WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Ibuprofen and Nimesulide Derivatives Selectively Induce Apoptosis in HER2-Positive Breast Cancer via Inhibition of the PLA2-COX-2-NF-κB Pathway(Springer, 2026) Bedir, Ipek; Cakirli, Egemen; Kucukguzel, S. Guniz; Yilmaz, Ozgur; Biliz, Yagmur; Telci, DilekBackground Chronic inflammation contributes to breast cancer development through the phospholipase A(2) (PLA(2))-cyclooxygenase-2 (COX-2)-nuclear factor kappa B (NF-kappa B) cascade, which regulates prostaglandin synthesis, oxidative stress, and transcription of pro-inflammatory and anti-apoptotic genes. This pathway is particularly active in HER2-positive breast cancer, promoting proliferation, invasion, and resistance to apoptosis. Non-steroidal anti-inflammatory drugs such as ibuprofen and nimesulide target COX enzymes and have shown potential in suppressing inflammation-driven tumorigenesis. In this study, we evaluated the anticancer and anti-inflammatory activity of newly synthesized, structurally modified ibuprofen and nimesulide derivatives designed to modulate PLA(2)-COX-2-NF-kappa B axis. Methods and Results Cytotoxicity was assessed in HER2-positive breast cancer cells (AU565 and SKBR3) and compared with normal dermal fibroblasts (HDF) and breast epithelial cells (MCF-12A), using WST-1 assays. Apoptosis, cell cycle distribution, caspase-3/7 activation, and ROS generation were analyzed by imaging-based assays, flow cytometry, and fluorescence methods. Gene expression of PLA2G2A and PTGS2 was quantified by qRT-PCR, and NF-kappa B translocation was analyzed by immunocytochemistry. Two ibuprofen triazole derivative (D1) and ibuprofen thioether derivative (D7) and one nimesulide derivative (D8) significantly reduced cell viability in a dose-dependent manner without affecting normal cells. These derivatives induced G(0)/G(1) arrest, caspase-3/7 activation, ROS reduction, and increased late apoptosis. Downregulation of PLA2G2A and PTGS2 expression and inhibition of NF-kappa B translocation confirmed disruption of the PLA(2)-COX-2-NF-kappa B cascade. Conclusion These findings demonstrate that structurally optimized ibuprofen and nimesulide derivatives exert dual anti-inflammatory and anticancer effects in HER2-positive breast cancer by suppressing PLA(2)-COX-2-NF-kappa B pathway and promoting apoptotic cell death.Article Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARS-CoV Vaccine on Organ Protection in Transgenic Mouse Model(Marmara University, Institute of Health Sciences, 2025) Telci, Dilek; Akpınar, Gürler; Tuğlu, Mehmet İbrahim; Ovalı, Ercüment; Oztatlıcı, Hulya; Şahin, Fikrettin; Demir, Sevda; Kancagi, Derya Dilek; Turan, Raife Dilek; Oztatlici, Mustafa; Karakus, Gozde Sir; Yurtsever, BulutObjective: Coronavirus disease 2019 (COVID-19) is an infectious outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) and virus-related deaths are increasing day by day. For this reason, vaccine studies and their urgent use are of great importance to prevent the pandemic. In this study, multi-organ damages caused by SARS-CoV-2 virus in human- angiotensin-converting enzyme type 2 (ACE2) transgenic mice and the protective effects of OZG-38.61.3 gamma irradiated SARS-CoV-2 vaccine against viral damage were investigated. Methods: For this purpose, transgenic K18-hACE2 BALB/c mice were randomly allocated into 4 groups, negative control group (NC), positive control group (PC, SARS-CoV-2 infected), and 2 different doses of OZG-38.61.3 vaccine (Challenge 1, dose of 10 13 and Ch2, 10 14 viral particle after SARS-CoV-2 infection). After the administrations, lung, heart and kidney tissues were examined by histopathological, immunohistochemical and TUNEL analysis. Results: Our results showed that the vaccine doses decreased the apoptosis, oxidative stress and inflammation parameters caused by virus in lung, heart, and kidney tissues. It was also found that the vaccine protected the expressions of tight junction proteins in the kidneys. Conclusion: According to our findings, it is suggested that the OZG-38.61.3 can be an effective and protective vaccine that can be safely used against the SARS-CoV-2 virus.
