WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Citation - WoS: 5Citation - Scopus: 5Multiorgan-On for Cancer Drug Pharmacokinetics-Pharmacodynamics (pk-Pd) Modeling and Simulations(Springer/plenum Publishers, 2025) Mohammed, Abdurehman Eshete; Kurucaovali, Filiz; Okvur, Devrim PesenCancer is one of the most common and fatal diseases worldwide and kills millions of people every year. Cancer drug resistance, lack of efficacy, and safety are significant problems in cancer patients. A multiorgan-on-a-chip (MOC) device consisting of breast and liver compartments was designed with AutoCAD software. The MOC molds were printed by a Formlabs Form 2 3D printer. MDA-MB-231, HepG2, and MCF-10 A cells were used for the MOC experiments. The cell lines were cultured at 37 degrees C with 5% CO2, and cell viability was assessed via Alamar blue dye to generate pharmacodynamics (PD) data. Drug concentrations from the cell culture media were analyzed via Agilent 1260 Infinity II HPLC with a Waters Symmetry C18 column and used to generate pharmacokinetics (PK) data. The PK and PD data were modeled and simulated by Monolix and Simulix software, respectively. The safety and efficacy of drug dosing regimens were compared, and the best dosing regimens were selected. This research designed and fabricated a unique MOC consisting of liver and breast compartments that overcomes the need for sealing or assembling. It was used for PK-PD modeling and simulations, and its functionality was proven experimentally. The new MOC will be helpful in preclinical trials to evaluate the efficacy and safety of drugs.Article Citation - WoS: 1Citation - Scopus: 1The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots(Wiley, 2024) Yücel, Müge; Onbaş, Rabia; Arslan Yıldız, Ahu; Yıldız, Ümit HakanThis study describes the formation, size control, and penetration behavior of polymer nanodots (Pdots) consisting of single or few chain polythiophene-based conjugated polyelectrolytes (CPEs) via nanophase separation between good solvent and poor solvent of CPE. Though the chain singularity may be associated with dilution nanophase separation suggests that molecules of a good solvent create a thermodynamically driven solvation layer surrounding the CPEs and thereby separating the single chains even in their poor solvents. This statement is therefore corroborated with emission intensity/lifetime, particle size, and scattering intensity of polyelectrolyte in good and poor solvents. Regarding the augmented features, Pdots are implemented into cell imaging studies to understand the nuclear penetration and to differentiate the invasive characteristics of breast cancer cells. The python based red, green, blue (RGB) color analysis depicts that Pdots have more nuclear penetration ability in triple negative breast cancer cells due to the different nuclear morphology in shape and composition and Pdots have penetrated cell membrane as well as extracellular matrix in spheroid models. The current Pdot protocol and its utilization in cancer cell imaging are holding great promise for gene/drug delivery to target cancer cells by explicitly achieving the very first priority of nuclear intake. The penetration capability of cationic soft nanodots in to tumor models of breast cancer is demonstrated. The image analysis based on fluorescence intensity variation reveals the characteristics of translocation of nanodots in dense mediums such as tumor models.imageArticle Citation - WoS: 5Citation - Scopus: 7Adaptive Resizer-Based Transfer Learning Framework for the Diagnosis of Breast Cancer Using Histopathology Images(Springer, 2023) Düzyel, Okan; Çatal, Mehmet Sergen; Kayan, Ceyhun Efe; Sevinç, Arda; Gümüş, AbdurrahmanBreast cancer is a major global health concern, and early and accurate diagnosis is crucial for effective treatment. Recent advancements in computer-assisted prediction models have facilitated diagnosis and prognosis using high-resolution histopathology images, which provide detailed information on cancerous tissue. However, these high-resolution images often require resizing, leading to potential data loss. In this study, we demonstrate the effect of a learnable adaptive resizer for breast cancer classification using the BreakHis dataset. Our approach incorporates the adaptive resizer with various convolutional neural network models, including VGG16, VGG19, MobileNetV2, InceptionResnetV2, DenseNet121, DenseNet201, and EfficientNetB0. Despite producing visually less appealing images, the learnable resizer effectively improves classification performance. DenseNet201, when jointly trained with the adaptive resizer, achieves the highest accuracy of 98.96% for input images of 448x448 resolution. Our experimental results demonstrate that the adaptive resizer performs better at a magnification factor of 40x compared to higher magnifications. While its effectiveness becomes less pronounced as image resolution increases to 100x, 200x, and 400x, the adaptive resizer still outperforms bilinear interpolation. In conclusion, this study highlights the potential of adaptive resizers in enhancing performance for medical image classification. By outperforming traditional image resizing methods, our work contributes to the advancement of deep neural networks in the field of breast cancer diagnostics.Review Citation - WoS: 14Citation - Scopus: 14Recent Advances in Lab-On Systems for Breast Cancer Metastasis Research(Royal Society of Chemistry, 2023) Fıratlıgil Yıldırır, Burcu; Yalçın Özuysal, Özden; NonappaBreast 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 Citation - WoS: 6Citation - Scopus: 4Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared With Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms(Mary Ann Liebert, 2023) Soran, Atilla; Bengur, Fuat Barış; Rodriguez, Wendy; Chroneos, Maria Z.; Sezgin, EfeIntroduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs.Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(>= 7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE.Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.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.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, EfeThe 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, SevilIn 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: 1Aso 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, EfeThe 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, EfeBackground/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.