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Öğe Abirateron ve Docetaxel Tedavileri Metastatik Prostat Kanseri Hücrelerinde Phospho-PTEN Ekspresyonunu Arttırır(2023) Soylu, Hakan; Istıl, Kübra Aksu; Ustunel, Ismail; Karaçor, Kayıhan; Beyazçiçek, ÖzgeAmaç: Prostat kanseri erkeklerde kanser ile ilişkili ölümlerde ikinci sırada yer almaktadır. Kastrasyona dirençli metastatik prostat kanseri tedavilerinde dosetaksel ve abirateron asetat yaygın olarak kullanılmaktadır. Phospho-PTEN, onkojenik Akt hiperaktivasyonuna sebep olarak hücrelerde proliferasyon, migrasyon, angiyogenez ve hayatta kalmayı tetikler. Bu çalışmada prostat kanseri tedavisinde yaygın olarak kullanılan dosetaksel ve abirateron asetat ajanlarının onkogenic yolağı uyaran phospho-PTEN ekspresyonu üzerine etkisinin araştırılması amaçlanmışır. Gereç ve Yöntemler: In vitro olarak antijen reseptör (+) ve androjen reseptör (-) metastatik prostat kanseri hücre hatlarında dosetaksel ve abirateron acetat’ın phospho-PTEN expresyonu üzerine etkisi immünofloresan yöntemi ile araştırılmıştır. Bulgular: Antijen reseptör (+) ve androjen reseptör (-) metastatik prostat kanseri hücre hatlarının her ikisinde de bulgular birbiriyle uyumluydu. Kontrol ve abirateron asetat grupları arasında phospho-PTEN ekspresyonununda istatistiksel olarak anlamlı bir fark gözlenmedi. Dosetaksel ve abirateron asetat+dosetaksel gruplarında phospho-PTEN ekspresyonu kontrole göre istatistiksel olarak anlamlı şekilde arttı. Bu artış iki ajanın birlikte verildiği kombine grupta dosetaksel grubuna kıyasla istatistiksel olarak anlamlı şekilde daha fazlaydı. Sonuç: Dosetaksel ve kombine tedavi gruplarında belirgin şekilde phospho-PTEN artışı gözlendi. Phospho-PTEN’in artışı onkojenik Akt hiperaktivasyonuna neden olmaktadır. Bu bilgilere göre, dosetaksel ve kombine ilaç tedavileri hastalarda phospho-PTEN artışına sebep olarak hücrelerde onkojenik yolağı destekliyor olabilir. Hastalarda bu etkilerinin bertaraf edilebilmesi için PTEN’i defosforile edici ajanlar ya da defosforilasyonu sağlayan yolakların uyarılmasını sağlayacak ajanların verilmesi hastaların toplam hayatta kalma sürelerini artırabilir.Öğe The effect of apelin-13 on gastric ischemia/reperfusion injury: the roles of sensory nerves and vagus nerve(Canadian Science Publishing, 2020) Birsen, Ilknur; Izgut-Uysal, V. Nimet; Soylu, Hakan; Ustunel, IsmailApelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-alpha increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.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 Expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) in mouse uterus during the peri-implantation period(Taylor & Francis Ltd, 2023) Soylu, Hakan; Aksu, Kübra; Gölal, Ezgi; Ustunel, Ismail; Izgut-Uysal, V. Nimet; Acar, NurayNuclear factor-erythroid 2-related factor- 2 (Nrf2) is a nuclear transcription factor that facilitates transcription of genes for detoxification enzymes and antioxidant proteins. We investigated the distribution and expression of Nrf2 during the peri-implantation period. We detected Nrf2 in uteri of mice during estrus (control) and on days 1, 4, 5, 6 and 8 of pregnancy using immunohistochemistry, quantitative real-time polymerase chain reaction and western blotting. Nrf2 immunostaining was significantly greater on days 1, 5 and 6 of pregnancy compared to controls, and on days 4 and 8 of pregnancy; western blotting results were consistent with immunohistochemical observations. Nrf2 mRNA levels on days 5 and 8 were significantly higher than for control uteri. Increased expression of Nrf2 on days 1, 5 and 6 of pregnancy may be important for uterine receptivity, implantation and decidualization by protecting the developing embryo and uterus from the adverse effects of oxidative stress.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.
