Die Auswirkung von Toxinen auf die Hitzeempfindlichkeit des Prostatakarzinoms
von Jörn Janzen geb. Töpperwien
Datum der mündl. Prüfung:2023-11-02
Erschienen:2023-11-01
Betreuer:Prof. Dr. Lutz Trojan
Gutachter:PD Dr. Petra Krause
Gutachter:Prof. Dr. Thomas Meyer
Zum Verlinken/Zitieren:
http://dx.doi.org/10.53846/goediss-10153
Dateien
Name:Dissertation Druck.pdf
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Zusammenfassung
Englisch
The aim of this experimental dissertation on the topic “The effect of toxins on the heat sensitivity of prostate cancer” was to determine the suitability of heat based therapy methods (such as HIFU) in combination with the local application of e.g. chemotherapy drugs as a possible treatment method for prostate cancer. For this purpose, an in vitro model was created that uses measurements in the form of the MTS assay and flow cytometry. These took place on the prostate cancer cell lines VCaP, 22rv1 and PC3. Each of the three cell lines was prepared for measurement in a multi-step process. In half of the cases, preparation for a measurement also included treatment with one of the drugs/toxins docetaxel, mitoxantrone, EPI-001 or dimethyl sulfoxide. All three cell lines examined reacted to the increasing temperatures with different responses/mechanisms even in their untreated state. As a result of treatment with active ingredients/toxins, the initial increase in vitality, which occurred at temperatures between 37°C and 57.8°C, was influenced, particularly in VCaP. The temperature sensitivity of both VCaP, PC3 and 22rv1 could be influenced by the active ingredients/toxins used. In particular, when VCaP was treated with docetaxel, there was a significant increase in the temperature sensitivity of this cell line. For the treatment of PCa using heat-based therapy methods such as HIFU, this means that VCaP should not be treated at temperatures around 41°C, as this could lead to a tumor proliferative stimulus. Furthermore, the work was able to show that safe cell death can only be achieved by applying heat at temperatures above 62°C. In VCaP in particular, the use of the active ingredients/toxins docetaxel, mitoxantrone and EPI-001 has shown an increase in temperature sensitivity, which could enable a heat-based form of therapy to be initiated in such a temperature range. As stated in 4.4, the limitations of this work were that the studies were carried out at the in vitro level and the results would first have to be reproduced at the in vivo level. The methodology used in this work, using a thermocycler to heat the cell lines instead of ultrasound, does not directly allow the direct transfer of our results to the possible application of a HIFU for the detected temperatures. In addition, the heating of the cell lines occurred in vitro and the temperature-reducing effects of the stoma or potential intraoperative bleeding could not be depicted in vivo (Mearini and Porena 2010; He et al. 2020). Ultimately, the present work was able to show that the examined PCa cell lines PC3, VCaP and 22rv1 react to heat and can be influenced in terms of their temperature sensitivity. To take the investigations to the next level, an animal model could be chosen to cultivate the PCa cells and an in vivo HIFU could be investigated for the treatment of the different PCa cell lines. With regard to the use of the active ingredients/toxins we use, docetaxel, mitoxantrone and EPI-001, a new therapeutic approach with local instillation would be conceivable, as is already used with coated doxorubicin nanoparticles. In this way, a symbiotic effect of local heat application could be achieved with the effect of the respective active ingredient/toxin (Zhang C et al. 2017).
Keywords: HIFU; prostatecancer
