Browsing by Author "Şahin E."

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    Evaluation of the CRISPR/Cas9 directed mutant TP53 gene repairing effect in human prostate cancer cell line PC-3
    (Springer, 2019) Batır M.B.; Şahin E.; Çam F.S.
    Prostate cancer is a common health problem among men worldwide and most of these prostate cancer cases are related to a dysfunctional mutant Tumor Protein p53 (TP53) gene. However, the CRISPR/Cas9 system can be used for repairing of a dysfunctional mutant TP53 gene in combination with donor single-stranded oligodeoxynucleotide (ssODN) via cells’ own homology-directed repair (HDR) mechanism. In this study, we aimed to evaluate the CRISPR/Cas9 repairing efficiency on TP53 414delC (p.K139fs*31) null mutation, located in the TP53 gene, of human prostate cancer cell line PC-3 in combination with ssODNs. According to the next-generation sequencing results, TP53 414delC mutation was repaired with an efficiency of 19.95% and 26.0% at the TP53 414delC position with ssODN1 and ssODN2 accompanied by sgRNA2 guided CRISPR/Cas9, respectively. Besides, qPCR and immunofluorescence analysis showed that PC-3 cells, the TP53 414delC mutation of which were repaired, expressed wild type p53 again. Also, significantly increased number of apoptotic cells, driven by the repaired TP53 gene were detected compared to the control cells by flow cytometry analysis. As a result, sgRNA2 guided CRISPR/Cas9 system accompanied by ssODN was shown to effectively repair the TP53 414delC gene region and inhibit the cell proliferation of PC-3 cells. Therefore, the effects of the TP53 414delC mutation repairment in PC-3 cells will be investigated in the in vivo models for tumor clearance analysis in the near future. © 2019, Springer Nature B.V.
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    Artificial neural network investigation of injectability and percolation of highly filled β -Tricalcium phosphate suspensions
    (Elsevier Ltd, 2022) Kulakoğlu S.; Yalamaç E.; Şahin E.
    Over the past few decades, calcium phosphate cement has been used successfully for bone reconstruction applications. As percutaneous surgical methods have developed, there is an increased interest in calcium phosphate cement injection behavior. The aim of this study is to minimize percolation (liquid phase migration under pressure) and maximize injectability (ratio of the extruded part to whole) of highly filled β-tri calcium phosphate (β-TCP) suspensions by varying capillary flow process parameters with an artificial neural network (ANN) approach. The effects of hydroxyethyl cellulose (HEC) and polyethylene glycol (PEG-400) were also studied as binder additives for injectable β-tri calcium phosphate pastes. Prepared suspensions were investigated by capillary and small amplitude oscillatory rheometry. The study predicted experimental input and output data by using Backpropagation Neural networks via the Levenberg-Marquardt algorithm. The ANN model was developed by feed-forward back propagation network and predict percolation (%) and injectability (%). A great agreement was observed between the predicted values by the ANN model and the experimental data for injectability (%) and percolation (regression coefficients) of 0.9984 and 0.9982 respectively. The results depict that ANNs can improve the accuracy of injectability and percolation results which can be used to optimize process and additive parameters for injectable bone cements and pastes. 2 wt% HEC was determined as the most effective factor to improve the rheological properties of highly filled β-TCP pastes which could be injected as much as 99.21 % at a rate of 15 mm/min through dies with L/D ratio of 15. Their percolation value was calculated as 0.82 %. Lubricative effect of PEG-400 additive with 2 wt% HEC to reduce injection force was also demonstrated. © 2022 Elsevier Ltd and Techna Group S.r.l.
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    Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy
    (BioMed Central Ltd, 2023) Karacin C.; Oksuzoglu B.; Demirci A.; Keskinkılıç M.; Baytemür N.K.; Yılmaz F.; Selvi O.; Erdem D.; Avşar E.; Paksoy N.; Demir N.; Göksu S.S.; Türker S.; Bayram E.; Çelebi A.; Yılmaz H.; Kuzu Ö.F.; Kahraman S.; Gökmen İ.; Sakin A.; Alkan A.; Nayır E.; Uğraklı M.; Acar Ö.; Ertürk İ.; Demir H.; Aslan F.; Sönmez Ö.; Korkmaz T.; Celayir Ö.M.; Karadağ İ.; Kayıkçıoğlu E.; Şakalar T.; Öktem İ.N.; Eren T.; Urul E.; Mocan E.E.; Kalkan Z.; Yıldırım N.; Ergün Y.; Akagündüz B.; Karakaya S.; Kut E.; Teker F.; Demirel B.Ç.; Karaboyun K.; Almuradova E.; Ünal O.Ü.; Oyman A.; Işık D.; Okutur K.; Öztosun B.; Gülbağcı B.B.; Kalender M.E.; Şahin E.; Seyyar M.; Özdemir Ö.; Selçukbiricik F.; Kanıtez M.; Dede İ.; Gümüş M.; Gökmen E.; Yaren A.; Menekşe S.; Ebinç S.; Aksoy S.; İmamoğlu G.İ.; Altınbaş M.; Çetin B.; Uluç B.O.; Er Ö.; Karadurmuş N.; Erdoğan A.P.; Artaç M.; Tanrıverdi Ö.; Çiçin İ.; Şendur M.A.N.; Oktay E.; Bayoğlu İ.V.; Paydaş S.; Aydıner A.; Salim D.K.; Geredeli Ç.; Yavuzşen T.; Doğan M.; Hacıbekiroğlu İ.
    Background: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET. © 2023, The Author(s).
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    Correction: Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy (BMC Cancer, (2023), 23, 1, (136), 10.1186/s12885-023-10609-8)
    (BioMed Central Ltd, 2023) Karacin C.; Oksuzoglu B.; Demirci A.; Keskinkılıç M.; Baytemür N.K.; Yılmaz F.; Selvi O.; Erdem D.; Avşar E.; Paksoy N.; Demir N.; Göksu S.S.; Türker S.; Bayram E.; Çelebi A.; Yılmaz H.; Kuzu Ö.F.; Kahraman S.; Gökmen İ.; Sakin A.; Alkan A.; Nayır E.; Uğraklı M.; Acar Ö.; Ertürk İ.; Demir H.; Aslan F.; Sönmez Ö.; Korkmaz T.; Celayir Ö.M.; Karadağ İ.; Kayıkçıoğlu E.; Şakalar T.; Öktem İ.N.; Eren T.; Erul E.; Mocan E.E.; Kalkan Z.; Yıldırım N.; Ergün Y.; Akagündüz B.; Karakaya S.; Kut E.; Teker F.; Demirel B.Ç.; Karaboyun K.; Almuradova E.; Ünal O.Ü.; Oyman A.; Işık D.; Okutur K.; Öztosun B.; Gülbağcı B.B.; Kalender M.E.; Şahin E.; Seyyar M.; Özdemir Ö.; Selçukbiricik F.; Kanıtez M.; Dede İ.; Gümüş M.; Gökmen E.; Yaren A.; Menekşe S.; Ebinç S.; Aksoy S.; İmamoğlu G.İ.; Altınbaş M.; Çetin B.; Uluç B.O.; Er Ö.; Karadurmuş N.; Erdoğan A.P.; Artaç M.; Tanrıverdi Ö.; Çiçin İ.; Şendur M.A.N.; Oktay E.; Bayoğlu İ.V.; Paydaş S.; Aydıner A.; Salim D.K.; Geredeli Ç.; Yavuzşen T.; Doğan M.; Hacıbekiroğlu İ.
    Following publication of the original article [1], the authors reported an error in the author name of Enes Erul. Incorrect: Enes Urul Correct: Enes Erul, The original article [1] has been corrected. © 2023, The Author(s).
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    Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study
    (Springer, 2024) Beypınar İ.; Demir H.; Yaslıkaya Ş.; Köşeci T.; Demir B.; Çolak G.; Ağaoğlu A.B.; Şahbazlar M.; Şancı P.C.; Çabuk D.; Işık U.; Şahin E.; Coşkun A.; Caner B.; Aykut T.; Artaç M.; Duygulu M.E.; Sever N.; Öksüz S.; Turan N.; Aykan M.B.; Tüzün E.K.; Uysal M.; Uğurlu İ.; Sakin A.; Acar C.; Özaşkın D.; Şakalar T.; Keskinkılıç M.; Yavuzşen T.; Köse N.; Ertürk İ.; Yıldırım N.; Balçık O.Y.; Alkan A.; Selvi O.; Erçin E.; Ünal O.Ü.; Karaçin C.
    Purpose: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. Method: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. Results: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. Conclusion: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
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    Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats
    (Elsevier B.V., 2024) Şahin S.; Şahin E.; Esenülkü G.; Renda G.; Gürgen S.G.; Alver A.; Abidin İ.; Cansu A.
    Background: Neuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. Objectives: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. Methods: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1β, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. Results: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. Conclusions: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS. © 2024 American Society for Nutrition