Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma
Abstract
:1. Introduction
2. Results
2.1. PDOX Models Derived from Primary and Recurrent Meningiomas
2.2. PDOX Models Recapitulate the Histopathologic Features of the Patient Tumors
2.3. PDOX Models Can also be Generated from Cryopreserved Cells
2.4. Gene Expression Profiles Were Maintained in the PDOX Tumors
2.5. High-Throughput in Vitro Chemical Screen Identify HDAC Inhibitors
2.6. Panobinostat Significantly Prolonged Animal Survival in the Recurrent Tumor Model
3. Discussion
4. Materials and Methods
4.1. Patient Tumor Tissue Specimen
4.2. Long-Term Storage of Xenograft Cells in Liquid Nitrogen
4.3. Direct Hetero-Transplantation of Primary Tumor Cells into Mouse Brain
4.4. Immunohistochemical (IHC) Staining and Western Blot Analysis
4.5. RNA-Seq Analysis
4.6. Small-Animal Magnetic Resonance Imaging
4.7. Primary Cell Culture Establishment and Propagation
4.8. High-Throughput Drug Screening
4.9. Testing Panobinostat Therapy in Mice
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Tumor ID | Age/Gender | WHO Grade | Type | Cell Tumorigenicity | ||
---|---|---|---|---|---|---|
Fresh | Cryo | |||||
K29 | (P) rimary | 72/F | Atypical (II) | C | 7/10 | 3/3 |
(R) ecurrent | 72/F | Anaplastic (III) | C | 1/4 | 9/10 | |
K57 | (P) rimary | 65/M | Atypical (II) | C | 0/10 | - |
K16 | (P) rimary | 71/F | Atypical (II) | C | 0/12 | - |
(R) ecurrent | 72/F | Atypical (III) * | B | 0/10 | - | |
K18 | (P) rimary | 27/M | Atypical (II) | C | 0/10 | - |
K20 | (P) rimary | 38/M | Atypical (II) | A | 0/10 | - |
K21 | (P) rimary | 59/M | Classic (I) | Not sequenced | 0/10 | - |
K26 | (P) rimary | 70/F | Classic (I) | A | 0/5 | - |
K28 | (P) rimary | 33/F | Classic (I) | A | 0/10 | - |
K30 | (P) rimary | 41/F | Classic (I) | B | 0/5 | - |
Drug Name | FDA Approved | Drug Name | FDA Approved |
---|---|---|---|
Barasertib | Trichostatin | ||
Bortezomib | yes | Cediranib | |
Decitabine | yes | Dasatinib | yes |
Enzastaurin | Panobinostat | ||
Lapatinib | yes | SAHA | yes |
MLN8237 | SNS-032 | ||
NAC | yes | Carfilzomib | |
Pazopanib | yes | Alvocidib | |
Ponatinib | AUY922 | ||
Quinacrine | yes | AZD-8931 | |
RO4929097 | BEZ 235 | ||
Ruxolitinib | Cabozantinib | ||
Selumetinib | Cilengitide | ||
SJ-172550 | Dinaciclib | ||
Sodium butyrate | yes | Entinostat | |
Sorafenib | yes | Fenretinide | |
SP600125 | Fostamatinib | ||
Temsirolimus | yes | Lenalidomide | |
Veliparib | Nilotinib | ||
Vismodegib | PF 562271 | ||
Zibotentan | Retinoic acid | ||
Crizotinib | yes | RO5045337 | |
GANT61 | Saracatinib | ||
BMS 754807 | SB-431542 | ||
OSI-906 | Tamoxifen | ||
MK-2206 | Vandetanib | ||
Pelitinib | Vemurafenib | ||
BIX 01294 | VER-155008 | ||
Tozasertib | ABT 737 | ||
Obatoclax | SJ-172550 |
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Zhang, H.; Qi, L.; Du, Y.; Huang, L.F.; Braun, F.K.; Kogiso, M.; Zhao, Y.; Li, C.; Lindsay, H.; Zhao, S.; et al. Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma. Cancers 2020, 12, 1478. https://doi.org/10.3390/cancers12061478
Zhang H, Qi L, Du Y, Huang LF, Braun FK, Kogiso M, Zhao Y, Li C, Lindsay H, Zhao S, et al. Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma. Cancers. 2020; 12(6):1478. https://doi.org/10.3390/cancers12061478
Chicago/Turabian StyleZhang, Huiyuan, Lin Qi, Yuchen Du, L. Frank Huang, Frank K. Braun, Mari Kogiso, Yanling Zhao, Can Li, Holly Lindsay, Sibo Zhao, and et al. 2020. "Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma" Cancers 12, no. 6: 1478. https://doi.org/10.3390/cancers12061478