Browsing by Author "Yilmaz, ES"

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    4-Propargyl-substituted 1H-pyrroles induce apoptosis and autophagy via extracellular signal-regulated signaling pathway in breast cancer
    Atmaca, H; Ilhan, S; Yilmaz, ES; Zora, M
    Novel pyrrole derivatives (PDs) with propargyl units (1-7) were investigated for their anticancer activity on breast cancer cells. The MTT assay was used to assess the cell viability. Morphological changes in human breast cancer cells were visualized under a phase-contrast microscope. Apoptosis and autophagy were detected using the DNA fragmentation assay and staining by autophagic vacuoles, respectively. The levels of apoptosis- and autophagy-related proteins such as cytochrome c, Bcl-2, LC3-I/II were investigated by Western blot analysis. The effect of PDs on the ERK1/2 signaling pathway was investigated using specific inhibitors. All the tested PDs were found to be active in the range of 36.7 +/- 0.2 to 459.7 +/- 4.2 mu M. Compounds 3 and 4 showed cytotoxic activity in breast cancer cells, but were found to be safer with lower cytotoxicity on human nontumorigenic epithelial breast cells. Compound 4 induced apoptosis, whereas compound 3 induced autophagy. Both compounds inhibited the ERK signaling pathway in breast cancer cells. The present study revealed that both synthesized PDs induced different programmed cell death types by inhibiting the ERK signaling pathway in two genotypically different breast cancer cells. Therefore, novel PDs might be promising anticancer agents for breast cancer therapy and further structural modifications of PDs may yield promising anticancer agents.
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    Novel Enyne-Modified 1,4-Thiazepines as Epidermal Growth Factor Receptor Inhibitors: Anticancer and Computational Studies
    Atmaca, H; Pulat,ÇÇ; Ilhan, S; Yilmaz, ES; Zora, M
    1,4-Thiazepines (TZEPs) featuring enyne modifications represent promising candidates in cancer therapy. We synthesized novel TZEP derivatives and assessed their cytotoxicity, apoptosis induction, EGFR inhibition, and molecular interactions. TZEPs exhibited cytotoxic effects against cancer cell lines, with compounds TZEP6 and TZEP7 showing significant activity. Flow cytometry analysis revealed TZEP7-induced apoptosis across various cancer types. RT-qPCR analysis demonstrated downregulation of antiapoptotic Bcl-2, upregulation of pro-apoptotic Bax, and increased caspase levels following TZEP7 treatment. Additionally, TZEP7 inhibited EGFR kinase activity in cancer cells, with molecular docking confirming strong binding affinities to EGFRWT and mutant EGFRT790M. AdmetSAR analysis indicated favorable pharmacokinetic properties for TZEP7. These findings underscore the potential of enyne-modified TZEPs as selective cytotoxic agents with apoptotic and EGFR inhibitory activities, highlighting their significance in cancer therapy.
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    Investigation of antimicrobial effects of a Pseudomonas-originated biosurfactant
    Yilmaz, ES; Sidal, U
    The aim of this work was to investigate the antimicrobial effects of biosurfactant (rhamnolipid) produced from Pseudomonas sp. Eight clinical test microorganisms were chosen, which were different groups, for the antimicrobial assays. Antimicrobial activity was evaluated according to the minimal inhibitor concentration (MIC) and disc-diffusion method. The highest activity for the rhamnolipid discs was obtained for beta-hemolytic Streptococcus sp., whereas the lowest activity was found for Pseudomonas aeruginosa. The biosurfactant (rhamnolipid) showed very strong antimicrobial activity against the microorganisms tested.
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    N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses
    Ilhan, S; Atmaca, H; Yilmaz, ES; Korkmaz, E; Zora, M
    Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic beta-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values > 2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed.
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    Production of Rhamnolipid (A Biosurfactant) Using Free and Immobilized Cells of Pseudomonas sp.
    Sidal, U; Yilmaz, ES
    This study presents a method for the production of rhamnolipid, a biosurfactant, by Pseudomonas sp. Pseudomonas sp. cells that were grown in nutrient agar were inoculated into sterile liquid medium. Following an incubation period of 24 h, 2 ml of cells were inoculated into a different liquid medium and the results were obtained at the end of 26 hours incubation time. In our study, the effects of temperature, pH, and glucose concentration on rhamnolipid production were also investigated. Later, the same procedure was applied to immobilized cells that were kept away from the free microorganisms. The production of rhamnolipid by free cells was found to be much higher than that of immobilized cells. Free cells could be used for rhamnolipid production effectively.
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    Lung cancer from suspicion to treatment: An indicator of healthcare access in Turkey
    Kizilirmak, D; Kaya, ZY; Gökçimen, G; Havlucu, Y; Özyurt, BC; Gündogus, B; Esendagli, D; Kaya, BS; Yilmam, I; Aydemir, Y; Çolak, M; Afsin, E; Çetin, N; Idikut, A; Degirmenci, C; Tapan, ÖO; Gürkan, CG; Kocatürk, CI; Simsek, GÖ; Kalafat, CE; Niksarlioglu, EYÖ; Serdaroglu, ME; Karcioglu, O; Özyurt, S; Madran, EK; Bayrak, BY; Alasgarova, Z; Toprak, OB; Uçar, EY; Topal, BN; Baris, SA; Guliyev, E; Güzel, E; Küçük, S; Ocakli, B; Ketencioglu, BB; Selçuk, NT; Akyüz, MS; Özgür, ES; Yetkin, NA; Çetinkaya, PD; Deniz, PP; Atli, S; Çetindogan, H; Karakas, FG; Yilmaz, ES; Ergün, D; Ergcn, R; Tulay, CM; Ünsal, M; Demirkaya, I; Marim, F; Kaya, I; Demirdögen, E; Dilektasli, AG; Ursavas, A; Çelik, P
    Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Before beginning lung cancer treatment, it is necessary to complete procedures such as suspecting lung cancer, obtaining a pathologic diagnosis, and staging. This study aimed to investigate the processes from suspicion of lung cancer to diagnosis, staging, and treatment initiation. Metbods: The study was designed as a multicenter and cross-sectional study. Patients with lung cancer from various health institutions located in all geographic regions of Turkey were included in the study. The socio-demographic and clinical characteristics of the patients, the characteristics of the health institutions and geographic regions, and other variables of the lung cancer process were recorded. The time from suspicion of lung cancer to pathologic diagnosis, radiologic staging, and treatment initiation, as well as influencing factors, were investigated. Results: The study included 1410 patients from 29 different medical centers. The mean time from the initial suspicion of lung cancer to the pathologic diagnosis was 48.0 +/- 52.6 days, 39.0 +/- 52.7 days for radiologic staging, and 74.9 +/- 65.5 days for treatment initiation. The residential areas with the most suspected lung cancer cases were highly developed socioeconomic zones. Primary healthcare services accounted for only 0.4% of pa-tients with suspected lung cancer. The time to pathologic diagnosis was longer in the Marmara region, and the wait time for staging and treatment initiation was longer in Eastern and Southeastern Anatolia. Patients who presented to chest disease referral hospitals with peripheral lesions, those with early-stage disease, and those who were diagnosed surgically had significantly longer wait times. Conclusion: The time between pathologic diagnosis, staging, and treatment initiation in lung cancer was longer than expected. Increasing the role of primary healthcare services and distributing socioeconomic resources more equally will contribute to shortening the time to diagnosis and improve treatment processes for lung cancer.
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    COVID-19: booster(s) vs. hospitalization and Intensive Care Unit admission
    Toprak, OB; Akpolat, T; Uzun, O; Deniz, PP; Kokturk, N; Varol, A; Guzel, E; Ercelik, M; Gultekin, O; Guner, R; Turan, S; Bekta, SG; Coskun, N; Bakan, N; Yakar, MN; Kutsoylu, OE; Ergan, B; Baris, SA; Basyigit, I; Boyaci, H; Cetinkaya, F; Colak, H; Aykac, N; Ketencioglu, BB; Yüce, ZT; Isik, SA; Yilmaz, ES; Karaoglanoglu, S; Safgi, SB; Ozkan, G; Kose, N; Kizilirmak, D; Havlucu, Y; Nural, S; Kerget, F; Sunal, O; Yuksel, A; Dursun, ZB; Deveci, F; Kuluozturk, M; Ataoglu, O; Dursun, M; Keskin, S; Sezgin, ME; Sezgin, ENA; Eser, F; Akyildiz, L; Almaz, MS; Kayaaslan, B; Hasanoglu, I; Bayrak, M; Gümüs, A; Sagcan, G; Cuhadaroglu, C; Kucuk, H; Onyilmaz, T; Mete, B; Kilinc, O; Itil, BO
    OBJECTIVE: As the pandem-ic continues, different vaccine protocols have been implemented to maintain the protection of vaccines and to provide protection against new variants. The aim of this study was to as-sess hospitalized patients' vaccination status and document the efficacy of boosters.PATIENTS AND METHODS: The patients that were hospitalized due to COVID-19 were enrolled from 28 hospitals in Turkey for five months from September 2021. 5,331 confirmed COVID-19 pa-tients from collaborating centers were random-ly enrolled to understand/estimate the distri-bution of vaccination status in hospitalized pa-tients and to compare the efficacy of vaccina-tion/booster protocols.RESULTS: 2,779 men and 2,552 women of which 2,408 (45.2%) were admitted to Intensive Care Units participated in this study. It was found that the highest risk reduction for all age groups was found in groups that received 4 doses. Four doses of vaccination for every 3.7 people under 50 years of age, for every 5.7 people in the 50-64 age group, and for every 4.3 people over 65 years of age will prevent 1 patient from being admitted to intensive care. Regardless of the type of vaccine, it was found that the risk of ICU hospitalization decreased in those who were vaccinated compared to those who were not vaccinated. Regardless of the type of vaccine, the ICU risk was found to decrease 1.25-fold in those who received 1 or 2 doses of vaccine, 1.18-fold in those who received 3 dos-es, and 3.26-fold in those who received 4 doses.CONCLUSIONS: The results suggested that the addition of a fourth dose is more effective in preventing intensive unit care even in disad-vantaged.
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    COVID-19: vaccination vs. hospitalization
    Uzun, O; Akpolat, T; Varol, A; Turan, S; Bektas, SG; Cetinkaya, PD; Dursun, M; Bakan, N; Ketencioglu, BB; Bayrak, M; Baris, SA; Guner, R; Gunal, O; Nural, S; Deniz, PP; Toprak, OB; Ozkan, G; Gumus, A; Kerget, F; Ercelik, M; Ataoglu, O; Yuksel, A; Ates, G; Kutsoylu, OE; Kose, N; Kizilirmak, D; Keskin, S; Gultekin, O; Coskun, N; Yilmaz, ES; Uslu, S; Basyigit, I; Ergan, B; Deveci, F; Yakar, MN; Zuhur, C; Sagcan, G; Yuce, ZT; Kuluozturk, M; Sezgin, ME; Sezgin, ENA; Havlucu, Y; Cuhadaroglu, C; Kilinc, O; Boyaci, H; Altunay, H; Akti, M; Dursun, ZB; Kalem, AK; Isik, SA; Akyildiz, L; Aykac, N; Almaz, MS; Kokturk, N; Itil, O
    Objective Vaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols. Setting Inoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose. Methods We collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status. Results We identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac. Conclusion Effective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination.