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Modulation der Hitzesensitivität im Prostatakarzinom in vitro: Der Einfluss der Androgenachse

dc.contributor.advisorTrojan, Lutz Prof. Dr.
dc.contributor.authorHeining, Franziska Maria
dc.date.accessioned2022-10-13T11:00:44Z
dc.date.available2022-10-19T00:50:08Z
dc.date.issued2022-10-13
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?ediss-11858/14290
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-9473
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc610de
dc.titleModulation der Hitzesensitivität im Prostatakarzinom in vitro: Der Einfluss der Androgenachsede
dc.typedoctoralThesisde
dc.title.translatedModulation of heat sensitivity in prostate carcinoma in vitro: the influence of the androgen axisde
dc.contributor.refereeTrojan, Lutz Prof. Dr.
dc.date.examination2022-10-11de
dc.description.abstractengFocal therapies are becoming increasingly important in the treatment of prostate cancer as an intermediate solution between definitive treatment options for localized prostate cancer and active surveillance. Many focal therapies are based on thermal effects. Our aim was to investigate whether pretreatment of prostate cancer cells with drugs - Finasterid and Bicalutamid - that interfere with the androgen balance of the cells has an effect on the sensitivity of prostate cancer cells to thermal treatment. The cell lines studied were BPH-1, rVCaP, VCaP, 22Rv2 and PC-3. As a first step, cells were heated at temperatures between 37-100°C using thermocyclers. The metabolic activity of the cells was then measured using MTS assays, generating individual heat profiles. As a third step, cells were medicated 48h prior to MTS assay to detect any difference in metabolic activity. Important thresholds were verified as a fourth step using FACS analysis. In the MTS assay without drug pretreatment, a continuous decrease in metabolic activity between 37-50°C was shown in the BPH-1, VCaP and 22Rv1 cell lines, whereas in the rVCaP and PC3 cell lines, the cells showed an increase in metabolic activity when heated to 50°C. The curve increase was most prominent in the rVCaP cell lines with a nearly 1.75x increase. An initial drop in metabolic activity <20% was seen around 60°C. Pretreatment with finasteride or bicalutamide showed no significant difference in heat sensitivity of prostate cancer cells in the MTS assay. These results were confirmed by the FACS analysis. However, it was demonstrated that the rVCaP and PC-3 cell lines showed higher viability around 60°C than the BPH-1, VCaP and 22Rv1 cell lines. As the most important part of the discussion, we considered the paradoxical metabolic increase in the MTS assay and the increased viability values in FACS analysis in the cell lines rVCaP and PC-3 at temperatures around 60°C. We evaluated this as reflecting increased HSP expression and consequent cytoprotection, which in vivo would correspond to treatment failure in the border zones of HIFU therapy. Future studies between HIFU therapy and ADT should consider the mechanical effects of HIFU therapy in addition to the thermal effects. Consideration could be given to increasing the dose or extending the stimulation times of our chosen drugs. The role of HSP under hyperthermic conditions should be investigated in the cell lines we used, both expression levels under normothermia and heat exposure including the role of testosterone in this context. The use of HSP inhibitors would also be interesting.de
dc.contributor.coRefereeKrause, Petra PD Dr.
dc.subject.gerHiFude
dc.subject.gerAndrogendeprivationde
dc.subject.gerProstatakarzinomde
dc.subject.gerThermosensitivitätde
dc.subject.gerFokale Therapiede
dc.subject.engHiFude
dc.subject.engandrogen deprivationde
dc.subject.engfocal therapyde
dc.subject.engprostate cancerde
dc.subject.engthermosensitivityde
dc.identifier.urnurn:nbn:de:gbv:7-ediss-14290-1
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullUrologie / Andrologie - Allgemein- und Gesamtdarstellungen (PPN619876131)de
dc.description.embargoed2022-10-19de
dc.identifier.ppn1818978695
dc.notes.confirmationsentConfirmation sent 2022-10-13T11:15:02de


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