Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma
Abstract
:1. Introduction
2. Results
2.1. PD-GBOs Can Be Generated from Resected Tumor Tissue
2.2. PD-GBOs Recapitulate Actual Glioblastoma Properties
2.3. Personalized 3D Drug Screens Using PD-GBOs
2.4. Transcriptome Analysis of Parental Tumor Tissue
3. Discussion
4. Materials and Methods
4.1. Drug Library Preparation
4.2. Glioblastoma Resection and Tissue Processing
4.3. Establishment of Acute Glioblastoma Spheroids
4.4. Cell Printing and Drug Screening on the 384-Pillar Array
4.5. Immunofluorescence, Histology, and Immunohistochemistry
4.6. Live-Cell Image Acquisition and Analysis
4.7. Analysis of Functional Drug Testing
4.8. RNA-Sequencing Data Processing
4.9. Pathway Enrichment Analysis
4.10. Correlation Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient ID | Weight of Tumor Tissue (g) a | Pattern of Tumor Progression b | Diagnosis | Ki67 | Time Until Lab Report (Days) |
---|---|---|---|---|---|
MA01 | 9.15 | Distant | GB WHO grade 4 MGMT methylated, IDH wt | 40% | 14 |
MA02 | 3.42 | Distant | GB WHO grade 4 MGMT methylated, IDH wt | 0% | 13 |
MA03 | 8.97 | Local | GB WHO grade 4 MGMT methylated, IDH wt | 2% | 15 |
MA04 | 16.16 | Distant | IDH mut astrocytoma grade 4 | 70% | 19 |
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Ratliff, M.; Kim, H.; Qi, H.; Kim, M.; Ku, B.; Azorin, D.D.; Hausmann, D.; Khajuria, R.K.; Patel, A.; Maier, E.; et al. Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma. Int. J. Mol. Sci. 2022, 23, 6572. https://doi.org/10.3390/ijms23126572
Ratliff M, Kim H, Qi H, Kim M, Ku B, Azorin DD, Hausmann D, Khajuria RK, Patel A, Maier E, et al. Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma. International Journal of Molecular Sciences. 2022; 23(12):6572. https://doi.org/10.3390/ijms23126572
Chicago/Turabian StyleRatliff, Miriam, Hichul Kim, Hao Qi, Minsung Kim, Bosung Ku, Daniel Dominguez Azorin, David Hausmann, Rajiv K. Khajuria, Areeba Patel, Elena Maier, and et al. 2022. "Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma" International Journal of Molecular Sciences 23, no. 12: 6572. https://doi.org/10.3390/ijms23126572