21 results on '"Ohmoto, A."'
Search Results
2. Apoptosis Induction With 5-Fluorocytosine/Cytosine Deaminase gene Therapy for Human Malignant Glioma Cells Mediated by Adenovirus
- Author
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Kurozumi, Kazuhiko, Tamiya, Takashi, Ono, Yasuhiro, Otsuka, Shinji, Kambara, Hirokazu, Adachi, Yoshiaki, Ichikawa, Tomotsugu, Hamada, Hirofumi, and Ohmoto, Takashi
- Published
- 2004
- Full Text
- View/download PDF
3. Adenovirus-mediated Gene Transfer of B7.1 Induces Immunological Anti-tumor Effects in a Murine Brain Tumor
- Author
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Morioka, Jun, Kajiwara, Koji, Yoshikawa, Koichi, Ideguchi, Makoto, Uchida, Tetsuya, Ohmoto, Yoshinori, and Suzuki, Michiyasu
- Published
- 2002
- Full Text
- View/download PDF
4. Prognostic Value of Loss of Heterozygosity around three Candidate Tumor Suppressor Genes on Chromosome 10q in Astrocytomas
- Author
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Terada, Kinya, Tamiya, Takashi, Daido, Shigeru, Kambara, Hirokazu, Tanaka, Hiroaki, Ono, Yasuhiro, Matsumoto, Kengo, Ito, Sachio, Ouchida, Mamoru, Ohmoto, Takashi, and Shimizu, Kenji
- Published
- 2002
- Full Text
- View/download PDF
5. Primary Ewing's Sarcoma/peripheral Primitive Neuroectodermal Tumor at the Vertex of the Skull with Elevated Serum Carcinoembryonic Antigen: Case Report
- Author
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Tamiya, Takashi, Ono, Yasuhiro, Daido, Shigeru, Tokunaga, Koji, Hamazaki, Shuji, Kawai, Akira, and Ohmoto, Takashi
- Published
- 2001
- Full Text
- View/download PDF
6. Intrathecal Chemotherapy with MX2 for Treating Glioma Dissemination in vivo
- Author
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Mizumatsu, Shinichiro, Matsumoto, Kengo, Ono, Yasuhiro, Tamiya, Takashi, Furuta, Tomohisa, and Ohmoto, Takashi
- Published
- 2000
- Full Text
- View/download PDF
7. Relationship between expression of a major apurinic/apyrimidinic endonuclease (APEX nuclease) and susceptibility to genotoxic agents in human glioma cell lines
- Author
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Ono, Yasuhiro, Matsumoto, Kengo, Furuta, Tomohisa, Ohmoto, Takashi, Akiyama, Kosuke, and Seki, Shuji
- Published
- 1995
- Full Text
- View/download PDF
8. Fluorescent dye rhodamine 6G as a molecular probe to study drug resistance of C6 rat glioma cells
- Author
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Matsumoto, Yoshihito, Sasaoka, Noboru, Tsuchida, Takahiro, Fujiwara, Takashi, Nagao, Seigo, and Ohmoto, Takashi
- Published
- 1992
- Full Text
- View/download PDF
9. [Untitled]
- Author
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Yasuhiro Ono, Kinya Terada, Mamoru Ouchida, Takashi Ohmoto, Shigeru Daido, Hirokazu Kambara, Hiroaki Tanaka, Kenji Shimizu, Sachio Ito, Kengo Matsumoto, and Takashi Tamiya
- Subjects
Cancer Research ,Prognostic variable ,biology ,Tumor suppressor gene ,Brain tumor ,Astrocytoma ,medicine.disease ,Loss of heterozygosity ,stomatognathic diseases ,Neurology ,Oncology ,Glioma ,Cancer research ,medicine ,biology.protein ,PTEN ,Neurology (clinical) ,neoplasms ,Grading (tumors) - Abstract
We thoroughly examined loss of heterozygosity (LOH) around three candidate tumor suppressor genes on chromosome 10q to determine whether LOH of each tumor suppressor gene is associated with the previously defined clinical prognostic indices. We also examined whether LOH can help predict prognostic variables in astrocytomas. We selected samples from 40 astrocytomas (grades 2-4), performed Ki-67 immunostaining, and counted positive cells. Using DNA from aliquots of tumor blocks and leukocytes, we investigated LOH around the PTEN, NEURL, and DMBTI genes (10q23.3-26.1) with the silver staining procedure. We then statistically evaluated the relationship among histological features, regional LOH on chromosome 10q, and survival. The mean survival period for patients with LOH around PTEN was 7.2 months after surgery, while that for patients without LOH around PTEN was 21.4 months. Thus, LOH around PTEN was closely associated with a reduced overall survival (p = 0.0020) but LOH at NEURL or DMBTI was not (p > 0.05). The combined features of an increase in histological grading and Ki-67-positive cells and the presence of LOH around PTEN significantly correlated with poor prognosis. These factors may be useful predictors of survival, and LOH analysis of tumor suppressor genes on chromosome 10q can contribute greatly to the treatment of patients with astrocytoma.
- Published
- 2002
10. [Untitled]
- Author
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Makoto Ideguchi, Tetsuya Uchida, Michiyasu Suzuki, Jun Morioka, Koichi Yoshikawa, Koji Kajiwara, and Yoshinori Ohmoto
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,animal structures ,viruses ,Genetic enhancement ,fungi ,Brain tumor ,Transfection ,Biology ,medicine.disease ,Viral vector ,Neurology ,Oncology ,In vivo ,Glioma ,embryonic structures ,Cancer research ,medicine ,Cytotoxic T cell ,Neurology (clinical) ,IL-2 receptor - Abstract
The purpose of the present study was to determine if adenovirus-mediated transfection of a syngeneic mouse brain tumor with the gene encoding B7.1 enhances immunogenicity against tumor. Malignant astrocytoma cells were transfected with adenoviral vectors carrying the B7.1 gene (AdB7). Immunocytochemical analysis confirmed the expression of B7.1 in vitro and in vivo. To investigate the effects of B7.1 expression on tumorigenicity of the malignant astrocytoma, mice were implanted intracerebrally with B7.1-transfected glioma cells. There was no significant difference in proliferation between B7.1-transfected cells and controls in vitro. Nevertheless, mice implanted with B7.1-transfected cells survived significantly longer than those in the control groups. Immunocytochemical analysis of the tumors showed that there was infiltration of a number of CD8+ T-cells and CD25+ activated T-cells in the brain implanted with B7.1-transfected glioma cells. The results showed the possibility that adenovirus-mediated B7.1 gene transfection to a brain tumor induced activation of CD8+ cytotoxic T-lymphocytes.
- Published
- 2002
11. [Untitled]
- Author
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Shuji Hamazaki, Yasuhiro Ono, Shigeru Daido, Takashi Tamiya, Akira Kawai, Koji Tokunaga, and Takashi Ohmoto
- Subjects
Cancer Research ,Chemotherapy ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Peripheral Primitive Neuroectodermal Tumor ,medicine.medical_treatment ,Ewing's sarcoma ,medicine.disease ,Radiation therapy ,Carcinoembryonic antigen ,Neurology ,Oncology ,biology.protein ,Medicine ,Neurology (clinical) ,Embolization ,Sarcoma ,business ,Neuroectodermal tumor - Abstract
A primary Ewing's sarcoma arising in the skull is relatively rare. Although a small number of case reports noted elevated carcinoembryonic antigen (CEA) in patients with primary central nervous system (CNS) neoplasms, there is no report of Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET) with elevated serum levels of CEA. A 7-year-old boy who had episodes of headache and vomiting had noticed a solid mass in the vertex of the head. Imaging studies revealed a large intra- and extracranial tumor at the vertex of the skull. Hematological examination demonstrated high serum levels of CEA: 91.09 ng/ml. The patient initially underwent an embolization of the bilateral middle meningeal arteries with Gelfoam particles. One week later, the patient was operated on and a subtotal resection of the tumor was performed. On histopathological and molecular genetic examination, the tumor was diagnosed as a Ewing's sarcoma/peripheral PNET. Immunohistochemical study showed strongly positive staining for CEA in the tumor cells. The serum level of CEA was normalized at 0.83 ng/ml after the tumor was removed and the boy underwent radiotherapy and 3 courses of chemotherapy. This is the first reported case of a primary Ewing's sarcoma/peripheral PNET at the vertex of the skull with elevated serum CEA.
- Published
- 2001
12. [Untitled]
- Author
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Takashi Tamiya, Takashi Ohmoto, Yasuhiro Ono, Kengo Matsumoto, Tomohisa Furuta, and Shinichiro Mizumatsu
- Subjects
Cancer Research ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Neurotoxicity ,Pharmacology ,medicine.disease ,Central nervous system disease ,Route of administration ,Neurology ,Oncology ,In vivo ,Glioma ,Anesthesia ,Toxicity ,medicine ,Neurology (clinical) ,Intrathecal chemotherapy ,business - Abstract
We examined whether the intrathecal MX2 chemotherapy for treating dissemination of malignant glioma would be a feasible therapy. In the toxicity study, physiological and histological neurotoxicity was not observed in the rats treated with less than 100 μg/kg of MX2 administered intracisternally. But physiological side effects were observed in the treatment group of more than 200 μg/kg and histological brain toxicity was in the treatment group of more than 1000 μg/kg. Dissemination models were induced in rats by intracisternal inoculation of C6 glioma cells. The median survival times of the rats treated with 100 μg/kg of intrathecal MX2 on day 1, 3, or 7 after tumor inoculation were prolonged by 52.4% (p=0.0006), 31.5% (p=0.0007), and 7.1% (p=0.0180), respectively, compared to that of untreated control animals. Intrathecal MX2 treatment also cured 33.6% of rats in the treatment group. These findings suggested that there was a possibility that intrathecal MX2 would be a safe and effective method for treating dissemination of malignant glioma.
- Published
- 2000
13. Relationship between expression of a major apurinic/apyrimidinic endonuclease (APEX nuclease) and susceptibility to genotoxic agents in human glioma cell lines
- Author
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Kengo Matsumoto, Shuji Seki, Kosuke Akiyama, Yasuhiro Ono, Tomohisa Furuta, and Takashi Ohmoto
- Subjects
Exonuclease ,Cancer Research ,Hot Temperature ,DNA Repair ,Carbon-Oxygen Lyases ,Drug Resistance ,Antineoplastic Agents ,AP endonuclease ,Endonuclease ,chemistry.chemical_compound ,Multienzyme Complexes ,DNA-(Apurinic or Apyrimidinic Site) Lyase ,Tumor Cells, Cultured ,Humans ,AP site ,RNA, Messenger ,Endodeoxyribonucleases ,biology ,Glioma ,Hydrogen Peroxide ,Base excision repair ,Molecular biology ,Methyl methanesulfonate ,Exodeoxyribonucleases ,Neurology ,Oncology ,chemistry ,Cell culture ,biology.protein ,Neurology (clinical) ,DNA ,Mutagens - Abstract
The multifunctional DNA repair enzyme (APEX nuclease) having apurinic/apyrimidinic (AP) endonuclease, 3'-5' exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities is thought to be involved in repair of AP sites and single-strand breaks with 3'-blocked termini. To investigate the biological role of the enzyme, we studied the correlation between APEX AP endonuclease activity in several human glioma cell lines having various degree of its expression and cellular susceptibility to cytotoxic agents such as methyl methanesulfonate (MMS), 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cis-diamminedichloroplatinum(II) (CDDP), etoposide (VP-16), hydrogen peroxide (H2O2), hyperthermia and X-ray. The cell lines having lower APEX expression showed higher sensitivity to MMS and H2O2 which are known to induce AP sites and single strand breaks on DNA, respectively. The cellular susceptibility to the other agents tested was not significantly correlated to the APEX expression. The present results are thought to support the notion that APEX nuclease plays an important role on repair of AP sites and single-strand DNA breaks with 3'-blocked termini in mammalian cells.
- Published
- 1995
14. The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas
- Author
-
Takashi Tamiya, Hirokazu Kambara, Takashi Ohmoto, Kazuhiko Kurozumi, Shinji Otsuka, Hiroyuki Michiue, Isao Date, Shigeru Daido, and Yasuhiro Ono
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,Cancer Research ,Pathology ,medicine.medical_specialty ,Brain Edema ,Cerebral edema ,Meningioma ,History, 17th Century ,chemistry.chemical_compound ,Vascularity ,Edema ,medicine ,Meningeal Neoplasms ,Humans ,Receptor ,Peritumoral Brain Edema ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,medicine.disease ,Immunohistochemistry ,Vascular endothelial growth factor ,Receptors, Vascular Endothelial Growth Factor ,Neurology ,Oncology ,chemistry ,cardiovascular system ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 ± 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 ± 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 ± 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 ± 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.
- Published
- 2005
15. Apoptosis induction with 5-fluorocytosine/cytosine deaminase gene therapy for human malignant glioma cells mediated by adenovirus
- Author
-
Takashi Ohmoto, Tomotsugu Ichikawa, Hirofumi Hamada, Yasuhiro Ono, Hirokazu Kambara, Shinji Otsuka, Takashi Tamiya, Kazuhiko Kurozumi, and Yoshiaki Adachi
- Subjects
Cancer Research ,Programmed cell death ,Antimetabolites ,Genetic Vectors ,Flucytosine ,Caspase 3 ,Apoptosis ,Caspase 8 ,Adenoviridae ,Cytosine Deaminase ,Glioma ,medicine ,Humans ,Enzyme Inhibitors ,Caspase ,biology ,Cytosine deaminase ,Cytochromes c ,Genetic Therapy ,Suicide gene ,medicine.disease ,Caspase Inhibitors ,Caspase 9 ,Enzyme Activation ,Neurology ,Oncology ,Caspases ,Cancer research ,biology.protein ,Neurology (clinical) ,Drug Screening Assays, Antitumor - Abstract
Previously, we evaluated the therapeutic efficacy of the adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for malignant gliomas. However, the molecular pathways that mediate the 5-FC/CD gene therapy-induced cell death remains to be elucidated. In this study, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells [Gli36delta5 (mutated p53) and U87MG (wild p53)]. The treatment with 5-FC/CD gene-therapy-induced apoptosis both in Gli36delta5 cells and in U87MG cells according to flow cytometric analysis. Immunoblot analysis revealed that caspases 3 and 9 were processed in response to 5-FC/CD in a concentration- and time-dependent manner, but caspase 8 was not. Each caspase 3 and 9 inhibitor significantly reduced apoptosis triggered by 5-FC/CD, but the caspase 8 inhibitor did not affect apoptosis induction. 5-FC/CD significantly promoted the release of cytochorme c from mitochondria in a concentration-dependent manner. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9. This is the first report concerning the apoptotic mechanism of 5-FC/CD gene therapy, and these findings could be used to increase the efficacy of suicide gene therapy systems for the treatment of malignant glioma.
- Published
- 2004
16. Adenovirus-mediated gene transfer of B7.1 induces immunological anti-tumor effects in a murine brain tumor
- Author
-
Jun, Morioka, Koji, Kajiwara, Koichi, Yoshikawa, Makoto, Ideguchi, Tetsuya, Uchida, Yoshinori, Ohmoto, and Michiyasu, Suzuki
- Subjects
Cytotoxicity, Immunologic ,Male ,Brain Neoplasms ,Genetic Vectors ,Genetic Therapy ,Astrocytoma ,CD8-Positive T-Lymphocytes ,Transfection ,Immunohistochemistry ,Adenoviridae ,Mice ,B7-1 Antigen ,Tumor Cells, Cultured ,Animals ,Immunotherapy ,Cell Division ,Neoplasm Transplantation - Abstract
The purpose of the present study was to determine if adenovirus-mediated transfection of a syngeneic mouse brain tumor with the gene encoding B7.1 enhances immunogenicity against tumor. Malignant astrocytoma cells were transfected with adenoviral vectors carrying the B7.1 gene (AdB7). Immunocytochemical analysis confirmed the expression of B7.1 in vitro and in vivo. To investigate the effects of B7.1 expression on tumorigenicity of the malignant astrocytoma, mice were implanted intracerebrally with B7.1-transfected glioma cells. There was no significant difference in proliferation between B7.1-transfected cells and controls in vitro. Nevertheless, mice implanted with B7. 1-transfected cells survived significantly longer than those in the control groups. Immunocytochemical analysis of the tumors showed that there was infiltration of a number of CD8+ T-cells and CD25+ activated T-cells in the brain implanted with B7.1-transfected glioma cells. The results showed the possibility that adenovirus-mediated B7.1 gene transfection to a brain tumor induced activation of CD8+ cytotoxic T-lymphocytes.
- Published
- 2002
17. Prognostic value of loss of heterozygosity around three candidate tumor suppressor genes on chromosome 10q in astrocytomas
- Author
-
Kinya, Terada, Takashi, Tamiya, Shigeru, Daido, Hirokazu, Kambara, Hiroaki, Tanaka, Yasuhiro, Ono, Kengo, Matsumoto, Sachio, Ito, Mamoru, Ouchida, Takashi, Ohmoto, and Kenji, Shimizu
- Subjects
Aged, 80 and over ,Male ,Brain Neoplasms ,Humans ,Loss of Heterozygosity ,Female ,Genes, Tumor Suppressor ,Astrocytoma ,Middle Aged ,Glioblastoma ,Prognosis ,Survival Analysis ,Aged - Abstract
We thoroughly examined loss of heterozygosity (LOH) around three candidate tumor suppressor genes on chromosome 10q to determine whether LOH of each tumor suppressor gene is associated with the previously defined clinical prognostic indices. We also examined whether LOH can help predict prognostic variables in astrocytomas. We selected samples from 40 astrocytomas (grades 2-4), performed Ki-67 immunostaining, and counted positive cells. Using DNA from aliquots of tumor blocks and leukocytes, we investigated LOH around the PTEN, NEURL, and DMBTI genes (10q23.3-26.1) with the silver staining procedure. We then statistically evaluated the relationship among histological features, regional LOH on chromosome 10q, and survival. The mean survival period for patients with LOH around PTEN was 7.2 months after surgery, while that for patients without LOH around PTEN was 21.4 months. Thus, LOH around PTEN was closely associated with a reduced overall survival (p = 0.0020) but LOH at NEURL or DMBTI was not (p0.05). The combined features of an increase in histological grading and Ki-67-positive cells and the presence of LOH around PTEN significantly correlated with poor prognosis. These factors may be useful predictors of survival, and LOH analysis of tumor suppressor genes on chromosome 10q can contribute greatly to the treatment of patients with astrocytoma.
- Published
- 2002
18. Primary Ewing's sarcoma/peripheral primitive neuroectodermal tumor at the vertex of the skull with elevated serum carcinoembryonic antigen: case report
- Author
-
T, Tamiya, Y, Ono, S, Daido, K, Tokunaga, S, Hamazaki, A, Kawai, and T, Ohmoto
- Subjects
Male ,Skull Neoplasms ,Humans ,Neuroectodermal Tumors, Primitive ,Sarcoma, Ewing ,Child ,Magnetic Resonance Imaging ,Translocation, Genetic ,Carcinoembryonic Antigen - Abstract
A primary Ewing's sarcoma arising in the skull is relatively rare. Although a small number of case reports noted elevated carcinoembryonic antigen (CEA) in patients with primary central nervous system (CNS) neoplasms, there is no report of Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET) with elevated serum levels of CEA. A 7-year-old boy who had episodes of headache and vomiting had noticed a solid mass in the vertex of the head. Imaging studies revealed a large intra- and extracranial tumor at the vertex of the skull. Hematological examination demonstrated high serum levels of CEA: 91.09 ng/ml. The patient initially underwent an embolization of the bilateral middle meningeal arteries with Gelfoam particles. One week later, the patient was operated on and a subtotal resection of the tumor was performed. On histopathological and molecular genetic examination, the tumor was diagnosed as a Ewing's sarcoma/peripheral PNET. Immunohistochemical study showed strongly positive staining for CEA in the tumor cells. The serum level of CEA was normalized at 0.83 ng/ml after the tumor was removed and the boy underwent radiotherapy and 3 courses of chemotherapy. This is the first reported case of a primary Ewing's sarcoma/peripheral PNET at the vertex of the skull with elevated serum CEA.
- Published
- 2001
19. Intrathecal chemotherapy with MX2 for treating glioma dissemination in vivo
- Author
-
S, Mizumatsu, K, Matsumoto, Y, Ono, T, Tamiya, T, Furuta, and T, Ohmoto
- Subjects
Male ,Dose-Response Relationship, Drug ,Brain Neoplasms ,Carubicin ,Brain ,Antineoplastic Agents ,Glioma ,Survival Analysis ,Rats ,Animals ,Feasibility Studies ,Nervous System Diseases ,Rats, Wistar ,Injections, Spinal ,Injections, Intraventricular - Abstract
We examined whether the intrathecal MX2 chemotherapy for treating dissemination of malignant glioma would be a feasible therapy. In the toxicity study, physiological and histological neurotoxicity was not observed in the rats treated with less than 100 microg/kg of MX2 administered intracisternally. But physiological side effects were observed in the treatment group of more than 200 microg/kg and histological brain toxicity was in the treatment group of more than 1000 microg/kg. Dissemination models were induced in rats by intracisternal inoculation of C6 glioma cells. The median survival times of the rats treated with 100 microg/kg of intrathecal MX2 on day 1, 3, or 7 after tumor inoculation were prolonged by 52.4% (p = 0.0006), 31.5% (p = 0.0007), and 7.1% (p = 0.0180), respectively, compared to that of untreated control animals. Intrathecal MX2 treatment also cured 33.6% of rats in the treatment group. These findings suggested that there was a possibility that intrathecal MX2 would be a safe and effective method for treating dissemination of malignant glioma.
- Published
- 2000
20. Fluorescent dye rhodamine 6G as a molecular probe to study drug resistance of C6 rat glioma cells
- Author
-
Noboru Sasaoka, Yoshihito Matsumoto, Seigo Nagao, Takahiro Tsuchida, Takashi Fujiwara, and Takashi Ohmoto
- Subjects
Cancer Research ,Vincristine ,Cell Membrane Permeability ,Time Factors ,Drug Resistance ,Biology ,Sensitivity and Specificity ,Glioma ,medicine ,Animals ,Fluorescent Dyes ,Cisplatin ,Rhodamines ,Membrane transport ,Flow Cytometry ,medicine.disease ,Molecular biology ,Rats ,Staining ,Multiple drug resistance ,Spectrometry, Fluorescence ,Neurology ,Oncology ,Biochemistry ,Molecular Probes ,Verapamil ,Neurology (clinical) ,Intracellular ,medicine.drug - Abstract
A study was made of the membrane transport of cytoplasm and mitochondria stained fluorescence dye Rhodamine 6G (R6G). In rat glioma C6 cells and 1-(4-amino-2-methyl-5-pyrymidinyl)-methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) and vincristine (VCR) resistant cell lines (C6/ACNU, C6/VCR), the rate of uptake of R6G decreased in C6/VCR cells, but verapamil increased the intracellular accumulation of R6G in C6/VCR. The intracellular accumulation of R6G of C6/ACNU cells was essentially the same as that of wild-type cells. C6/ACNU cells did not show cross resistance and were sensitive to VCR and cisplatin. C6/VCR cells showed cross resistance to ACNU and CDDP, but C6/VCR cells in the presence of verapamil were more sensitive to drugs than C6/VCR cells in the absence of verapamil. We conclude that the reduction of R6G fluorescence staining intensity in C6/VCR cells compared to wild-type cells may be associated with the mechanism of multidrug resistance (MDR) but does not reflect the mechanism of resistance to ACNU. Verapamil increased the accumulation of R6G in C6/VCR cells and overcame MDR, suggesting that there is a correlation between the MDR overcoming effect and enhancement of R6G accumulation, and that this correlation validates the use of the R6G staining test for clinical and laboratory investigation of MDR.
- Published
- 1992
21. The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas.
- Author
-
Shinji Otsuka, Takashi Tamiya, Yasuhiro Ono, Hiroyuki Michiue, Kazuhiko Kurozumi, Shigeru Daido, Hirokazu Kambara, Isao Date, and Takashi Ohmoto
- Abstract
We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 ± 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 ± 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 ± 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 ± 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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