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Yayın Anti-proliferative effects of paroxetine alone or in combination with sorafenib in HepG2 cells(Univ Sao Paulo, Conjunto Quimicas, 2022) Çakıl, Yaprak Dönmez; Güneş Özünal, Zeynep; Kayali, Damla Gokceoğlu; Aktas, Ranan Gülhan; Saglam, EsraHepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as singleagents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.Yayın Culturing, Freezing, Processing, and Imaging of Entire Organoids and Spheroids While Still in a Hydrogel(Journal of Visualized Experiments, 2022) Tok, Olgu Enis; Demirel, Gamze; Saatci, Yusuf; Akbulut, Zeynep; Kayalar, Özgecan; Aktas, Ranan GülhanOrganoids and spheroids, three-dimensional growing structures in cell culture labs, are becoming increasingly recognized as superior models compared to two-dimensional culture models, since they mimic the human body better and have advantages over animal studies. However, these studies commonly face problems with reproducibility and consistency. During the long experimental processes -with transfers of organoids and spheroids between different cell culture vessels, pipetting, and centrifuging -these susceptible and fragile 3D growing structures are often damaged or lost. Ultimately, the results are significantly affected, since the 3D structures cannot maintain the same characteristics and quality. The methods described here minimize these stressful steps and ensure a safe and consistent environment for organoids and spheroids throughout the processing sequence while they are still in a hydrogel in a multipurpose device. The researchers can grow, freeze, thaw, process, stain, label, and then examine the structure of organoids or spheroids under various high-tech instruments, from confocal to electron microscopes, using a single multipurpose device. This technology improves the studies' reproducibility, reliability, and validity, while maintaining a stable and protective environment for the 3D growing structures during processing. In addition, eliminating stressful steps minimizes handling errors, reduces time taken, and decreases the risk of contamination.