BACKGROUND: Recently, isocitrate dehydrogenase 1 (IDH1) was identified as a major participant in glioma pathogenesis. At present, the enzymatic activity of the protein has been the main topic in investigating its physiological function, but its signaling pathway allocation was unsuccessful. Interestingly, proteins regulated by phosphoinositide 3-kinase (PI3K)/Akt signaling, are among the top downregulated genes in gliomas associated with high percentage of IDH1 and IDH2 mutations. The aim of this study was to investigate a hypothetical relation between IDH1 and PI3K signaling. METHODS: The presence of mutant IDH1 and markers for active PI3K/ Akt signaling, present as phosphorylated Akt and podoplanin (PDPN), were investigated in a discovery cohort of 354 patients with glioma. In vitro experiments were used to confirm functional links. RESULTS: This study shows an inverse correlation between mutant IDH1 and markers for active PI3K/Akt signaling. In support of a functional link between these molecules, in vitro expression of mutant IDH1 inhibited Akt phosphorylation in a 2-hydroxyglutarate-dependent manner. CONCLUSIONS: This study provides patient tumor and in vitro evidence suggesting that mutant IDH1 inhibits PI3K/Akt signaling. Cancer 2014;120:2440-7. V C 2014 American Cancer Society.KEYWORDS: astrocytoma, glioma, glioblastoma, PDPN, IDH1, Akt. INTRODUCTIONRecent reports have identified a subgroup of gliomas with better prognosis characterized by mutations in the genes encoding isocitrate dehydrogenase 1 (IDH1) and IDH2. 1 Despite intense research, it is still unclear how IDH1 and IDH2 influence prognosis in patients with cancer. Recent reports show that the mutated form decreases proliferation of glioma cell lines 2 and blocks differentiation of nontransformed cells. 3 PI3K/Akt signaling is aberrantly activated in many cancer types, including human glioma. 4 In most cases, loss of the PI3K inhibitor PTEN (phosphatase and tensin homolog) or a gain-of-function mutations of PI3KCA 5 are the underlying cause. Activation of PI3K/Akt signaling is associated with a more aggressive behavior in human glial tumors 6 and causes faster clinical and histological tumor progression in a platelet-derived growth factor (PDGF)-driven mouse glioma model. 7 Intriguingly, 2 proteins linked to PI3K signaling, podoplanin (PDPN) and retinol binding protein 1 (RBP1), are some of the top downregulated genes in a subset of gliomas associated with high frequency of IDH1 mutations. 8 Interestingly AKT1 was downregulated on the RNA level, and immunocytochemistry showed a reduced staining intensity for phospho-Akt in IDH1R132H-expressing glioma cells in vitro. 2 There is a growing body of evidence suggesting that PDPN, a downstream effector of PI3K signaling, 9 plays a major role in glioma pathogenesis. PDPN contributes to cancer progression by inducing collective cell migration and tumor invasion, 10 and its expression correlates with tumor grade in human glioma 11 and serves as a marker of reduced overall survival in glioblastoma patients...

Neurosurgery as a distinct speciality has been around for 100 years. Some of the earliest women neurosurgeons were European, emerging from the 1920 0 s onwards. Here we detail the rise of women in neurosurgery across Europe with a decade by decade account of big events and firsts across the continent. The emerging themes are seen in stories of pioneers with enormous resilience, camaraderie, trailblazing and triumphing in a system with great obstacles and challenges. Our journey through this chronology brings us to the modern day, where most European countries have or have had a woman neurosurgeon and the future for women in neurosurgery in the continent is very bright.

This study describes our experience with the treatment of cervical degenerative pathology through anterior cervical decompression and fusion technique. We evaluated the clinical outcome and complications after 6-months follow-up and analysed the data to optimize the efficacy and safety of this particular surgical treatment in order to minimize the risks of complications. The presented study included 111 patients (74 men and 37 women; mean age 56.5 years) treated in the Neurosurgical Department of UMBAL Sv. Ivan Rilski Hospital in Sofia, Bulgaria, for cervical degenerative multilevel pathology with myelopathy. The operations included only anterior cervical approach with single-level or multilevel corpectomy, considering the pathology and neurological deficit in each particular case, followed by instrumented fusion with titanium mesh and locking plates. We analysed the data for intraoperative, early and late postoperative complications and the neurological results were examined and compared with the aid of Nurick and mJOA scales for myelopathy. The mean mJOA score preoperatively was 11.37 (SD ± 2.63) and postoperatively the mean mJOA score was 13.27 (SD ± 2.61), p < 0.0001. Since the emerging of this technique more than 50 years ago, it has improved in many ways, although there are still some contradictory results. Still, the most important aspect should be to consider the individual's pathology in order to better understand the underlying problems and think of ways to resolve them appropriately.

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