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Öğe Antiandrogen abiraterone and docetaxel treatments affect Notch1, Jagged1 and Hes1 expressions in metastatic prostate cancer cells(Academic Press Inc., 2021) Soylu, Hakan; Kırça, Mustafa; Avcı, Sema; Özpolat, Bülent; Üstünel, İsmailBackground: Prostate cancer is the most common cancer in men. A Notch signaling pathway is an important pathway in cell proliferation, differentiation, and fate. However, currently, the effects of abiraterone based-anti-androgene therapy and docetaxel, the most commonly used standard chemotherapy in prostate cancer treatment, on Notch signaling pathway are unknown. This study aimed to investigate the effects of abiraterone acetate and docetaxel on the expression of Notch1, Jagged1 and Hes1 in prostate cancer cell lines. Methods: In vitro effects of abiraterone acetate and docetaxel were examined on Notch1, Jagged1, and Hes1 expression in LNCaP and PC3 PCa cell lines by immunofluorescence, Western blot, and qRT-PCR. MTT proliferation assay was used to evaluate cell proliferation and survival. Results: We found that in the treatment of PC3 cells with abiraterone acetate, docetaxel, and their combination, only mRNA expressions of Notch1, Jagged1 and Hes1 were affected compared to control, but these expression differences were not observed in protein expression. In LNCaP cells, abiraterone acetate and the combination groups reduced Notch1 protein expression. All treatment groups did not alter Jagged1 expression compared to control, but significantly increased the Hes1 gene and protein expression. Conclusion: Our findings suggest that abiraterone and docetaxel treatments affects the expression of Notch signal pathway proteins. But these drugs especially cause significant upregulation in Hes1 expression in PCa cells. Therefore, co-application of Notch signaling inhibitors together with docetaxel and abiraterone chemotherapy, it was thought that decreased Hes1 expression could be stopped the deterioration of the prognosis of the patient. © 2021 Elsevier Inc.Öğe Evaluation of angiogenic apelin/apelin receptor axis in normal prostate, high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma(Malaysian Journal Pathology, 2022) Soylu, Hakan; Unal, Betul; Aksu, Kubra; Avci, Sema; Caylan, Ahmet Ender; Ustunel, IsmailIntroduction and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in American men. Apelin is an endogenous peptide identified as the ligand of the G protein-associated apelin receptor. Apelin and apelin receptor have many tissues distribution and they participate in pathological processes, such as cancer. Apelin stimulates cancer angiogenesis. However, there are insufficient data in the literature regarding the role of apelin/apelin receptor in normal tissue, highgrade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma tissues. Therefore, this study aimed to investigate the apelin and apelin receptor expression levels in tissues of normal prostate tissue, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. Materials and Methods: In this study, 38 samples of patients undergoing radical prostatectomy were used. Among 38 samples; 20 patients were with prostatic adenocarcinoma, 18 patients were with high-grade prostatic intraepithelial neoplasia and adjacent normal prostatic tissue areas. The immunolocalisation of apelin and apelin receptor in these tissues were determined immunohistochemically. Results: Apelin and apelin receptor expressions were higher in prostatic adenocarcinoma than normal prostate tissue and high-grade prostatic intraepithelial neoplasia. Apelin receptor expression was also increased in high-grade prostatic intraepithelial neoplasia compared to normal tissue. Conclusion: Apelin and apelin receptor are increase in the process of prostate carcinogenesis. This increase may adversely affect the clinical course of prostate cancer patients by stimulating angiogenesis, which is important for invasion and metastasis in prostate cancer.Öğe Expressions of Notch signalling pathway members during early pregnancy in mice(Springer, 2023) Acar, Nuray; Soylu, Hakan; Avci, Sema; Ustunel, IsmailAlthough pregnancy is initiated and maintained through highly complex mechanisms, it is essential to understand the events that occur before and during early pregnancy to understand a healthy implantation process. The Notch signal, thought to be involved in this process, is frequently the subject of research with its different aspects. To better understand the role of Notch signaling in the peri-implantation period of the mouse uterus, we investigated the state of expression and localization of Notch 3, Notch 4, Rbp-J, Hes1, Hes7, Hey2, HeyL, and Fbw7 in the uterus and implantation sites in early pregnancy. Balb/C mice were divided into groups D1, D4, D5, D6, and D8. For D5 and D6 groups, implantation sites were identified by intravenous injection of Chicago blue. IHC, WB, and QRT-PCR methods were used. Notch 3 was very strong positive on the 4th day of pregnancy. Notch 4 was highly expressed on days 4, 5, 6, and 8 of pregnancy when P-4 levels were high. Hes 1 level was at the lowest on the 4th day of pregnancy. Hes 7 protein expression gradually increased from D1 to D8 in the uteri and implantation sites. Hey 2 expression was at the highest level on the 1st and 4th days. Hey L expression was on the apical of the glands. Fbxw7 that expression was high on the 1st and 4th days of pregnancy. Notch signaling may play an essential role in regulating endometrial receptivity. In addition, our Hes7 results are new to the literature.Öğe İnsan Serviks Dokusunda Misoprostol İndüksiyonunun Notch Sinyal Yolağı Reseptör Ve Ligand Ekspresyonları Üzerine Etkisinin Araştırılması(2017) Üstünel, İsmail; Şimşek, Mehmet; Avcı, Sema; Soylu, HakanÖnerilen bu projede, Misoprostolle indüklenmiş insan serviks dokusu kullanılarak Notch sinyal yolağı reseptör ve ligandlarının ekspresyon düzeylerinin belirlenmesi amaçlandı. Alınan servikse ait biyopsi örneklerinde; Notch 1-4, Delta-like 1, 3, 4 ve Jagged 1, 2? nin immünolokalizasyonları ve protein düzeyleri incelendi. Sonuçta, Notch sinyal yolağının doğum indüksiyonu için önemli bir sinyal yolağı olabileceği sonucuna varıldı.












