PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
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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.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.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.Article Citation - WoS: 12Citation - Scopus: 12Sema6d 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, ÖzdenSemaphorin 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 cancerArticle Citation - WoS: 2Citation - Scopus: 2Importance 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, EfeNext-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: 15Citation - Scopus: 14Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel Ef2 Kinase Inhibitor Suppresses Breast Cancer Growth in Vivo(American Chemical Society, 2021) Önder, Ferah Cömert; Kahraman, Nermin; Atıcı, Esen Bellur; Çağır, Ali; Kandemir, Hakan; Tatar, Gizem; Taşkın Tok, TuğbaEukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications. We designed and synthesized several generations of potential inhibitors. The effect of the inhibitors at the binding pocket of eEF-2K was analyzed after developing a 3D target model by using a domain of another a-kinase called myosin heavy-chain kinase A (MHCKA) that closely resembles eEF-2K. In silico studies showed that compounds with a coumarin-chalcone core have high predicted binding affinities for eEF-2K. Using in vitro studies in highly aggressive and invasive (MDA-MB-436, MDA-MB-231, and BT20) and noninvazive (MCF-7) breast cancer cells, we identified a lead compound that was highly effective in inhibiting eEF-2K activity at submicromolar concentrations and at inhibiting cell proliferation by induction of apoptosis with no toxicity in normal breast epithelial cells. In vivo systemic administration of the lead compound encapsulated in single lipid-based liposomal nanoparticles twice a week significantly suppressed growth of MDA-MB-231 tumors in orthotopic breast cancer models in nude mice with no observed toxicity. In conclusion, our study provides a highly potent and in vivo effective novel small-molecule eEF-2K inhibitor that may be used as a molecularly targeted therapy breast cancer or other eEF-2K-dependent tumors.Letter Citation - Scopus: 3Reply: the Effect of Primary Surgery in Patients With Stage Iv Breast Cancer With Bone Metastasis Only (protocol Bomet Mf 14-01): a Multi-Center, Registry Study(Springer, 2021) Soran, Atilla; Sezgin, Efe; Özbaş, Serdar; Doğan, LütfiDear Editor, We’d like to thank Drs. Ishizuka and Horimoto for their letter to the editor. We’re glad to see their interest to our prospective study. Regarding their recommendation that univariate Kaplan–Meier analysis does not eliminate confounding factors, such as age, tumor size, number of bone metastasis, etc., we employed propensity score methods for the results, including Fig. 1.Conference Object Citation - WoS: 83Citation - Scopus: 87Primary Surgery With Systemic Therapy in Patients With De Novo Stage Iv Breast Cancer: 10-Year Follow-Up; Protocol Mf07-01 Randomized Clinical Trial(Elsevier, 2021) Soran, Atilla; Özmen, Vahit; Özbaş, Serdar; Karanlık, Hasan; Müslümanoğlu, Mahmut; İğci, Abdullah; Cantürk, Nuh Zafer; Utkan, Zafer; Evrensel, Türkkan; Sezgin, EfeBackground: The aim of this randomized clinical trial was to evaluate the overall survival (OS) data of patients diagnosed with de novo stage IV breast cancer (BC) who received locoregional treatment (LRT) over a 10-year follow-up. Study Design: The MF07-01 is a 1:1 multicenter, randomized clinical trial comparing the LRT with systemic therapy (ST), where ST was given to all patients either immediately after randomization or after surgical resection of the intact primary tumor. Results: A total of 278 patients were randomized and 265 patients were in the final analysis. At 10-year follow-up, survivals were 19% (95% CI 13%–28%) and 5% (95% CI 2%–12%) in the LRT group and ST group, respectively. Median survival was 46 months for the LRT group and 35 months for the ST group, and hazard of death was 29% lower in the LRT group compared with the ST group (hazard ratio [HR] 0.71; 95% CI 0.59–0.86; p = 0.0003). Conclusions: Patients with a diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 14% higher chance of OS by the end of the 10-year follow-up compared with the patients who received only ST. The longer study follow-up revealed that LRT should be presented to patients when discussing treatment options. © 2021 American College of SurgeonsArticle Citation - WoS: 21Citation - Scopus: 22Daily Application of Low Magnitude Mechanical Stimulus Inhibits the Growth of Mda-Mb Breast Cancer Cells in Vitro(BioMed Central Ltd., 2014) Ölçüm, Melis; Özçivici, EnginIntroduction: Mechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth. Methods: The signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays. Results: Compared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells. Conclusion: Combined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.Article Citation - WoS: 16Citation - Scopus: 18Connexin 32 Induces Pro-Tumorigenic Features in Mcf10a Normal Breast Cells and Mda-Mb Metastatic Breast Cancer Cells(Elsevier, 2020) Yalçın Özuysal, Özden; Adak, Aslı; Ünal, Yağmur Ceren; Yücel, Simge; Vural, Zehra; Turan, Fatma Başak; Meşe, GülistanConnexins (Cx), the basic subunit of gap junctions, play important roles in cell homeostasis, and their abnormal expression and function are associated with human hereditary diseases and cancers. In tumorigenesis, connexins were observed to have both anti-tumorigenic and pro-tumorigenic roles in a context- and stage-dependent manner. Initially, Cx26 and Cx43 were thought to be the only connexins involved in normal breast homeostasis and breast cancer. Later on, association of Cx32 expression with lymph node metastasis of breast cancer and subsequent demonstration of its expression in normal breast tissue suggested that Cx32 contributes to breast tissue homeostasis. Here, we aimed to determine the effects of Cx32 on normal breast cells, MCF10A, and on breast cancer cells, MDA-MB-231. Cx32 overexpression had profound effects on MCF10A cells, decreasing cell proliferation by increasing the doubling time of MCF10A. Furthermore, MCF10A cells acquired mesenchymal-like appearance upon Cx32 expression and had increased migration capacity and expression of both E-cadherin and vimentin. In contrast, Cx32 overexpression altered the EMT markers of MDA-MB-231 by increasing the expression of mesenchymal markers, such as slug and vimentin, and decreasing E-cadherin expression without affecting their proliferation and morphology. Our results indicate, for the first time in the literature, that Cx32 has tumor-promoting roles in MCF10A and MDA-MB-231 cells.
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