Person: BAYRAKLI, FATİH
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BAYRAKLI
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FATİH
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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 Changing treatment strategy of cavernous sinus meningiomas: experience of a single institution(ELSEVIER SCIENCE INC, 2005) BAYRAKLI, FATİH; Pamir, MN; Kilic, T; Bayrakli, F; Peker, SBackground: Oncological treatment of a neoplasm is more than surgical removal of the tumor. Probably, this truth is the reason for the ongoing discussion on cavernous sinus meningiomas in the last decade. Debate on optimal management of cavernous sinus meningiomas aims to compare the different treatment strategies: (a) radical surgical resection and (b) conservative surgical resection complemented with radiosurgical treatment. Materials and Methods: Natural history of the change in the management strategy of cavernous sinus meningiomas in our department before and after GK facility became available in 1997 allowed us to compare the 2 aforementioned strategies. Before installation of a Leksell GK unit at the hospital in 1997, the neurosurgical team at Marmara University Institute of Neurological Sciences and Faculty of Medicine (Istanbul, Turkey) treated patients with cavernous sinus meningioma using radical resection (radical strategy, group A, 10 patients). After 1997, the same neurosurgical team used understanding of surgical removal of the extracavernous sinus tumor component with GK irradiation of the intracavernous part (conservative strategy, group B, 12 patients). Another group of patients, who were treated with GK as a first-step treatment, was analyzed (GK group, group C, 26 patients). Results: At the end of the third year, more stable tumor volume control was achieved in groups B and C; after the second year, an incline in the tumor volume-time graph was detected. Group B resulted in less cranial nerverelated complications; a certain degree of improvement in cranial nerve deficits was observed. Conclusion: Comparing 2 different management strategies for cavernous sinus meningiomas in the same hospital setting using the same neurosurgical group, we conclude that extracavernous resection followed by GK is as effective as radical surgery. Considering cranial nerve complications and third-year tumor volume control achievement, conservative approach yielded better results. Longer follow-up with larger series is necessary. (c) 2005 Elsevier Inc. All rights reserved.Publication Metadata only Gamma-knife radiosurgery in the treatment of trigeminal schwannomas(SPRINGER WIEN, 2007) BAYRAKLI, FATİH; Peker, S.; Bayrakli, F.; Kilic, T.; Pamir, M. N.Background. Trigeminal nerve schwannomas account for 0.07%-0.28% of all intracranial tumours. Advances in skull base surgery have led to more aggressive resection of these tumours, but surgery may associated with development of new neurological deficits. Methods. In this report, we analyse the long-term results 15 patients with newly diagnosed or residual/recurrent trigeminal schwannoma who underwent gamma-knife treatment. Findings. During a mean 61 months of follow-up, MRI revealed reduction of tumour size in 13 and no size change in 2 patients. The tumour growth control rate was 100% and only 1 patient had transient facial numbness and diplopia. Conclusions. For patients with small to moderate size trigeminal schwannomas, gamma-knife radiosurgery is associated with good tumour control and a minimal risk of adverse radiation effects.Publication Metadata only New candidate chromosomal regions for chordoma development(ELSEVIER SCIENCE INC, 2007) GÜNEY, AHMET İLTER; Bayrakli, Fatih; Guney, Ilter; Kilic, Turker; Ozek, Memet; Pamir, Mustafa NecmettinBackground: Chordomas are rare, slow growing, infiltrative tumors thought to arise from vestigial or ectopic notochord. Chordoma can occur along the axial skeleton, predominantly in the sphenooccipital, vertebral, and sacrococcygeal regions. Although most chordomas are sporadic, familial cases have also been reported. The most common molecular cytogenetic abnormalities in these tumors are monosomy of chromosome I and gain of chromosome 7. In addition, a variety of other chromosomal changes, which are associated with losses and gains of different chromosomes, have also been described in chordomas, such as 1q, 2p, 3p, 5q, 9p, 10, l2q, 13q, 17, and 20q. Methods: In this study, using molecular cytogenetics (iFISH), we have studied 1p36, 1q25, 3p13p14, 7q33, 17p13.1 (p53 gene locus), 2p13 (TGF-alpha locus), 6p12 (VEGF locus), and 4q26-q27 (bFGF/FGF2 locus) loci in chordoma tissues from seven patients with 7 primary tumors and 11 recurrences. Results: We found that chromosomes 1p36, 1q25, 2p13, and 7q33 are affected in primary chordomas, and these aberrations persist in recurrences. However, the chromosome 6p12 aberration was seen only in primary chordomas, but not in recurrences, indicating that this locus may be associated with chordoma genesis. Conclusions: Our descriptive data from interphase FISH analyses suggest that future studies should incorporate a larger number of patients and should focus on identifying the candidate genes in chordoma pathogenesis. Such studies may use a whole-genomic approach, in addition to the regions identified in this study and others. (C) 2007 Elsevier Inc. All rights reserved.Publication Metadata only Gamma knife radiosurgery for cavernous sinus plasmacytoma in a patient with breast cancer history(ELSEVIER SCIENCE INC, 2005) BAYRAKLI, FATİH; Peker, S; Abacioglu, U; Bayrakli, F; Kilic, T; Pamir, MNBackground: Multiple myeloma (MM) presentation with cerebral mass lesion is unusual. Gamma knife radiosurgery for plasmacytoma has not been reported so far. Case Report: We report a 70-year-old female with a medical history of infiltrative ductal carcinoma of the breast. She developed cavernous sinus syndrome (CSS) 5 months before admission to the hospital. The magnetic resonance imaging revealed an isointense solitary mass in the left cavernous sinus in noncontrast T1-weighted images. The lesion was highly enhancing with gadolinium-diethylenetriaminopentaacetic acid. She was operated by using Dolenc technique, and the tumor was partially resected. The pathological examination of the tumor tissue revealed a plasmacytoma. Systemic evaluation was positive for the diagnosis of MM. She underwent gamma knife radiosurgery for the residual cavernous sinus tumor. Chemotherapy with prednisolone and melphalan was given. Follow-up magnetic resonance images 6 months after the treatment demonstrated complete tumor disappearance. However, she died of sepsis 26 months after the diagnosis. Conclusion: This is an unusual MM case with a history of breast cancer, which had CSS and which demonstrated an excellent response to gamma knife radiosurgery. (C) 2005 Elsevier Inc. All rights reserved.Publication Metadata only Surgical treatment of trigeminal schwannomas(SPRINGER, 2007) BAYRAKLI, FATİH; Pamir, M. Necmettin; Peker, Selcuk; Bayrakli, Fatih; Kilic, Tuerker; Oezek, M. MemetSchwannomas that arise from the trigeminal nerve are rare, but this nerve is the second most frequent intracranial site of schwannoma occurrence next to the vestibular nerve. The advent of microsurgical techniques and skull-base approaches has greatly enhanced the surgical management of these tumors, and outcomes have improved markedly. This report documents 18 cases of histologically verified schwannomas that arose from the trigeminal nerve and were treated surgically in our clinic between January 1992 and July 2005. The patients were ten women and eight men of age 39.7 years (range, 22-62 years). The tumor was located in the middle fossa (type A) in five cases, in the middle and posterior fossae (type C) in nine cases, in the posterior fossa (type B) in two cases, and in the branches of the trigeminal nerve (type D) in two cases. Total excision was achieved in 17 cases, and there was no mortality in the series. Our results indicate that trigeminal schwannomas, regardless of type, can be removed via skull-base approaches. We present an algorithm for surgical management of trigeminal schwannomas based on our experience and information from the literature.Publication Metadata only MicroRNA-Mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment(KARGER) YILMAZ, BETÜL; Aydin, Busra; Arslan, Sema; Bayrakli, Fatih; Karademir, Betul; Arga, Kazim YalcinIntroduction: Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors in the clinic. The preferred first-line therapy is a medical treatment with dopamine agonists (DAs), mainly cabergoline, to reduce serum prolactin levels, tumor volume, and mass effect. However, in some cases, patients have displayed DA resistance with aggressive tumor behavior or are faced with recurrence after drug withdrawal. Also, currently used therapeutics have notorious side effects and impair the life quality of the patients. Methods: Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerges to exhibit essential roles in the behavior and progression of prolactinomas; in this work, we integrated mRNA- and microRNA (miRNA)-level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma. Results: We identified 8 drug candidates through drug repurposing based on mRNA-miRNA-level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven repurposed drugs including 5-fluorocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing the PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and Western blotting. Discussion: We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA-level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of the PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments.Publication Metadata only Deep brain stimulation as treatment for dystonic storm in pantothenate kinase-associated neurodegeneration syndrome: case report of a patient with homozygous C.628 2 T > G mutation of the PANK2 gene(SPRINGER WIEN, 2015) DAĞÇINAR, ADNAN; Tanrikulu, Bahattin; Ozen, Ali; Gunal, Dilek Ince; Turkdogan, Dilsad; Bayrakli, Fatih; Bayri, Yasar; Dagcinar, Adnan; Seker, AskinPantothenate kinase-associated neurodegeneration (PKAN) syndrome is an autosomal-recessive neurodegenerative disease that causes progressive generalized dystonia. Currently, the disorder remains pharmacologically intractable. Herein we report the first case in which deep brain stimulation helped to relieve dystonic storm in a patient with PKAN syndrome who had homozygous c.628 2 T > G mutation of the PANK2 gene. A 10-year-old boy with PKAN disease presented with dystonic storm and was admitted to the emergency department. Examination revealed generalized dystonia and impaired breathing due to involvement of the respiratory muscles. The patient underwent surgery for bilateral globus pallidus internus deep brain stimulation. The patient showed marked response to treatment.Publication Metadata only Past, present, and future of therapies for pituitary neuroendocrine tumors: need for omics and drug repositioning guidance(2022-03-01) ERDOĞAN, ONUR; ARĞA, KAZIM YALÇIN; BOZKURT, SÜHEYLA; BAYRAKLI, FATİH; YILMAZ, BETÜL; TURANLI, BESTE; Aydin B., Yildirim E., ERDOĞAN O., ARĞA K. Y., Yilmaz B., BOZKURT S., BAYRAKLI F., TURANLI B.Innovation roadmaps are important, because they encourage the actors in an innovation ecosystem to creatively imagine multiple possible science future(s), while anticipating the prospects and challenges on the innovation trajectory. In this overarching context, this expert review highlights the present unmet need for therapeutic innovations for pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas. Although there are many drugs used in practice to treat PitNETs, many of these drugs can have negative side effects and show highly variable outcomes in terms of overall recovery. Building innovation roadmaps for PitNETs\" treatments can allow incorporation of systems biology approaches to bring about insights at multiple levels of cell biology, from genes to proteins to metabolites. Using the systems biology techniques, it will then be possible to offer potential therapeutic strategies for the convergence of preventive approaches and patient-centered disease treatment. Here, we first provide a comprehensive overview of the molecular subtypes of PitNETs and therapeutics for these tumors from the past to the present. We then discuss examples of clinical trials and drug repositioning studies and how multi-omics studies can help in discovery and rational development of new therapeutics for PitNETs. Finally, this expert review offers new public health and personalized medicine approaches on cases that are refractory to conventional treatment or recur despite currently used surgical and/or drug therapy.Publication Metadata only Intractable yawning caused by foramen magnum meningioma in a patient with neurofibromatosis type 2(2015) DAĞÇINAR, ADNAN; Bayri, Yasar; Tanrikulu, Bahattin; Bayrakli, Fatih; Koç, Demet Yalçinkaya; Dağçinar, Adnan