Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Letter Citation - WoS: 1Citation - Scopus: 2C-Met Activation Promotes Extravasation of Hepatocellular Carcinoma Cells Into 3d-Cultured Hepatocyte Cells in Lab-On Device(Elsevier, 2023) Solmaz, Gülhas; Bağcı, Gülsün; Çömez, Dehan; Topel, Hande; Yılmaz, Yeliz; Bağırsakçı, Ezgi; Güneş, Aysim; Batı Ayaz, Gizem; Tahmaz, İsmail; Bilgen, Müge; Pesen Okvur, DevrimActivation of c-Met signaling is associated with an aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC); however, its contribution to organ preference in metastasis remains unclear. In this study, using a Lab on a Chip device, we defined the role of aberrant c-Met activation in regulating the extravasation and homing capacity of HCC cells. Our studies showed that (i) c-Met overexpression and activation direct HCC cells preferentially towards the hepatocytes-enriched microenvironment, and (ii) blockage of c-Met phosphorylation by a small molecule inhibitor attenuated extravasation and homing capacity of HCC cells. These results, thus, demonstrate the role of c-Met signaling in regulating the colonization of HCC cells preferentially in the liver. © 2023 Elsevier B.V.Article Citation - WoS: 11Citation - Scopus: 13Fli1 and Fra1 Transcription Factors Drive the Transcriptional Regulatory Networks Characterizing Muscle Invasive Bladder Cancer(Nature Research, 2023) Güneri Sözeri, Perihan Yağmur; Özden Yılmaz, Gülden; Kısım, Aslı; Çakıroğlu, Ece; Eray, Aleyna; Uzuner, Hamdiye; Karakülah, Gökhan; Pesen Okvur, Devrim; Şentürk, Şerif; Erkek Özhan, Serapis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac ChIP-seq and used an integrative approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as two critical transcription factors differentially regulating MIBC regulatory landscape. We show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these transcription factors and link this information with their target genes. Finally, we show that knock-down of FRA1 and FLI1 result in significant reduction of invasion capacity of MIBC cells towards muscle microenvironment using IC-CHIP assays. Our results collectively highlight the role of these transcription factors in selection and design of targeted options for treatment of MIBC.Conference Object Detection and Restoration Pipeline for Phase Contrast Microscopy Time Series Images(IEEE, 2022) Iheme, Leonardo O.; Uçar, Mahmut; Önal, Sevgi; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Töreyin, Behçet U.; Ünay, DevrimWe propose a pre-processing pipeline for the de-tection and restoration of distorted frames in phase-contrast microscopy time-series images. The analysis is based on the average intensity values of the frames within any given time- series image. The extent of the correction of intensity variation in frames is determined by the normalization of the difference between the current frame's average intensity and the median of average intensity of all frames. Our restoration algorithm preserves regional trans-passing pixels, does not cause new distortions, and increases the histogram similarity between the distorted and non-distorted frames. The algorithm was validated on 15,395 time-series image frames from 27 experiments and the results were found to be visually and quantitatively accurate.Article Citation - WoS: 3Citation - Scopus: 6Improved Cell Segmentation Using Deep Learning in Label-Free Optical Microscopy Images(TÜBİTAK - Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2021) Ayanzadeh, Aydın; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Önal, Sevgi; Töreyin, Behçet Uğur; Ünay, DevrimThe recently popular deep neural networks (DNNs) have a significant effect on the improvement of segmentation accuracy from various perspectives, including robustness and completeness in comparison to conventional methods. We determined that the naive U-Net has some lacks in specific perspectives and there is high potential for further enhancements on the model. Therefore, we employed some modifications in different folds of the U-Net to overcome this problem. Based on the probable opportunity for improvement, we develop a novel architecture by using an alternative feature extractor in the encoder of U-Net and replacing the plain blocks with residual blocks in the decoder. This alteration makes the model superconvergent yielding improved performance results on two challenging optical microscopy image series: a phase-contrast dataset of our own (MDA-MB-231) and a brightfield dataset from a well-known challenge (DSB2018). We utilized the U-Net with pretrained ResNet-18 as the encoder for the segmentation task. Hence, following the modifications, we redesign a novel skip-connection to reduce the semantic gap between the encoder and the decoder. The proposed skip-connection increases the accuracy of the model on both datasets. The proposed segmentation approach results in Jaccard Index values of 85.0% and 89.2% on the DSB2018 and MDA-MB-231 datasets, respectively. The results reveal that our method achieves competitive results compared to the state-of-the-art approaches and surpasses the performance of baseline approaches.Conference Object Citation - Scopus: 2Yara İyileşmesi Mikroskopi Görüntü Serilerinin Otomatik Analizi - Bir Ön-çalışma(IEEE, 2020) Mayalı, Berkay; Şaylığ, Orkun; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Töreyin, Behçet Uğur; Ünay, DevrimCollective cell analysis from microscopy image series is important for wound healing research. Computer-based automation of such analyses may help in rapid acquisition of reliable and reproducible results. In this study phase -contrast optical microscopy image series of an in-vitro wound healing essay is manually delineated by two experts and its analysis is realized, traditional image processing and deep learning based approaches for automated segmentation of wound area are developed and their perlOrmance comparisons are carried out.Conference Object Citation - Scopus: 1A Preliminary Study on Cell Motility Analysis From Phase-Contrast Microscopy Image Series(IEEE, 2020) Kayan, Emre; Kavuşan, Tarık; Önal, Sevgi; Pesen Okvur, Devrim; Yalçın Özuysal, Özden; Töreyin, Behçet Uğur; Ünay, DevrimAnalyses of morphology, polarity, and motility of cells is important for cell biology research such as metastatic and invasive capacity of cells, wound healing, and embryonic development. Automation of such analyses using image series of phase-contrast optical microscopy, which allows label-free imaging of live cells in their living environment, is a need. With this purpose, in this study image series of a cell motility experiment is manually annotated, and an automation algorithm realizing motion and shape analyses of cells using the annotated data is developed. In addition, due to the low number of annotated data at hand, a U-Net based solution is devised for automated segmentation of the cells and its performance is evaluated.Article Citation - WoS: 10Citation - Scopus: 11A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices(Elsevier, 2020) Gökçe, Begüm; Akçok, İsmail; Çağır, Ali; Pesen Okvur, DevrimDrug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.Article Citation - WoS: 20Citation - Scopus: 21Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop(Elsevier, 2021) Önal, Sevgi; Türker Burhan, Merve; Batı Ayaz, Gizem; Yanık, Hamdullah; Pesen Okvur, DevrimBreast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively. © 2020 Elsevier LtdConference Object Citation - WoS: 7Citation - Scopus: 11Cell Segmentation of 2d Phase-Contrast Microscopy Images With Deep Learning Method(Institute of Electrical and Electronics Engineers Inc., 2019) Ayanzadeh, Aydın; Yağar, Hüseyin Onur; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Töreyin, Behçet Uğur; Unay, Devrim; Önal, SevgiThe quantitative and qualitative ascertainment of cell culture is integral to the robust determination of the cell structure analysis. Microscopy cell analysis and the epithet structures of cells in cell cultures are momentous in the fields of the biological research process. In this paper, we addressed the problem of phase-contrast microscopy under cell segmentation application. In our proposed method, we utilized the state-of-the-art deep learning models trained on our proposed dataset. Due to the low number of annotated images, we propose a multi-resolution network which is based on the U-Net architecture. Moreover, we applied multi-combination augmentation to our dataset which has increased the performance of segmentation accuracy significantly. Experimental results suggest that the proposed model provides superior performance in comparison to traditional state-of-the-art segmentation algorithms.Article Citation - WoS: 1Cellular Distribution of Invadopodia Is Regulated by Nanometer Scale Surface Protein Patterns(Elsevier Ltd., 2017) Batı Ayaz, Gizem; Can, Ali; Pesen Okvur, DevrimInvadopodia are proteolytic structures formed by cancer cells. It is not known whether their cellular distribution can be regulated by the organization of the extracellular matrix or the organization of the golgi complex or whether they have an adhesion requirement. Here, we used electron beam lithography to fabricate fibronectin (FN) nanodots with isotropic and gradient micrometer scale spacings on K-casein and laminin backgrounds. Investigating cancer cells cultured on protein nanopatterns, we showed that (i) presence of FN nanodots on a K-casein background decreased percent of cells with neutral invadopodia polarization compared to FN control surfaces; (ii) presence of a gradient of FN nanodots on a K-casein background increased percent of cells with negative invadopodia polarization compared to FN control surfaces; (iii) polarization of the golgi complex was similar to that of invadopodia in agreement with a spatial link; (iv) local adhesion did not necessarily appear to be a prerequisite for invadopodia formation.