Keishi Tsunoda

Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion

Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-κB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-κB in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-κB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-κB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12-myristate-13-acetate (PMA)-induced RelA/NF-κB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-κB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-κB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.

Immunohistochemical expression of E-cadherin in metastatic brain tumors

The adhesion molecule E-cadherin has been shown to influence malignant transformation of tumors, including local and distant metastases. We examined the expression of E-cadherin to determine its relationship to the development of metastasis in metastatic brain tumors. Immunohistochemistry for E-cadherin and Ki-67 was carried out in 76 formalin-fixed, paraffin-embedded archival specimens of metastatic brain tumors and in 14 corresponding available primary tumors from patients who received treatment for metastatic brain tumors. The primary tumors were mainly lung cancers (51.3%), followed by gastrointestinal tumors (28.9%). E-cadherin was expressed in 62 (81.5%) of 76 cases examined. In metastatic adenocarcinomas, a consistent tendency for E-cadherin expression was noted, regardless of the degree of differentiation or the extent of spread of the disease (P=0.4). There was a direct correlation between E-cadherin expression and high MIB-1 index in all metastatic brain tumors (P=0.0007). Pairwise analysis in 14 primary tumors and the corresponding metastatic specimens revealed high E-cadherin and MIB-1 staining in metastatic brain tumors. These results provide a unique association between E-cadherin, systemic metastasis, and proliferation potential in metastatic brain tumors.

Positional vertebral artery compression and vertebrobasilar insufficiency due to a herniated cervical disc

The authors report a case of vertebrobasilar insufficiency caused by vertebral artery (VA) compression due to a herniated cervical disc, which was surgically treated with the aid of intraoperative angiography. This 78-year-old man visited the hospital because of syncope following head rotation. Admission CT scans revealed a calcified mass adjacent to the right lateral process of the C-4 spine. Cervical angiography demonstrated an obstruction of the right VA at this region on rotation of the head to the right. The operation revealed a cervical disc protruding toward the right VA. The disc was surgically removed, and then the decompression of the right VA was confirmed on intraoperative angiography studies. A histopathological examination showed fibrohyaline cartilage, indicating an ossified intervertebral disc. The postoperative course was uneventful, and he has not experienced any syncope since treatment. A cervical disc herniation could be a cause of vertebrobasilar insufficiency by exerting positional compression of the VA. Intraoperative angiography could be quite useful to confirm this condition during decompression surgery for a cervical VA.

Bow Hunter’s Stroke Due to Stretching of the Vertebral Artery Fenestration: A Case Report

Bow Hunter’s syndrome is an unusual symptomatic vertebrobasilar insufficiency resulting from intermittent mechanical compression of the vertebral artery, and is rarely a trigger for cerebral infarction following thrombus formation on the damaged endothelial vessels (Bow Hunter’s stroke). The authors present an extremely rare case of a 45-year-old man showing Bow Hunter’s stroke due to congenital vertebral artery fenestration stretching and sliding between C1 and C2 after head rotation to the right. Congenital vertebral artery anomaly rarely causes cerebral infarction, but could cause embolic strokes by mechanical stretching without bony abnormalities.

Non-Traumatic Anterior Atlas Fracture Following C1 Laminectomy - Case Report

Atlas fracture usually result from traumatic injury but only 3 cases of non-traumatic atlas fracture have described in the literature. The authors hereby describe a case of non-traumatic anterior atlas fracture following C1 laminectomy following the decompressive surgical procedure for the ossification of posterior longitudinal ligament. Originally droopy posture and iatrogenic disruption of the posterior arch with invading musculoligamentous structures from axis laminoplasty might increase the stress for anterior atlas. Due to the failure of bony fusion despite the use of an external orthosis, surgical intervention was necessary.