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Astrocytoma and oligodendroglioma are primary brain tumors classified as gliomas. Because there is difference in the prognostic significance of the extent of resection between IDH-mutant astrocytoma and oligodendroglioma, intraoperative differential diagnosis between them provides important information for optimal extent of resection. Although the characteristics of genetic mutations and chromosomal aberrations in both tumors have been reported, there is no molecular diagnostic methods that is able to be used quickly and simply for differentiate the two tumors. Therefore, we aimed to search for biomarker candidates for differentiating them with metabolome analysis using liquid chromatography/tandem mass spectrometry and develop a molecular diagnostic method based on quantitative analysis. We searched for peaks that differed in two types of gliomas using global metabolomics. Next, we identified five biomarker candidates as hypoxanthine, inosine, cystine, proline and uric acid, respectively. Next, we developed an LC/MS/MS analytical method for five biomarker candidates and quantified them in brain tumors. Cystine had significantly lower amounts in astrocytomas than in oligodendrogliomas. We developed two prediction models for differentiation of the two gliomas and validated them using the separated two dataset. The logistic regression model with only cystine provided the best prediction performance. It was suggested that mass spectrometric analysis of cystine in surgery might be useful for differentiating astrocytoma and oligodendroglioma with 91.7% positive prediction value and 80.0% specificity whereas negative predictive value and sensitivity was lesser than 70%, so that further exploration for unknown metabolite is mandatory. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy. Methods: Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O2). Results: OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10. Conclusion: Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment. [ABSTRACT FROM AUTHOR]

Background: While hemodynamic stress can result in aneurysm formation, it rarely contributes to the development of peripheral aneurysms in collateral pathways. We report two patients with ruptured distal aneurysms in a collateral pathway associated with stenosis of a major cerebral artery. Case Description: A 67-year-old man presented with intracerebral hemorrhage in the right frontal lobe. Digital subtraction angiography (DSA) revealed severe stenosis of the right middle cerebral artery and two aneurysms in the collateral pathway of the right anterior cerebral artery. The ruptured aneurysm was trapped and resected; histologically, it was a true saccular aneurysm. The unruptured aneurysm was clipped and the patient was discharged without additional neurological deficits. The second patient was a 73-year-old woman with subarachnoid hemorrhage. DSA revealed three arterial dilations. On the 7th day of hospitalization, one of the aneurysms in a posterior inferior cerebellar artery–anterior inferior cerebellar artery anastomosis that functioned as a collateral pathway in the presence of severe basilar artery stenosis was found to be enlarged. It was treated by selective aneurysmal coil embolization with parent artery preservation. Her postoperative course was uneventful and she was discharged without any neurological deficits. Conclusion: We document the successful treatment of two patients with ruptured aneurysms in the peripheral portion of a collateral pathway. We discuss the histology of peripheral aneurysms and present a review of the literature. [ABSTRACT FROM AUTHOR]

Abstract  The pattern of recurrence and predictive factors for tumor progression, dissemination and survival in oligodendroglial tumors were investigated. 56 consecutive patients with oligodendroglial tumors were retrospectively analyzed to determine the predictive significance of various factors, including World Health Organization grade, loss of chromosomes 1p and 19q, and immunohistochemical features of TP53, O6-methylguanine-deoxyribonucleic-acid-methyltransferase, CD44H, nestin, and Ki-67. Eleven patients developed dissemination, and had significantly shorter post-progression survival compared to ten patients with local recurrence. Univariate analysis showed that retention of chromosome 1p or 19q, Ki-67 labeling index ≥ 25%, diffuse expression of nestin, and p53 labeling index ≥ 10% were unfavorable factors for overall, progression-free, and dissemination-free survival. Multivariate analysis showed that Ki-67 labeling index ≥ 25% and diffuse expression of nestin were significant for dissemination-free survival. In conclusion, post-progression survival shows significant differences between patients with local and disseminated recurrence. Ki-67 labeling index and nestin expression pattern are useful markers to predict dissemination. [ABSTRACT FROM AUTHOR]