Browsing by Author "Bektas, H"

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    Design and synthesis of benzimidazole derivatives as apoptosis-inducing agents by targeting Bcl-2 protein
    Ilhan, S; Pulat, ÇÇ; Oguz, F; Bektas, H; Mentese, E; Atmaca, H
    Bcl-2, an anti-apoptotic protein, is a well-known and appealing cancer therapy target. Novel series of benzimidazole derivatives were synthesized and tested for their activity as Bcl-2 inhibitors on T98G glioblastoma, PC3 prostate, MCF-7 breast, and H69AR lung cancer cells. MTT assay was used to evaluate the cytotoxic effect. PI Annexin V Apoptosis Detection Kit was used to detect apoptosis. Expression levels of the Bcl-2 protein were examined by the Western blot analysis and qRT-PCR. All synthesized benzimidazole derivatives exhibited a cytotoxic effect on cancer cells with IC50 values in the range of 25.2-88.2 mu g/mL. Among all derivatives, compounds C1 and D1 demonstrated a higher cytotoxic effect on cancer cells with IC50 values < 50 mu g/mL, while a lower cytotoxic effect against human embryonic kidney cells with IC50 values of > 100 mu g/mL. C1 and D1 caused a significant increase in the percentage of apoptotic cells in all types of cancer cell cells and both Bcl-2 mRNA and protein levels were significantly reduced. These results suggest that the novel benzimidazole derivatives may be candidates for apoptosis-inducing agents in cancer treatment by targeting anti-Bcl-2 proteins in cancer cells. [GRAPHICS]
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    Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies
    Atmaca, H; Ilhan, S; Batir, MB; Pulat, CC; Güner, A; Bektas, H
    The aim of the study was to synthesize a new series of benzimidazole derivatives and to investigate the underlying molecular mechanisms of the potential cell cycle inhibition and apoptotic effects against a panel of selected human cancer cell lines along with HEK-293 human embryonic kidney cells. MTT assay was used to evaluate cytotoxic effects. MuseT Cell Analyzer was used to assess cell cycle progression. Annexin-V/PI staining assay was used for detecting apoptosis. All the synthesized compounds showed a significant cytotoxic effect against cancer cells with the IC50 values between 9.2 and 166.1 mu g/mL. Among the tested derivatives, compound 5 showed significant cytotoxic activity against MCF-7, DU-145 and H69AR cancer cells with the IC50 values of 17.8 +/- 0.24, 10.2 +/- 1.4 and 49.9 +/- 0.22 mu g/mL respectively. The compounds 5 was also tested on HEK-293 human embryonic kidney cells and found to be safer with lesser cytotoxicity. The results revealed that compound 5 significantly increased cell population in the G2/M-phase which is modulated by a p53 independent mechanism. Compound 5 caused an increase in the percentage of late apoptotic cells in all tested cancer cells in a concentration-dependent manner. Among all synthesized derivatives, compound 5 the bromo-derivative, showed the highest cytotoxic potential, induced G2/M cell cycle arrest and apoptotic cell death in genotypically different human cancer cells. These results suggest that compound 5 might be a promising agent for cancer therapy and further structural modifications of benzimidazole derivatives may create promising anticancer agents.
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    Gastrostomy in Hospitalized Patients with Acute Stroke: NoroTek Turkey Point Prevalence Study Subgroup Analysis
    Topçuoglu, MA; Özdemir, AÖ; Aykaç, Ö; Milanoglu, A; Gökçe, M; Bavli, S; Çabalar, M; Yayla, V; Erdogan, HA; Özkul, A; Günes, A; Degirmenci, B; Aluçlu, U; Kozak, HH; Güngör, L; Erdogan, M; Acar, ZÖ; Cenikli, U; Kablan, Y; Yilmaz, A; Genç, H; Nazliel, B; Çaglayan, HB; Gencer, ES; Ay, H; Demirbas, H; Akdogan, Ö; Emre, U; Yildiz, ÖK; Bolayir, A; Demir, T; Tanriverdi, Z; Tekan, ÜY; Akpinar, ÇK; Özkan, E; Ilik, F; Sirin, H; Güler, A; Önder, H; Bektas, H; Öcek, L; Bakar, M; Ongun, N; Krespi, Y; Isikay, CT; Aslanbaba, E; Sorgun, M; Gürkas, E; Karadeli, HH; Midi, I; Ilgezdi, I; Bilgiç, AB; Akyol, S; Epçeliden, MT; Atmaca, MM; Kursun, O; Keskin, O; Sirinocak, PB; Baydemir, R; Akçakoyunlu, M; Öztürk, S; Özel, T; Ünal, A; Dora, B; Yürekli, VA; Arlier, Z; Eren, A; Yilmaz, A; Kisabay, A; Acar, B; Bastan, B; Acar, Z; Niflioglu, B; Güven, B; Kaya, D; Afsar, N; Yazici, D; Aytaç, E; Yaka, E; Toplutas, E; Degirmenci, E; Ince, FB; Büyükserbetçi, G; Aydin, I; Çetiner, M; Sen, M; Turgut, N; Kale, N; Çoban, E; Yesilot, N; Ekizoglu, E; Kizek, Ö; Birgili, Ö; Yevgi, R; Kunt, R; Giray, S; Akkas, SY; Senadim, S; Yoldas, T; Asil, T; Duman, T; Atasoy, T; Çinar, BP; Demir, T; Can, U; Ünsal, YÖ; Eskut, N; Aslan, Y; Bas, DF; Sener, U; Yilmaz, Z; Bozdogan, Z; Alioglu, Z; Arsava, EM
    Objective: Nutritional status assessment, dysphagia evaluation and enteral feeding decision are important determinants of prognosis in acute neurovascular diseases. Materials and Methods: NoroTek is a point prevalence study conducted with the participation of 87 hospitals spread across all health sub regions of Turkey conducted on 10-May-2018 (World Stroke Awareness Day). A total of 972 hospitalized neurovascular patients [female: 53%, age: 69 +/- 14; acute ischemic stroke in 845; intracerebral hematoma (ICH) in 119 and post-resuscitation encephalopathy (PRE) in 8] with complete data were included in this sub-study. Results: Gastrostomy was inserted in 10.7% of the patients with ischemic stroke, 10.1% of the patients with ICH and in 50% of the patients with PRE. Independent predictors of percutaneous endoscopic gastrostomy (PEG) administration were The National Institutes of Health Stroke Scale score at admission [exp (ss): 1.09 95% confidence interval (CI): 1.05-1.14, per point] in ischemic stroke; and mechanical ventilation in ischemic [exp (ss): 6.18 (95% CI: 3.16-12.09)] and hemorrhagic strokes [exp (ss): 26.48 (95% CI: 1.36-515.8)]. PEG was found to be a significant negative indicator of favorable (modified Rankin's scale score 0-2) functional outcome [exp (ss): 0.032 (95% CI: 0.004-0.251)] but not of in-hospital mortality [exp (ss): 1.731 (95% CI: 0.785-3.829)]. Nutritional and swallowing assessments were performed in approximately two-thirds of patients. Of the nutritional assessments 69% and 76% of dysphagia assessments were completed within the first 2 days. Tube feeding was performed in 39% of the patients. In 83.5% of them, tube was inserted in the first 2 days; 28% of the patients with feeding tube had PEG later. Conclusion: The NoroTek study provided the first reliable and large-scale data on key quality metrics of nutrition practice in acute stroke in Turkey. In terms of being economical and accurate it makes sense to use the point prevalence method.
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    Atrial Fibrillation Management in Acute Stroke Patients in Türkiye: Real-life Data from the NöroTek Study
    Topçuoglu, MA; Arsava, EM; Özdemir, AÖ; Aykaç, Ö; Çetiner, M; Gencer, ES; Günes, A; Krespi, Y; Yaka, E; Öcek, L; Tanriverdi, Z; Tekan, ÜY; Özkul, A; Özkan, E; Sirin, H; Güler, A; Kursun, O; Kunt, R; Cenikli, U; Acar, B; Kablan, Y; Yilmaz, A; Isikay, CT; Aslanbaba, E; Sorgun, M; Bektas, H; Çabalar, M; Yayla, V; Erdogan, HA; Gökçe, M; Bavli, S; Ongun, N; Keskin, AO; Akdogan, Ö; Emre, U; Yildiz, ÖK; Bolayir, A; Akpinar, ÇK; Karadeli, HH; Özel, T; Ünal, A; Dora, B; Arlier, Z; Eren, A; Milanoglu, A; Nazliel, B; Çaglayan, HB; Güven, B; Erdogan, M; Acar, ZÖ; Bakar, M; Giray, S; Senadim, S; Asil, T; Demir, T; Ünsal, YÖ; Eskut, N; Aslan, Y; Bas, DF; Sener, U; Degirmenci, B; Aluçlu, U; Bastan, B; Acar, Z; Niflioglu, B; Yazici, D; Aytaç, E; Ince, FB; Ay, H; Önder, H; Kozak, HH; Ilgezdi, I; Bilgiç, AB; Akyol, S; Güngör, IL; Atmaca, MM; Sen, M; Yevgi, R; Akkas, SY; Yoldas, T; Atasoy, HT; Çinar, BP; Yilmaz, A; Genç, H; Kisabay, A; Ilik, F; Demirbas, H; Midi, I; Sirinocak, PB; Duman, T; Demir, T; Can, U; Yürekli, VA; Bozdogan, Z; Alioglu, Z; Kaya, D; Afsar, N; Gürkas, E; Toplutas, E; Degirmenci, E; Büyükserbetçi, G; Aydin, I; Epçeliden, MT; Turgut, N; Kale, N; Çoban, E; Yesilot, N; Ekizoglu, E; Kizek, Ö; Bilgili, Ö; Baydemir, R; Akçakoyunlu, M; Yilmaz, Z; Öztürk, S
    Objective: Atrial fibrillation (AF) is the most common directly preventable cause of ischemic stroke. There is no dependable neurology-based data on the spectrum of stroke caused by AF in Turkiye. Within the scope of NoroTek-Turkiye (TR), hospital-based data on acute stroke patients with AF were collected to contribute to the creation of acute-stroke algorithms.Materials and Methods: On May 10, 2018 (World Stroke Awareness Day), 1,790 patients hospitalized at 87 neurology units in 30 health regions were prospectively evaluated. A total of 929 patients [859 acute ischemic stroke, 70 transient ischemic attack (TIA)] from this study were included in this analysis.Results: The rate of AF in patients hospitalized for ischemic stroke/TIA was 29.8%, of which 65% were known before stroke, 5% were paroxysmal, and 30% were diagnosed after hospital admission. The proportion of patients with AF who received effective treatment [international normalization ratio >= 2.0 warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) at a guideline dose] was 25.3%, and, either no medication or only antiplatelet was used in 42.5% of the cases. The low dose rate was 50% in 42 patients who had a stroke while taking NOACs. Anticoagulant was prescribed to the patient at discharge at a rate of 94.6%; low molecular weight or unfractionated heparin was prescribed in 28.1%, warfarin in 32.5%, and NOACs in 31%. The dose was in the low category in 22% of the cases discharged with NOACs, and half of the cases, who received NOACs at admission, were discharged with the same drug.Conclusion: NoroTekTR revealed the high but expected frequency of AF in acute stroke in Turkiye, as well as the aspects that could be improved in the management of secondary prophylaxis. AF is found in approximately one-third of hospitalized acute stroke cases in Turkiye. Effective anticoagulant therapy was not used in three-quarters of acute stroke cases with known AF. In AF, heparin, warfarin, and NOACs are planned at a similar frequency (one-third) within the scope of stroke secondary prophylaxis, and the prescribed NOAC dose is subtherapeutic in a quarter of the cases. Non-medical and medical education appears necessary to prevent stroke caused by AF.
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    Acute Stroke Management in Türkiye: Intravenous Tissue Plasminogen Activator and Thrombectomy NöroTek: Türkiye Neurology Single Day Study
    Topçuoglu, MA; Özdemir, AÖ; Arsava, EM; Günes, A; Aykaç, Ö; Gencer, ES; Çabalar, M; Yayla, V; Erdogan, HA; Erdogan, M; Acar, ZÖ; Giray, S; Kablan, Y; Tanriverdi, Z; Tekan, ÜY; Asil, T; Akpinar, ÇK; Yürekli, VA; Acar, B; Sirin, H; Güler, A; Baydemir, R; Akçakoyunlu, M; Öcek, L; Çetiner, M; Nazliel, B; Çaglayan, HB; Ongun, N; Eren, A; Arlier, Z; Cenikli, U; Gökçe, M; Bavli, S; Yaka, E; Özkul, A; Degirmenci, B; Aluçlu, U; Isikay, CT; Aslanbaba, E; Sorgun, M; Aytaç, E; Ay, H; Kunt, R; Senadim, S; Ünsal, YÖ; Eskut, N; Alioglu, Z; Yilmaz, A; Genç, H; Yilmaz, A; Milanoglu, A; Gürkas, E; Degirmenci, E; Bektas, H; Ilgezdi, I; Bilgiç, AB; Akyol, S; Güngör, L; Kale, N; Çoban, E; Yesilot, N; Ekizoglu, E; Kizek, Ö; Kursun, O; Yildiz, ÖK; Bolayir, A; Kisabay, A; Bastan, B; Acar, Z; Niflioglu, B; Güven, B; Kaya, D; Afsar, N; Yazici, D; Toplutas, E; Özkan, E; Ilik, F; Ince, FB; Büyükserbetçi, G; Önder, H; Karadeli, HH; Kozak, HH; Demirbas, H; Midi, I; Aydin, I; Epçeliden, MT; Atmaca, MM; Bakar, M; Sen, M; Turgut, N; Keskin, O; Akdogan, Ö; Emre, U; Bilgili, Ö; Sirinocak, PB; Yevgi, R; Akkas, SY; Yoldas, T; Duman, T; Özel, T; Ünal, A; Dora, B; Atasoy, T; Çinar, BP; Demir, T; Demir, T; Can, U; Aslan, Y; Bas, DF; Sener, U; Yilmaz, Z; Bozdogan, Z; Özdemir, G; Krespi, Y; Öztürk, S
    Objective: To reveal the profile and practice in patients with acute stroke who received intravenous tissue plasminogen activator (IV tPA) and/or neurointerventional therapy in Turkiye. Materials and Methods: On World Stroke Awareness Day, May 10, 2018, 1,790 patients hospitalized in 87 neurology units spread over 30 health regions were evaluated retrospectively and prospectively. Results: Intravenous tPA was administered to 12% of 859 cases of acute ischemic stroke in 45 units participating in the study. In the same period, 8.3% of the cases received neurointerventional treatment. The rate of good prognosis [modified Rankin score (mRS) 0-2] at discharge was 46% in 83 patients who received only IV tPA [age: 67 +/- 12 years; National Institutes of Health Stroke Scale (NIHSS): 12 +/- 6; hospital stay, 24 +/- 29 days]; 35% in 51 patients who underwent thrombectomy (MT) alone (age: 64 +/- 13 years; NIHSS: 14.1 +/- 6.5; length of hospital stay, 33 +/- 31 days), 19% in those who received combined treatment (age: 66 +/- 14 years; NIHSS: 15.6 +/- 5.4; length of hospital stay, 26 +/- 35 days), and 56% of 695 patients who did not receive treatment for revascularization (age: 70 +/- 13 years; NIHSS: 7.6 +/- 7.2; length of hospital stay, 21 +/- 28 days). The symptom-to-door time was 87 +/- 53 minutes in the IV treatment group and 200 +/- 26 minutes in the neurointerventional group. The average door-to-needle time was 66 +/- 49 minutes in the IV tPA group. In the neurothrombectomy group, the door-to-groin time was 103 +/- 90 minutes, and the TICI 2b-3 rate was 70.3%. In 103 patients who received IV tPA, the discharge mRS 0-2 was 41%, while the rate of mRS 0-1 was 28%. In 71 patients who underwent neurothrombectomy, the mRS 0-2 was 31% and mRS 0-1 was 18%. The door-to-groin time was approximately 30 minutes longer if IV tPA was received (125 +/- 107 and 95 +/- 83 minutes, respectively). Symptomatic bleeding rates were 4.8% in IV recipients, 17.6% among those who received only MT, and 15% in combined therapy. Globally, the hemorrhage rate was 6.8% in patients receiving IV tPA and 16.9% in MT. Conclusion: IV thrombolytic and neurointerventional treatment applications in acute ischemic stroke in Turkiye can provide the anticipated results. Heterogeneity has begun to be reduced in our country with the dissemination of the system indicated by the Directive on Health Services to be Provided to Patients with Acute Stroke.
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    Newly Synthesized Benzimidazoles Inhibit Vascular Endothelial Growth Factor and Matrix Metalloproteinase-2 and-9 Levels in Prostate Cancer Cells
    Ilhan, S; Dilekci, G; Guner, A; Bektas, H
    Background: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. Objective: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the possible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). Methods: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. Results: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. Conclusion: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment.