TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Differential Effects of Sertraline and Penfluridol on EMT and ECM Remodeling in Glioblastoma Cell Lines(Dokuz Eylul Univ inst Health Sciences, 2025-01-31) Keleş Bartık, Didem; Oktay, Gulgun; Surer,Seniz Inanc; Sipahi, Murat; Keles, DidemPurpose: Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis due to rapid recurrence, chemoresistance, and limited efficacy of standard therapies. Epithelial-to-mesenchymal transition (EMT) and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling are critical processes in GBM progression and metastasis. The aim of this study is to examine the potential effects of sertraline and penfluridol on the EMT process and gelatinase activity in human glioblastoma cell lines. Material and Methods: U87 and U251 human glioblastoma cells were treated with sertraline and penfluridol at previously identified IC50 doses. Protein levels of EMT markers, E-cadherin, vimentin, Snail, Slug, Twist1, phospho-Akt (p-Akt), and tissue inhibitor of metalloproteinases-2 (TIMP-2), were evaluated using Western blotting. Additionally, the impact of sertraline and penfluridol on the release and activity of MMP-2 and MMP-9 were assessed through gelatin zymography. Results: Both sertraline and penfluridol significantly reduced vimentin expression in U251 cells, indicating inhibition of the mesenchymal phenotype. Conversely, these drugs increased vimentin levels in U87 cells, highlighting cell line-specific differences. Sertraline and penfluridol also increased TIMP-2 levels in U251 cells but not in U87 cells. Neither drug altered MMP-2 or MMP-9 activity in either cell line, suggesting that their effects on ECM remodeling may be mediated through TIMP-2 upregulation rather than direct modulation of gelatinase activity. Conclusion: These findings suggest that sertraline and penfluridol potentially inhibit EMT and reduce ECM degradation in U251 cells but exert contrasting effects in U87 cells. This highlights the heterogeneity of GBM tumors and the importance of personalized therapeutic approaches.Article Citation - WoS: 2Citation - Scopus: 3Effects of Vertebral Fusion on Levels of Pro-Inflammatory and Catabolic Mediators in a Rabbit Model of Intervertebral Disc Degeneration(Turkish Assoc Orthopaedics Traumatology, 2021-05-27) Dumanlidag, Davut; Keles, Didem; Oktay, Gulgun; Kosay, CanObjective: The aim of this study was to explore the alterations in levels of pro-inflammatory and catabolic mediators following vertebral fusion in a rabbit model of intervertebral disc degeneration. Methods: In this study, 24 female New Zealand albino rabbits (aged 4 to 5 months and weighing 3 to 3.5 kg) were used. All the animals were randomly categorized into four groups, and dorsal spinal exposure of all lumbar vertebrae was routinely performed in each group. While disc degeneration was created in groups B, C, and D, spinal fusion was added to disc degeneration in groups C and D. Disc degeneration was typically created by puncturing the discs with an 18-gauge needle under the guidance of C-arm imaging. Fusion was achieved with posterior/posterolateral decortication and iliac bone grafts. The rabbits in groups A, B, and C were euthanized, and the discs were removed in the first week after the surgery. The rabbits in Group D were sacrificed, and the discs were harvested at 5 weeks after the surgery. The levels of Interleukin (IL)-1 beta, IL-6, Nitric Oxide (NO), Matrix Metalloproteinase (MMP)-3, MMP-13, and Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in the discs were analyzed using enzyme-linked immunosorbent assay kits. Results: Significant increase was observed in the protein levels of both pro-inflammatory and catabolic mediators in disc degeneration groups (Group B, C, and D) compared to Group A. In the fusion groups (Group C and D), these increased mediators decreased, compared to non-fusion group (Group B), (IL1-beta P = 0.017, TIMP-1 P = 0.03, NO P = 0.03). However, there was no statistically significant difference in mediator levels between the short- and long-term fusion (Group C versus D). Conclusion: The results of this study have shown that a significant decrease in pro-inflammatory and catabolic mediators may be expected after vertebral fusion whereas there may be no significant difference between the first and fourth week of fusion surgery. These findings may contribute to clarifying the mechanism of action of vertebral fusion in the treatment of low back pain.
