Pkc Alpha Phosphorylates Cytosolic Nf-Kappab/P65 and Pkc Delta Delays Nuclear Trans Location of Nf-Kappab/P65 in U1242 Glioblastoma Cells

AIM: Protein kinase-C (PKC) and NF-kappaB are involved in cell survival, proliferation, migration and radioresistance in glioblastoma multiforme (GBM). We sought to determine the interaction between PKC and NF-kappaB pathways. MATERIAL and METHODS: The activation of NF-kappaB by PKC a and PKC delta was assessed by Western blotting after the stimulation with Phorbol 12-Myristate 13-Acetate (PMA). Gene silencing of PKC alpha, PKC delta and NF-kappaB/p65 with siRNA interference was utilized to evaluate their roles in NF-kB activation and cell proliferation. RESULTS: PMA induced the phosphorylation of NF-kappaB/p65 by PKC alpha. Gene silencing with siRNA against NF-kappaB/p65 inhibited [3H]-thymidine incorporation in U1242 GBM cells. PKC delta decelerated the nuclear translocation of activated NF-kappaB/p65 up to 4 hours after the stimulation. PMA induced death was not observed in PKC delta silenced cells where activated NF-kappaB/p65 was located immediately in the nucleus. CONCLUSION: NF-kappaB/p65 is pro-survival and proliferative factor in U1242 GBM cells. PKC alpha is needed to phosphorylate NF-kappaB/p65. PKC delta delays the translocation of active NF-kappaB/p65 into the nucleus. PMA-induced cell death occurred if the phospho-NF-kappaB/p65 was prohibited from entering the nucleus in PKC delta positive cells. Translocation of phosphorylated form of NF-kappaB into the nucleus is critical in GBM cell proliferation.WoSScopu

A novel acute phase rehabilitation approach: Vibration therapy in insular glioma patients

Acute phase rehabilitation has beneficial effects on functional results, activities of daily living, mobility and cognition in glioma patient. Two insular glioma patients had acute phase rehabilitation were presented in this study. The Karnofsky Performance Scale, The Stroke Rehabilitation Assesment of Movement Scale, the Berg Balance Scale, and the Functional Independence Measure were used to assess patients. While Case 1 was treated with Neurodevelopmental Therapy (Bobath approach) (12 sessions), Case 2 was treated with cervical vibration in addition to Neurodevelopmental Therapy (15 sessions). Besides observing positive developments in the balance and functional levels of the two cases after treatment, there was more improvement in the balance parameter of Case 2. As a result of the study, cervical vibration application in addition to the rehabilitation program of patients with insular tumor could be useful in terms of balance development. [Med-Science 2018; 7(2.000): 448-50

The Added Value of Diffusion Magnetic Resonance Imaging in the Diagnosis and Posttreatment Evaluation of Skull Base Chordomas

Objectives To determine the use of diffusion-weighted imaging (DWI) in the pre- and posttreatment evaluation of skull base chordomas. Design Retrospective study. Setting Tertiary care university hospital. Participants In total, 17 patients with histopathological diagnosis of chordoma who had magnetic resonance (MR) imaging and DWI were evaluated. Of them, 13 patients had posttreatment MR imaging including DWI. Main Outcome Measures Three apparent diffusion coefficient (ADC) values were obtained from tumor, and an ADC value was measured from pons for the purpose of normalization. ADC values of the subtypes of chordomas (typical and chondroid chordomas) were compared. Results Ten (59%) masses had increased signal on trace DWI at pretreatment evaluation. The mean ADC(entire) (tumor)/ADC(pons) was calculated as 1.55 +/- 0.44. The mean ADC(entire) (tumor) values of typical and chondroid chordomas were 1.26 +/- 0.29 x 10(-3) mm(2)/s and 0.99 +/- 0.46 x 10(-3) mm(2)/s, respectively. There was no statistically significant difference between ADC values of the subtypes (p > 0.05). For posttreatment evaluation, DWI enabled detection of residual tumor in the majority (85%) of cases. Conclusions DWI is useful in diagnosis and posttreatment evaluation of skull base chordomas. However, ADC values in our series did not distinguish the subtypes of chordomas.Wo

Nöroşirurji Ders Kitabı

Bu kitap, Tıp Fakültesi öğrencilerine nöroşirurjinin güncellenmiş temel bilgilerini sunmak amacı ile yazılmıştır. Titiz bir çalışma ile hazırlanmasına rağmen gözden kaçmış eksiklik ve hataların hoşgörü ile karşılayacağını umuyoruz. Öğrencilerimize yararlı olması dileği ile..

The efficacy of silver-embedded polypropylene-grafted polyethylene glycol-coated ventricular catheters on prevention of shunt catheter infection in rats

Purpose: Catheter-related infection is a major complication of ventriculoperitoneal shunt in children. The aim of this study is to determine inflammatory response and the efficacy of polypropylene-grafted polyethylene glycol (PP-g- PEG) copolymer and silver nanoparticle-embedded PP-g- PEG (Ag-PP-g-PEG) polymer-coated ventricular catheters on the prevention of catheter-related infections on a new experimental model of ventriculoperitoneal shunt in rats. Methods: Thirty six Wistar albino rats were divided into six groups: group 1, unprocessed sterile silicone catheterembedded group; group 2, sterile PP-g-PEG-coated catheter group; group 3, sterile Ag-PP-g-PEG-coated catheter group; group 4, infected unprocessed catheter group; group 5, infected PP-g-PEG-coated catheter group; and group 6, infected Ag-PP-g-PEG-coated catheter group, respectively. In all groups, 1-cm piece of designated catheters were placed into the cisterna magna. In groups 4, 5, and 6, all rats were infected with 0.2 mL of 10×106 colony forming units (CFU)/mL Staphylococcus epidermidis colonies before the catheters were placed. Thirty days after implantation, bacterial colonization in cerebrospinal fluid and on catheter pieces with inflammatory reaction in the brain parenchyma was analyzed quantitatively. Results: Sterile and infected Ag-PP-g-PEG-covered groups revealed significantly lower bacteria colony count on the catheter surface (ANOVA, 0±0, p<0.001; 1.08±0.18, p< 0.05, respectively). There was moderate inflammatory response in the parenchyma in group 4, but in groups 5 and 6, it was similar to that of the sterile group (ANOVA, 16.33± 3.02, p<0.001; 4.00±0.68, p<0.001, respectively). Conclusions: The PP-g-PEG, especially Ag-PP-g-PEG polymer-coated ventricular catheters are more effective in preventing the catheter-related infection and created the least inflammatory reaction in the periventricular parenchyma. © Springer-Verlag 2012

Farnesylthiosalicylic Acid-Loaded Lipid-Polyethylene Glycol-Polymer Hybrid Nanoparticles For Treatment Of Glioblastoma

ObjectivesWe aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. MethodFarnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both invitro (in comparison with non-malignant cell line, L929) and invivo. Key findingsScanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. ConclusionFarnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments.Wo

Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor–related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-α (PKC-α) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-α small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate–induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-α/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-α and PI3K could provide a new treatment paradigm for glioblastomas