 17548411 nnns volume:15 year:2022 number:4 https://doi.org/10.1242/dmm.049109 kostenfrei https://doaj.org/article/61dea9b1204249fe97e11002a8215fb4 kostenfrei http://dmm.biologists.org/content/15/4/dmm049109 kostenfrei https://doaj.org/toc/1754-8403 Journal toc kostenfrei https://doaj.org/toc/1754-8411 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2022 4 |
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10.1242/dmm.049109 doi (DE-627)DOAJ028890485 (DE-599)DOAJ61dea9b1204249fe97e11002a8215fb4 DE-627 ger DE-627 rakwb eng RB1-214 Xiaolin Ai verfasserin aut Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. zebrafish glioblastoma heterogeneity blood–brain barrier pdx pdox Medicine R Pathology Zengpanpan Ye verfasserin aut Chaoxin Xiao verfasserin aut Jian Zhong verfasserin aut Joseph J. Lancman verfasserin aut Xuelan Chen verfasserin aut Xiangyu Pan verfasserin aut Yu Yang verfasserin aut Lin Zhou verfasserin aut Xiang Wang verfasserin aut Huashan Shi verfasserin aut Dongmei Zhang verfasserin aut Yuqin Yao verfasserin aut Dan Cao verfasserin aut Chengjian Zhao verfasserin aut In Disease Models & Mechanisms The Company of Biologists, 2011 15(2022), 4 (DE-627)578531917 (DE-600)2451104-3 17548411 nnns volume:15 year:2022 number:4 https://doi.org/10.1242/dmm.049109 kostenfrei https://doaj.org/article/61dea9b1204249fe97e11002a8215fb4 kostenfrei http://dmm.biologists.org/content/15/4/dmm049109 kostenfrei https://doaj.org/toc/1754-8403 Journal toc kostenfrei https://doaj.org/toc/1754-8411 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2022 4 |
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An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. |
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An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. |
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An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity. |
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