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Butz H.,Semmelweis University | Liko I.,Gedeon Richter Plc | Czirjak S.,National Institute of Neurosurgery | Igaz P.,Semmelweis University | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: The tumorigenic mechanisms involved in pituitary adenomas, especially of nonfunctional pituitary adenomas (NFAs), remains unclear. Various cell cycle inhibitors have been found to be underexpressedinpituitarytumors; however, Wee1 kinase, a nuclear protein that delays mitosis and was recently recognized as a tumor suppressor gene, has not been previously investigated in pituitary tumors. Objective: Our objective was to examine the expression of Wee1 in pituitary tumors and to identify microRNAs (miRs) that can regulate its expression. Design: Expression of Wee1 was examined by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Identification of miRs targeting the Wee1 3́-untranslated region was performed bymiRarray followed by expression analysis of identified miRs using qRT-PCR. Dual-luciferase assay and transient transfection of miRs into Hela cells followed by immunoblot analysis of Wee1 protein and cell proliferation analysis were carried out. Patients: A total of 57 pituitary tissue samples including 27 NFAs, 15 GH-producing adenomas with or without prolactin overproduction, and 15 normal pituitary glands were analyzed. Results: Wee1 protein expression was decreased in NFAs and GH-producing tumors with or without prolactin production, but no change in mRNA expression was observed with qRT-PCR. A specific subset of five miRNAs revealed by in silico target prediction was significantly overexpressed in NFA samples; three miRs (miR-128a, miR-155, and miR-516a-3p) targeted the 3′-untranslated region of the Wee1 transcript, and exogenous overexpression of these miRs inhibited Wee1 protein expression and HeLa cell proliferation. Conclusions: To our knowledge, this is the first report suggesting that regulation of Wee1 kinase by miRs may be linked to pituitary tumorigenesis. Copyright © 2010 by The Endocrine Society.

Butz H.,Semmelweis University | Liko I.,Gedeon Richter Plc | Czirjak S.,National Institute of Neurosurgery | Igaz P.,Semmelweis University | And 4 more authors.
Pituitary | Year: 2011

MicroRNAs (miRs) are small, 16-29 nucleotide long, non-coding RNA molecules which regulate the stability or translational efficiency of targeted mRNAs via RNA interference. MiRs participate in the control of cell proliferation, cell differentiation, signal transduction, cell death, and they play a role in carcinogenesis. The aims of our study were to analyse the expression profile of miRs in sporadic clinically non-functioning pituitary adenomas (NFPA) and in normal pituitary tissues, and to identify biological pathways altered in these pituitary tumors. MiR expression profiles of 12 pituitary tissue specimens (8 NFPA and 4 normal pituitary tissues) were determined using miR array based on quantitative real-time PCR with 678 different primers. Five overexpressed miRs and mRNA expression of Smads (Smad1-9), MEG and DLK1 genes were evaluated with individual Taqman assays in 10 NFPA and 10 normal pituitary tissues. Pathway analysis was performed by the DIANA-mirPath tool. Complex bioinformatical analysis by multiple algorithms and association studies between miRs, Smad3 and tumor size was performed. Of the 457 miRs expressed in both NFPA and normal tissues, 162 were significantly under- or overexpressed in NFPA compared to normal pituitary tissues Expression of Smad3, Smad6, Smad9, MEG and DLK1 was significantly lower in NFPA than in normal tissues. Pathway analysis together with in silico target prediction analysis indicated possible downregulation of the TGFβ signaling pathway in NFPA by a specific subset of miRs. Five miRs predicted to target Smad3 (miR-135a, miR-140-5p, miR-582-3p, miR-582-5p and miR-938) were overexpressed. Correlation was observed between the expression of seven overexpressed miRs and tumor size. Downregulation of the TGFβ signaling through Smad3 via miRs may have a possible role in the complex regulation of signaling pathways involved in the tumorigenesis process of NFPA. © 2010 Springer Science+Business Media, LLC.

Nelson P.K.,NYU Langone Medical Center | Lylyk P.,Eneri Instituto Medico | Szikora I.,National Institute of Neurosurgery | Wetzel S.G.,University of Basel | And 2 more authors.
American Journal of Neuroradiology | Year: 2011

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (>4 mm), had unfavorable dome/neck ratios (<1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42-76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms. Copyright © 2011 by the American Society of Neuroradiology.

Szogedi I.,University of Pecs | Zrinyi M.,Teva Hungary Ltd. | Betlehem J.,University of Pecs | Ujvarine A.S.,Debrecen University | Toth H.,National Institute of Neurosurgery
European Journal of Cardiovascular Nursing | Year: 2010

Aim: to assess whether problem-based learning (PBL) is more effective over conventional teaching methods by comparing final resuscitation exam results of nursing students who received cardiopulmonary resuscitation (CPR) training either by traditional or by a PBL approach. Methods: A retrospective and comparative research design was implemented. Data on final CPR exam grades, collected both from PBL and traditionally trained students, were obtained for a total of 1775 students between 2000 and 2007 in three major schools of health sciences in Hungary. Comparison between PBL and traditional teaching methods as well as across schools was made. Results: t-tests on means yielded significant differences (t = 3.569; p < 0.001) between PBL and conventional training favoring PBL instructed students. Students who received PBL training had better final CPR exam grades than traditionally trained peers. The only significant difference among schools was found for PBL training. There was no difference across schools in final CPR grades when traditional training was concerned. Conclusion: PBL was a superior instruction method for CPR training. Students who attended PBL classes achieved greater theoretical knowledge and demonstrated better resuscitation skills when tested. Whether or not PBL is superior in real-life application of CPR practice is yet to be confirmed. © 2009 European Society of Cardiology.

Borbely K.,National Institute of Oncology | Wintermark M.,University of Virginia | Martos J.,National Institute of Neurosurgery | Fedorcsak I.,National Institute of Neurosurgery | And 2 more authors.
Journal of the Neurological Sciences | Year: 2010

Since the introduction of FDG into the field of molecular imaging with positron emission tomography (PET) more than three decades ago, FDG has been the tracer of choice for oncology PET imaging. Despite the relative disadvantages of FDG and the relative benefits of its challengers, FDG remains the most commonly used glioma tracer nowadays. The present article surveys the expectations of the field and gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal second-generation PET biomarker for glioma. Mini-abstract: The present article gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal PET biomarker for glioma. © 2010 Elsevier B.V.

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