Malignant gliomas represent over 50% of the tumours which originate within the central nervous system. Current treatment modalities are in large part unsuccessful, and less than 10% of patients with high grade glioblastomas survive beyond 2 years. Understanding the cause of the rapid growth rate of malignant gliomas would be useful in devising new therapeutic strategies to treat this disorder. Previous work from this laboratory suggested that the enzyme protein kinase C (PKC) was a critical regulator of the hyperproliferative state of glioma cells. The results presented in this thesis demonstrate that (1) PKC activity was differentially increased in glioma cell lines when compared to other fast growing cell types of non-glial origin, (2) inhibitors of PKC (staurosporine, tamoxifen, CGP 41 251) block the proliferation rate of glioma cells at IC50 values that correspond to their respective IC50's for inhibition of PKC activity, (3) of the PKC isoforms, rat astrocytes and rat glioma cells contain $ alpha, beta, delta, varepsilon$ and $ zeta$, but not $ gamma$, (4) of the expressed isoforms, the activity and amounts of PKC$ alpha$ correlate with cellular growth and (5) an anti-sense oligonucleotide directed against PKC$ alpha$ decreases the proliferation rate of glioma cells. These observations suggest that aberrations in PKC signal transduction (particularly PKC$ alpha$) are important factors in the growth of glioma and have led to clinical trials utilizing PKC inhibitors as adjuncts in the therapy of patients harbouring these incurable neoplams.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.28984 |
| Date | January 1995 |
| Creators | Baltuch, Gordon Hirsh |
| Contributors | Yong, Voon Wee (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001468307, proquestno: NN08078, Theses scanned by UMI/ProQuest. |
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