Object Cancer testis antigens (CTAs) were initially identified by their ability to elicit autologous T-cell–mediated immune responses in patients with melanoma. The CTA genes are widely expressed in a variety of human cancers, such as melanoma, breast cancer, lung cancer, esophageal cancer, and hepatocellular carcinoma; however, their expression in pediatric brain tumors, such as medulloblastoma (MB), has not been the subject of in-depth analysis. The MAGE proteins are members of the CTA family and have been shown to correlate with tumor development, aggressive clinical course, or resistance to chemotherapeutic agents. The authors undertook this study to examine the expression and role of MAGE proteins in human MB cell lines and specimens. Methods From a transcriptional profiling study in which 47,000 genes in MB cell lines were examined, the authors identified members of the MAGE and GAGE families as being highly expressed. A series of MB tumors was examined using both immunohistochemistry and Western blot analysis with antibodies to the MAGE-A family, MAGE-A1, and GAGE proteins. Results Western blot analysis showed expression of these 3 proteins (MAGE-A family, MAGE-A1, and GAGE) in 62, 46, and 84%, respectively, of MB specimens examined. In addition, a correlation was observed between the expression of MAGE and GAGE genes and resistance of MB cells to chemotherapeutic agents. The functional significance of this correlation was examined in MAGE knockdown studies, and increased drug-induced cytotoxicity was observed in UW426 MB cells following treatment with chemotherapeutic drugs. Cleaved caspase-3 was found in UW426/MAGE small interfering (si)RNA–inhibited cells treated with cisplatin, but not in UW426 cells treated with cisplatin alone at the same concentration. Conclusions These data show that MAGE and GAGE family members are expressed in MB cell lines and specimens, and that inhibition of MAGE and GAGE genes by siRNA increases apoptosis of MB cells and sensitizes them to certain chemotherapeutic agents such as cisplatin and etoposide.

Intracranial pseudoaneurysm formation due to ruptured non-traumatic saccular aneurysm is extremely rare. We experienced two cases of large pseudoaneurysm formation due to rupture of a saccular aneurysm. The neuroradiological ghost-like appearance of the aneurysms led to misdiagnoses as large partially thrombosed aneurysm. Two cases of large intracranial pseudoaneurysm formation due to rupture of a saccular aneurysm occurred in a 77-year-old comatose woman with an aneurysm on the anterior wall of the internal carotid artery and a 73-year-old comatose woman with an anterior cerebral artery (azygos) aneurysm. Both patients suffered subarachnoid hemorrhage associated with intracerebral and intraventricular hematomas. Angiography showed peculiar "ghost-like" appearance of the aneurysm including delayed filling, changing shape, retention of the contrast material after the venous phase, and unclear location of neck. Neck clipping surgeries were performed, but were difficult because of the preoperative misdiagnosis as large partially thrombosed aneurysm. The entity of "ghost aneurysm" caused by rupture of a saccular aneurysm should be considered in the clinical diagnosis.

Glioblastoma is the most malignant form of primary brain tumor in adults, with no effective therapy and a low survival rate. TRAIL is a member of the TNF family, which selectively induces apoptosis in certain neoplastic cells, but not normal cells. In this study, we investigated the sensitivity of 7 human glioblastoma cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These glioblastoma cell lines expressed TRAIL-R2, but not TRAIL-R1, R3, or R4. However, no correlation was observed between the TRAIL sensitivity and the TRAIL-R2 expression level, suggesting that there is an additional determinant of TRAIL sensitivity.

A 2-year-old girl who had previously been treated for stage IV intra-abdominal neuroblastoma presented with headache and vomiting. Computed tomography (CT) showed hematoma in the right temporal lobe. Two months previously, she had suffered a generalized seizure but brain CT was unremarkable. The hematoma was removed completely without evidence of vascular anomaly or tumor. Four weeks after surgery, magnetic resonance imaging with gadolinium showed a developing mass lesion in the hematoma bed. A second operation for tumor removal confirmed the rare diagnosis of intraparenchymal metastasis. Metastatic neuroblastoma to the central nervous system (CNS) occasionally can cause massive hemorrhage. Therefore, early detection of CNS metastasis can be important. The related factors in this patient with abdominal neuroblastoma included elevated serum lactate dehydrogenase, N-myc gene amplification, and coexisting orbital metastasis, which all occurred within 22 months from initial diagnosis. The median interval from diagnosis of the primary tumor to diagnosis of CNS metastasis in neuroblastoma is 12-22 months, which indicates relatively late metastasis presentation. The initial presentation of this late metastasis is hemorrhage that can have sudden detrimental consequences, so a patient with neuroblastoma must be followed up carefully, particularly if elevated serum lactate dehydrogenase, orbital metastasis, N-myc gene amplification, or clinical symptoms are present, even if brain CT is unremarkable. The understanding that intraparenchymal hematoma can occur prior to detectable CNS metastasis may be important for early detection of this life-threatening condition.