PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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: 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 Citation - WoS: 34Citation - Scopus: 32Lymphedema After Sentinel Lymph Node Biopsy: Who Is at Risk?(Mary Ann Liebert, Inc., 2021) Işık, Arda; Soran, Atilla; Grasi, Ariel; Barry, Noran; Sezgin, EfeAim: Sentinel lymph node biopsy (SLNB) is the accepted approach to stage the clinically negative axilla. The incidence of lymphedema (LE) after SLNB is about 5%. We hypothesize that patients undergoing axillary excision of >5 lymph nodes (LNs) are at increased risk of developing LE. Methods and Results: A single institution prospective breast cancer database was retrospectively reviewed from January 2013 to December 2017, to identify patients who underwent SLNB and were diagnosed with LE. Inclusion criteria was (1) de novo breast cancer, (2) SLNB in clinically node negative patients, and (3) no preoperative diagnosis LE of an extremity. Exclusion criteria was history of axillary lymph node dissection. Age, body mass index, tumor-node-metastasis status, surgery type, neoadjuvant or adjuvant chemotherapy, radiotherapy, and hormone therapy were analyzed. Of the 3325 patients identified, 2940 patients met the inclusion criteria and were included in the final analysis. Median follow-up time was 24 months. Forty-seven (2%) patients were diagnosed with LE, and nine patients (19%) had >5 LNs excised. LE was diagnosed in 3.7% of patients who had >5 LNs excised versus 1.4% of patients with <= 5 LNs excised. Incidence of LE was higher in patients with >5 LNs excision (p = 0.006). Conclusion: Our study showed that patients have a higher likelihood of developing LE when >5 LNs are excised.Article Citation - WoS: 63Citation - Scopus: 63The Effect of Primary Surgery in Patients With De Novo Stage Iv Breast Cancer With Bone Metastasis Only (protocol Bomet Mf 14-01): a Multi-Center, Prospective Registry Study(Springer, 2021) Soran, Atilla; Doğan, Lütfi; Işık, Arda; Özbaş, Serdar; Trabulus, Didem Can; Demirci, Umut; Sezgin, EfeBackground More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). Methods The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). Results We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). Conclusion In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.Article Citation - WoS: 24Citation - Scopus: 23On-Chip Determination of Tissue-Specific Metastatic Potential of Breast Cancer Cells(Wiley, 2021) Fıratlıgil Yıldırır, Burcu; Batı Ayaz, Gizem; Tahmaz, İsmail; Bilgen, Müge; Pesen Okvur, Devrim; Yalçın Özuysal, ÖzdenMetastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of custom platforms to predict metastatic potential and homing choices of cancer cells. Here, two organ-on-chip platforms, invasion/chemotaxis (IC-chip) and extravasation (EX-chip) were used for the quantitative assessment of invasion and extravasation towards specific tissues. Lung, liver and breast microenvironments were simulated in the chips using tissue-specific cells embedded in matrigel. In the IC-chip, invasive MDA-MB-231, but not noninvasive MCF-7 breast cancer cells invaded into lung and liver microenvironments. In the EX-chip, MDA-MB-231 cells extravasated more into the lung compared to the liver and breast microenvironments. In addition, lung-specific MDA-MB-231 clone invaded and extravasated into the lung microenvironment more efficiently than the bone-specific clone. Both invasion/chemotaxis and extravasation results were in agreement with published clinical data. Collectively, our results show that IC-chip and EX-chip, simulating tissue-specific microenvironments, can distinguish different in vivo metastatic phenotypes, in vitro. Determination of tissue-specific metastatic potential of breast cancer cells is expected to improve diagnosis and help select the ideal therapy.Article Citation - WoS: 8Citation - Scopus: 8The Role of Connexins in Breast Cancer: From Misregulated Cell Communication To Aberrant Intracellular Signaling(Taylor & Francis, 2022) Ünal, Yağmur Ceren; Yavuz, Büşra; Özçivici, Engin; Meşe Özçivici, GülistanIn spite of clinical advancements and improved diagnostic techniques, breast cancers are the leading cause of cancer-associated deaths in women worldwide. Although 70% of early breast cancers can be cured, there are no efficient therapies against metastatic breast cancers. Several factors including connexins and gap junctions play roles in breast tumorigenesis. Connexins are critical for cellular processes as a linkage between connexin mutations and hereditary disorders demonstrated their importance for tissue homeostasis. Further, alterations in their expression, localization and channel activities were observed in many cancers including breast cancer. Both channel-dependent and independent functions of connexins were reported in initiation and progression of cancers. Unlike initial reports suggesting tumor suppressor functions, connexins and gap junctions have stage, context and isoform dependent effects in breast cancers similar to other cancers. In this review, we tried to describe the current understanding of connexins in tumorigenesis specifically in breast cancers.Article Citation - WoS: 12Citation - Scopus: 15The Role of Loco-Regional Treatment in Long-Term Quality of Life in De Novo Stage Iv Breast Cancer Patients: Protocol Mf07-01q(Springer Verlag, 2021) Soran, Atilla; Soyder, Aykut; Özbaş, Serdar; Özmen, Vahit; Karanlık, Hasan; İğci, Abdullah; Sezgin, EfeBackground/objective Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey. Methods SF-12 (V2) forms were completed during visits of patients who were living 36 months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3 years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65 years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. Results There were 81 patients in this analysis; 68% of patients (n = 55) had LRT, and 32% (n = 26) received ST. General health was good or very good in 62% (n = 34) in the LRT group and 66% (n = 17) in the ST-only group (p = 0.63). Mean PCS-12 score was 40.8 + 1.6, and mean MCS-12 score was 43.4 + 2.0 (p = 0.34 and p = 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3 + 12.8 and MCS-12 = 46.8 + 13.0) and stage I-III BC patients (PCS-12 = 51.1 +/- 0.5, MCS-12 = 45.7 +/- 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3 years vs. at diagnosis of BC in de novo stage IV BC patients (p > 0.05), these variables were significantly better in stage I-III BC patients (p < 0.001). Conclusion The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3 years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.