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Tetsuya Ueba

Publications and source records attributed to Tetsuya Ueba.

11 recordsLinked to original sources
PubMed2006

A dyad symmetry element in the fibroblast growth factor-2 gene promoter with different levels of activity in astrocytoma and hepatocelluar carcinoma cell lines.

Fibroblast growth factor-2 (FGF-2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF-2 gene expression. Here, we report the characterization of a unique element in the FGF-2 gene promoter. We investigated the transcriptional regulation of the FGF-2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF-2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied. Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF-2 gene expression.

Astrocytoma↗
PubMed2006

Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group.

OBJECT: This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.

Adult↗
PubMed2004

Overexpression of RFT induces G1-S arrest and apoptosis via p53/p21(Waf1) pathway in glioma cell.

The regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) has been reported to be a transcriptional repressor of FGF-2 and induce glioma cell death by its overexpression. Here we report that RFT regulates cell cycle as well as apoptosis by a novel mechanism. RFT expressed in some glioma cell lines, U138MG and T98G, but neither in U87MG nor U251MG. Overexpressed RFT-induced apoptosis in U87MG and U138MG with functioning-type p53 but neither in U251MG nor T98G with non-functioning-type p53. Administration of FGF-2 failed to prevent RFT-induced apoptosis. Overexpression of RFT caused G1-S arrest and upregulated both the phosphorylation of p53 at Ser-15 and the expression level of p21(Waf1). Furthermore, RNAi knockdown of p53 abolished RFT-induced apoptosis in U87MG. Taken together, our results support that RFT regulates G1-S transition and apoptosis via p53/p21(Waf1) pathway.

Apoptosis↗
PubMed2004

The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas.

BACKGROUND: The most relevant factor in the progression-free survival (PFS) of patients with meningiomas is the malignant grade. However, using only the current World Health Organization (WHO) definition that does not consider precise quantitative indicators, an unequivocal diagnosis of the malignant grade is difficult. In our retrospective study of the PFS of meningioma patients, we focused on mitoses and the Ki-67 staining index of tumor specimens obtained at the initial surgery. METHODS AND RESULTS: A total of 349 patients with intracranial meningioma, operated between 1978 and 2000, were followed for a mean of 7 years. According to the mitotic index (MI), we classified them into 3 groups. In Group A (n = 326), slide-mounted tumor samples exhibited no mitoses; in Group B (n = 15) there were fewer than 4 mitoses, and in Group C (n = 8) 4 or more mitoses were seen per 10 high-power fields (HPF). The estimated 5-year PFS rates in Groups A, B, and C were 93%, 10%, and 13% respectively. The mean PFS for Group A was 148 months; in Groups B and C the median PFS was 43 and 16 months, respectively. A Ki-67 staining index (SI) of less than 1% corresponded with no mitosis, while an SI exceeding 5% was indicative of the presence of mitoses. CONCLUSION: In meningioma patients, no mitoses and/or a Ki-67 SI <1% signals a favorable outcome. An SI >5% or the presence of mitoses, even fewer than 4 in 10 HPF, is suggestive of a short PFS irrespective of other pathologic features. We suggest that in combination, assay of the Ki-67 SI and the MI represents a reliable, quantitative tool for predicting PFS in meningioma patients.

Adolescent↗
PubMed2004

MRI and CT findings of neurohypophyseal germinoma.

OBJECTIVE: Magnetic resonance (MR) imaging and computed tomography (CT) findings of neurohypophyseal germinoma have not previously been described in detail. The purpose of the present study was to establish the spectrum of MR imaging and CT findings in neurohypophyseal germinomas. MATERIALS AND METHODS: MR and CT images of 13 consecutive patients (seven males, six females; mean age: 15 years; range: 6-31 years) with neurohypophyseal germinoma were retrospectively analyzed. The diagnosis had been made either histologically (n=8) or clinically according to established criteria (n=5). All patients had been examined using MR imaging and CT before treatment. RESULTS: On MR imaging, infundibular thickening (up to 16 mm) was observed in all 13 cases. Hyperintensity of the posterior pituitary on T1-weighted image was absent in all 13 cases (100%) and 12 of the 13 displayed central diabetes insipidus. Ten germinomas (77%) were isointense to cerebral cortex on T1-weighted image, but variable intensities were exhibited on T2-weighted image. MR images revealed intratumoral cysts in six cases (46%), most of which demonstrated intra-third ventricular extension. Eleven of the 13 cases (85%) revealed hyperdense solid components on unenhanced CT. Calcification was absent in all cases (100%). CONCLUSION: Infundibular thickening, absence of the posterior pituitary high signal on T1-weighted image, lack of calcification and hyperdensity on unenhanced CT are common imaging features of neurohypophyseal germinoma.

Adolescent↗
PubMed2003

Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function.

DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.

Animals↗
PubMed2003

In vitro growth suppression of human glioma cells by a 16-mer oligopeptide: a potential new treatment modality for malignant glioma.

Fibroblast growth factor-2 (FGF-2) is involved as an autocrine growth factor in the autonomous proliferation of glioma cells. To develop a new strategy for treating patients with glioma, we studied the effect on human glioma cells of a 16-mer oligopeptide with conformational similarity to the putative receptor-binding domain of FGF-2. A synthesized oligonucleotide was assessed its receptor-binding activity by BIAcore instrument. Its biological effect on glioma cell lines was examined in vitro by MTT assay. The peptide suppressed the in vitro growth of human glioma cells U87MG, T98G and U251MG cells, but not of A431 cells whose growth is not dependent on FGF-2. Apoptotic bodies were noted after 24-h incubation in the presence of the peptide; Ac-YVAD-CHO, a caspase-3 inhibitor, suppressed apoptosis. Furthermore, we examined the modulation of the cytotoxic effect of anticancer drugs by the oligopeptide. The addition of this oligopeptide to the chemotherapeutic agents CDDP, ACNU and VP16 had additive effects in vitro. These results suggest that the pathway of the FGF-2 autocrine loop through the FGF receptor plays an important role in the proliferation of glioma cells. New drugs targeting this loop may be highly effective in treating FGF-2-dependent tumors. Our results suggest that its addition to the therapeutic arsenal may lead to improved treatment regimens for patients with FGF-2-dependent tumors.

Antineoplastic Agents↗
PubMed2003

Liliequist membrane: three-dimensional constructive interference in steady state MR imaging.

PURPOSE: To evaluate the Liliequist membrane in healthy volunteers by using three-dimensional (3D) Fourier transformation constructive interference in steady state (CISS) magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 31 volunteers, the authors performed 3D CISS MR imaging. They divided the membrane into three segments: the sellar, diencephalic, and mesencephalic segments. MR images were evaluated to identify the segments, superior and inferior attachments, lateral border, and thickness of the Liliequist membrane. RESULTS: Three-dimensional CISS MR imaging depicted the sellar, diencephalic, and mesencephalic segments of the Liliequist membrane in the sagittal plane in 25 (81%), 16 (52%), and five (16%) of the 31 subjects, respectively. Transverse MR imaging depicted these segments in 24 (77%), 10 (32%), and two (6%) subjects, respectively, and coronal MR imaging depicted them in 24 (77%), 12 (39%), and two (6%) subjects, respectively. Clear attachment of the membrane to the dorsum sellae was observed in 22 (88%) of 25 subjects in whom the sellar segment was identified. Clear attachment to the mamillary body was identified in eight (50%) of 16 subjects in whom the diencephalic segment was identified. The Liliequist membrane was attached to the oculomotor nerve on seven (14%) of 50 sides of the lateral border and to the arachnoid membrane around the oculomotor nerve on 28 (56%) sides. In the sagittal plane, the thickness of the membrane was less than one-half the thickness of the third ventricle floor in 22 (88%) of 25 subjects. CONCLUSION: The Liliequist membrane can be visualized by using 3D CISS MR sequences.

Adult↗
PubMed2002

Effects of combination chemotherapy with biscoclaurine-derived alkaloid (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines.

In the treatment of malignant glioma, chemotherapy plays a critical role as do surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived alkaloid, reportedly potentiates the effects of antitumor agents and induces apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and in combination with nimustine hydrochloride (ACNU), on the in vitro proliferation of malignant glioma cells. The cell lines used were U87MG, U251MG, and T98G. At concentrations from 1 to 10 microg/ml, CEP-promoted cell proliferation somewhat; growth inhibition was noted at concentrations of 15 microg/ml and higher. Phase-contrast microscopy showed that cells tended to detach from the culture dishes and that cell density became sparse at the higher concentrations. DAPI fluorescence nuclear staining revealed condensation and fragmentation of nuclei, indicating the induction of apoptosis. To examine the cascade of apoptosis, the caspase inhibitors YVAD and DEVD were added. They inhibited CEP-induced apoptosis in U251MG cells (a p53-mutant cell line), but not in U87MG cells (a p53 wild-type cell line), suggesting that in CEP-induced apoptosis two possible cascades are in play. In combination with ACNU, the effects of the higher concentrations of CEP were enhanced.

Alkaloids↗
PubMedDate not supplied

High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM-1) in astrocytomas.

OBJECTIVE: Impaired regulation of Aurora-B/AIM-1 expression in human cells causes chromosomal abnormality and instability, and recent observations of high expression but not mutation of Aurora-B/AIM-1 in human cancers imply that Aurora-B/AIM-1 might be a candidate molecule for cancer progression. We analyzed the effects of modification of Aurora-B/AIM-1 expression on the growth of a human glioma cell line and the expression of Aurora-B/AIM-1 in astrocytomas. METHODS: A glioma cell line, U251MG was transfected with wild type (WT) of Aurora-B/AIM-1 or kinase-inactive mutant of Aurora-B/AIM-1 in order to test the effects of overexpression of WT or kinase-inactive Aurora-B/AIM-1 on cell morphology and cell growth. Brain tissue samples were obtained during surgery and processed for reverse transcription-polymerase chain reaction, immunofluorescence in order to analyze the expression of Aurora-B/AIM-1 mRNA and protein. RESULTS: Exogenous overexpression of WT of Aurora-B/AIM-1 in cultured cells of U251MG produced multinuclearity and increased ploidy, and inhibited the growth of tumor cells. Exogenous overexpression of kinase-inactive Aurora-B/AIM-1 in a human glioma cell line also suppressed the tumor cell growth without affecting ploidy. Aurora-B/AIM-1 was highly expressed in astrocytomas and U251MG, and mRNA and protein levels of Aurora-B/AIM-1 in tumor tissues well correlated with their histological malignancy (World Health Organization grading). Survival time also negatively correlated with the levels of Aurora-B/AIM-1 mRNA in tumor samples. CONCLUSION: Aurora-B/AIM-1 was highly expressed in high-grade gliomas and its expression was well correlated with histological malignancy and clinical outcomes. The modification of the level of Aurora-B/AIM-1 expression might be a new target for glioma therapy.

Adult↗