D'Urso P.I.,Kings College Hospital |
D'Urso O.F.,University of Salento |
Gianfreda C.D.,Neurosurgery Operative Unit |
Mezzolla V.,CNR Institute of Sciences of Food Production |
And 2 more authors.
Malignant gliomas are lethal primary intracranial tumors. To date, little information on the role of deregulated genes in gliomas have been identified. As the involvement of miRNAs in the carcinogenesis is well known, we carried out a pilot study to identify, as potential biomarkers, differentially expressed microRNAs in blood samples of patients affected by glioma. We studied the miRNAs' expression, by means of microarray and Real-Time PCR, in 30 blood samples from glioma patients and in 82 blood samples of patients suffering from: (a) various neurological disorders (n=30), (b) primary B-lymphoma of the Central Nervous System (PCNSL, n=36) and (c) secondary brain metastases (n=16). By quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR), we identified significantly increased levels of two candidate biomarkers, miR-15b and miR-21, in blood of patients affected by gliomas. ROC analysis of miR-15b biomarker levels allowed to differentiate patients with tumour from patients without glioma. Furthermore, combined expression analyses of miR15b and miR-21 distinguished between patients with and without glioma (90% sensitivity and 100% specificity). In addition, a decrement in the expression levels of miR-16 characterized glioblastomas compared to low grade and anaplastic gliomas. In conclusion, this pilot study suggest that it's possible to identify the disease state by meaning miR-15b and miR-21 markers in blood, while miR-16 can be used to distinguish glioblastoma from other grade gliomas. They can potentially be used as biomarkers for non-invasive diagnosis of gliomas; further studies are mandatory to confirm our preliminary findings. © 2015 Bentham Science Publishers. Source
D'Urso P.I.,University of Salento |
D'Urso O.F.,University of Salento |
Storelli C.,University of Salento |
Mallardo M.,University of Naples Federico II |
And 5 more authors.
International Journal of Oncology
An altered expression of microRNAs (miRNAs) contributes both to the development of cancer and to the progression of the disease. Malignant tumours and tumour cell lines have widespread deregulated expressions of miRNAs compared to normal tissues. In this study, we investigated the expression profiles of 340 mammalian miRNAs in 93 cases of multiform glioblastoma (primary and secondary glioblastoma tumours), by means of DNA microarrays. We show that the expression profiles of 10 miRNAs can distinguish primary from secondary glioblastoma types. Moreover, we found elevated miR-155 levels in primary and secondary glioblastoma tissues as well as in glioblastoma primary cultures. We hypothesised that γ-aminobutyric acid A receptor 1 (GABRA1) is a miR-155 target, and studied the correlation between miR-155 up-regulation and the GABRA1 protein in cultured glioblastoma cells by miRNA silencing. We show that a decrease in miR-155 expression to normal levels restores the expression of GABRA1, making glioblastoma cells sensitive to signals that inhibit cell proliferation mediated by GABRA1. In conclusion, the expression patterns of different miRNAs characterise primary and secondary glioblastomas. The aberrant overexpression of miR-155 contributes to the malignant phenotype of glioblastoma cells removing growth inhibition. Source
D'Urso P.I.,U.O. Neurosurgery |
Catapano G.,U.O. Neurosurgery |
Gianfreda C.D.,Neurosurgery Operative Unit |
Montinaro A.,Neurosurgery Operative Unit
Journal of Neuro-Oncology
Aberrant methylation of CpG islands in the promoter regions of tumour cells results in loss of gene function. In addition to genetic lesions, changes in the methylation profile of the promoters may be considered a factor for tumour-specific aberrant expression of the genes.We investigated the methylation status of E-cadherin gene (CDH1) promoter in low-grade glioma and correlated it with clinical outcome. Eighty-four cases of low-grade glioma (43 diffuse astrocytomas, 27 oligodendrogliomas and 14 oligoastrocytomas) with assessable paraffin-embedded tumour blocks and normal brain tissue, derived from non-cancerous tissue adjacent to tumour and commercially normal brain tissue, were collected, from which we determined CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry, respectively. CDH1 promoter was found hypermethylated in 54 out of 84 low grade gliomas (64%) compared with 84 normal brain tissue. CDH1 hypermethylation was found in 65% astrocytomas, 66% oligodendrogliomas and 57% oligoastrocytomas. A significant correlation between hypermethylation status, patient survival and progression-free survival was found (P = 0.04). Survival and progression-free survival were lower in patients with hypermethylated CDH1 promoter. We found that 15 astrocytomas, 9 oligodendrogliomas and 6 oligoastrocytomas were immunoreactive for E-cadherin. The incidence of loss of immunoreactivity for E-cadherin decreased significantly with age, overall survival and progression-free survival (P = 0.001, Kaplan-Meier test). We have demonstrated that CDH1 promoter hypermethylation significantly associated with down-regulated E-cadherin expression and overall survival of patients. This may have a bearing on the prognosis of low-grade glioma. © 2010 Springer Science+Business Media, LLC. Source
Catapano G.,Neurosurgery Operative Unit |
de Notaris M.,Neurosurgery Operative Unit |
Di Maria D.,Unit of Otorhinolaryngology |
Di Nuzzo G.,Neurosurgery Operative Unit |
And 3 more authors.
Background: The evolution of skull base surgery over the past decade has been influenced by advancement in visualization technology. Recently, as a result of such improvements, three-dimensional (3-D) scopes have been widely used during endoscopic endonasal approaches. In the present study, we describe the use of 3-D stereoscopic endoscope for the treatment of a variety of skull base lesions. Methods: From January 2010 to June 2015, a 3-D endoscopic endonasal approach (4 and 4.9 mm, 0°, and 30° rigid endoscopes) was performed in 70 patients with the following lesions: 42 large extrasellar pituitary macroadenomas, seven tuberculum sellae meningiomas, seven clivus chordomas, five craniopharyngiomas, three fibrous dysplasia of the clivus, three sinonasal malignancies, one orbital lymphangioma, one trigeminal neurinoma, one primary suprasellar lymphoma. Results: Total tumor removal was obtained in 50 patients (71.4 %) while in 14 (20 %), subtotal removal was possible in six (8.6 %) only partial removal was achieved. Overall complications included diabetes insipidus in eight patients (11.4 %), hypopituitarism in seven patients (10 %), CSF leak in five patients (7.1 %), cranial nerve injury in two patients (2.8 %), panhypopituitarism in two patients (2.8 %), meningitis in one (1.4 %) and one postoperative central retinal artery occlusion (1.4 %). There was no mortality in the series. The mean follow-up time was 39 months (range, 6–72 months). Conclusions: In our experience, the 3-D endoscope represents a critical development in visualization, thus enabling improved hand–eye coordination and depth perception, which are mandatory for the management of complex intradural neurovascular structures during tumor removal surgery. © 2016, Springer-Verlag Wien. Source
Cavallo L.M.,University of Naples Federico II |
Di Somma A.,University of Naples Federico II |
De Notaris M.,Neurosurgery Operative Unit |
Prats-Galino A.,University of Barcelona |
And 6 more authors.
Introduction A certain interest for the extended endoscopic endonasal approach for the management of sellar-suprasellar lesions extending inside the third ventricle has been growing in recent years. The aim of this anatomical study was to evaluate the possibilities in terms of exposure and access to the different areas of the third ventricle, with the endoscopic endonasal technique, as compared with the microscopic or endoscopic view provided via different transcranial approaches. The advantages and limitations of both surgical pathways were analyzed. Materials and Methods Ten human cadaver heads were dissected. In order to standardize the comparison between the endonasal and the transcranial routes, the third ventricle cavity has been divided into four areas by means of two ideal planes, one passing through the optic chiasm and the interthalamic commissure and one passing through the posterior edge of the foramen of Monro and the interthalamic commissure. Accordingly, two anterior (infundibular and foraminal) and two posterior (mesencephalic and tectal) areas have been defined. Results The endoscopic endonasal approach allows for exploration and surgical maneuverability, especially in the anterior areas of the third ventricle. In the infundibular and foraminal areas the surgical maneuverability seems to be better as compared with that obtained inside the mesencephalic region, while via the endonasal route the tectal area could not be reached. In particular, the infundibular area can be explored either passing through the lamina terminalis or via the tuber cinereum; this latter trajectory enables visualization of the foramina of Monro and the floor of the third ventricle up to the pineal recess. Conclusion This anatomical study shows that the lamina terminalis and, above all, the tuber cinereum represent two safe entry points defining possible surgical corridors to be considered for the extended endoscopic endonasal approach to the third ventricle. © 2015 Elsevier Inc. Source