WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7150

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Now showing 1 - 10 of 29
  • Review
    Citation - WoS: 14
    Citation - Scopus: 14
    Recent Advances in Lab-On Systems for Breast Cancer Metastasis Research
    (Royal Society of Chemistry, 2023) Fıratlıgil Yıldırır, Burcu; Yalçın Özuysal, Özden; Nonappa
    Breast cancer is the leading cause of cancer-related deaths in women. Multiple molecular subtypes, heterogeneity, and their ability to metastasize from the primary site to distant organs make breast cancer challenging to diagnose, treat, and obtain the desired therapeutic outcome. As the clinical importance of metastasis is dramatically increasing, there is a need to develop sustainable in vitro preclinical platforms to investigate complex cellular processes. Traditional in vitro and in vivo models cannot mimic the highly complex and multistep process of metastasis. Rapid progress in micro- and nanofabrication has contributed to soft lithography or three-dimensional printing-based lab-on-a-chip (LOC) systems. LOC platforms, which mimic in vivo conditions, offer a more profound understanding of cellular events and allow novel preclinical models for personalized treatments. Their low cost, scalability, and efficiency have resulted in on-demand design platforms for cell, tissue, and organ-on-a-chip platforms. Such models can overcome the limitations of two- and three-dimensional cell culture models and the ethical challenges involved in animal models. This review provides an overview of breast cancer subtypes, various steps and factors involved in metastases, existing preclinical models, and representative examples of LOC systems used to study and understand breast cancer metastasis and diagnosis and as a platform to evaluate advanced nanomedicine for breast cancer metastasis.
  • 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, Özden
    Objectives: 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.
  • Erratum
    Correction: Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-Institutional Registry Study–imet, Protocol Mf 14-02
    (Springer, 2023) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, Lütfi; Şenol, Kazım; Sezgin, Efe
    The authors‘ given names are correct as reflected here. © Society of Surgical Oncology 2022.
  • Conference Object
    Peptıde Targeted Core Cross-lınked Mıcelles For Dox Delıvery To Her2 Expressıng Cancer Cells
    (Mary Ann Liebert, 2022) Bayram, Nazende Nur; Ulu, Gizem Tuğçe; Gürdap, Seda; İşoğlu, İsmail Alper; Baran, Yusuf; Dinçer İşoğlu, Sevil
    In this study, we prepared a novel targeted and extra stable micellar nanocarrier that can facilitate intracellular drug release. First, ((N-3-sulfopropyl-N, N-dimethylammonium)ethyl methacrylate was synthesized by RAFT polymerization, and it was followed by copolymerization of macroCTA with AEM in the presence of an aciddegradable cross-linker. Then, a peptide estimated by phage display for HER-2 recognition was incorporated into these core cross-linked micelles with carbodiimide reaction.
  • Article
    Citation - WoS: 1
    Aso Visual Abstract: Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients-Prospective, Multi-Institutional Registry Study: Imet; Protocol Mf 14-02
    (Springer, 2022) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, L.; Şenol, Kazım; Dağ, Ahmet; Karanlık, Hasan; Aytaç, Özgür; Karadeniz Çakmak, Güldeniz; Dalcı, Kubilay; Doğan, Mutlu; Sezer, Atakan Y.; Gökgöz, Şehsuvar; Özyar, Enis; Sezgin, Efe
    The aim of our prospective, multicenter registry study was to investigate the importance of interventions for operable lung and/or liver metastasis for breast cancer (BC) survival (https://doi.org/10.1245/s10434-022-12239-z). The results reveal that surgical resection or ablative interventions may contribute to survival in patients with BC with limited number and operable metachronous hepatic/pulmonary metastases. Ultimately, randomized studies will determine whether intervention on lung and liver metastatic sites should be performed. In the meantime, such interventions can be considered on select patients.
  • Conference Object
    Intervention To Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-Institutional Registry Study-Imet; Protocol Mf 14-02
    (Springer, 2022) Soran, Atilla; Özbaş, Serdar; Özçınar, Beyza; Işık, Arda; Doğan, Lütfi; Şenol, Kazım; Dağ, Ahmet; Karanlık, Hasan; Aytaç, Özgür; Karadeniz Çakmak, Güldeniz; Dalcı, Kubilay; Doğan, Mutlu; Sezer, Atakan Y.; Gökgöz, Şehsuvar; Özyar, Enis; Sezgin, Efe
    Background/Objective: One‐fourth of early‐stage breast cancer (BC) becomes metastatic at follow‐up. Limited metastases represents a clinical state of metastatic disease that is limited in the number of metastatic sites and extent of disease, and amenable to metastasis‐directed intervention. The aim of this prospective study is to evaluate intervention to limited metastases in lung and/or liver.
  • Conference Object
    Survival Impact of Intervention To Distant Metastatic Lesions in Patients With Breast Cancer
    (Springer, 2022) Abidi, Hira; Ayoade, Oluwaseun; McAuliffe, Priscilla; Johnson, Ronald; Lee, Joanna; Keenan, Donald; Steiman, Jennifer; Sezgin, Efe; Soran, Atilla
    INTRODUCTION: Approximately 25% of patients (pts) with stage I - III breast cancer (BC) develop distant metastatic disease, a significant cause of mortality. The aim of this study is to evaluate whether intervention to metastatic lesions, in pts initially presenting with stage I–III BC, impacts overall survival (OS) and post-distant recurrence survival (PDRS). METHODS: This is a singleinstitution retrospective study of 201 pts with stage I–III BC, who subsequently develop metastatic lesions to the liver, lung, and/or bone, from 2006-2016. The cohorts included pts receiving intervention to their metastases (IM, n=100) versus no intervention to their metastases (NI, n=101). Two pts in the IM group were lost to follow up and excluded from the survival analysis. The primary study outcomes are OS and PDRS. The characteristics of the pts were compared with X2 test. OS curves were calculated by Kaplan-Meier method and multivariable analysis by Cox regression. Statistical significance was set at p< 0.05.
  • Article
    Citation - WoS: 12
    Citation - Scopus: 12
    Sema6d Differentially Regulates Proliferation, Migration, and Invasion of Breast Cell Lines
    (American Chemical Society, 2022) Günyüz, Zehra Elif; Sahi İlhan, Ece; Küçükköse, Cansu; İpekgil, Doğaç; Tok, Güneş; Meşe, Gülistan; Özçivici, Engin; Yalçın Özuysal, Özden
    Semaphorin 6D (SEMA6D), a member of the class 6 semaphorin family, is a membrane-associated protein that plays a key role in the development of cardiac and neural tissues. A growing body of evidence suggests that SEMA6D is also involved in tumorigenesis. In breast cancer, high SEMA6D levels are correlated with better survival rates. However, very little is known about the functional significance of SEMA6D in breast tumorigenesis. In the present study, we aimed to investigate the effects of SEMA6D expression on the normal breast cell line MCF10A and the breast cancer cell lines MCF7 and MDA MB 231. We demonstrated that SEMA6D expression increases the proliferation of MCF10A cells, whereas the opposite effect was observed in MCF7 cells. SEMA6D expression induced anchorage-independent growth in both cancer cell lines. Furthermore, migration of MCF10A and MCF7 cells and invasion of MDA MB 231 cells were elevated in response to SEMA6D overexpression. Accordingly, the genes related to epithelial-mesenchymal transition (EMT) were altered by SEMA6D expression in MCF10A and MCF7 cell lines. Finally, we provided evidence that SEMA6D levels were associated with the expression of the cell cycle, EMT, and Notch signaling pathway-related genes in breast cancer patients' data. We showed for the first time that SEMA6D overexpression has cell-specific effects on the proliferation, migration, and invasion of normal and cancer breast cell lines, which agrees with the gene expression data of clinical samples. This study lays the groundwork for future research into understanding the functional importance of SEMA6D in breast cancer
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Importance of Multigene Panel Test in Patients With Consanguineous Marriage and Family History of Breast Cancer
    (Spandidos Publications, 2022) Özmen, Vahit; Çağlayan, Ahmet Okay; Yararbaş, Kanay; Ordu, Çetin; Aktepe, Fatma; Özmen, Tolga; Sezgin, Efe
    Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 6
    Improved 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, Devrim
    The 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.