The vacuolar H+ ATPase is a novel therapeutic target for glioblastoma

The vacuolar H+ ATPase (V-ATPase) is a proton pump responsible for acidification of cellular microenvironments, an activity exploited by tumors to survive, proliferate and resist to therapy. Despite few observations, the role of V-ATPase in human tumorigenesis remains unclear.We investigated the expression of ATP6V0C, ATP6V0A2, encoding two subunits belonging to the V-ATPase V0 sector and ATP6V1C, ATP6V1G1, ATPT6V1G2, ATP6V1G3, which are part of the V1 sector, in series of adult gliomas and in cancer stem cell-enriched neurospheres isolated from glioblastoma (GBM) patients. ATP6V1G1 expression resulted significantly upregulated in tissues of patients with GBM and correlated with shorter patients' overall survival independent of clinical variables.ATP6V1G1 knockdown in GBM neurospheres hampered sphere-forming ability, induced cell death, and decreased matrix invasion, a phenotype not observed in GBM monolayer cultures. Treating GBM organotypic cultures or neurospheres with the selective V-ATPase inhibitor bafilomycin A1 reproduced the effects of ATP6V1G1 siRNA and strongly suppressed expression of the stem cell markers Nestin, CD133 and transcription factors SALL2 and POU3F2 in neurospheres.These data point to ATP6V1G1 as a novel marker of poor prognosis in GBM patients and identify V-ATPase inhibition as an innovative therapeutic strategy for GBM

The vacuolar H+ ATPase is a novel therapeutic target for glioblastoma

The vacuolar H+ ATPase (V-ATPase) is a proton pump responsible for acidification of cellular microenvironments, an activity exploited by tumors to survive, proliferate and resist to therapy. Despite few observations, the role of V-ATPase in human tumorigenesis remains unclear.We investigated the expression of ATP6V0C, ATP6V0A2, encoding two subunits belonging to the V-ATPase V0 sector and ATP6V1C, ATP6V1G1, ATPT6V1G2, ATP6V1G3, which are part of the V1 sector, in series of adult gliomas and in cancer stem cell-enriched neurospheres isolated from glioblastoma (GBM) patients. ATP6V1G1 expression resulted significantly upregulated in tissues of patients with GBM and correlated with shorter patients' overall survival independent of clinical variables.ATP6V1G1 knockdown in GBM neurospheres hampered sphere-forming ability, induced cell death, and decreased matrix invasion, a phenotype not observed in GBM monolayer cultures. Treating GBM organotypic cultures or neurospheres with the selective V-ATPase inhibitor bafilomycin A1 reproduced the effects of ATP6V1G1 siRNA and strongly suppressed expression of the stem cell markers Nestin, CD133 and transcription factors SALL2 and POU3F2 in neurospheres.These data point to ATP6V1G1 as a novel marker of poor prognosis in GBM patients and identify V-ATPase inhibition as an innovative therapeutic strategy for GBM

Aneurismi giganti

Giant aneurysms (> 2.5 cm) represent only 5-7% of all aneurysms. Nevertheless, their management is rather difficult due to their atypical natural history and peculiar treatment. Clinical history of giant aneurysms does not differ from that of the smaller ones regarding the incidence of subarachnoid hemorrhage, but it is complicated by much more neurologic deficits and by the occurrence of chronic intracranial hypertension syndrome. Diagnosis is essentially based upon CT scan and MR imaging in order to detect the morphological mass features and anatomical relationships, and upon angiography to appreciate characteristics regarding arterial flow and vascular relationships. The goal of treatment lies in the exclusion of the aneurysmal sac from the blood-stream and in the reduction of the mass effect. The treatment may be either surgical, endovascular or both. The most common surgical techniques consist in the direct occlusion of the neck of the aneurysm by means of metallic clips, or by fastening or trapping the carrier vessel or by removing the aneurysmal sac with the reconstruction of the arterial aspect when severe mass effect is detectable. The use of endovascular techniques goes for occlusion of the carrier vessel with balloons or for dynamic study of the collateral vascular districts with temporary occlusions

Giant aneurysms

Abstract Giant aneurysms (> 2.5 cm) represent only 5-7% of all aneurysms. Nevertheless, their management is rather difficult due to their atypical natural history and peculiar treatment. Clinical history of giant aneurysms does not differ from that of the smaller ones regarding the incidence of subarachnoid hemorrhage, but it is complicated by much more neurologic deficits and by the occurrence of chronic intracranial hypertension syndrome. Diagnosis is essentially based upon CT scan and MR imaging in order to detect the morphological mass features and anatomical relationships, and upon angiography to appreciate characteristics regarding arterial flow and vascular relationships. The goal of treatment lies in the exclusion of the aneurysmal sac from the blood-stream and in the reduction of the mass effect. The treatment may be either surgical, endovascular or both. The most common surgical techniques consist in the direct occlusion of the neck of the aneurysm by means of metallic clips, or by fastening or trapping the carrier vessel or by removing the aneurysmal sac with the reconstruction of the arterial aspect when severe mass effect is detectable. The use of endovascular techniques goes for occlusion of the carrier vessel with balloons or for dynamic study of the collateral vascular districts with temporary occlusions

Low-cost self-irrigating bipolar forceps

A low cost method for providing continuous saline drip in bipolar diathermy is described, which use is adaptable to any type of standard bipolar forceps. The advantages of this system versus commercially available self-irrigating forceps are reported

Stereotactically guided endoscopy for the treatment of arachnoid cysts

Arachnoid cysts are well known to the neurosurgeon, and the evolution of their surgical treatment has followed technological advances in neurosurgical procedures and techniques. With the recent mastering of neuroendoscopy by the neurosurgeons, it is becoming the modality of choice for the treatment of arachnoid cysts. A neonate harboring a middle parasagittal arachnoid cyst benefited from stereotactically guided endoscopy. We report this case because of its peculiarities and introduce technical details about the procedure which are not found in the literature

Localization accuracy of AC-PC line and functional pallidal target using BRW stereotactic implementation system and axial CT scanning : an experimental study

BACKGROUND: Ventriculography is still considered an unavoidable step for functional target localization, even though this method is invasive and requires stereotactic rooms, orthogonal frames, and parallax-free X-ray equipment. In this experimental study, the authors investigated the feasibility of performing stereotactic lesions using a conventional, widely employed frame, such as the Brown-Roberts-Wells (BRW) apparatus, and computerized axial tomography (CAT) imaging. METHODS: Five ex vivo models consisting of cadaveric brains enclose in a plastic shell were fixed in a BRW frame. A simple BRW implementation was used to ensure more symmetrical placement of the basal ring. Two-millimeter plastic balls were inserted at the level of the anterior (AC) and posterior commissures (PC) and at the target in the pallidus. Their final position was measured on the anatomical specimens and compared with Schaltenbrand Atlas maps. RESULTS: The error in estimating the length of the intercommissural line ranged from 0.5 mm to 2.0 mm, with a maximum backward angulation of four degrees in predicting the AC-PC plane. Upon dissection, in four out of five cases, the balls were found within the area of the pallidus defined by Laitinen for posteroventral pallidotomy. CONCLUSIONS: The authors conclude that anatomical identification of the AC-PC line and the pallidus target, using the BRW stereotactic system and CAT axial images alone offers sufficient accuracy. They suggest that functional neurosurgery for movement disorders could be safely and successfully carried out without ventriculography if neurophysiological monitoring is also employed

Percutaneous treatment of gas-containing lumbar disc herniation : report of two cases

A limited number of cases have been reported in which gas-containing lumbar disc herniation caused compression of nerve roots. The authors describe two patients in whom computerized tomography scanning revealed a large intraspinal gas collection that appeared to be causing nerve root compression and that was successfully evacuated by percutaneous needle aspiration