TR Dizin İndeksli Yayınlar / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7149
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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; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyObjectives: 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: 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.; Sezgin, Efe; Sezgin,E.; Bhargava,R.; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyObjective: 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).
