Search Results (2)

Background: Energy delivered at different wavelengths causes different types of damage to DNA. Methods: PC-3, FaDu, 4T1 and B16-F10 cells were irradiated with different wavelengths of ultraviolet light (UVA/UVC) and ionizing radiation (X-ray). Furthermore, different photosensitizers (ortho-iodo-Hoechst33258/psoralen/trioxsalen) were tested for their amplifying effect. Survival fraction and damage analysis using the $\mathrm{\gamma }$H2A.X assay (double-strand breaks) and the ELISA assay (cyclobutane pyrimidine dimers) were compared. Results: The PC-3 cells were found to be the most sensitive cells to the treatment strategies used. FaDu and PC-3 showed a strong sensitivity to UVA. Analysis of the damage showed that the cell lines exhibited different sensitivities. Conclusions: Thus, an enhancing effect of photosensitizers (PS) in combination with UVA could be demonstrated in some cases. However, this is cell- and dose-dependent. Full article

Background: New therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC) have been developed in the past to achieve the best response rates. Most recently, the use of combination therapies has been explored to optimize patient outcomes. Poly(ADP-ribose) polymerase inhibitors (PARPi) may help to treat mCRPC more effectively. Objectives: This study aimed to determine whether the combination of a PARPi with different radiation qualities results in different levels of radiosensitization of PC-3 cells. Methods: The radiosensitizing potential of Olaparib in combination with ¹⁷⁷Lu, ²²³Ra, X-rays and photodynamic therapy (PDT) using the UVA light-activated photosensitizer ortho-iodoHoechst33258 (oIH) was evaluated by determining the clonogenic survival, DNA damage and cell cycle analysis. Results: Here, we show that this combination strategy differentially sensitized PC-3 cells to different radiation qualities. The combination of ¹⁷⁷Lu with Olaparib increased the numbers of persistent double-strand breaks (DSBs) by a factor of 3.3 and cell death in PC-3 cells. Overall, the β-emitter ¹⁷⁷Lu indicated a higher radiosensitization efficacy compared to ²²³Ra, with X-rays corresponding to dose modification factors (DMF) of 1.77, 1.17 and 1.16 respectively. Even in the case of the α-emitter ²²³Ra, the effects were much less pronounced than for ¹⁷⁷Lu. PARPi also showed a slight potentiation of the cytotoxic effects both in co-treatment with X-rays and with PDT. Conclusions: The results of our study indicate a potential role for Olaparib in further optimizing the PSMA radioligand therapy (PRLT) outcomes. However, further evaluation of the combination of PARPi with PRLT is needed to gain more insights into improving the benefit to patients suffering from mCRPC. Full article