Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Knittelfelder, M.
ADVANCING IONTRONIC IMPLANTS: TARGETED CHEMOTHERAPY WITH GEMCITABINE FOR GLIOBLASTOMA MULTIFORME
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 69
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Schindl Rainer
- Waldherr Linda
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- Abstract:
- Background: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite surgical resection, intensive systemic chemotherapy with Temozolomide (TMZ), and concurrent radiotherapy, the average survival period after diagnosis is only 15 months. The limited selection of chemotherapeutic drugs available for GBM treatment is particularly challenging, as most drugs are unable to penetrate the blood-brain barrier (BBB). The development of the organic electronic ionic pump (OEIP) for local chemotherapy in GBM could enable the use of novel and more effective chemotherapeutic agents, such as Gemcitabine (Gem). This study examined the antineoplastic effect of the chemotherapeutic agent Gem compared to the current gold standard, TMZ, in three different GBM cell lines. Methods: In the in vitro part of the study, the respective IC50 values of Gem and TMZ were determined in the GBM cell lines A-172, U-251 MG, and LN-18. The cells were treated with a wide range of drug concentrations for 72 hours (h). The mean value was calculated from the collected data and statistically analyzed using Prism GraphPad software. To verify the results in an in vivo environment, GBM tumors of the LN-18 cell line were cultivated on the chorioallantoic membrane (CAM) of chicken embryos and treated with a singular administration of 100 µM Gem or 1.5 mM TMZ. The treated tumors were compared with an untreated control group. After immunohistochemical staining, Ki-67-positive tumor cells were determined using the histoanalytical software QuPath, and the Ki-67 proliferation index was calculated for evaluation. Results: An up to 105-fold more potent antineoplastic effect of Gem compared to TMZ was observed in the in vitro experiments. However, under in vivo conditions, no significant difference between the three treatment groups (p = 0.417) was found. Conclusion: The IC50 values of Gem and TMZ that were determined demonstrated that Gem has an antineoplastic effect on all three GBM cell lines at significantly lower concentrations. While the results of the in vivo model did not show any significance between all three treatment groups, this outcome can be attributed to the treatment regimen of one singular drug administration.