Researcher:
Aksu, Ali Cenk

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PhD Student

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Ali Cenk

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Aksu

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Aksu, Ali Cenk

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Now showing 1 - 10 of 10
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    Publication
    Nesprin-1 impact on tumorigenic cell phenotypes
    (Springer, 2020) Hussain, Muhammed Sajid; Asif, Maria; Noegel, Angelika A.; Sur, İlknur Erdem; Değirmenci, Nareg Pınarbaşı; Aksu, Ali Cenk; Faculty Member; PhD Student; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; N/A; N/A; N/A
    The largest protein of the nuclear envelope (NE) is Nesprin-1 which forms a network along the NE interacting with actin, Emerin, Lamin, and SUN proteins. Mutations in the SYNE1 gene and reduction in Nesprin-1 protein levels have been reported to correlate with several age related diseases and cancer. In the present study, we tested whether Nesprin-1 overexpression can reverse the malignant phenotype of Huh7 cells, a human liver cancer cell line, which carries a mutation in the SYNE1 gene resulting in reduced Nesprin-1 protein levels, has altered nuclear shape, altered amounts and localization of NE components, centrosome localization and genome stability. Ectopic expression of a mini-Nesprin-1 led to an improvement of the nuclear shape, corrected the mislocalization of NE proteins, the centrosome positioning, and the alterations in the DNA damage response network. Additionally, Nesprin-1 had a profound effect on cellular senescence. These findings suggest that Nesprin-1 may be effective in tumorigenic cell phenotype correction of human liver cancer.
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    A micropillar-based microfluidic viscometer for newtonian and non-newtonian fluids
    (Elsevier, 2020) Tanyeri, Melikhan; Erten, Ahmet; Department of Physics; N/A; N/A; N/A; N/A; Kiraz, Alper; Yalçın, Özlem; Mustafa, Adil; Aksu, Ali Cenk; Eser, Ayşenur; Faculty Member; Faculty Member; PHD Student; PHD Student; Master Student; Department of Physics; College of Sciences; School of Medicine; Graduate School of Sciences and Engineering; School of Medicine; Graduate School of Sciences and Engineering; 22542; 218440; N/A; N/A; N/A
    In this study, a novel viscosity measurement technique based on measuring the deflection of flexible (poly) dimethylsiloxane (PDMS) micropillars is presented. The experimental results show a nonlinear relationship between fluid viscosity and the deflection of micropillars due to viscoelastic properties of PDMS. A calibration curve, demonstrating this nonlinear relationship, is generated, and used to determine the viscosity of an unknown fluid. Using our method, viscosity measurements for Newtonian fluids (glycerol/water solutions) can be performed within 2-100 cP at shear rates gamma = 60.5-398.4 s(-1). We also measured viscosity of human whole blood samples (non-Newtonian fluid) yielding 2.7-5.1 cP at shear rates gamma = 120-345.1 s(-1), which compares well with measurements using conventional rotational vis-cometers (3.6-5.7 cP). With a sensitivity better than 0.5 cP, this method has the potential to be used as a portable microfluidic viscometer for real-time rheological studies. (C) 2020 Elsevier B.V. All rights reserved.
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    Publication
    Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001
    (Ios Press, 2019) Cirrik, Selma; Oronsky, Bryan; Cabrales, Pedro; N/A; Uğurel, Elif; Aksu, Ali Cenk; Yalçın, Özlem; Researcher; PhD Student; Faculty Member; School of Medicine; Graduate School of Health Sciences; School of Medicine; N/A; N/A; 218440
    Background: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. Objective: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. Methods: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. Results: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). Conclusions: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.
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    Publication
    Differential effects of adenylyl cyclase-protein kinase a cascade on shear-induced changes of sickle cell deformability
    (IOS Press, 2019) Connes, Philippe; Renoux, Celine; Joly, Philippe; Gauthier, Alexandra; Hot, Arnaud; Bertrand, Yves; Cannas, Giovanna; N/A; N/A; N/A; N/A; N/A; N/A; Uğurel, Elif; Yalçın, Özlem; Yavaş, Gökçe; Eğlenen, Buse; Aksu, Ali Cenk; Turkay, Mine; Researcher; Faculty Member; Undergraduate Student; Undergraduate Student; PhD Student; Undergraduate Student; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; School of Medicine; N/A; 218440; N/A; N/A; N/A; N/A
    Background: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. Objective: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. Methods: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). Results: Red blood cell deformability increased of 2.5-6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10 mu M) (p < 0.05). The inhibition of AC with SQ22536 (100 mu M) produced more significant rise in deformability (+4.8-12%, p < 0.01). No significant change was observed by the inhibition of PKA with H89 (10 mu M). Conclusion: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability.
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    Publication
    Overcoming chemoresistance in triple negative breast cancer by bromodomain inhibition
    (Elsevier Sci Ltd, 2022) Philpott, M.; Cribbs, A.; Oppermann, U.; Onder, T. T.; Department of Molecular Biology and Genetics; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Bayram, Özlem Yedier; Cingöz, Ahmet; Aksu, Ali Cenk; Değirmenci, Nareg Pınarbaşı; Esin, Beril; Kayabölen, Alişan; Cevatemre, Buse; Ayhan, Ceyda Açılan; Önder, Tuğba Bağcı; Researcher; Researcher; PhD Student; PhD Student; Master Student; PhD Student; Researcher; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; College of Engineering; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; N/A; School of Medicine; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 219658; 184359
    Background: Triple negative breast cancer (TNBC) is an aggressive subtypeofbreastcancerwithpoorprognosis.TNBCcellsdonotexpress receptorsforestrogen,progesteroneorHer2,eliminatingthepossibilityof targetedtherapyapplications.Therefore,current treatmentoptionforTNBC is limitedwithsurgery followedbyconventional chemotherapy.However, acquiredresistancetochemotherapyisamajorchallengethatisassociated withrelapse,whichisdrivenbycoordinatedactionsofgeneticandepigenetic events. MaterialsandMethods:Weaimedtoelucidatetherolesoffullspectrum ofepigeneticmodifiersinmaintenanceandreversionofchemoresistancein TNBC.TogenerateinvitromodelsofchemoresistantTNBC,weexposed3 different TNBC cell lines to escalating doses of taxane (paclitaxel). Transcriptome analysis by RNA-sequencingwere performed to reveal changesthat regulatechemoresistance.Withourcustomepigenome-wide CRISPR-Cas9library(EpigeneticKnock-OutLibrary-EPIKOL)targetingall chromatinreaders,writers,erasersandassociatedproteins,wesystematicallyinterrogatedtherolesofepigeneticmodifiersinchemoresistantTNBC cells.Wealsoconductedmediumscalechemicalscreensutilizingepigenetic probelibrariesinchemoresistantcells. Results:RNAsequencingonpairedsensitiveandchemoresistancecell linesrevealedABCB1upregulationasamajordriverofresistance.Inhibition of themembersofMLLandSWI/SNFcomplexes, aswell as thegenes relatedwithhistoneubiquitinationandacetyl-mark readers re-sensitized chemoresistantcellstopaclitaxel.Amemberof thebromodomainprotein family,BRPF1,cameasacommonhit inourchemical screenaswellas geneticscreens.KnockoutofBRPF1or itschemical inhibitioncompletely abolishedpaclitaxel resistanceandmodulatedABCB1expression. Conclusions:ThroughEPIKOLscreensonchemoresistantTNBCcells coupledwithchemicalscreens,weidentifiednovelepigeneticmodifiersthat arecrucial formaintainingandovercomingdrug resistance.Collectively, thesefindingsprovideabasistodevelopcombinationtherapiestoefficiently killchemoresistantTNBC.
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    Bringing packed red blood cells to the point of combat injury: are we there yet?
    (Galenos Yayınevi, 2018) Unlu, Aytekin; Yilmaz, Soner; Uyanik, Metin; Petrone, Patrizio; Cetinkaya, Riza Aytac; Eker, Ibrahim; Urkan, Murat; Ozgurtas, Taner; Avci, Ismail Yasar; Zeybek, Nazif; Yalçın, Özlem; Aksu, Ali Cenk; Faculty Member; PhD Student; School of Medicine; Graduate School of Health Sciences; 218440; N/A
    Objective: Hemorrhage is the leading cause of injury-related prehospital mortality. We investigated worst-case scenarios and possible requirements of the Turkish military. As we plan to use blood resources during casualty transport, the impact of transport-related mechanical stress on packed red blood cells (PRBCs) was analyzed. Materials and Methods: The in vitro experiment was performed in the environmental test laboratories of ASELSAN((R)). Operational vibrations of potential casualty transport mediums such as Sikorsky helicopters, Kirpi((R)) armored vehicles, and the NATO vibration standard MIL-STD-810G software program were recorded. The most powerful mechanical stress, which was created by the NATO standard, was applied to 15 units of fresh (<= 7 days) and 10 units of old (>7 days) PRBCs in a blood cooler box. The vibrations were simulated with a TDS v895 Medium-Force Shaker Device. On-site blood samples were analyzed at 0, 6, and 24 h for biochemical and biomechanical analyses. Results: The mean (+/- standard deviation) age of fresh and old PRBCs was 4.9 +/- 2.2 and 32.8 +/- 11.8 days, respectively. Six-hour mechanical damage of fresh PRBCs was demonstrated by increased erythrocyte fragmentation rates (p=0.015), hemolysis rates (p=0.003), and supernatant potassium levels (p=0.003) and decreased hematocrit levels (p=0.015). Old PRBC hemolysis rates (p=0.015), supernatant potassium levels (p=0.015), and supernatant hemoglobin (p=0.015) were increased and hematocrit levels were decreased (p=0.015) within 6 h. Two (13%) units of fresh PRBCs and none of the old PRBCs were eligible for transfusion after 6 h of meehanical stress. Conclusion: When an austere combat environment was simulated for 24 h, fresh and old PRBC hemolysis rates were above the quality criteria. Currently, the technology to overcome this mechanical damage does not seem to exist. In light of the above data, a new national project is being performed. / Amaç: Kan kayıpları, hastane öncesi dönemdeki yaralanmalara bağlı ölümlerin en sık sebebidir. Türk ordusu için en kötü senaryoları ve olası ihtiyaçları araştırdık. Çatışma alanından nakil esnasında kan kaynaklarını kullanmayı planladığımız için nakil işleminden kaynaklı mekanik stresin eritrosit konsantreleri üzerine etkisini analiz edilmiştir. Gereç ve Yöntemler: İn vitro çalışmalar ASELSAN®’ın dış ortam test laboratuvarlarında gerçekleştirildi. Çatışma alanında kan taşıma işleminde kullanılması muhtemel olan Sikorsky helikopteri ve Kirpi® araçlarının operasyonel vibrasyonları ve NATO MIL-STD-810G titreşim standart yazılımı kayıt altına alındı. NATO standardının en güçlü titreşime neden olduğu hesaplandı. Kan saklama çantası içindeki 15 ünite taze (≤7 gün) ve 10 ünite taze olmayan eritrosit konsantresi (>7 gün), NATO standardı olan mekanik strese maruz bırakıldı. Titreşim TDS v895 Medium-Force Shaker cihazı tarafından simüle edildi. Simülasyonun 0., 6. ve 24. saatinde biyokimyasal ve biyomekanik analiz için kan örnekleri alındı. Bulgular: Taze ve taze olmayan eritrosit konsantreleri sırasıyla ortalama 4,9 [standart deviasyon (SD) ±2,2] ve 32,8 (SD ±11,8) günlüktü. Taze eritrosit konsantrelerinde 6. saatte gelişen mekanik hasar; artmış eritrosit fragmentasyonu (p=0,015), hemoliz oranı (p=0,003) ve supernatant potasyum (p=0,015) düzeyleri ile gösterildi. Taze olmayan eritrosit konsantrelerinin 6. saatte hemoliz oranı (p=0,015) ve supernatant potasyum düzeyi (p=0,015) yükselirken, hematokrit değerleri (p=0,015) düştü. İlk 6 saat içerisinde taze eritrosit konsantrelerinin 2’si (%13) transfüze edilebilir kalitede kalırken, taze olmayanların ise hiçbirisi uygun değildi. Sonuç: Taze ve taze olmayan eritrosit konsantrelerinin hemoliz oranları, bu ürünleri muharebe sahasında taşıdığımızda, çoğunun kullanılamaz hale geleceğini göstermektedir. Halihazırda eritrositler üzerinde oluşan mekanik hasarlanmanın önüne geçebilecek bir teknoloji bulunmamaktadır. Yukarıdaki verilerin ışığı altında yeni bir ulusal proje gerçekleştirilmektedir.
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    Publication
    Dependence of erythrocyte deformability on mechanical stress and oxygenation
    (Federation amer Soc Exp Biol, 2017) N/A; N/A; N/A; Department of Physics; N/A; Yalçın, Özlem; Uğurel, Elif; Sağlam, Gökay; Erten, Ahmet Can; Aksu, Ali Cenk; Faculty Member; Researcher; Undergraduate Student; Teaching Faculty; PhD Student; Department of Physics; School of Medicine; School of Medicine; School of Medicine; College of Engineering; Graduate School of Health Sciences; 218440; N/A; N/A; N/A; N/A
    Mechanical properties of erythrocytes are known to be affected by their oxygenation status. Several studies suggested that cytoskeletal rearrangements are carried out in an oxygen dependent manner. The structure of the cytoskeleton determines the mechanical properties of erythrocyte membrane. However, oxygen-dependent mechanical characteristics of erythrocyte are poorly studied whether oxygenated state could alter erythrocyte deformability. In this study, we investigated shear stress induced improvements in erythrocyte deformability through their oxygenation status. Venous blood was collected from male, healthy volunteers (n=10) between 25–50 ages. An informed written consent was obtained from each subject participated in the study according to Declaration of Helsinki. The hematocrit of blood samples adjusted to 0.4 l/l with autologous plasma. Whole blood samples were diluted with polyvinylpyrrolidone (PVP) solution (Mechatronics, Hoorn, Netherlands) with a dilution ratio of 1/200. Blood samples were equilibrated with either ambient air or nitrogen gas for at least 10 minutes at room temperature. Erythrocyte deformability was measured by a laser-assisted optical rotational cell analyzer (LORRCA MaxSis, Mechatronics, Netherlands) applying shear stresses (SS) ranging between 0.3 to 50 Pa. Then, a constant SS of 5, 10 and 20 Pa were applied continuously for 300 seconds and erythrocyte deformability was measured immediately afterwards. Maximal erythrocyte elongation index (EImax) and the SS required for one-half of this maximal deformation (SS1/2) were calculated by using the linear Lineweaver-Burke (LB) model. Deoxygenation of blood samples significantly decreased SS1/2 values both before and after SS applications (p < 0.001). EImax was significantly increased in deoxygenated blood before applying 5 Pa SS (p < 0.05). However, there were no significant differences after continuous SS in oxygenated and deoxygenated blood. Deoxygenation significantly decreased SS1/2/EImax values both before and after SS applications (p < 0.01). SS1/2/EImax values in both oxygenated and deoxygenated blood were significantly decreased after 5 and 10 Pa continuous SS applications although they were not significantly decreased after applying 20 Pa SS. Our study showed for the first time that erythrocyte deformability is improved in deoxygenated conditions in contrast to results presented in previous studies. This deformability improvement may control blood flow and consequently erythrocyte distribution within hypoxic tissues. Our study also demonstrated the relationship of oxygenation-deoxygenation shifts and magnitude of shear stress on erythrocyte deformability.
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    PublicationOpen Access
    EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities
    (Nature Portfolio, 2022) Philpott, Martin; Cribbs, Adam P.; Kung, Sonia H.Y; Bayram, Özlem Yedier; Gökbayrak, Bengül; Kayabölen, Alişan; Aksu, Ali Cenk; Cavga, Ayşe Derya; Cingöz, Ahmet; Kala, Ezgi Yağmur; Karabıyık, Göktuğ; Esin, Beril; Morova, Tunç; Uyulur, Fırat; Önder, Tuğba Bağcı; Syed, Hamzah; Lack, Nathan Alan; Önder, Tamer Tevfik; PhD Student; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 184359; 318138; 120842; 42946
    Dysregulation of the epigenome due to alterations in chromatin modifier proteins commonly contribute to malignant transformation. To interrogate the roles of epigenetic modifiers in cancer cells, we generated an epigenome-wide CRISPR-Cas9 knockout library (EPIKOL) that targets a wide-range of epigenetic modifiers and their cofactors. We conducted eight screens in two different cancer types and showed that EPIKOL performs with high efficiency in terms of sgRNA distribution and depletion of essential genes. We discovered novel epigenetic modifiers that regulate triple-negative breast cancer (TNBC) and prostate cancer cell fitness. We confirmed the growth-regulatory functions of individual candidates, including SS18L2 and members of the NSL complex (KANSL2, KANSL3, KAT8) in TNBC cells. Overall, we show that EPIKOL, a focused sgRNA library targeting similar to 800 genes, can reveal epigenetic modifiers that are essential for cancer cell fitness under in vitro and in vivo conditions and enable the identification of novel anti-cancer targets. Due to its comprehensive epigenome-wide targets and relatively high number of sgRNAs per gene, EPIKOL will facilitate studies examining functional roles of epigenetic modifiers in a wide range of contexts, such as screens in primary cells, patient-derived xenografts as well as in vivo models.
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    PublicationOpen Access
    From experiments to simulation: shear-induced responses of red blood cells to different oxygen saturation levels
    (Frontiers, 2020) Pişkin, Şenol; N/A; Uğurel, Elif; Yalçın, Özlem; Aksu, Ali Cenk; Eser, Ayşenur; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; N/A; 218440; N/A; N/A
    Red blood cells (RBC) carry and deliver oxygen (O-2) to peripheral tissues through different microcirculatory regions where they are exposed to various levels of shear stress (SS). O-2 affinity of hemoglobin (Hb) decreases as the blood enters the microcirculation. This phenomenon determines Hb interactions with RBC membrane proteins that can further regulate the structure of cytoskeleton and affect the mechanical properties of cells. The goal of this study is to evaluate shear-induced RBC deformability and simulate RBC dynamics in blood flow under oxygenated and deoxygenated conditions. Venous blood samples from healthy donors were oxygenated with ambient air or deoxygenated with 100% nitrogen gas for 10 min and immediately applied into an ektacytometer (LORRCA). RBC deformability was measured before and after the application of continuous 5 Pa SS for 300 s by LORRCA and recorded as elongation index (EI) values. A computational model was generated for the simulation of blood flow in a real carotid artery section. EI distribution throughout the artery and its relationships with velocity, pressure, wall SS and viscosity were determined by computational tools. RBC deformability significantly increased in deoxygenation compared to oxygenated state both before and after 5 Pa SS implementation (p < 0.0001). However, EI values after continuous SS were not significant at higher SS levels (>5.15 Pa) in deoxygenated condition. Simulation results revealed that the velocity gradient dominates the generation of SS and the shear thinning effect of blood has a minor effect on it. Distribution of EI was calculated during oxygenation/deoxygenation which is 5-10 times higher around the vessel wall compared to the center of the lumen for sections of the pulsatile flow profile. The extent of RBC deformability increases as RBCs approach to the vessel wall in a real 3D artery model and this increment is higher for deoxygenated condition compared to the oxygenated state. Hypoxia significantly increases shear-induced RBC deformability. RBCs could regulate their own mechanical properties in blood flow by increasing their deformability in hypoxic conditions. Computational tools can be applied for defining hypoxia-mediated RBC deformability changes to monitor blood flow in hypoxic tissues.
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    PublicationOpen Access
    Drug repositioning screen on a new primary cell line identifies potent therapeutics for glioblastoma
    (Frontiers, 2020) Şenbabaoğlu, Filiz; Cingöz, Ahmet; Şeker-Polat, Fidan; Önder, Tuğba Bağcı; Aksu, Ali Cenk; Börklü Yücel, Esra; Solaroğlu, İhsan; PhD Student; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; Koç University Hospital; N/A; N/A; N/A; 184359; N/A; N/A; 102059
    Glioblastoma is a malignant brain cancer with limited treatment options and high mortality rate. While established glioblastoma cell line models provide valuable information, they ultimately lose most primary characteristics of tumors under long-term serum culture conditions. Therefore, established cell lines do not necessarily recapitulate genetic and morphological characteristics of real tumors. In this study, in line with the growing interest in using primary cell line models derived from patient tissue, we generated a primary glioblastoma cell line, KUGBM8 and characterized its genetic alterations, long term growth ability, tumor formation capacity and its response to Temozolomide, the front-line chemotherapy utilized clinically. In addition, we performed a drug repurposing screen on the KUGBM8 cell line to identify FDA-approved agents that can be incorporated into glioblastoma treatment regimen and identified Topotecan as a lead drug among 1,200 drugs. We showed Topotecan can induce cell death in KUGBM8 and other primary cell lines and cooperate with Temozolomide in low dosage combinations. Together, our study provides a new primary cell line model that can be suitable for both in vitro and in vivo studies and suggests that Topotecan can offer promise as a therapeutic approach for glioblastoma.