Toshikazu Hidaka

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification (=CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma.

Geminin: A good prognostic factor in high‐grade astrocytic brain tumors

Geminin is a nuclear protein that belongs to the DNA replication inhibitor group. It inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance protein onto chromatin, as is required for DNA replication. For this study, the authors investigated geminin expression in high‐grade astrocytic tumors, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), with a view to predicting clinical outcomes on this basis in patients with these malignant brain tumors.

A pituitary abscess showing high signal intensity on diffusion-weighted imaging.

The utility of diffusion-weighted imaging (DWI) for the diagnosis of intracranial abscesses has already been established. However, the use of DWI for pituitary abscesses has not been previously reported. We present a case of postoperative pituitary abscess in which T1-weighted and T2-weighted magnetic resonance imaging (MRI) revealed a supra-sellar cystic mass, with the cyst contents showing high intensity on DWI. This case suggests that DWI is useful for the diagnosis of pituitary abscesses.

Treatment of ruptured vertebral artery dissecting aneurysms. A short report.

We evaluated the outcomes of endovascular or surgical treatment of ruptured vertebral artery dissecting aneurysms (VADAs), and investigated the relations between treatment complications and the development and location of the posterior inferior cerebellar artery (PICA). We treated 14 patients (12 men, two women; mean age, 56.2 years) with ruptured VADAs between March 1999 and June 2012 at our hospital. Six and eight patients had Hunt and Hess grades 1–3 and 4–5, respectively. Twelve patients underwent internal endovascular trapping, one underwent proximal endovascular occlusion alone, and one underwent proximal endovascular occlusion in the acute stage and occipital artery (OA)-PICA anastomosis and surgical trapping in the chronic stage. The types of VADA based on their location relative to the ipsilateral PICA were distal, PICA-involved, and non-PICA in nine, two, and three patients, respectively. The types of PICA based on their development and location were bilateral anterior inferior cerebellar artery (AICA)-PICA, ipsilateral AICA-PICA, extradural, and intradural type in one, two, two, and nine patients, respectively. Two patients with high anatomical risk developed medullary infarction, but their midterm outcomes were better than in previous reports. The modified Rankin scale indicated grades 0–2, 3–5, and 6 in eight, three, and three patients, respectively. A good outcome is often obtained in the treatment of ruptured VADA using internal endovascular trapping, except in the PICA-involved type, even with high-grade subarachnoid hemorrhage. Treatment of the PICA-involved type is controversial. The anatomical location and development of PICA may be predicted by complications with postoperative medullary infarction.

Extracranial Internal Carotid Artery Pseudoaneurysm Associated With Neurofibromatosis Type 1 Treated With Endovascular Stenting and Coil Embolization

An internal carotid artery (ICA) pseudoaneurysm associated with neurofibromatosis type 1 (NF-1) is rare. We report the first case of unruptured extracranial pseudoaneurysm of the ICA in a patient with NF-1 successfully treated with endovascular stenting and coil embolization.A 66-year-old woman diagnosed with NF-1 had sudden left neck pain and massive swelling 3 years earlier. Radiological examination showed a ruptured pseudoaneurysm of the left internal thoracic artery (ITA). The posttreatment computed tomography (CT) scan revealed complete obliteration of the aneurysm of the left ITA and an unruptured pseudoaneurysm of the right ICA. After 3 years of follow-up, a CT scan revealed the enlargement of the pseudoaneurysm of the right extracranial ICA. Endovascular stenting and coil embolization were performed to prevent rupture, and the lesion was completely obliterated. Follow-up angiography at 6 months revealed good flow of the ICA through the stent without any filling of the aneurysm.

Retinoblastoma protein prevents staurosporine-induced cell death in a retinoblastoma-defective human glioma cell line.

Objective: To investigate the mechanism of staurosporine-induced glioma cell death and cell cycle arrest using adenovirus-mediated gene transfection, as well as the function of retinoblastoma (Rb) and genetic instability induced by staurosporine. Methods: Cell cycle regulation, cell death and nuclear abnormalities induced by staurosporine were examined using an adenovirus vector expressing Rb, p16 or p21 genes in human glioma cell lines. Results: The Rb-defective SF-539 cell line was resistant to staurosporine compared with cell lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became multinucleated and then died. Multinucleation was prevented in SF-539 cells transfected with the Rb gene, thus decreasing the death rate of these cells. Conclusions: These results imply that enforced Rb expression protects cells from genomic instability induced by staurosporine regardless of its upstream molecular effects.

A Comparison of Computed Tomography–Based Scales with and without Consideration of the Presence or Absence of Intraventricular Hemorrhage in Patients with Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE There has been controversy as to whether intraventricular hemorrhage (IVH) after aneurysmal subarachnoid hemorrhage (SAH) contributes to angiographic cerebral vasospasm (aCV) and delayed cerebral ischemia (DCI). Computed tomography-based SAH scales that did and did not consider IVH were compared in terms of ability to predict aCV, DCI, and outcome. METHODS We reviewed 390 patients with ruptured aneurysms who had been treated surgically by day 3 by the same surgeon (T.I.). aCV was graded as 0-4. Outcome at 6 months was classified using the Glasgow Outcome Scale. Inagawa SAH grades and scores, for which only SAH was evaluated, were compared with scales that evaluated both SAH and IVH (Fisher, Claassen, and Frontera grades, and Hijdra score). The area under the receiver operating characteristic curve was calculated to compare severe aCV (grade 3-4), DCI, or poor outcome (Glasgow Outcome Scale score 1-3). RESULTS The Inagawa grade showed constant and significant intergrade differences in both aCV and DCI. The Inagawa grade area under the receiver operating characteristic curve values were highest among the scales examined. In the Fisher, Claassen, and Frontera grades, IVH was unlikely to be related to aCV and DCI. There was no significant difference in aCV grade or DCI occurrence between the Inagawa and Hijdra scores. In contrast, the presence of IVH was significantly associated with poor outcome. CONCLUSIONS In patients with aneurysmal SAH, IVH is an important factor affecting patient outcome, whereas computed tomography-based SAH scales that do not consider IVH are superior to scales that do consider it for prediction of aCV or DCI.

A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm

Reports on the trans-lamina terminalis and trans-third ventricular approach are rare. The risk associated with this approach is unknown. After an unsuccessful endovascular surgery, we performed direct surgical clipping via the third ventricle on a 78-year-old woman presenting with an extremely high-positioned, ruptured basilar tip aneurysm. She experienced transient hypothermia for 5 days, and it was considered that this was due to hypothalamic dysfunction. It is necessary to recognize that there is the potential for hypothermia after surgery via the lamina terminalis and third ventricle, even though the mechanisms of hypothalamic thermoregulation are still unclear.