Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies
Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvir...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5113 |
| _version_ | 1797561986746155008 |
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| author | Amber E. Kerstetter-Fogle Peggy L. R. Harris Susann M. Brady-Kalnay Andrew E. Sloan |
| author_facet | Amber E. Kerstetter-Fogle Peggy L. R. Harris Susann M. Brady-Kalnay Andrew E. Sloan |
| author_sort | Amber E. Kerstetter-Fogle |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, the high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have established orthotopic patient-derived xenografts (PDX) from 37 GBM patients with human GBM. Of the 69 patient samples analyzed, we were successful in passaging 37 lines three or more generations (53.6%). After phenotypic characterization of the xenografted tumor tissue, two different growth patterns emerged highly invasive or localized. The phenotype was dependent on malignancy and previous treatment of the patient from which the xenograft was derived. Physiologically, mice exhibited symptoms more quickly with each subsequent passage, particularly in the localized tumors. Study of these physiologically relevant human xenografts in mice will enable therapeutic screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which may eventually be used for simulating treatment. |
| first_indexed | 2024-03-10T18:21:29Z |
| format | Article |
| id | doaj.art-ea98ac0cdb884847b249221a345b9ec7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:21:29Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea98ac0cdb884847b249221a345b9ec72023-11-20T07:18:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114511310.3390/ijms21145113Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical StudiesAmber E. Kerstetter-Fogle0Peggy L. R. Harris1Susann M. Brady-Kalnay2Andrew E. Sloan3Department of Neurological Surgery, Case Western Reserve University and University Hospitals Cleveland, OH 44106, USADepartment of Neurological Surgery, Case Western Reserve University and University Hospitals Cleveland, OH 44106, USACase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Neurological Surgery, Case Western Reserve University and University Hospitals Cleveland, OH 44106, USAGlioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, the high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have established orthotopic patient-derived xenografts (PDX) from 37 GBM patients with human GBM. Of the 69 patient samples analyzed, we were successful in passaging 37 lines three or more generations (53.6%). After phenotypic characterization of the xenografted tumor tissue, two different growth patterns emerged highly invasive or localized. The phenotype was dependent on malignancy and previous treatment of the patient from which the xenograft was derived. Physiologically, mice exhibited symptoms more quickly with each subsequent passage, particularly in the localized tumors. Study of these physiologically relevant human xenografts in mice will enable therapeutic screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which may eventually be used for simulating treatment.https://www.mdpi.com/1422-0067/21/14/5113GBMintracranialpatient-derived xenograftpreclinical |
| spellingShingle | Amber E. Kerstetter-Fogle Peggy L. R. Harris Susann M. Brady-Kalnay Andrew E. Sloan Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies International Journal of Molecular Sciences GBM intracranial patient-derived xenograft preclinical |
| title | Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies |
| title_full | Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies |
| title_fullStr | Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies |
| title_full_unstemmed | Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies |
| title_short | Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies |
| title_sort | generation of glioblastoma patient derived intracranial xenografts for preclinical studies |
| topic | GBM intracranial patient-derived xenograft preclinical |
| url | https://www.mdpi.com/1422-0067/21/14/5113 |
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