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Author: search.filters.author.Sav, AydinHas files: Yes

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    DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues
    (PUBLIC LIBRARY SCIENCE, 2012-01-01) Craig, Justin M.; Vena, Natalie; Ramkissoon, Shakti; Idbaih, Ahmed; Fouse, Shaun D.; Ozek, Memet; Sav, Aydin; Hill, D. Ashley; Margraf, Linda R.; Eberhart, Charles G.; Kieran, Mark W.; Norden, Andrew D.; Wen, Patrick Y.; Loda, Massimo; Santagata, Sandro; Ligon, Keith L.; Ligon, Azra H.
    Whole-genome copy number analysis platforms, such as array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) arrays, are transformative research discovery tools. In cancer, the identification of genomic aberrations with these approaches has generated important diagnostic and prognostic markers, and critical therapeutic targets. While robust for basic research studies, reliable whole-genome copy number analysis has been unsuccessful in routine clinical practice due to a number of technical limitations. Most important, aCGH results have been suboptimal because of the poor integrity of DNA derived from formalin-fixed paraffin-embedded (FFPE) tissues. Using self-hybridizations of a single DNA sample we observed that aCGH performance is significantly improved by accurate DNA size determination and the matching of test and reference DNA samples so that both possess similar fragment sizes. Based on this observation, we developed a novel DNA fragmentation simulation method (FSM) that allows customized tailoring of the fragment sizes of test and reference samples, thereby lowering array failure rates. To validate our methods, we combined FSM with Universal Linkage System (ULS) labeling to study a cohort of 200 tumor samples using Agilent 1 M feature arrays. Results from FFPE samples were equivalent to results from fresh samples and those available through the glioblastoma Cancer Genome Atlas (TCGA). This study demonstrates that rigorous control of DNA fragment size improves aCGH performance. This methodological advance will permit the routine analysis of FFPE tumor samples for clinical trials and in daily clinical practice.
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    Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype
    (OXFORD UNIV PRESS INC, 2015-01-01) Bergthold, Guillaume; Bandopadhayay, Pratiti; Hoshida, Yujin; Ramkissoon, Shakti; Ramkissoon, Lori; Rich, Benjamin; Maire, Cecile L.; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Ozek, Memet; Sav, Aydin; Santagata, Sandro; Wen, Patrick Yung; Goumnerova, Liliana C.; Ligon, Azra H.; Stiles, Charles; Segal, Rosalind; Golub, Todd; Grill, Jacques; Ligon, Keith L.; Chan, Jennifer A.; Kieran, Mark W.; Beroukhim, Rameen
    Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity. We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain. Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. ``Not otherwise specified{''} (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs. Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related.
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    Intradural Solitary Fibrous Tumor of the Lumbar Spine: A Distinctive Case Report
    (HINDAWI LTD, 2015-01-01) Basaran, Recep; Kaksi, Mustafa; Onoz, Mustafa; Balkuv, Ece; Sav, Aydin
    Background. Solitary fibrous tumors are ubiquitous mesenchymal neoplasms of putative fibroblastic origin. They were originally described in the pleura but subsequently have been reported in many extraserosal sites. Solitary fibrous tumors may also occur in the meninges, central nervous system parenchyma, and spinal cord. Case. A 67-year-old male patient with progressive lower extremity weakness, urinary urgency, and sexual dysfunction has been admitted to our hospital. On his lumbar MRI, we detected an intradural lesion posterior to the L3 vertebral corpus. We resected the lesion by L3 total laminectomy. Immunohistological findings revealed strong and diffuse immunopositivity with vimentin, CD34, and bcl-2. Ki-67 proliferation index was 5-8\%. We did not detect any recurrence 12 months after his operation. Conclusion. SFT is mostly seen in young and middle-aged patients and should be considered among differential diagnosis in cases suffering from pain, hypoesthesia, and urinary dysfunction. Gross total resection should be primary treatment. Tumors that have high Ki-67 labeling should be followed up for potential recurrences.
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    Neuroprotective Effect of Memantine on Hippocampal Neurons in Infantile Rat Hydrocephalus
    (TURKISH NEUROSURGICAL SOC, 2011-01-01) Cabuk, Burak; Etus, Volkan; Bozkurt, Suheyla Uyar; Sav, Aydin; Ceylan, Savas
    AIM:The effect of memantine administration on hippocampal neurons of the infantile rats with kaolin induced hydrocephalus was investigated. MATERIAL and METHODS: Hydrocephalus was induced by injecting kaolin into the cisterna magna of 3-weeks old Sprague-Dawley rat pups. One group received a single daily dose of 20mg/kg memantine i.p. following hydrocephalus induction for a period of two weeks. By the end of the two-week period, animals were radiologically evaluated by magnetic resonance imaging and then sacrificed to get their cerebrums removed. Both immunohistochemical analysis of nitric oxide synthase activity and quantification of spared neurons in CA1, CA2 and CA3 regions of hippocampus were performed. RESULTS: In hydrocephalus-induced rats considerable neuronal loss associated with significantly increased nitric oxide synthase immunoreactivity were determined in all hippocampal regions. However, memantine treated rats showed significantly higher number of spared neuron counts and reduced nitric oxide synthase immunoreactivity in CA1 and CA2 regions compared with the non-treated rats. CONCLUSION:The findings of the study show that hippocampal neurons may constitute important targets for injury secondary to hydrocephalic process in experimental infantile hydrocephalus. Early anti-excitotoxic treatment with memantine seems to have a neuroprotective effect especially in the CA1 and CA2 subunits of the hippocampus.
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    Spinal Intramedullary Metastasis of Breast Cancer
    (HINDAWI LTD, 2014-01-01) Basaran, Recep; Tiryaki, Mehmet; Yavuzer, Dilek; Efendioglu, Mustafa; Balkuv, Ece; Sav, Aydin
    Objective. Breast cancer accounts for approximately one-third of all cancers in females. Approximately 8.5 \% of all central nervous system metastases are located in the spinal cord. These patients have rapidly progressing neurological deficits and require immediate examination. The aim of surgery is decompression of neural tissue and histological evaluation of the tumor. In this paper, we present a case of breast cancer metastasis in thoracic spinal intramedullary area which had been partially excised and then given adjuvant radiotherapy. Case. A 43-year-old female patient with breast cancer for 8 years was admitted to our hospital with complaints of weakness in both legs. Eight years ago, she received chemotherapy and radiotherapy. On her neurological examination, she had paraparesis (left lower extremity: 2/5, right lower extremity: 3/5) and urinary incontinence. Spinal MRI revealed a gadolinium enhancing intramedullary lesion. Pathologic examination of the lesion was consistent with breast carcinoma metastasis. The patient has been taken into radiotherapy. Conclusion. Spinal intramedullary metastasis of breast cancer is an extremely rare situation, but it has a high morbidity and mortality rate. Microsurgical resection is necessary for preservation or amelioration of neurological state and also for increased life expectancy and quality.
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    Cauda Equina Paraganglioma with Ependymoma-Like Histology: A Case Report
    (TURKISH NEUROSURGICAL SOC, 2012-01-01) Midi, Ahmet; Yener, Arzu Nese; Sav, Aydin; Cubuk, Rahmi
    Paraganglioma affecting the cauda equina region is very rare and can be misinterpreted as an ependymoma which is more common at this site. A 38-year-old woman with a paraganglioma in the cauda equina is presented. MRI revealed a well-circumscribed, intradural, extramedullary tumor nodule with the dimensions of 2.5x1x1 cm. The patient underwent L3 laminectomy and total excision of the tumor. The tumor was diagnosed as ependymoma and the patient was decided to undergo adjuvant radiotherapy. The patient applied to our medical center for a second opinion. Histopathologically, her tumor was found to be a paraganglioma with ependymal features. Therefore no adjuvant therapy was applied. There is no evidence of recurrence or metastases for 15 months after her operation. Paraganglioma in the cauda equina/ filum terminale is very rare and can be misdiagnosed as ependymoma especially when it exhibits ependymoma-like histology. This rare form of paraganglioma behaves like a WHO grade I tumor of CNS like classic paraganglioma. No recurrence or metastasis is expected when it is totally resected. Morphology can be misleading hence immunohistochemistry and/or ultrastructural study is necessary for correct diagnosis.
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    Intrasellar arachnoid cyst: A case report and review of the literature
    (ELSEVIER SCI LTD, 2016-01-01) Guduk, Mustafa; HamitAytar, Murat; Sav, Aydin; Berkman, Zafer
    INTRODUCTION: Arachnoid cysts (ACs) are frequently found on intracranial imaging studies but intrasellar arachnoid cysts are rarely encountered. PRESENTATION OF CASE: We present a 49-year old patient who had headaches for 6 months and cystic sellar mass was found in his cranial imaging. We operated him by transnasal transsphenoidal route. Our intraoperative diagnosis was an arachnoid cyst and pathologic studies verified our observation. He did well postoperatively and after a 1 year follow-up he was left free from future follow-ups. DISCUSSION: As common cystic lesions occupying the sellar region can simulate ACs both clinically and radiologically, neurosurgeon can fail to include ACs in making the initial diagnosis preoperatively. CONCLUSION: Although a rare entity, arachnoid cysts should be considered in the differential diagnosis of sellar region. (C) 2016 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.