@conference{
author = "Jovanović Stojanov, Sofija and Dragoj, Miodrag and Jovanović, Mirna and Stojkovska, Jasmina and Stankovic, Tijana and Dinić, Jelena and Podolski-Renić, Ana and Stepanović, Ana and Obradović, Bojana and Pešić, Milica",
year = "2021",
abstract = "Glioblastoma (GMB) is the most common and aggressive primary malignant brain tumor. Median life expectancy with the only clinically approved treatment option, Stupp protocol, is 11-15 months. This protocol involves surgical resection followed by 6 weeks of radiation and chemotherapy and then 6 cycles of 5-day chemotherapy treatment and 23 days of recovery. The only approved chemotherapeutic drug currently used is temozolomide (TMZ) that improves patients' survival for 2.5 months compared to radiotherapy alone. Such limited therapeutic options could be partly due to the lack of appropriate glioblastoma models for testing novel drugs and new treatment modalities.
Therefore we established a novel long-term 3D glioblastoma biomimicking model system that would enable optimal drug testing in clinically more relevant duration. Glioblastoma U87 cells were immobilized in alginate microtubes and cultivated for 28 days, initially under static conditions. Cell viability, morphology and aggregate formation were monitored under fluorescent and confocal microscopes upon double staining with calcein-AM/propidium iodide. Most importantly, we investigated the effects of two different TMZ treatment modalities on cell viability and expression of resistance-related genes, MGMT and ABCB1. All treatments with 100 μm TMZ started on day 7 (X=7). We compared 3-day subsequent treatment modality (day by day treatments, X+1) with protractive treatment modality (every 7th day, X+7).
In established 3D model system, cells managed to grow for up to 28 days without propagation, formed aggregates and constantly increased their number. Both treatment modalities had the same effects on cell viability. However, three day treatment in a row led to a tremendous increase in the expression of resistance markers, which was significantly higher compared to protractive treatment modality.
The results showed that our 3D model system is suitable for drug testing and revealed that protractive treatment modality could be more beneficial for GBM patients.",
publisher = "The European Association for Cancer Research",
journal = "Goodbye Flat Biology: Next Generation Cancer Models; 2021 Oct 5-6; Virtual event, Worldwide",
title = "Evaluation of different temozolomide treatment modalities in a novel long-term 3D glioblastoma cell culture",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4904"
}