Person: ERZİK, CAN
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ERZİK
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CAN
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Publication Metadata only Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing(2023-09-01) ERDOĞAN, ONUR; ERZİK, CAN; ARĞA, KAZIM YALÇIN; BAYRAKLI, FATİH; ERDOĞAN O., Özkaya Ş. Ç., ERZİK C., Bilguvar K., ARGA K. Y., BAYRAKLI F.Precision/personalized medicine in oncology has two key pillars: molecular profiling of the tumors and personalized reporting of the results in ways that are clinically contextualized and triangulated. Moreover, neurosurgery as a field stands to benefit from precision/personalized medicine and new tools for reporting of the molecular findings. In this context, glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Precision/personalized medicine has emerged as a promising approach for personalized therapy in GBM. In this study, we performed whole exome sequencing of tumor tissue samples from six newly diagnosed GBM patients and matched nontumor control samples. We report here the genetic alterations identified in the tumors, including single nucleotide variations, insertions or deletions (indels), and copy number variations, and attendant mutational signatures. Additionally, using a personalized cancer genome-reporting tool, we linked genomic information to potential therapeutic targets and treatment options for each patient. Our findings revealed heterogeneity in genetic alterations and identified targetable pathways, such as the PI3K/AKT/mTOR pathway. This study demonstrates the prospects of precision/personalized medicine in GBM specifically, and neurosurgical oncology more generally, including the potential for genomic profiling coupled with personalized cancer genome reporting. Further research and larger studies are warranted to validate these findings and advance the treatment options and outcomes for patients with GBM.Publication Metadata only Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma(ELSEVIER SCI LTD, 2008) YEGEN, BERRAK; Iseri, Sevgin Oezlem; Gedik, Ismail Ertugrul; Erzik, Can; Uslu, Bahar; Arbak, Serap; Gedik, Nursal; Yegen, Berrak C.Transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in gastrointestinal tissues due to ischemia, which is followed by reperfusion injury. Oxytocin (OT), a hypothalamic nonapeptide, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in immune and inflammatory processes. To assess the possible protective effect of oxytocin (OT) against burn-induced gastric injury, Sprague-Dawley rats (250-300 g) were randomly divided into three groups as control (n = 8), OT-treated burn (n = 8) and saline-treated burn (n = 8) groups. Under anesthesia, the shaved dorsal skin of rats was exposed to 90 degrees C water for 10 s to induce burn injury covering 30% of total body surface area in a standardized manner. Either oxytocin (5 mu g/kg) or saline was administered subcutaneously immediately after and at 24 h following burn, and the rats were decapitated at 48 h. Serum samples were assayed for TNF-alpha, and stomach was taken for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, DNA fragmentation rate (%) and histopathological examination. MDA and MPO were assayed for products of lipid peroxidation and as an index of tissue neutrophil infiltration, respectively. When compared to control group, burn caused significant increases in gastric MDA and MPO activity and increased microscopic damage scores at 48 h (p < 0.001). Oxytocin treatment reversed the burn-induced elevations in MDA and MPO levels and reduced the gastric damage scores (p < 0.001, p < 0.01), while TNF-alpha levels, which were increased significantly at 48th h after injury (p < 0.001), were abolished with OT treatment (p < 0.001). The results of this study suggest that oxytocin may provide a therapeutic benefit in diminishing burn-induced gastric inflammation by depressing tissue neutrophil infiltration and decreasing the release of inflammatory cytokines, but requires further investigation as a potential therapeutic agent in ameliorating the systemic effects of severe burn. (C) 2007 Elsevier Ltd and ISBI. All rights reserved.Publication Metadata only Bizarre parosteal osteochondromatous proliferation of the little toe(AMER PODIATRIC MED ASSN, 2006) ERZİK, CAN; Saygi, B; Karadag-Saygi, E; Erzik, C; Erkan, M; Yildirim, YA 19-year-old woman presented with pain at the lateral side of the fifth toe of her left foot, which was separated from the adjacent toe. Initial examination suggested dislocation of the fifth metatarsophalangeal joint due to a past fracture. Radiographs showed a mass arising from the proximal phalanx of the little toe, with no medullary and cortical continuity. Excisional biopsy of the mass was performed, and a histologic diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora's lesion) was made.Publication Metadata only Response Assessment With Molecular Characterization of Circulating Tumor Cells and Plasma MicroRNA Profiling in Patients With Locally Advanced Breast Cancer During Neoadjuvant Chemotherapy(CIG MEDIA GROUP, LP, 2020) ERZİK, CAN; Akkiprik, Mustafa; Koca, Sinan; Ugurlu, M. Umit; Ekren, Ruchan; Eyuboglu, Irem Peker; Alan, Ozkan; Erzik, Can; Amuran, Gokce Gullu; Telli, Tugba Akin; Gulluoglu, M. Bahadir; Sezerman, Ugur; Yumuk, Perran FuldenPeripheral blood samples from 36 patients with locally advanced breast cancer who had undergone neoadjuvant chemotherapy were collected for circulating tumor cell (CTC) and plasma microRNA (miR) analysis. Pretreatment CTC and ALDH1 positivity (P = .0245) correlated, with miR-146b-5p and miR-199a-5p accompanied by CTC positivity. CTC and miR profiling of serial samples during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course. Background: Cells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy. Patients and Methods: Markers of breast cancer, epithelial-mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing. Resutts: The proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P= .0245). These CTCs with stemness properties were observed in most hormone receptor-positive, human epidermal growth factor receptor 2 -negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis. Conclusions: Molecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies. (C) 2020 Elsevier Inc. All rights reserved.Publication Metadata only Neoadjuvan kemoterapi alan lokal ileri evre meme kanseri hastalarında dolaşımdaki tümör hücresi moleküler analizleri(2017-10-26) UĞURLU, MUSTAFA ÜMİT; ERZİK, CAN; PEKER EYÜBOĞLU, İREM; AKKİPRİK M., YUMUK P. F., UĞURLU M. Ü., KOCA S., ERZİK C., ALAN Ö., PEKER EYÜBOĞLU İ., GÜLLÜ AMURAN G., ÖZER S. A.Amaç: İzole edilen dolaşımdaki tümör hücrelerinin (CTC) analizi bir "sıvı biyopsi" olarak kanser tedavisinin ve prognozunun öngörülebilmesini sağlayan invaziv olmayan bir kişiye özel tıp uygulamasıdır. Bu çalışmanın amacı neoadjuvan kemoterapi alan lokal ileri evre meme kanserli hastalardan tedavi öncesi ve sonrası periferal kan örnekleri alınarak, CTC moleküler karakterizasyonunu yapmak ve tedaviye verilen yanıt ile ilişkisini ortaya koymaktır. Gereç-Yöntem: Çalışmaya 36 neoadjuvan kemoterapi alan lokal ileri evre meme kanserli hasta dahil edilmiş ve hastalardan tedavi öncesi ve sonrası 10 ml kan örnekleri alınmıştır. CTC izolasyonu, tanımlanması ve moleküler analizlerinde immuno-magnetik temelli AdnaTest kitleri kullanılmış, meme kanseri (GA733-2, Muc-1 ve Her-2, Aktin), EMT (PI3Kα, Akt-2, TWIST1) ve kök hücre (ALDH1) markerları incelenmiştir. Görüntüleme Agilent 2100 Bioanalyzer cihazı kulllanılarak DNA 1000 LabChip ile gerçekleştirilmiştir. CTC pozitifliği ve çalışılan markerlar ile tedaviye yanıt (patolojik tam cevap (PCR) ve rezidual hastalık) açısından anlamlılık, Fisher’s Exact test ile analiz edilmiştir. Bulgular: Otuzaltı hastanın 6'sında (%16,7) tedavi öncesinde CTC pozitifliği saptanmıştır. CTC pozitif olan 6 hastanın 4'ünde kök hücre markeri olan ALDH1 pozitifliği gözlenmiştir (p=0,0245) (Tablo 1). EMT markerlarından PI3Kα ise 3 hastada pozitif bulunmuştur. Hasta takipleri ve tedaviye verilen cevaplar izlenmeye devam etmektedir. Sonuç: Neoadjuvan kemoterapi alan lokal ileri evre meme kanseri hastalarında CTC pozitifliği ve kök hücre markerlarının analizi tedaviye verilecek olan cevabın ve hasta sağkalım oranlarının ön görülebilmesi için önemli bir yöntem olabilir. Çalışmalarımız bu kapsamda devam etmektedir.Publication Metadata only Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha IVS1-397C/C genotype and established coronary artery disease(KARGER, 2006) ERZİK, CAN; Emre, Ayse; Sahin, Sinan; Erzik, Can; Nurkalem, Zekeriya; Oz, Dilaver; Cirakoglu, Beyazit; Yesilcimen, Kemal; Ersek, BirsenEffect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha (ER-alpha) IVS1-397 C/C genotype and established coronary artery disease. Background/ Aims: Associations between various ER-a polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-a IVS1-397 polymorphism on the response to treatment with HRT. Methods: The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-alpha IVS1-397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and TI-201 scintigraphy were performed at the end of each treatment period. Results: HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r =-0.62, p < 0.01) and rest scores (r =-0.52, p < 0.05) in the CC genotype group. Conclusion: These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-alpha IVS1-397 CC genotype. Copyright (c) 2006 S. Karger AG, Basel.Publication Metadata only Role of TRF2 and TPP1 regulation in idiopathic recurrent pregnancy loss(ELSEVIER SCIENCE BV, 2019) ERZİK, CAN; Pirzada, Rameez Hassan; Orun, Oya; Erzik, Can; Cagsin, Huseyin; Serakinci, NedimeTelomeres are the tandem repeats (TTAGGG) present at the ends of the chromosomes that ensure chromosome stability and protect chromosomes from degradation. Telomeres in somatic human cells shorten after every cellular division and are linked to the cellular senescence. In this study we have investigated telomere length and expression of shelterin genes in aborted fetus material from idiopathic recurrent pregnancy losses. Telomere length was measured using Telomere Restriction Fragment Length (TRF) analysis. The gene expression levels for important shelterin complex proteins (TRF1, TRF2, POT1, and TPP1) were determined by Real-time Quantitative Reverse Transcriptase PCR (qRT-PCR). Our results demonstrated down regulation of TRF2 and TPP1 and a strong decline in average telomere length in abort material from women suffering from idiopathic recurrent pregnancy loss. We suggest that shorter telomere length and downregulation of the major shelterin components TRF2 and TPP1 leading to telomere uncapping, might play a critical role in recurrent pregnancy loss. (C) 2019 Elsevier B.V. All rights reserved.Publication Metadata only The impact of vitamin B12 deficiency on infant gut microbiota(SPRINGER, 2020) ERZİK, CAN; Boran, Perran; Baris, Hatice Ezgi; Kepenekli, Eda; Erzik, Can; Soysal, Ahmet; Dinh, Duy M.Although physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively, less is known about their impact on developing gut microbiota. Vitamin B12 deficiency is a common micronutrient deficiency in infants. We aimed to analyze the gut microbial composition of exclusively breastfed infants aged between 4 and 6 months with and without vitamin B12 deficiency by 16S rRNA gene sequencing. In a subgroup of infants with vitamin B12 deficiency, stool samples are recollected and reanalyzed after vitamin B12 supplementation. A total of 88 infants' stool samples (median age 4 months [IQR 4-5], 50% males) were analyzed, of which 28 (31.8%) were vitamin B12 sufficient and 60 (68.2%) were vitamin B12 insufficient. Comparisons between vitamin B12-sufficient and vitamin B12-insufficient infants revealed no evidence of differences in the microbiota. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the most abundant phyla in all groups. There was no difference between the pre- and post-treatment composition of gut microbiota. Conclusion: Vitamin B12-deficient infants have similar gut microbial composition as vitamin B12-sufficient infants. Since the samples were collected at an early period of life and the exposure to deficiency was relatively short, it may be possible that the effects were not fully established.Publication Metadata only Resveratrol protects against irradiation-induced hepatic and ileal damage via its anti-oxidative activity(TAYLOR & FRANCIS LTD, 2009) VELİOĞLU ÖĞÜNÇ, AYLİZ; Velioglu-Ogunc, Ayliz; Sehirli, Ozer; Toklu, Hale Z.; Ozyurt, Hazan; Mayadagli, Alpaslan; Eksioglu-Demiralp, Emel; Erzik, Can; Cetinel, Sule; Yegen, Berrak C.; Sener, GoekselThe present study was undertaken to determine whether resveratrol (RVT) could ameliorate ionizing radiation-induced oxidative injury. After a 10-days pre-treatment with RVT (10 mg/kg/day p.o.), rats were exposed to whole-body IR (800 cGy) and the RVT treatment was continued for 10 more days after the irradiation. Irradiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the liver and ileum tissues. Similarly, plasma lactate dehydrogenase and pro-inflammatory cytokine levels, 8-hydroxy-2'-deoxyguanosine and leukocyte apoptosis were elevated, while antioxidant-capacity was reduced in the irradiated rats as compared with the control group. Furthermore, Na-1, K-1 -ATPase activity was inhibited and DNA fragmentation was increased in the ileal tissues. Resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. In conclusion, supplementing cancer patients with adjuvant therapy of resveratrol may have some benefit for a more successful radiotherapy.Publication Metadata only Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury(SPRINGER/PLENUM PUBLISHERS, 2021) ERZİK, CAN; Kuru Bektasoglu, Pinar; Koyuncuoglu, Turkan; Akbulut, Selin; Akakin, Dilek; Eyuboglu, Irem Peker; Erzik, Can; Yuksel, Meral; Kurtel, HizirPlasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective effects. In this study, it was aimed to investigate the possible protective effects of PAI-1 antagonists in a rat mild traumatic brain injury (TBI) model. Sprague-Dawley male rats were grouped as sham (n = 7), TBI (n = 9), and TBI + PAI-1 antagonist (5 and 10 mg/kg TM5441 and TM5484; n = 6-7). Under anesthesia, TBI was induced by dropping a metal 300-g weight from a height of 1 m on the skull. Before and 24-h after trauma neurological examination, tail suspension, Y-maze, and novel object recognition tests were performed. Twenty-four hours after TBI, the rats were decapitated and activities of myeloperoxidase, nitric oxide release, luminol-, and lucigenin-enhanced chemiluminescence were measured. Also, interleukin-1 beta, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-beta, caspase-3, cleaved caspase-3, and PAI levels were measured with the ELISA method in the brain tissue. Brain injury was graded histopathologically following hematoxylin-eosin staining. Western blot and immunohistochemical investigation for low-density lipoprotein receptor, matrix metalloproteinase-3, and nuclear factor-kappa B were also performed. Data were analyzed using GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA) and expressed as means +/- SEM. Values of p < 0.05 were considered to be statistically significant. Higher levels of myeloperoxidase activity in the TBI group (p < 0.05) were found to be suppressed in 5 and 10 mg/kg TM5441 treatment groups (p < 0.05-p < 0.01). The tail suspension test score was increased in the TBI group (p < 0.001) and decreased in all treatment groups (p < 0.05-0.001). The histologic damage score was increased statistically significantly in the cortex, dentate gyrus, and CA3 regions in the TBI group (p < 0.01-0.001), decreased in the treatment groups in the cortex and dentate gyrus (p < 0.05-0.001). PAI antagonists, especially TM5441, have antioxidant and anti-inflammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.