Wanders, L. (Lieske) (2013) Sub-classification of preclinical glioblastoma models: is there a correlation with therapeutic sensitivity? thesis, Medicine.
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Abstract
Glioblastoma Multiforme (GBM) is a frequent occurring and fatal brain tumor in adults. GBM is highly resistant to current radio- and chemotherapy standards and contributes to poor prognosis. Traditionally these tumors are classified using histopathological analyses. However, a new classification system has emerged based on transcriptional profiling, dividing GBMs in classical (CLAS), proneural (PN) and mesenchymal (MES) subtypes. The subtypes appear to have prognostic value, of which the MES subtype has the worst prognosis. In addition, it has been seen that some tumors shift towards the MES subtype upon recurrence, which may be accompanied by the induction of resistance towards treatment. Currently, the therapeutic sensitivity of the different GBM subtypes and the possibility of therapy-induced changes in subtype have hardly been studied in preclinical models. The aim of this study is to subtype newly generated GBM cell lines and to assess sensitivity to Temozolomide (TMZ) and radiotherapy in cells representing different subtypes. Furthermore, it has been studied whether therapy could lead to a change in subtype in vitro. It has been found that four out of six cultured Groningen Glioblastoma (GG) cell lines, derived from primary patient material, show similar subtype characteristics as the original tumor in the characterization study, while two GG cell lines differ from their primary tumor material. Initial findings indicated that the CLAS cell line is most sensitive to TMZ, whereas the PN cell line is most sensitive to radiotherapy. The MES cell line appears to be most resistant to TMZ as well as radiotherapy. Furthermore, preliminary experiments do not suggest a difference in GBM marker expression due to TMZ treatment. However, GBM subtype-specific marker expression was found to be variable upon culturing and requires further investigation. Overall, this study provides the first evidence for possible GBM subtype-dependent differences in therapeutic sensitivity in a preclinical model.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Kruyt, Prof. Dr. F.A.E. and Joseph, J. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:00 |
| Last Modified: | 25 Jun 2020 11:00 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2024 |
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