Metabolic and functional mapping of the spinal cord using 1H-MR spectroscopy

課題番号：2189002

The TAO-Gen Algorithm for Identifying Gene Interaction Networks with Application to SOS Repair in E. coli

One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts

Malignant Lymphoma in the Parasellar Region

The entity of pituitary (sellar or parasellar) lymphoma includes primary pituitary lymphoma (PPL) and secondary pituitary lymphoma (SPL). The latter has an involvement of systemic lymphoma. Both of these lymphomas are extremely rare. We describe a patient with SPL showing a good prognosis. A 78-year-old woman presented with diplopia, left ptosis, and back pain. Magnetic resonance (MR) imaging revealed a parasellar mass lesion extending to the upper clivus and another mass lesion with compression fracture of the Th3 vertebral body. Transsphenoidal exploration was performed, and it showed diffuse large B-cell lymphoma. Based on the positive tumor cells in the following bone marrow aspiration and hepatosplenomegaly in computed tomography (CT) findings, this patient was diagnosed as having a pituitary involvement of systemic lymphoma. After chemotherapy, she achieved complete remission for 4 years. The entity of pituitary lymphoma is extremely rare. Nineteen cases of PPL and 16 cases of SPL have been reported. Generally, clinical and radiological diagnosis was difficult because there are no specific findings. Therefore, biopsy was necessary in all of the cases. T2 hypointensity of a lesion in MR imaging in addition to an elevated serum level of soluble interleukin-2 receptor (sIL-2R) in a patient with a sellar lesion can be useful clues for the differential diagnosis of this rare disease

Prediction of Boron Concentrations in Blood from Patients on Boron Neutron Capture Therapy

Background: In boron neutron capture therapy, blood boron concentration is the key factor to calculate radiation dose, however, blood sampling is difficult during neutron irradiation. Materials and Methods: The prediction of blood boron concentrations for BNCT treatment planning has been prospectively investigated using patient data obtained at first craniotomy after the infusion of a low dose of sodium undecahydroclosododecaborate. Results: The boron biodistribution data showed a biexponential pharmacokinetic profile. If the final boron concentration at 6 or 9 hours after the end of the infusion is within the 95% confidence interval of the prediction, direct prediction from biexponential fit will reduce the error of blood boron concentrations during irradiation to around 6%. Conclusion: Actual boron concentrations during BNCT were reasonably and accurately predictable from the test data

Correlations of Vascular Architecture and Angiogenesis with Pituitary Adenoma Histotype

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesi

Huge Greater Superficial Petrosal Nerve Schwannoma with Intradural Peritumoral Cyst

BackgroundSchwannoma originating from the greater superficial petrosal nerve is an extremely rare type of facial nerve schwannoma located in the middle cranial fossa around the midportion of the petrous bone. Here, we provide the first report of greater superficial petrosal nerve schwannoma presenting with contralateral facial palsy and hemiparesis due to compression of the pyramidal tract by associated intradural peritumoral cyst.Case DescriptionA 69-year-old woman presented with a 6-month history of gradually worsening gait unsteadiness. Magnetic resonance imaging demonstrated a well-defined tumor occupying the right middle cranial fossa and extending into the tympanic cavity. Notably, the tumor accompanied a large cyst in the intradural space, resulting in a leftward midline shift. Extradural exploration through thinned periosteal dura mater revealed the tumor within the interdural space. After debulking of most of the tumor in a pull-out, piecemeal fashion, intradural exploration revealed the peritumoral cyst located between the meningeal dura mater and brain parenchyma. Following the disappearance of the mass effect from the tumor, fenestration of the peritumoral cyst, which had been deeper-seated than the tumor, was easily achieved while avoiding excessive retraction of the temporal lobe. Postoperatively, mild left hemiparesis involving the face resolved completely and no new symptoms such as right facial palsy, hearing disturbance, or xerophthalmia developed as postoperative complications.ConclusionThe combination of extradural and intradural approaches in the appropriate order is essential for fenestration of an intradural peritumoral cyst along with removal of an interdural tumor

Efficacy of bevacizumab therapy in recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location

Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OSBev) (6.0 months, 95% confidence interval (CI) 1.4–10.7) compared to those in the local/distant group (11.8 months, 95% CI 6.1–17.4). The median OSBev of the infratentorial tumor group and supratentorial tumor group were 9.2 months (95% CI 5.0–13.4) and 10.4 months (95% CI 6.6–14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OSBev. Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination

Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma

Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma

Despite cumulative evidence supporting the idea that gross total resection (GTR) contributes to prolonged survival of patients with glioblastoma (GBM), the survival outcome of such patients remains unsatisfactory. To develop more effective postoperative therapeutic strategies for patients who underwent GTR, identification of prognostic factors influencing survival is urgently needed. Here we retrospectively analyzed prognostic factors for patients who underwent GTR of newly diagnosed GBM, with a particular focus on the influence of the subventricular zone (SVZ) as the tumor location. Forty-eight consecutive patients with newly diagnosed GBM who underwent GTR during the initial operation were investigated. Tumor involvement of the SVZ was significantly associated with overall survival (OS). The SVZ-positive group had a significantly shorter median OS of 12.2 months, compared to 34.9 months for the SVZ-negative group. The occurrence of leptomeningeal dissemination was significantly influenced by tumor involvement of the SVZ, but was not significantly influenced by ventricular opening during surgery. We observed a statistically significant difference in OS according to radiation modality. The median OS was 36.9 months for patients treated with high-dose proton beam therapy, compared with 26.2 months for patients treated with conventional radiotherapy. We demonstrated that tumor involvement of the SVZ was associated with poor survival of patients who underwent GTR of newly diagnosed GBM, suggesting the potential need for therapeutic strategies that specifically target tumors in the SVZ. Further prospective studies to evaluate whether radiotherapy targeting the SVZ improves survival of patients with tumor involvement of the SVZ who had undergone GTR are warranted