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Toshihiro Kumabe

Publications and source records attributed to Toshihiro Kumabe.

16 recordsLinked to original sources
PubMed2004

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↗
PubMed2004

PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma.

Dissemination of glioblastomas is often observed, but the underlying mechanism is not well clarified especially from the genetic viewpoints. The present study examined whether PTEN gene mutations and MIB-1 labeling index (LI) correlate with the dissemination in 39 consecutive patients with glioblastomas. Dissemination was defined as leptomenigeal enhancement by magnetic resonance imaging performed in all patients every 2-3 months. We examined PTEN mutations in 26 patients using cDNA-based direct sequencing and MIB-1 LI in 38 patients. Median survival time of the 39 patients was 16.2 months. Dissemination was found in 17 of 39 patients (43.6%). PTEN mutation was significantly associated with dissemination (P=0.0140), and higher MIB-1 LI (> or =35%) resulted in earlier dissemination (P=0.0156). Kaplan-Meier survival plots showed a significantly poorer survival for patients with PTEN mutation (P=0.0012). The results indicate that the evaluation of PTEN mutation and MIB-1 LI are useful to predict dissemination and prognosis of glioblastomas.

Adult↗
PubMed2004

Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma.

OBJECT: Cerebrospinal fluid (CSF) seeing of high-grade astrocytoma is common, but the early clinical symptoms are not well characterized. Here, we report five patients with disseminated high-grade astrocytoma in the fourth ventricle region who presented with intractable vomiting prior to the detection of the metastatic deposits with enhancement. PATIENTS AND METHODS: From 1994 to 2000, 133 patients of high-grade astrocytoma were treated in our institute and were followed up until December 2002. Follow-up magnetic resonance (MR) imaging was performed in all patients every 2-3 months. The CSF seeding was defined as leptomeningeal enhancement. Signs and symptoms of CSF seeding were checked at the monthly outpatient examination. RESULTS: Among them, 5 patients aged from 27 to 58 years (mean 43.8 years) with one anaplastic astrocytoma and four glioblastomas showed intractable vomiting without signs of high intracranial pressure as evaluated by MR imaging or ocular fundus examination prior to the detection of the fourth ventricle dissemination. Fourth ventricle dissemination appeared 1-3 months after vomiting in five patients. One patient with glioblastoma received gamma knife radiotherapy for a fourth ventricle lesion appearing as a high intensity area on T2-weighted imaging before the appearance of the enhanced nodule, and this lesion was cured. Four patients died of progression of the fourth ventricle lesion. CONCLUSION: Intractable vomiting may be an early clinical symptom of CSF seeding to the fourth ventricle in patients with high-grade astrocytoma. Early detection and immediate radiotherapy for this lesion are recommended to control fourth ventricle dissemination.

Adult↗
PubMed2004

Two different mechanisms of apoptosis resistance observed in interferon-beta induced apoptosis of human glioma cells.

Interferon (IFN)-beta is known to exert cytostatic or cytocidal effects in human glioma cells and is widely used in the treatment for gliomas. However, precise mechanisms of cell death induced by IFN-beta are not well understood. In this study, the authors investigated the intracellular signal transduction of IFN-beta in human glioma cells. The cell death process observed in susceptible cells SK-MG-1 was accompanied by characteristic morphological changes of apoptosis, processing of caspases, and DNA fragmentation. Use of caspase inhibitors confirmed the activation of caspases, however activated executioner caspase was caspase-7 rather than caspases-3 or -6. Activation of DNA endonuclease, DNase-gamma was also observed. Observation of other IFN-beta relatively resistant glioma cells (U251SP, T98G, U251MG, U87MG, SK-AO2) revealed two different mechanisms of apoptosis resistance. In contrast to T98G, U87MG, and SK-AO2 which showed no activation of caspases, surprisingly, all the apoptosis process except DNase-gamma activation was observed in U251SP and U251MG cells. Collectively, these findings indicate that IFN-beta induced apoptosis in human glioma cells through activation of caspase-7 and activation of DNase-gamma. The similar activations of caspases were found also in some of the apoptosis resistant cells. These findings may help to improve the IFN-beta therapy in near future.

Antineoplastic Agents↗
PubMed2004

Spontaneous regression of a primary cerebral tumor following vasospasm caused by subarachnoid hemorrhage due to rupture of an intracranial aneurysm--case report.

A 40-year-old man demonstrated spontaneous regression of a malignant glioma following vasospasm caused by subarachnoid hemorrhage due to rupture of an intracranial aneurysm. The patient had been treated under a diagnosis of malignant glioma for 5 years. He presented with a ruptured aneurysm manifesting as subarachnoid hemorrhage. Single photon emission computed tomography with N-isopropyl-p-123I-iodoamphetamine and diffusion-weighted magnetic resonance (MR) imaging revealed severe flow reduction due to vasospasm in the bilateral temporoparietal cortical regions, including the tumor. MR imaging performed 5 months later showed marked tumor regression. The present case suggests that treatment targeting angiogenesis of malignant gliomas may be effective as a part of multimodality treatment.

Adult↗
PubMed2003

Symptomatic spinal dissemination of malignant astrocytoma.

OBJECT: Symptomatic spinal dissemination of malignant astrocytoma is rarely found except at autopsy. This study evaluated the clinical incidence and characteristics of spinal dissemination and the effect on outcome. PATIENTS AND METHODS: Patients treated for primary malignant astrocytoma, including 33 with anaplastic astrocytoma and 35 with glioblastoma, at our department between 1997 and 1999 were followed up until April 30, 2001. Head magnetic resonance (MR) imaging of all patients was obtained every 2-3 months. Signs and symptoms of leptomeningeal spread were checked at monthly outpatient examinations. Spinal MR imaging was performed if any symptoms indicating spinal dissemination were found. RESULTS: Median survival times of patients with anaplastic astrocytoma and glioblastoma were 40.5 and 16.0 months, respectively. Seventeen patients (25%) developed intracranial dissemination and 15 of these died. Six patients (8.8%), one with anaplastic astrocytoma and five with glioblastoma, developed spinal dissemination. All patients with spinal dissemination also had intracranial dissemination. Five of the six patients died, despite systemic radiochemotherapy in four patients. All patients died of extensive whole brain and spinal dissemination or nodular mass enlargement at the upper cervical cord, not of local massive tumor progression. CONCLUSIONS: Symptomatic spinal dissemination of malignant astrocytoma is not so rare, and is the cause of death. The relatively high incidence of symptomatic leptomeningeal dissemination must be considered in the treatment of malignant astrocytomas.

Adolescent↗
PubMed2003

Apoptotic DNA endonuclease (DNase-gamma) gene transfer induces cell death accompanying DNA fragmentation in human glioma cells.

AIMS: Both the genetic restoration of the apoptotic pathway and the introduction of proapoptotic molecules are now drawing attention. Concerning apoptosis of human glioma cells induced by human interferon-beta protein, we found that DNA endonuclease (DNase-gamma) acts as an executive molecule. The authors investigated whether gene transfer of this DNase-gamma exerts some therapeutic effects on human glioma cells. METHODS: We transduced U251SP, U251MG, and T98G human glioma cells with DNase-gamma gene via multilamellar cationic liposomes, monitored the growth of those cells, and carefully observed the cell-death pattern. RESULTS: DNase-gamma gene transfer resulted in an overexpression of DNase-gamma protein and induced DNA fragmentation in gene-transferred cells. The cytotoxic effect rose with multiple inoculations of the liposome, suggesting a relationship between its expression and the therapeutic effect. CONCLUSIONS: These results demonstrate that DNase-gamma gene transfer can induce apoptosis in human glioma cells, indicating its potential to become a future gene therapy strategy.

Apoptosis↗
PubMed2003

Leptomeningeal dissemination of cerebellar malignant astrocytomas.

Primary malignant astrocytomas of the cerebellum are extremely rare, and the dissemination patterns and effectiveness of postoperative radiation therapy are unclear. Five consecutive cases of histologically proven cerebellar malignant astrocytoma, two anaplastic astrocytomas, one anaplastic pilocytic astrocytoma, and two glioblastomas, were treated between 1997 and 2001. Four patients underwent surgical removal, local irradiation, and chemotherapy, and one patient with anaplastic pilocytic astrocytoma received subtotal removal followed by gamma knife radiosurgery for the residual tumor. Two patients had no recurrence at the primary site. All patients developed leptomeningeal dissemination. Four patients had supratentorial dissemination and two patients had spinal metastases. The time interval between the diagnosis of the primary cerebellar tumor and the diagnosis of leptomeningeal dissemination was 5-29 months (mean 14.6 +/- 10.4 months). All patients died at 10-38 months (mean survival 22.2 +/- 13.6 months). Intensive treatment including chemotherapy and radiotherapy may be required in cerebellar malignant astrocytomas, considering the high incidence of symptomatic leptomeningeal dissemination.

Adult↗
PubMed2003

Inflammatory demyelinating disease mimicking malignant glioma.

UNLABELLED: The differential diagnosis between inflammatory demyelinating disease and malignant glioma is difficult based only on neuroimaging methods. METHODS: Four patients with inflammatory demyelinating disease who presented with clinical and neuroimaging findings strongly suggestive of malignant glioma were examined. RESULTS: MRI showed a mass lesion with prolonged T1 and T2 values and gadolinium enhancement in all cases. Proton MR spectroscopy and (201)Tl SPECT showed findings supportive of the diagnosis of malignant glioma in all cases. However, surgical biopsy revealed inflammatory demyelinating disease. After the diagnosis, 2 patients were treated by steroid administration and 2 were just observed. The gadolinium enhancement of all lesions decreased and finally disappeared. CONCLUSION: Such cases illustrate the importance of considering a demyelinating lesion in the differential diagnosis of a mass lesion. The difficulties encountered in establishing the correct diagnosis of inflammatory disease are related to the variations in the radiologic appearance, which require exclusion of gliomas or other brain tumors by surgical biopsy before the therapeutic strategy can be selected.

Adult↗
PubMed2003

[MR spectroscopy findings of a case of intravascular malignant lymphoma: usefulness for differential diagnosis].

We report a 49-year-old previously healthy woman with acute onset of decrease in attention, dysarthria and ataxia, accompanied by drowsiness. On admission, there were cloudness of consciousness, hallucination and left hemiparesis. Cerebrospinal fluid study revealed a cell count of 1/mm3, and the cytology was class I with a slight increase in protein. MRI of the brain performed on admission showed multiple gadolinium-enhanced lesions with a T2 weighted high intensity area in the cerebral white matter. At first the patient was diagnosed as acute disseminated encephalomyelitis (ADEM), and treated with methylprednisolon pulse therapy. Soon after, she showed transient clinical improvement, but her condition soon worsened. MR spectroscopy revealed elevated choline peak, decreased NAA peak and lactate peak, which indicated a neoplastic lesion. The brain biopsy disclosed diffuse intravascular lymphoma (IVL). MRS was useful in the differential diagnosis of IVL from ADEM.

Brain↗
PubMed2002

Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas.

BACKGROUND: Intraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established. METHODS: During the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12--15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location. RESULTS: In the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group. CONCLUSIONS: IORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone.

Adult↗
PubMed2002

Fatal hemorrhage after radiochemotherapy for leptomeningeal dissemination of glioma: report of two cases.

BACKGROUND: Dissemination of malignant gliomas is often observed, but the treatment of choice for leptomeningeal dissemination has not been established. CASE DESCRIPTIONS: A 55-year-old man suffered fatal hemorrhage 1 day after whole brain irradiation (2 Gy) along with intravenous administration of 150 mg of nitrosourea (ACNU) for leptomeningeal dissemination of glioblastoma. A 14-year-old boy suffered hemorrhage after intrathecal administration of 10 mg of methotrexate for recurrence of leptomeningeal dissemination of anaplastic astrocytoma 4 months after local brain irradiation and ACNU administration, and died 19 days later. CONCLUSION: Massive fatal hemorrhage is an unusual but possible acute complication after radiochemotherapy for leptomeningeal dissemination of gliomas.

Adolescent↗
PubMed2002

Progesterone production and actions in the human central nervous system and neurogenic tumors.

Progesterone has been suggested to be involved in the functions of the nervous system, but it has yet to be examined in humans. Progesterone has also been postulated to be involved in the biological behavior of various human neurogenic tumors via progesterone receptors A and B (PR-A and PR-B). In this study we examined the expression of PR and the enzymes responsible for progesterone biosynthesis (P450scc, 3betahydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) in human brain. We also examined the distribution of PR isoforms in neurogenic tumors using immunohistochemistry and RT-PCR analysis. The presence of PR and mRNA for P450scc, 3beta-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein was detected in human brain. PR isoforms were detected in neurogenic tumors. PR-A and PR-B were equally expressed in meningiomas, but PR-B was the predominant isoform compared with PR-A in astrocytic tumors and Schwannomas. There was a statistically significant inverse correlation between PR-A and the proliferation index in meningiomas and astrocytic tumors. These findings suggest that progesterone is locally synthesized and exerts its actions through PR in the human central nervous system, and that progesterone may be involved in regulation of the growth and development of neurogenic tumors via PR, especially in the inhibition of tumor cell proliferation via PR-A.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

[Recurrence of intracranial germinoma initially treated with chemotherapy only].

Irradiation for intracranial germinoma may be associated with significant neuroendocrinological sequelae, so the establishment of lower effective doses of radiation is desirable. Eight consecutive patients with intracranial germinoma underwent combination chemotherapy with BEP (bleomycin, etoposide, and cisplatin) or PE (cisplatin and etoposide) without irradiation between 1996 and 1997. The diagnosis was based on endoscopic or stereotactic biopsy, or transsphenoidal surgery in 7 cases. These 7 patients obtained complete response (CR) after treatment with chemotherapy only. The diagnosis of pure germinoma was based on neuroradiographic appearances and the normal levels of tumor markers in patients with suprasellar and pineal-region germ cell tumors. Although all patients obtained CR, 5 patients relapsed at a mean period of 19 months after the initial therapy. The mean follow-up period was 53 months. Two of these 5 patients had recurrence around the ventricle wall. Additional chemotherapy and total ventricle irradiation (24 Gy) achieved CR, but delayed seeding in the optic nerves outside the irradiated field was detected. One patient suffered peritoneal dissemination via a ventriculoperitoneal shunt with intracranial dissemination. Another patient obtained CR after PE therapy, but there was not histological verification. However, 35 months after the initial therapy, surgical extirpation of the recurrent tumor revealed immature teratoma. One patient refused treatment for recurrence at the initial tumor site and died 42 months after the initial treatment. Adequate initial therapy is absolutely essential for the treatment of intracranial germinoma. The chemotherapy regimens in use today cannot be recommended as initial therapy without irradiation because of the high recurrence rates.

Adolescent↗
PubMed2002

[A case of primary cerebellar glioblastoma in childhood].

Primary cerebellar glioblastomas are exceedingly rare in childhood, with only 19 cases having been reported. We treated a 7-year-old girl with primary cerebellar glioblastoma, who rapidly deteriorated due to cerebrospinal fluid dissemination. The 7-year-old girl was admitted to our hospital with a history of headache for one month. On admission, increased intracranial pressure and left cerebellar signs were observed. Magnetic resonance imaging (MRI) revealed a ring-enhanced mass in the left cerebellar hemisphere and a low intensity lesion in the pons. The tumor had compressed the fourth ventricle and caused obstructive hydrocephalus. Gross total resection of the left cerebellar tumor was performed. Histological examination revealed nuclear atypia, mitoses, and necrosis, which satisfied the World Health Organizations histological criteria for grade IV astrocytoma. The MIB-1 labeling index was more than 60%. She was treated with adjuvant therapies consisting of 60.2 Gy local irradiation to the posterior fossa, including the brain stem lesion, and chemotherapy using 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). However, the patient developed of anorexia and vomiting 4 months after surgery, and MRI disclosed local recurrence at the left middle cerebellar peduncle and diffuse dissemination along the lateral ventricle wall. The patient was treated with three-drug chemotherapy using ifosfamide, cisplatin, and etoposide and 39.2 Gy of whole-brain irradiation. However, her condition deteriorated gradually and she died 10 months after admission (6 months after the onset of tumor recurrence). Primary cerebellar glioblastomas in children carry a very poor prognosis and tend to cause cerebrospinal fluid dissemination.

Cerebellar Neoplasms↗