Preferential Association of Lissencephaly-1 Gene Expression with CD133+ Glioblastoma Cells.

Lissencephaly-1 (Lis1) protein is a dynein-binding protein involved in neural stem cell division, morphogenesis and motility. To determine whether Lis1 is a key factor in glioblastoma, we evaluated its expression and function in CD133+ glioblastoma cells. Global, Lis1 gene expression is similar in glioblastoma and normal samples. Interestingly, immunohistochemistry data indicate increased Lis1 expression colocalized with CD133 in a subset of glioma cells, including the tumor cells with perivascular localization. Lis1 gene expression is increased up to 60-fold in CD133 positive cells isolated from primary cultures of glioblastoma and U87 glioblastoma cell line as compared to CD133 negative cells. To investigate the potential role of Lis1 in CD133+ glioblastoma cells, we silenced Lis1 gene in U87 cell line obtaining shLis1-U87 cells. In shLis1-U87 cell culture we noticed a significant decrease of CD133+ cells fraction as compared with control cells and also, CD133+ cells isolated from shLis1-U87 were two times less adhesive, migratory and proliferative, as compared with control transfected U87 CD133+ cells. Moreover, Lis1 silencing decreased the proliferative capacity of irradiated U87 cells, an effect attributable to the lower percentage of CD133+ cells. This is the first report showing a preferential expression of Lis1 gene in CD133+ glioblastoma cells. Our data suggest a role of Lis1 in regulating CD133+ glioblastoma cells function.

Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas.

GFAP-δ, the delta isoform of the glial fibrillary acidic protein, is particularly expressed in the subventricular zone (SVZ) of the brain. GFAP-δ positive cells in the SVZ co-express the neural stem cells (NSCs) marker nestin. According to the theory of glioma oncogenesis, transformation of a cell population with stem features which resides in the SVZ could be the origin of astrocytomas. Moreover, it is known that cancer stem cells promote tumor invasion in cerebral astrocytomas. Therefore, we investigated the immunostaining of GFAP-δ and nestin in cerebral astrocytomas and evaluated the correlation between the positive cell ratio of these markers and the neuroimaging features associated with tumor invasion in forty-four cases of grade II, III and IV cerebral astrocytomas (World Health Organization's classification). Tissue samples were obtained by stereotactic biopsies in all cases. According to the preoperative neuroimaging criteria, tumors were categorized into highly invasive and low invasive. Most of the low-grade and high-grade astrocytomas express GFAP-δ and nestin. The positive cell ratio of GFAP-δ and the positive cell ratio of nestin were statistically significantly higher in highly invasive tumors compared with low-invasive tumors (p < 0.05). Altogether, these results suggest that GFAP-δ and nestin could be clinically relevant markers associated with tumor invasiveness in cerebral astrocytomas.

Perioperative management of patients with lung carcinoma and cerebral metastases.

OBJECTIVE: The present study proposes to present the importance of perioperative therapeutic management in survival prolongation and the quality of life for patients that have undergone surgery for cerebral metastases secondary to pulmonary tumors. METHOD: During 2001-2009, 40 patients with ages between 43-74 years have been diagnosed in our clinic with pulmonary tumor and cerebral metastases. The patients presented single cerebral lesion (excepting one patient with 2 cerebral metastases) and pulmonary tumor. Intracranial pressure (ICP) was high in all cases. All patients have undergone operation with general anesthesia. RESULTS: For all patients the reduction of ICP and keeping an optimal CPP (cerebral perfusion pressure) was pursued. In 38 cases, general anesthesia was performed with Sevoflurane and opioids (fentanyl, remifentanyl, sufentanyl) and in 2 cases the TIVA (total intravenous anesthesia) technique was used with propofol and remifentanyl. 14 of the patients required intraoperative depletive treatment through administering mannitol 20%. 37 patients (92%) have been discharged with improved neurological condition without showing signs of intracranial hypertension, convulsive seizures and with partially or totally remitted hemiparesis and one patient had worse postoperative neurological status. CONCLUSION: Pulmonary tumor with cerebral metastases represent an important cause for death rate. To solve secondary cerebral lesions, the perioperative management must include assesment and choosing an anesthesia technique with a proper intraoperative management.