Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Cx32 Cellular Localization Is Related To Epithelial To Mesenchymal Transition in Breast Cells(Pleiades Publishing inc, 2025) Oz, Sercan; Turan, Fatma Basak; Yondem, Eyup; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Ozcivici, Engin; Mese, GulistanConnexins (Cx) play both gap junction-related and -independent roles in cells, and their localization is essential for their function in cellular processes. Besides membrane localization, connexins can also be localized to the cytoplasm and nucleus, especially in cancer cells. The differential localization of connexins including Cx32 was observed in different stages of cancers. Cx32 was upregulated and observed in cytoplasms of cells in lymph-node metastasis of breast cancer samples compared to primary tumors. However, the significance of the increase in Cx32 expression and alteration of Cx32 cellular localization in epithelial-to-mesenchymal transition (EMT) is not known. To determine if Cx32 overexpression and/or localization over one week would induce the EMT process, we first examined the cellular localization of Cx32 in MCF10A and MDA-MB-231 cells at different time points using Western blot and RT-PCR as well as immunostaining with confocal microscopy. Then, we correlated the changes of Cx32 expression and localization with EMT marker expression. We showed that Cx32 had altered cellular localization and Cx32 overexpression increased Slug levels while it reduced E-cadherin and Snail expression in MDA-MB-231 for 7 days. In contrast, E-cadherin and Vimentin were reduced in MCF10A-Cx32 cells compared with controls over 7 days, and the expression pattern for nuclear Cx32 and Zeb2 was following similar pattern in MCF10A cells. Our results suggest a previously unknown time-dependent relation between Cx32 and the regulation of the EMT process.Article Citation - WoS: 2Citation - Scopus: 2Invasion/Chemotaxis- and Extravasation-Chip Models for Breast Cancer Bone Metastasis(Public Library Science, 2024) Firatligil-Yildirir, Burcu; Bati-Ayaz, Gizem; Nonappa, Devrim; Pesen-Okvur, Devrim; Yalcin-Ozuysal, OzdenBone is one of the most frequently targeted organs in metastatic cancers including the breast. Breast cancer bone metastasis often results in devastating outcomes as limited treatment options are currently available. Therefore, innovative methods are needed to provide earlier detection and thus better treatment and prognosis. Here, we present a new approach to model bone-like microenvironments to detect invasion and extravasation of breast cancer cells using invasion/chemotaxis (IC-) and extravasation (EX-) chips, respectively. Our results show that the behaviors of MDA-MB-231 breast cancer cells on IC- and EX-chip models correlate with their in vivo metastatic potential. Our culture model constitutes cell lines representing osteoblasts, bone marrow stromal cells, and monocytes embedded in three-dimensional (3D) collagen I-based extracellular matrices of varying composition and stiffness. We show that collagen I offers a better bone-like environment for bone cells and matrix composition and stiffness regulate the invasion of breast cancer cells. Using in situ contactless rheological measurements under cell culture conditions, we show that the presence of cells increased the stiffness values of the matrices up to 1200 Pa when monitored for five days. This suggests that the cellular composition has a significant effect on regulating matrix mechanical properties, which in turn contribute to the invasiveness. The platforms we present here enable the investigation of the underlying molecular mechanisms in breast cancer bone metastasis and provide the groundwork of developing preclinical tools for the prediction of bone metastasis risk.Article Blank Frame and Intensity Variation Distortion Detection and Restoration Pipeline for Phase-Contrast Microscopy Time-Lapse Images(Aves, 2024) Ucar, Mahmut; Iheme, Leonardo O.; Onal, Sevgi; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Toreyin, Behcet U.; Unay, DevrimIn this study, we propose a preprocessing pipeline for the detection and correction of distorted frames in time-lapse images obtained from phase-contrast microscopy. The proposed pipeline employs the average intensities of frames as a foundational element for the analysis. In order to evaluate the degree of correction required for intensity variance, a normalization technique is applied to the difference between the average intensity of a specific frame and the median average intensity of all frames within the study. Our restoration method increases the histogram similarity between the distorted and non-distorted frames, preserves trans-passing pixels in regions of interest, and mitigates the development of additional distortions. The efficacy of the proposed method was evaluated using 15 395 time-lapse image frames from 27 experiments using our own dataset and 830 time-lapse images from four different experiments obtained from the cell tracking challenge. The results of the validation demonstrate a high degree of numerical and visual accuracy of the proposed pipeline.