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Item Mitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cells(2021) Karakas, Bahriye; Aka, Yeliz; Giray, Asli; Temel, Sehime Gulsum; Acikbas, Ufuk; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur; 34294688Breast cancer is the most common cancer with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status is an important prognostic factor and endocrine therapy is the choice of first-line treatment in ER-positive breast cancer. However, most tumors develop resistance to endocrine therapy. Here we demonstrate that BH3 profiling technology, in particular, dynamic BH3 profiling can predict the response to endocrine therapy agents as well as the development of acquired resistance in breast cancer cells independent of estrogen receptor status. Immunofluorescence analysis and subcellular fractionation experiments revealed distinct ER-alpha and ER-beta subcellular localization patterns in breast cancer cells, including mitochondrial localization of both receptor subtypes. shRNA-mediated depletion of ER-beta in breast cancer cells led to resistance to endocrine therapy agents and selective reconstitution of ER-beta in mitochondria restored sensitivity. Notably, mitochondria-targeted ER-alpha did not restore sensitivity, even conferred further resistance to endocrine therapy agents. In addition, expressing mitochondria-targeted ER-beta in breast cancer cells resulted in decreased mitochondrial respiration alongside increased total ROS and mitochondrial superoxide production. Furthermore, our data demonstrated that mitochondrial ER-beta can be successfully targeted by the selective ER-beta agonist Erteberel. Thus, our findings provide novel findings on mitochondrial estrogen signaling in breast cancer cells and suggest the implementation of the dynamic BH3 technique as a tool to predict acquired endocrine therapy resistance.Item Incidence and outcome of occult uterine sarcoma: A multi-centre study of 18604 operations performed for presumed uterine leiomyoma(2020) Yorganci, Aycag; Meydanli, Mehmet Mutlu; Kadioglu, Nezaket; Taskin, Salih; Kayikcioglu, Fulya; Altin, Duygu; Atasoy, Latife; Haberal, Asuman Nihan; Kinay, Tugba; Akgul, Mehmet Akif; Tapisiz, Omer Lutfi; Evliyaoglu, Ozlem; Tekin, Ozlem Moraloglu; Ortac, U. Firat; Ayhan, Ali; 0000-0001-9852-9911; 0000-0001-7369-5470; 31499285; AAJ-5802-2021; AAK-4587-2021; AAI-8793-2021Item The effect of helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia : a retrospective single center research(2020) Suna, N.; Etik, D.; Ocal, S.; Gunduz, C.; Acikgoz, A.; Bildik, I; Gursoy, A.; Kasgoz, I; Tuleylioglu, H.; Boyacioglu, A.; 0000-0003-3719-9482; 0000-0002-4724-0728; 0000-0001-6234-7788; 33094583; ABH-4817-2020; AAJ-4707-2021; AAI-8822-2021Background and study aims : Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide. Helicobacter pylori (Hp) plays an important role in gastric carcinogenesis by inducing precancerous changes such as atrophic gastritis (AG) and intestinal metaplasia (IM). In our study, we aim to compare the grade of AG and IM before and after Hp eradication in patients who underwent esophagogastroduodenoscopy (EGD) in our center. Patients and methods : The data of 40.060 patients who underwent EGD for various reasons in our Endoscopy Unit between June 2011 and November 2017 were retrospectively evaluated. The grade of AG and IM before and after Hp eradication of patients meeting the study criteria were compared with each other. In addition, these findings were compared using OLGA and OLGIM staging systems. Results : A total of 175 patients, 89 (50.9%) women and 86 (49.1%) men, were included in the study. The mean age was 55 +/- 12 years. The mean time between two EGD examinations was 38 +/- 14 months. Significant improvement was observed in the grade of AG on corpus and antrum after Hp eradication (P=0.000, P=0.008). In the corpus and antrum, the grade of IM was regressed but this was not significant (P=0.80 and P=0.370 respectively). There was a decrease in OLGA stages after Hp eradication (P=0.000). There was also a reduction in the OLGIM stages, but this was not significant(P=0.341). Conclusion: Our study demonstrates that Hp eradication may reduce the risk of developing GC by providing an improvement in AG and IM which are precancerous changes in GC.Item Epoetin receptor status may alter the outcomes in head and neck cancers treated with radiotherapy and darbepoetin-alpha(2019) Topkan, Erkan; Yildirim, Berna Akkus; 0000-0001-8120-7123; 30414758; AAG-2213-2021Item FUNCTIONAL CHARACTERIZATION OF SPERMINE FAMILY TRANSPORTER caf5(+) IN Schizosaccharomyces pombe (Lindner)(2019) Ors Gevrekci, AslihanPolyamines are well conserved polycationic molecules that are known to interact with nucleic acids and contribute to multiple functions including cell cycle and stress response. The transport of polyamines in and out of the cell is driven by polyamine transporters that play a significant role in polyamine homeostasis. Schizosaccharomyces pombe (Lindner) caf5(+) gene codes for a spermine family transporter that is yet to be characterized functionally. This study aims to understand the contribution of caf5(+) on different processes previously associated with polyamines, by reverse genetics. Deletion mutants of caf5(+), which are viable in normal conditions, were scanned for multiple cellular processes. The results showed that caf5(+) deletion caused shorter cell length and slightly faster growth rate at the optimum conditions. caf5. cells also showed sensitivity to high doses of UV irradiation, while no sensitivity was observed against osmotic stress or another DNA damaging agent hydroxyurea. The mutants could successfully go through different phases of mitosis and meiosis as observed by DNA and septum staining. In summary, caf5(+) gene is involved in normal growth and cell cycle progression, as well as stress response upon UV irradiation.Item Therapeutic Potential of Apigenin, a Plant Flavonoid, for Imatinib-Sensitive and Resistant Chronic Myeloid Leukemia Cells(2014) Solmaz, Soner; Gokbulut, Aysun Adan; Cincin, Birsu; Ozdogu, Hakan; Boga, Can; Cakmakoglu, Bedia; Kozanoglu, Ilknur; Baran, YusufDespite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.Item Myelodysplastic features and cellular senescence in autoimmune disorders: a pilot study on patients with collagen tissue disorders and immune thrombocytopenic purpura(2015) Olcay, Lale; Billur, Deniz; Erdemli, Esra; Baskin, Sidika Esra; Balci, Havva Fatma; Yetgin, Sevgi; 26281349Item Single-Nucleotide Polymorphisms on the RYD5 Gene in Nasal Polyposis(2015) Ozdas, Sibel; Izbirak, Afife; Ozdas, Talih; Ozcan, Kursat Murat; Erbek, Selim S.; Koseoglu, Sabri; Dere, Huseyin; 26204469Nasal polyposis (NP) is a chronic inflammatory disease. Several genes play major roles in the pathophysiology of the disease. We analyzed RYD5 gene polymorphisms to determine the effect of these variants or their genetic combinations on NP. We genotyped the RYD5 gene in 434 participants (196 patients with NP and 238 controls). Data were analyzed with SPSS, SNPStats, and multifactor dimensionality reduction (MDR) software. We genotyped 10 single-nucleotide polymorphisms (SNPs) in the RYD5 gene. RYD5 (+152G>T) (p.Gly51Va) has not been reported previously. The PolyPhen and PROVEAN predicted the missense mutation as deleterious, but sorting intolerant from tolerant (SIFT) did not. In the genotype analysis, we found that four SNPs (RYD5 [-264A>G], [-103G>A], [+57-14C>T], and [+66A>G]) were significantly associated with NP. The individuals with combined genotypes of six risk alleles (RYD5-264G, -103A, +13C, +57-14T, +66G, and +279T) had significantly higher risks for NP compared with the ones with one or four risk alleles. Haplotype analysis revealed that the two haplotypes were associated with risk of NP. As indicated by MDR analysis, RYD5 (-264A>G and -103G>A) and RYD5 (-264A>G, -177C>A, and -103G>A) were the best predictive combinations and they had the highest synergistic interaction on NP. In addition, RYD5 (+13C>T) was significantly associated with increased risk of both NP with asthma and NP with allergy and asthma. Some SNPs and their combinations in the RYD5 gene are associated with increased probability for developing NP. We emphasize the importance of genetic factors on NP and NP-related clinical phenotypes.