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Öğe A PLK1 inhibitor, RO3280, suppresses proliferation of SNU-16 gastric cancer cells via apoptosis(Bangladesh Pharmacological Soc, 2024) Yulak, Fatih; Keskin, ZekeriyaThis study examines the anti -tumor, pro-apoptotic, and genotoxic effects of polo -like kinase 1 (PLK1) inhibitor RO3280 on the gastric cancer cell line SNU16. Using the XTT assay, the antiproliferative effect of the compound was identified and showed a significant antiproliferative effect (p<0.01) with the IC50 value of 9.64 M for 24 hours. RO3280 considerably enhanced the expression of Bax and cleaved caspase-3 (p<0.01) and dramatically lowered the BCL-2 level (p<0.01), demonstrating an apoptotic effect. It greatly raised the expression of 8-oxo-dG, a DNA damage marker, and cleaved PARP, a degraded version of the PARP enzyme involved in DNA repair (p<0.05 and p<0.01, respectively). In addition, flow cytometric studies for annexin V and caspase3/7 revealed that RO3280 markedly improved the apoptotic cell profile (p<0.01). It reduced the mitochondrial membrane potential and DNA damage (p<0.01). These findings suggest that RO3280 has an antitumor impact by damaging DNA and inducing apoptosis in SNU-16 gastric cancer cells.Öğe Determination of the Percentage of Patients Using Warfarin to Reach Target INR(Sivas Cumhuriyet Üniversitesi, 2024) Keskin, Zekeriya; Gedikli, Mustafa AsımObjective: Warfarin is the most commonly used oral anticoagulant in the treatment and prophylaxis of thromboembolic diseases. In order to prevent thrombosis and to avoid hemorrhagic complications, the patient's International Normalized Ratio (INR) is kept within a certain range according to the indication and monitored at certain intervals. Our aim in our study is to determine the percentage of patients using warfarin for various indications reaching target INR values. Methods: Patients who used warfarin for various indications at our hospital's Internal Medicine outpatient clinic between May 2023 and November 2023 were included in our study, and their INR results were recorded by retrospectively scanning them. Results: A study group was formed with a total of 130 patients. Patients using warfarin due to metallic heart valve replacement, AF, PTE and CVD were evaluated separately according to the target INR value. The percentage of patients with metallic heart valve replacement reaching the target INR value of 2.5-3.5 was calculated as 38.5% (n: 27). The percentages of patients with AF, PTE and CVD reaching their target INR values of 2-3 were calculated as 40% (n:16), 54% (n:7), 70% (n:5), respectively. Considering the entire study group, the percentage of reaching the target INR was calculated as 42% (n: 55). Conclusion: As a result, warfarin not being within the therapeutic range causes serious morbidity and mortality. In our study, the percentage of patients reaching the target INR was found to be 42%. This percentage is very low, and in order to increase this rate, it is necessary to increase patient awareness, increase the frequency of follow-up of patients and develop more effective follow-up strategies.Öğe Evaluation of the Antitumor Activity of Omipalisib, a PI3K/AKT/MTOR Pathway Inhibitor, on Burkitt Lymphoma Cell Line(2023) Keskin, Zekeriya; Yulak, Fatih; Terzi, Hatice; İnanır, MerveThere are many challenges in the treatment of Burkitt lymphoma, especially in immunocompromised individuals, elderly patients, and patients with relapsed or refractory disease. Therefore, there is a need for new and less toxic therapeutic agents. The aim of this study was to determine the antitumoral activity of omipalisib, a PI3K/AKT/mTOR pathway inhibitor, in the Burkitt lymphoma. Raji cell line was used in the study. Omipalisib was administered to the cell line and then the cytotoxic effect of omipalisib on Raji cells was evaluated by the XTT test. The IC50 value was calculated according to the results of the XTT test. Apoptosis and cell cycle experiments were studied with the calculated IC50 value. The flow cytometric method was used to determine the effect of omipalisib on apoptosis and cell death. The results of the study showed a statistically significant cytotoxic effect of increasing concentrations of omipalisib on Raji cells. The apoptosis experiment performed revealed that omipalisib strongly induced apoptosis. The cell cycle experiment showed that omipalisib stimulated the cell cycle arrest at the G0/G1 phase. It was concluded that omipalisib exhibited antitumoral activity on Burkitt lymphoma cells with its cytotoxic effect and induced apoptosis and cell cycle arrest. Considering this effect, targeting the PI3K/AKT/mTOR pathway with omipalisib can be a new treatment option.Öğe PI3K/AKT/MTOR yolağı inhibisyonunun burkitt lenfoma hücre hattı üzerinde antitümoral etkinliğinin değerlendirilmesi(Sivas Cumhuriyet Üniversitesi, 2021) Keskin, Zekeriya; Terzi, Hatice; Ergül, MerveBurkitt lenfoma oldukça agresif bir B hücreli non Hodgkin lenfomadır. En yaygın olarak genç yetişkinlerde ve çocuklarda görülür. Yetişkinlerdeki lenfomaların yaklaşık %1-2'sini oluşturur. Klinik olarak çok hızlı progrese olabilmektedir. Burkitt lenfoma kemoterapiye yüksek duyarlı bir hastalıktır ve sadece kemoterapi ile iyileşme sağlanan nadir kanserlerden birisidir. Ancak hayatta kalma oranları artmasına rağmen özellikle bağışıklığı baskılanmış, yaşlı hastalar ve Relaps/Refrakter hastaların tedavilerinde birçok zorluk görülmektedir ve bu tür hastalarda prognoz kötüdür. Bu nedenle, Burkitt lenfoma patogeneziyle ilgili biyolojik yolları hedefleyen yeni ve daha az toksik terapötik ajanlara ihtiyaç duyulmaktadır. Bu bilgilere göre bizim çalışmamızda bir PI3K/AKT/mTOR yolağı inhibitörü olan omipalisibin Burkitt lenfoma hücre hattı üzerinde antitümoral etkinliğinin saptanması amaçlanmıştır. Çalışmada Burkitt lenfoma Raji hücre hattı kullanılmıştır. Omipalisib 50, 25, 12.5, 1, 0.1, 0.01 ?M konsantrasyonlarda hücre hattına uygulanmış sonrasında in vitro XTT hücre canlılık testi ile omipalisibin Raji hücreleri üzerindeki sitotoksik etkisi değerlendirilmiştir. XTT testinde alınan sonuçlara göre IC50 değeri hesaplanmıştır. Hesaplanan IC50 değeri ile apoptozis ve hücre döngüsü deneyleri flow sitometri yöntemi aracılığı ile çalışılmıştır. Çalışmada Burkitt lenfoma Raji hücreleri üzerine artan konsantrasyonlarda omipalisib uygulanmasının istatistiksel olarak anlamlı bir sitotoksik etkisi olduğu gösterildi. Hesaplanan IC50 değeri ile yapılan apoptoz deneyinde omipalisibin apoptozu güçlü bir şekilde indüklediği tespit edildi. Hücre döngüsü deneyinde ise IC50 değerinde uygulanan omipalisibin hücre döngüsünü G0/G1 fazında durduğu belirlenmiştir.Sonuç olarak omipalisibin sitotoksik etkisi, apoptozu indüklemesi ve hücre döngüsünü durdurması ile Burkitt lenfoma hücreleri üzerinde antitümoral etkinliği olduğu gösterilmiştir. Bu etki göz önüne alınarak özellikle Relaps/Refrakter Burkitt lenfoma ve intensif kemoterapileri tolere edemeyen hastalarda omipalisibin ve PI3K/AKT/mTOR yolağının hedeflenmesi yeni bir tedavi seçeneği olarak karşımıza çıkmaktadır. Ancak bu konuyla ilgili daha fazla hayvan deneyi ve klinik faz çalışmasına ihtiyaç vardır.Öğe Retrospective Detection of Adrenal Incidentaloma Prevalence on Computed Tomography in a District Hospital(Çanakkale Onsekiz Mart University, 2024) Keskin, Zekeriya; Gedikli, Mustafa AsımIntroduction: With the increasing use of imaging methods, adrenal incidentalomas (AIs) have become more common. Despite most being non-functional adenomas, their potential for malignancy and hormonal activity has posed a significant clinical challenge. The aim of this study is to determine the prevalence of adrenal incidentalomas in the adult population. Materials and Methods: Contrast-enhanced and non-contrast abdominal CT images taken between February 2022 and September 2023 at our hospital were screened. Study group was formed with a total of 908 patients. Images of patients were classified based on adrenal lesion characteristics, including location, size, hyperplasia, and thickening, into normal, hyperplastic, and adenomatous. Results: A total of 908 patients aged 18 and above were included in the study. Patients aged 18 to 64 constituted 67% of the study group, while patients aged 65 and above constituted 33%. Adenoma was observed in 1% of cases. Of these adenomas, 3 were observed in patients aged 18-64, while 6 adenomas were observed in those aged 65 and above. The prevalence of AI was calculated as 1% for all age groups, 0.5% for those aged 18-64, and 2% for those aged 65 and above. Conclusion: Due to the increasing frequency of imaging methods, adrenal incidentaloma is becoming more common and is becoming a medical problem that should be taken seriously. Accurate determination of the prevalence of AI will increase awareness of this disease. Thus, after appropriate examinations in patients with AI and appropriate treatment of the detected disease, morbidity and mortality will be reduced.
