The "steppingstone" phenomenon: a new endoscopic finding in slit-ventricle syndrome.

Slit-ventricle syndrome (SVS) seems to encompass various pathophysiological abnormalities, including overdrainage of cerebrospinal fluid (CSF) and craniocerebral disproportion after extracranial CSF shunt placement. These pathologies result in small ventricle morphologically, and the ventricular catheter is obstructed by the collapsed ventricular walls. Patients with intermittent headaches, small ventricles on neuroimaging, and slow refill of the shunt reservoir are diagnosed with SVS. In this report, we present a case of SVS treated endoscopically. We detected bulges in a zigzag line on the ventricular walls according to side holes of the ventricular tube, and named them "steppingstone" phenomenon. It is a curious finding which directly shows that the intermittent obstruction of the ventricular tube occurs in patients with SVS. No previous articles have reported this phenomenon, and it indicates adequate treatment for SVS should be provided.

The usage of the three-dimension distractor in the NAVID system for plagiocephaly-three case reports.

BACKGROUND: Distraction osteogenesis is a standard method for craniosynostosis. However, the technique using conventional devices still has some disadvantages, especially for anterior or posterior plagiocephaly with complex deformities. In the Nakajima's angle-variable internal distraction (NAVID) system originally for maxillary surgeries, the cranial three-dimension (D) distractor with three dimensionally movable joint at the anterior arm has been developed recently in order to prevent the interference in the distraction process and excessive force. CASE REPORTS: In this paper, we first reported two cases of anterior plagiocephaly, and one case of posterior plagiocephaly received distraction osteogenesis using new 3-D distractor in the NAVID system. In two cases of anterior plagiocephaly, the reshaping of supra-orbital bar in reference of simulating by the 3-D skull model was performed. In all cases, we fixed two paralleled 2-D distractors and a 3-D distractor in the upper frontal or parietal region. CONCLUSION: Within the limitations of this study, we believe that the NAVID system is suitable for infant plagiocephaly due to the simple and small joint arm. Furthermore, the usage of the 3-D distractor would reduce the interference with 2-D distractors and easily lead to attainment of targeted distracting distance.

The evolution and application of techniques in molecular biology to human brain tumors: a 25 year perspective.

Since the establishment of the AANS/CNS Section on Tumors in 1984, neurosurgeons have been actively involved in basic science research of human brain tumors that has moved the field forward considerably. Here, we chronicle the major advances that have been made with respect to our understanding of the concepts guiding the biology of human malignant brain tumors. Numerous technical advances in science, such as the development of gene transfer techniques, the polymerase chain reaction, the discovery of oncogenes and tumor suppressor genes, and the refinement of approaches to cancer cytogenetics have enabled researchers to identify many of the non-random genetic alterations associated with brain tumor growth, invasion, immunology, angiogenesis and apoptosis. These data led to some astounding progress, for example with the use of gene therapy, whereby in the 1990s several human clinical trials were conducted for patients with brain tumors. More recently, the human genome project has been completed providing a blueprint for the human species. What has followed are exciting new techniques in molecular biology such as transcriptional profiling, single nucleotide polymorphism (SNP)-arrays, array comparative genomic hybridization (array-CGH), microRNA profiling, and detection of epigenetic silencing of tumor suppressor genes. The cancer genome is now being sequenced at break neck speed using advanced DNA sequencing techniques. We are on the threshold of cataloguing the major genetic alterations observed in all human brain tumors. What will follow is modeling of these genetic alterations in systems that will allow for the development of novel pharmacotherapeutics and translational research therapies.

The role of the membrane cytoskeleton cross-linker ezrin in medulloblastoma cells.

Medulloblastoma is a highly malignant brain tumor that occurs predominantly in children. The molecular pathogenesis of medulloblastoma is under investigation. Previously, we used complementary DNA microarray analysis to compare patterns of gene expression in medulloblastoma samples versus normal cerebellum. The cytoskeletal protein ezrin was found to be overexpressed in medulloblastoma compared with normal cerebellum, an observation that was further validated by immunohistochemistry and real-time PCR analysis. To assess the role of ezrin in medulloblastoma, we studied ezrin's role in medulloblastoma migration, invasion, and adhesion. Western blotting and immunofluorescence showed high expression of ezrin in four medulloblastoma cell lines, and ezrin was primarily localized to filopodia. Ezrin-specific small interfering RNA suppressed the formation of filopodia and in vitro migration, invasion, and adhesion. We also used a stably transfected medulloblastoma cell line to study the effect of ezrin overexpression. We showed that high expression of ezrin promotes filopodia formation and in vitro invasion. Finally, athymic mice implanted with ezrin-overexpressing DAOY medullo-blastoma cell clones in the cerebellum showed shortened survival compared with controls. These findings suggest that, in addition to other cytoskeletal proteins, ezrin plays an important role in medulloblastoma adhesion, migration, and invasion.

Inhibition of Aurora-B function increases formation of multinucleated cells in p53 gene deficient cells and enhances anti-tumor effect of temozolomide in human glioma cells.

Cell division is an elemental process, and mainly consists of chromosome segregation and subsequent cytokinesis. Some errors in this process have the possibility of leading to carcinogenesis. Aurora-B is known as a chromosomal passenger protein that regulates cell division. In our previous studies of giant cell glioblastoma, we reported that multinucleated giant cells resulted from aberrations in cytokinesis with intact nuclear division occurring in the early mitotic phase, probably due to Aurora-B dysfunction. In this study, as we determined p53 gene mutation occurring in multinucleated giant cell glioblastoma, we investigated the role of Aurora-B in formation of multinucleated cells in human neoplasm cells with various p53 statuses as well as cytotoxity of glioma cells to temozolomide (TMZ), a common oral alkylating agent used in the treatment of gliomas. The inhibition of Aurora-B function by small-interfering (si)RNA led to an increase in the number of multinucleated cells and the ratios of G2/M phase in p53-mutant and p53-null cells, but not in p53-wild cells or the cells transduced adenovirally with wild-p53. The combination of TMZ and Aurora-B-siRNA remarkably inhibited the cell viability of TMZ-resistant glioma cells. Accordingly, our results suggested that Aurora-B dysfunction increases in the appearance of multinucleated cells in p53 gene deficient cells, and TMZ treatment in combination with the inhibition of Aurora-B function may become a potential therapy against p53 gene deficient and chemotherapeutic-resistant human gliomas.

Susceptibility to exogenously added interferon-beta protein depends on intracellular interferon-beta mRNA level in human glioma cells.

Exogenously added human interferon-beta (HuIFN-beta) protein possesses a remarkable antiproliferative activity in human glioma and melanoma. Endogenous HuIFN-beta protein, which is produced by its gene transfer using cationic liposomes, has much more effective antiproliferative activity against these tumors, even in cells resistant to exogenously added HuIFN-beta protein. As the first step to elucidate the possible difference in antiproliferative mechanisms between exogenous and endogenous HuIFN-beta protein, we here investigated the relationship between the intracellular level of its mRNA and susceptibility to exogenously added HuIFN-beta protein. In this study, we used seven human glioma cell lines (SK-MG-1, SK-MG-4, SK-AO2, U87MG, U251SP, U251MG and T98) and one human melanoma cell line (MMAN). At first, we examined the relationship between spontaneous expression of HuIFN-beta mRNA and susceptibility to exogenously added HuIFN-beta protein (50 IU/ml) in human glioma cells and then confirmed a significant correlation between them. Next, we confirmed that administration of 0-100 IU/ml exogenously added HuIFN-beta protein upregulated the HuIFN-beta mRNA in a dose-dependent manner using the RT-PCR technique and that the HuIFN-beta mRNA was suppressed by siRNA for HuIFN-beta in SK-MG-1 and MMAN cells. Furthermore, we confirmed that the siRNA for HuIFN-beta significantly suppressed the antiproliferative effect of SK-MG-1 cells treated with 10-100 IU/ml HuIFN-beta protein and MMAN cells with 25 and 50 IU/ml HuIFN-beta protein. We found this phenomenon in another human glioma cell line, U87MG cells, as well. This finding would suggest that susceptibility to exogenously added HuIFN-beta protein is related to the amount of intracellular HuIFN-beta mRNA in human glioma and melanoma cells.

Growth inhibition of human pancreatic cancer cells by human interferon-beta gene combined with gemcitabine.

We examined the anti-tumor effect of cationic multilamellar liposome containing human IFN-beta (huIFN-beta) gene against cultured human pancreatic cancer cells. We also evaluated the combined effect of huIFN-beta gene entrapped in liposomes and gemcitabine. Furthermore, we examined the anti-tumor mechanisms of the therapy, with emphasis on the Ras-related signal pathway. Three human pancreatic cancer cell lines (AsPc-1, MIAPaCa-2, and PANC-1) were used in this study. The growth inhibition together with the therapy were evaluated by WST-1 assay; the production of huIFN-beta protein was measured by ELISA; the cell cycle and apoptosis were analyzed using a FACScan flow cytometer; the protein levels of Son of sevenless (SOS-1) and Ras-GAP were measured by Western blotting; and the activation of Ras-GTP was evaluated by the immunoprecipitation method. As a result, we found that huIFN-beta gene entrapped in liposomes demonstrated a strong anti-tumor effect against human pancreatic cancer cells. The treatment that combined huIFN-beta gene entrapped in liposomes and gemcitabine was more effective than each treatment alone. Although gemcitabine remarkably reduced the level of SOS-1, the above combined therapy reduced the level of SOS-1 even more significantly. Both huIFN-beta gene entrapped in liposomes and the com-bination of huIFN-beta gene entrapped in liposomes and gemcitabine increased the level of Ras-GAP, and decreased the activity of Ras-GTP. These results suggest that this combination therapy can induce strong anti-tumor activity against human pancreatic cancer cells through the regulation of the Ras-related signal pathway.

De novo cerebral aneurysms manifesting as repeated subarachnoid hemorrhage and cerebral ischemic stroke--case report.

A 29-year-old man suffered repeated subarachnoid hemorrhage and cerebral ischemic stroke over a period of 6 years. Cerebral angiography at each episode disclosed development of multiple de novo aneurysms at the bilateral middle cerebral arteries (MCAs), internal carotid arteries, right anterior cerebral artery, and right vertebral artery. Two of the ruptured aneurysms were treated by surgical and endovascular treatment, but he died of the effects of rupture of a de novo right MCA aneurysm. Histological examination at autopsy disclosed marked degenerative changes in all layers of the cerebral vessels, which were probably congenital in origin.