WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Epithelial-Mesenchymal Transition as a Potential Route for Dapt Resistance in Breast Cancer Cells(Walter de Gruyter GmbH, 2023) Tellı, Kubra; Ozuysal, Ozden Yalcın; Telli, Kübra; Yalçın Özuysal, ÖzdenObjectives: Notch is a conserved pathway involved in cell- fate determination and homeostasis. Its dysregulation plays a role in poor prognosis and drug resistance in breast cancer. Targeting Notch signaling via inhibition of the gamma- secretase complex is in the spotlight of modern cancer treat- ments. Gamma-secretase inhibitors (GSI) have shown suc- cessful clinical activity in treating cancers, yet the possible resistance mechanism remains unstudied. Modeling the resistance and understanding culprit molecular mechanisms can improve GSI therapies. Accordingly, the aim of this study is to generate and analyze GSI-resistant breast cancer cells. Methods: Gradually increasing doses of DAPT, a well-known GSI, were applied to MCF-7 breast cancer cell lines to generate resistance. Cell viability, migration and gene expressions were assessed by MTT, wound healing and qRT-PCR analyses. Results: DAPT-resistant MCF-7 cells exhibited abnormal expression of Notch receptors, Notch targets (HES1, HES5, HEY1), and epithelial-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, SNAIL2, N-cadherin) to overcome the continuous increase in DAPT toxicity by increased migration through mesenchymal transition. Conclusions: This study prospects into the role of EMT in the potential resistance mechanism against DAPT treatment for breast cancer cells. Complementary targeting of EMT should be investigated further for a possible effect to potentiate DAPT’s anti-cancer effects.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.Article Citation - WoS: 9Citation - Scopus: 10Effects of Notch Signalling on the Expression of Sema3c, Hmga2, Cxcl14, Cxcr7, and Ccl20 in Breast Cancer(TÜBİTAK, 2019) Küçükköse, Cansu; Yalçın Özuysal, ÖzdenMetastasis is the main reason for death in breast cancer. Understanding the molecular players in metastasis is crucial for diagnostic and therapeutic purposes. Notch signalling plays an oncogenic role in breast tumorigenesis and is involved in metastasis. Downstream mediators of Notch signalling in prometastatic processes are not yet fully discovered. Here we aimed to investigate whether Notch signalling regulates the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20, which are involved in prometastatic processes, in breast cell lines. To this end, expression of the selected genes was analysed following Notch activation by overexpression of the Notch1 intracellular domain in the normal breast epithelial cell line MCF10A, and inhibition by silencing of the Notch transcriptional mediator RBPj kappa in the breast cancer cell line MDA MB 231. SEMA3C and HMGA2 mRNA were decreased, while CXCL14 and CXCR7 mRNA were increased significantly in response to Notch activation in MCF10A cells. Notch inhibition in MDA MB 231 cells significantly decreased HMGA2 and CCL20 mRNA. Protein levels were not significantly altered by Notch modulation. In conclusion, we showed that Notch signalling regulates expression of SEMA3C, CXCL14, CCL20, CXCR7, and HMGA2, which are prominent candidate genes that might function downstream of Notch to induce prometastatic processes.Article Citation - WoS: 5Citation - Scopus: 6The Correlation of Magee Equationstm and Oncotype Dx® Recurrence Score From Core Needle Biopsy Tissues in Predicting Response To Neoadjuvant Chemotherapy in Er+ and Her2- Breast Cancer(Galenos Publishing House, 2020) Soran,A.; Tane,K.; Sezgin,E.; Bhargava,R.Objective: Oncotype DX® recurrence score (RS) can be predicted from Magee EquationsTM (MS) postoperatively. The aim of this study is to investigate correlation of MS with RS from pretreatment core needle biopsy (CNB) tissues, and their clinical usefulness in prediction of response to neoadjuvant chemotherapy (NCT) in estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer (BC). Materials and Methods: Pretreatment CNB tissue samples from 60 patients with ER+/HER2- invasive BC were analyzed for MS and RS correlation. MS and RS were categorized as follows: low (<18), intermediate (18–30), and high (≥ 31). Percentage Tumor size Reduction (%TR) was used to assess tumor response to NCT, and substantial %TR was defined as at least 50% reduction (≥50%TR). Correlation between MS and RS, and predictive factors for the ≥50%TR achievement were assessed. Results: MS and RS represented a strong correlation (Spearman's correlation; r=0.58, p<0.0001) as a continuous variable. As a categorical variable, the concordance between MS and RS was 43.3%, and it increased to 80% (r=0.61, p=0.003) with the exclusion of the intermediate risk categories. Although, there was pathologic complete response (pCR), MS showed the highest predictive power for the ≥50% TR achievement, none of the factors were statistically significant (p≥0.07). Conclusion: Our study demonstrated that there was a strong correlation between MS and RS from pretreatment biopsy tissue samples in ER+ and HER2- invasive BC. © 2020 by the Author(s).