Preoperative surgical approach planning for metastatic pituitary stalk tumor using multimodal fusion imaging in a neuronavigation system--case report.

A 72-year-old woman presented with a metastatic brain tumor around the pituitary stalk compressing the chiasm anteriorly and upward. After tumor resection by a left pterional approach failed, a three-dimensional (3D) image of the area of interest was reconstructed using the Vecter Vision navigation system and iPlan Cranial planning software version 2.5. Preoperative 3D computed tomography and magnetic resonance imaging data were fused to demonstrate the anatomical relationship between vessels, nerves, and tumor. Clearer demonstration of the optic nerves utilized thin slice axial and sagittal views along the nerves. The 3D reconstructed image demonstrated the spatial relationship of the tumor and surrounding tissue, and suggested the necessity of a right orbitozygomatic approach to create adequate working space for tumor resection. Second surgery according to this preoperative planning was successful. High quality multimodal fusion images in a navigation system has distinct advantages in preoperative assessment of essential structural relationships allowing adequate exposure of certain lesions and surrounding structures in individual patients by defining specific surgical approaches.

Enhanced expression of cancer testis antigen genes in glioma stem cells.

Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients.

Clinico-pathological significance of RCAS1 expression in gliomas: a potential mechanism of tumor immune escape.

RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape.

A rapidly enlarging nocardial brain abscess mimicking malignant glioma.

Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, (201)TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.

Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma.

We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90% of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation.

Primitive neuroectodermal tumor (PNET) treated with interferon-beta after surgical removal and irradiation: case report.

This case report describes an 11-year-old boy with primitive neuroectodermal tumor (PNET), which remains the pediatric brain tumor with the worst prognosis despite combination treatment with surgery, irradiation and anti-cancer drugs. The boy was successfully treated with intratumoral administration of interferon-beta (IFN-beta) following surgical resection and irradiation. Two million units of IFN-beta were locally administered into the post-operative cavity through the Ommaya's reservoir every two weeks after discharge. He was managed as an outpatient without serious side-effects to IFN. The patient has shown no tumor recurrence, mental retardation, or neuroendocrine impairment for over three years and has lived a normal school life with a full Karnofsky Performance Status score. The local administration of IFN-beta may be warranted for maintenance therapy in children with PNET.

Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils.

We investigated whether or not a combination of the selective thrombin inhibitor, argatroban, and the free radical scavenger, edaravone (MCI-186), ameliorates postischemic hypoperfusion and decreases mortality after 15 min of forebrain ischemia in the gerbil. Argatroban or edaravone alone significantly increased postischemic cerebral blood flow and attenuated brain edema after reperfusion. However, only the combination increased the survival ratio (P<0.05 by Mantel-Cox) and protected the damage of neuronal cells. The present study indicates that anticoagulants and free radical scavengers reciprocally function to inhibit the progression of ischemic cell damage and that a combination of these types of drugs will help to improve the outcomes after cerebral ischemia.