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Characterization and modulation of MitoTam-induced cell death in breast carcinoma cells
Hrysiuk, Mariia ; Anděra, Ladislav (advisor) ; Dráber, Peter (referee)
Although recent years brought many breakthrough discoveries in anti-cancer research and therapy, malignant diseases such as breast cancer (BC) still present one of the major health threats worldwide. Cancer cells usually gain resistance to the activation of regulated cell death (RCD) modalities such as caspase-dependent apoptosis. Among novel RCD-inducing agents belongs to mitochondria-targeted tamoxifen - MitoTam, which is also the major focus of this Thesis. In a panel of BC cells, we determined the energetic (mitochondrial respiration vs. glycolysis) and major RCD-related proteins (Western blotting) profiles, and using Lumascope LS720-assisted time-lapse monitoring we analyzed their sensitivity to MitoTam-induced RCD. We found out that glycolysis-preferring BC cells as MDA-MB-231 are more resistant to MitoTam treatment than mitochondrial respiration-biased MDA-MB-453 cells. However,the majority of tested BC cells can be sensitized to MitoTam by BH3 mimetics such as BCL-XL targeting A1155463 and some cellular metabolism-modulating compounds such as lactate dehydrogenase inhibitor (R)-GNE-140, especially in the pre-treatment regime. Also, other metabolism-modulating compounds such as Pyruvate Dehydrogenase Kinases inhibitor JX06 potently enhanced the efficacy and kinetics of MitoTam-induced RCD....
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Unconventional protocols in treatment of glioblastoma
Potomová, Petra ; Kubíková, Iva (advisor) ; Škvárová, Karolina (referee)
Glioblastoma multiforme is one of the tumours defying the treatment that is currently in use (radiotherapy and chemotherapy). Due to the failure in its complete repression, new methods were developed, methods that do not fulfil the traditional expectation about oncological treatment. But it's these methods that could lead to inhibition of further proliferation and growth of the tumour. Therapies, like anti-angiogenesis, ketogenic diet, photothermal therapy or ferroptosis, can be targeted against the tumour and significantly tip the oncological treatment in favour of patients and doctors. Despite the need to optimize them due to side effects, added toxicity or development of resistance, they play a vital role in the future of oncology. Keywords: glioblastoma multiforme, oncological treatment; anti-angiogenic therapy, ketogenic diet, photothermal therapy, ferroptosis
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