Kunikazu Kurosaki

Pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. Case report.

The authors report on a rare case of pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. This 5-year-old boy presented to the outpatient clinic with headache and vomiting. Computed tomography and magnetic resonance imaging studies revealed a mass lesion with partial hemorrhage in the suprasellar region extending into the third ventricle. Partial resection via a transcallosal approach was performed. Because the pathological diagnosis was pilomyxoid astrocytoma, chemotherapy was administered. However, 4 months after the first operation, during chemotherapy, the boy presented with massive intratumoral and intraventricular hemorrhage with hydrocephalus. Although emergent external ventricular drainage was performed, the patient died. In this report, the authors review the literature and discuss the clinical features and treatment of pilomyxoid astrocytoma.

Therapeutic Basis of Vidarabine on Adenovirus-Induced Haemorrhagic Cystitis

When adenovirus causes haemorrhagic cystitis in immunocompromised patients, vidarabine is used for its treatment because therapeutic choice is limited. Although vidarabine has been reported to be effective for these patients, its therapeutic basis has not yet been established. Vidarabine dose-dependently inhibited viral replication as assessed by a yield reduction assay. Viral protein synthesis was dose-dependently inhibited by vidarabine but not at all by acyclovir, and the degree of inhibition by vidarabine was different for each of the viral proteins, ranging from 0–40% of the untreated control. These results indicated the specificity and mechanism of action of vidarabine against adenovirus. The concentration of vidarabine and its metabolite in the bladder is suggested to exhibit effective anti-adenoviral activity in suppressing the replication of adenovirus. Thus, our results support vidarabine therapy as a possible candidate for adenovirus-induced haemorrhagic cystitis in immunocompromised patients.

Multiple aneurysms arising from the origin of a duplication of the middle cerebral artery

Duplication of the middle cerebral artery is an anomalous vessel arising from the internal carotid artery. There have only been 14 reports of aneurysms arising from the origin of a duplication of the middle cerebral artery and 5 of these patients had multiple aneurysms. Aneurysms at this site have a high rupture rate compared to aneurysms in other locations and aggressive management is indicated.

Thrombin-induced cell proliferation and platelet-derived growth factor-AB release from A172 human glioblastoma cells

Background: In a previous study, we found that thrombin induced proliferation of TM‐1 and T98G human glioma cells and that the mitogenic effect was abolished by hirudin. Objectives: We investigated thrombin’s effects on the proliferation of A172 human glioblastoma cells and the induction of growth factors. Furthermore, we examined whether or not the expression of heparin cofactor II (HCII) in A172 cells using adenovirus vector could suppress thrombin’s effects. Methods: The effect of thrombin on cell proliferation was assessed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide assay. The amount of growth factors in the conditioned medium was measured by enzyme‐linked immunosorbent assay. The level of platelet‐derived growth factor (PDGF)‐B mRNA was assessed by reverse transcriptase‐polymerase chain reaction analysis. Results: Thrombin‐induced proliferation of A172 cells primarily depended on the enhanced secretion of PDGF‐AB by thrombin. The action of thrombin depended on its proteolytic activity. However, thrombin‐induced PDGF‐AB secretion was not abolished by anti‐protease‐activated receptor (PAR) antibody. The PAR‐1 agonist peptide had no effect on cell growth and PDGF‐AB levels. Thrombin did not increase PDGF‐B gene expression. Expression of HCII effectively suppressed thrombin‐induced PDGF‐AB release. Conclusions: These results indicate that thrombin may play an important role in the proliferation of A172 cells by inducing PDGF‐AB secretion and that thrombin’s action is mediated by its proteolytic activity. Inhibition of thrombin’s proteolytic activity may be a new therapeutic method for gliomas.

Reversal of Cognitive Dysfunction by Total Removal of a Large Lateral Ventricle Meningioma: A Case Report with Neuropsychological Assessments

Although cognitive impairment is one of the major symptoms of ventricular tumors, few studies have reported the details of cognitive impairment before and after their surgical removal. The expected effects on cognitive function should also be considered when choosing a surgical approach. We report the case of a large lateral ventricle meningioma in which cognitive impairment was detected on detailed neuropsychological examinations. The tumor was totally removed through the right superior temporal gyrus. Postoperative neuropsychological assessment revealed the reversal of cognitive impairment. As cognitive impairment is complex and easily overlooked, it is important to precisely assess neuropsychological function in patients with large brain tumors.

Herpes simplex virus-induced, death receptor-dependent apoptosis and regression of transplanted human cancers.

Inoculation of a live attenuated herpes simplex virus (HSV) vector, bH1, into human U87MG glioblastoma cells transplanted into athymic nude mice induced complete regression of tumors. The infected cells underwent histochemically confirmed apoptosis without lymphocyte infiltration after expressing CD30, CD30 ligand (CD30L), tumor necrosis factor (TNF)‐a, TNF receptor 1 (TNF‐R1), FAS, and FAS ligand (FAS‐L) with activation of caspases 3 and 8. Induction of the transcripts of these receptors and ligands in inoculated tumors was confirmed by quantitative RT‐PCR. To examine the specificity of apoptosis in the transplanted tumor, we inoculated bH1 into transplanted human lung, breast, gastric, and colon cancer tumors, and similar tumor regression with apoptosis was observed in all tumors. We analyzed the roles of expression of CD30, CD30L, TNF‐a, TNF‐R1, FAS, and FAS‐L in the tumors, and found that HSV‐induced apoptosis was suppressed by the respective antibodies. These findings indicate that the CD30/CD30L, TNF‐a/TNF‐R1, and FAS/FAS‐L interactions resulted in apoptosis and tumor regression in immunocompromised mice. In addition to the death receptor‐dependent apoptosis induced by HSV, the expressed ligands and receptors might enhance the susceptibility of tumor cells to cell‐mediated cyto‐toxicity and augment the activation of tumor‐killing lymphocytes in immunocompetent models.