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Biomedical subjects

Toshihiro Kumabe

Publications and source records attributed to Toshihiro Kumabe.

At least 19 recordsLinked to original sources

Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome.

A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. The parasitic cysts and glioblastoma were microsurgically removed. Histological examination of surgical specimens revealed neurocysticercosis between the normal brain tissue and glioblastoma. The clinical course and histological findings suggest that the parasitic infection and/or genetic changes contributed to the malignant transformation of the astrocytic tumour.

Astrocytoma↗

[A case of cavernous angioma at the septum pellucidum].

A 35-year-old female presented with a cavernous angioma of the septum pellucidum manifesting as headache and nausea. Computed tomography and magnetic resonance imaging revealed a mass at the septum pellucidum with intraventricular hemorrhage and mild hydrocephalus. Digital subtraction angiography showed no abnormal finding and thallium-201 single photon emission computed tomography showed no uptake in the lesion. The preoperative diagnosis was intraventricular tumor, such as subependymoma. The lesion was completely resected through the transcallosal approach. The histological diagnosis was cavernous angioma. Cavernous angiomas are usually located in the cerebral parenchyma and rarely occur in the cerebral ventricles. In particular, cavernous angioma at the septum pellucidum is very rare. If magnetic resonance imaging does not clearly show the typical peripheral hypointense rim, neuroimaging diagnosis will be difficult. Surgical resection should be considered to confirm the histopathology, in particular if bleeding and hydrocephalus are present.

Adult↗

Spinal intramedullary metastasis of medulloblastoma at initial diagnosis.

CASE REPORT: Spinal magnetic resonance imaging of a 4-year-old boy with medulloblastoma at the initial presentation showed intramedullary lesion without enhancement effect and slight cord swelling from C-5 to T-1. After complete response to the initial therapy, this lesion recurred and slowly expanded. Cervical 11C-methionine-positron emission tomography could establish the diagnosis of intramedullary metastasis. CONCLUSION: Spinal intramedullary metastasis of medulloblastoma at initial diagnosis is extremely rare, but must be considered.

Antineoplastic Agents↗

Surgical treatment of paraventricular cavernous angioma: fibre tracking for visualizing the corticospinal tract and determining surgical approach.

Surgical treatment of deep-seated lesions involving the corticospinal tract is one of the most challenging areas of contemporary neurosurgery, even given the recent development of radiological methods including three-dimensional anisotropy contrast magnetic resonance imaging (MRI) axonography. Fibre tracking using diffusion tensor imaging is another MRI technique that can be used to visualize anisotropy and the orientation of white matter tracts in the brain. We report herein a patient with a paraventricular cavernous angioma manifesting as hemiparesis caused by haemorrhage. Preoperative conventional MRI failed to determine the anatomical relationship between the paraventricular lesion and the corticospinal tract, whereas fibre tracking using free software (dTV for MR-DTI analysis) indicated that the corticospinal tract was displaced anterolaterally from the medial side. The paraventricular lesion was completely removed without damaging the corticospinal tract using a transcortical transventricular approach. Preoperative fibre tracking is useful in surgical planning for procedures involving deep-seated lesions adjacent to the corticospinal tract, and may avoid postoperative morbidity due to corticospinal tract injury.

Adult↗

Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis.

PURPOSE: To retrospectively assess the apparent diffusion coefficient (ADC) for prediction of malignancy and prognosis of malignant astrocytic tumors. MATERIALS AND METHODS: The institutional review board approved this study and did not require patient informed consent. Findings from 37 consecutive patients (21 men, 16 women; mean age, 43 years) with pathologically proved malignant astrocytic tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs) were retrospectively evaluated. The minimum ADC value of each tumor was preoperatively determined from several regions of interest defined in the tumor, preferably with avoidance of cystic or necrotic components, on ADC maps derived from isotropic diffusion-weighted images. Surgical intervention, followed by radiation therapy, was undertaken in all cases according to hospital protocol. Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation, was also determined. The patients were classified into two groups, progressive and stable, according to the 2-year observation after the initial treatment. Correlation analysis (Pearson product moment correlation), Student t test, Welch test, receiver operating characteristic analysis, and Kaplan-Meier method with log-rank test were used for statistical evaluation. RESULTS: There was a significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P < .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001, Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(-1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(-1) for minimum ADC for differentiation of patients with a favorable prognosis from those with a poor prognosis provided the best combination of sensitivity (79%) and specificity (81%) (receiver operating characteristic analysis). The significant difference in the prognosis between two groups classified by using this cutoff value of minimum ADC was noted (P = .002, log-rank test). CONCLUSION: The minimum ADC of malignant astrocytomas can provide additional information about their clinical malignancy related to posttreatment prognosis.

Adult↗

Safety and efficacy of convection-enhanced delivery of ACNU, a hydrophilic nitrosourea, in intracranial brain tumor models.

Convection-enhanced delivery (CED) is a local infusion technique, which delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED distribution is significantly increased if the infusate is hydrophilic. This study evaluated the safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a hydrophilic nitrosourea, in rat 9 L: brain tumor models. The local neurotoxicity of ACNU delivered via CED was examined in normal rat brains, and the maximum tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD produced significantly longer survival time than systemic administration (P < 0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor occurred only in the CED-treated rats. The tissue concentration of ACNU was measured by high-performance liquid chromatography, which revealed that CED of ACNU at the dose of 100-fold less total drug than intravenous injection carried almost equivalent concentrations of ACNU into rat brain tissue. CED of hydrophilic ACNU is a promising strategy for treating brain tumors.

Animals↗

[Choroid plexus tumors: report of 7 cases in a single institution].

The management of seven patients with choroid plexus tumors, 4 adults and 3 children (mean age 17.5 years) at our institution was reviewed. There were 4 cases of papilloma and 3 of carcinoma located in the lateral ventricle in 1 case, the third ventricle in 1 case, and the fourth ventricle in 5 cases. Total surgical excision was attempted in all patients. Total resection was achieved in three patients, resulting in no deficit in two and persistence of preoperative dysphagia in one. There was no recurrence after total resection. Subtotal resection was achieved in four patients, one of whom underwent second surgery resulting in total resection, and one patient died of respiratory disturbance after the third operation because of regrowth of the tumor. Complete excision could not be achieved in 3 of the 5 tumors located in the fourth ventricle because of extension to the brainstem. The median survival was 59.5 months for patients with papilloma, and 67.7 months for those with carcinoma. Adjuvant therapy was also required for carcinoma, one patient was treated by radiotherapy, and two by radiotherapy plus chemotherapy. Only one patient with papilloma was treated by radiotherapy plus chemotherapy postoperatively.

Adult↗

[Precocious puberty caused by hCG-producing germinoma involving the bilateral basal ganglia and cerebral white matter without 1ypical radiologic findings: case report].

An 8-year-old boy presented with a rare case of germinoma involving the bilateral basal ganglia and cerebral white matter manifesting as precocious puberty. Magnetic resonance (MR) imaging at the initial presentation demonstrated mild hyperintense areas in the bilateral basal ganglia and corpus callosum on T1-weighted images, and a small hyperintense spot in the right internal capsule on T2-weighted images. Human chorionic gonadotropin (hCG) level was elevated in the cerebrospinal fluid (CSF), so we strongly suspected that threre was a hCG-producing germinoma originating in the bilateral basal ganglia. Stereotactic biopsy was performed. Histological examination revealed two-cell pattern germinoma. After three cycles of combination chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by whole brain irradiation with a total dose of 24 Gy, the CSF hCG level fell below the detection limit, but MR imaging demonstrated no significant change. Intracranial hCG-producing germinoma should be suspected in patients presenting with precocious puberty and elevated CSF hCG level. Moreover, slight intensity change on MR imaging is important to identify germinoma arising from the basal ganglia in the early stage.

Basal Ganglia Diseases↗

["Disease targeting therapy" for neurosurgical disorders: molecular targeting and drug delivery].

Recent progress in molecular biology introduced a concept of molecular targeting therapy against many diseases including neurosurgical disorders. Molecular targeting therapy is promising, because targeting a disease-specific molecule it may provide cure without inducing unfavorable side effects. Focusing mainly on CNS (central nervous system) malignancies, authors discuss the current development of molecular targeting therapy with a special concern to strategies using DNA, RNA, immunotoxin, and molecular selective inhibitors. Strategies using DNA include gene therapy and DNA vaccine. RNA interference (RNAi) is one of the promising molecular targeting strategies using RNA. Immunotoxins such as recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium is now under clinical investigation. Many molecular targeted agents such as selective inhibitors for protein kinases are now in preclinical and clinical development for patients with malignant glioma. Additionally, authors introduce their attempts to visualize the local drug delivery using real-time MRI monitoring. Visualization of drug delivery, while achieving effective drug distribution using convection-enhanced delivery (CED), may also contribute to the disease targeting. These strategies together should help us develop the effective 'disease-targeting therapy' for CNS disorders.

Biotechnology↗

The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library.

Tumor suppressor p53 forms a homo-tetramer through its COOH-terminal oligomerization domain and acts as a sequence-specific transcription factor. We have analysed the interrelation among the transcriptional activities, the structure and the cancer-related mutations in the oligomerization domain by using a comprehensive missense mutation library. Here, we examined the ability of 184 mutant p53s in the domain to form an oligomer by expressing these mutant p53s in yeast, and compared the data with the previous information. We showed that specific residues in the alpha-helix and the beta-strand of the oligomerization domain were critical for both oligomer formation and sequence-specific transactivation, and the activities were closely related. In particular, the alpha-helix was more sensitive to amino-acid substitutions than the beta-strand. We found identity in the interrelation between the two activities, that is, monomer mutants were transcriptionally inactive whereas dimer and tetramer mutants retained their transcriptional activities. In TP53 mutation databases, a small number of mutations have been reported in this domain. Surprisingly, most do not encode p53s defective in functional properties. These results indicate that, although oligomer formation is essential for p53 transactivation function, the inactivation of oligomer formation and therefore the inactivation of transactivation may not be essential for tumor suppression by p53 because they do not lead to oncogenic proteins.

Biopolymers↗

Minute glioma identified by 3.0 Tesla magnetic resonance spectroscopy--case report.

A 33-year-old man presented with a minute tumor incidentally detected by magnetic resonance (MR) imaging screening. 1.5 Tesla MR spectroscopy indicated normal brain tissue whereas 3.0 Tesla MR spectroscopy indicated neoplasm. The tumor was completely resected. The histological diagnosis was fibrillary astrocytoma. Minute glioma, measuring less than 15 mm in diameter on MR imaging, can be completely resected, resulting in a good prognosis. 3.0 Tesla MR spectroscopy can establish the diagnosis in the early stage of glioma.

Adult↗

201Tl-SPECT and 1H-MRS study of benign lateral ventricle tumors: differential diagnosis of subependymoma.

The introduction of computed tomography (CT) and magnetic resonance (MR) imaging has resulted in the detection of increasing numbers of asymptomatic intraventricular tumors. Establishing the correct preoperative diagnosis is important to prevent unnecessary surgical intervention. Our study includes nine cases of benign lateral ventricle tumors including two cases of central neurocytoma, two of subependymal giant cell astrocytoma, two of pilocytic astrocytoma and three of subependymoma treated surgically between 1996 and 2003. MR imaging, proton MR spectroscopy ((1)H-MRS) and thallium-201 single photon emission computed tomography ((201)Tl-SPECT) were performed in all patients. All three types of tumor demonstrated heterogeneous enhancement on MR imaging with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and increased choline (Cho) peak and decreased N-acetyl aspartate (NAA) and creatine (Cre) peaks on (1)H-MRS. (201)Tl-SPECT showed high uptake of (201)Tl without wash out in all cases of central neurocytoma, subependymal giant cell astrocytoma and pilocytic astrocytoma, but no uptake in cases of subependymoma. Absence of (201)Tl uptake in contrast with enhancement on MR imaging and the (1)H-MRS features of modest elevation of the Cho/Cre ratio, reduction of the NAA peak and presence of lactate/lipid peaks are characteristic features of subependymomas and useful to establish a preoperative diagnosis.

Adolescent↗

Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma.

Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.

Animals↗