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Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles. [ABSTRACT FROM AUTHOR]

The paper addresses the role of Czech public service television in a polarized society. The research on public service media (PSM) is salient concerning their specific role; however, it is increasingly questioned in a fragmented and polarized environment. The paper builds on data from 27 semi-structured interviews and a survey conducted in 2019–2020 (N = 3,251). While for some audiences, Czech television is a trustworthy medium protecting exemplary sets of values, for others, it is biased and hostile. The study reveals the deeper interplay between political attitudes and media practices, potentially endangering PSM's role and position in polarized settings. [ABSTRACT FROM AUTHOR]