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Biomedical subjects

Y Sawamura

Publications and source records attributed to Y Sawamura.

At least 127 records · Page 7Linked to original sources

Receptor protein tyrosine kinase DDR is up-regulated by p53 protein.

We have previously reported on radiation-induction of ptk-3 in rat astrocyte culture [Sakuma et al. (1995) Radiat. Res. 143, 1-7]. Ptk-3 was considered to be a rat version of human DDR (discoidin domain receptor). We cloned and analyzed genomic DNA of the DDR and its promoter region. We discovered that the promoter region contained a consensus sequence of the p53 tumor suppressor binding site. Adenovirus-mediated p53 transfection induced a high level of DDR mRNA in SAOS2 human osteosarcoma cells. These results indicate that DDR is up-regulated by the p53 protein.

Blotting, Northern↗

Clonality and stability of the p53 gene in human astrocytic tumor cells: quantitative analysis of p53 gene mutations by yeast functional assay.

Mutation of the p53 gene is found in about one third of astrocytic brain tumors, and expansion of tumor cell clones containing mutant p53 has been implicated in astrocytic tumor progression. However, admixture of normal cells in astrocytic tumor specimens limits the power of traditional studies of tumor cell clonality. To address this problem we have employed a yeast p53 functional assay that scores the content of mutant p53 alleles in tumors and cell lines quantitatively. We have analyzed 17 cases where matching tumor material and derived cell lines were available. The yeast assay gave > 20% red (i.e., mutant p53-containing) yeast colonies in 7 out of 17 cases. One case had no mutations in the primary tumor but gave 76% red colonies in a recurrence, clearly demonstrating tumor overgrowth by a mutant clone. During early passages of cultured tumor cells, mutant p53 content increased rapidly with passage due to outgrowth of mutant clones from a heterogeneous starting population. In addition, de novo p53 mutations appeared during culture in 2 cases. This indicates that there is stronger selective pressure for mutation during the establishment of cell lines in vitro than during tumor growth in vivo. Our results demonstrate the utility of the p53 functional assay for studies of clonality and support the hypothesis of clonal progression of brain tumors in vivo.

Astrocytoma↗

Localization of mRNA for Ca2+/calmodulin-dependent protein kinase I in the brain of developing and mature rats.

The gene expression of Ca2+/calmodulin-dependent protein kinase I (CaM kinase I) in the brain of developing and adult rats was examined by in situ hybridization histochemistry. During the development, CaM kinase I showed two chronological expression patterns; the persistent and relative high expression as observed in the olfactory bulb and cerebellar cortex, and the gradual decrease in the expression during the postnatal development as observed in most other brain regions. The gene expression was not detected in the germinal ventricular zone and cerebellar external granular layer. In the mature brain, CaM kinase I mRNA was expressed widely, though weakly in general, in almost all neurons, except for the olfactory bulb, cerebellum and hippocampus expressing at high intensity. These findings suggest that CaM kinase I may play a variety of neuronal Ca2+/calmodulin-mediated signaling processes in the developing and mature brains.

Animals↗

Acoustic cellular schwannoma invading the petrous bone: case report.

Cellular schwannoma, a variant of benign schwannomas characterized by a high pseudosarcomatous cellularity, rarely involves the cranial nerves. In this report, we present the case of a 74-year-old woman with a cellular schwannoma of the VIIIth cranial nerve, which recurred from an ordinary schwannoma resected 9 years before. The tumor has been controlled for 35 months by a simple re-excision, indicating the benign nature of this tumor, although the tumor showed bone destruction and a high MiB-1 labeling ratio.

Animals↗

Current diagnosis and treatment of central nervous system germ cell tumours.

Central nervous system germ cell tumours can be cured with high quality posttreatment neuropsychological and endocrinological measures. In order to firmly establish a histological diagnosis, surgery is essential. Management should be planned precisely according to histological and biological malignancy and the extent of the disease. Patients with germinoma can be cured by preirradiation chemotherapy followed by reduced dose irradiation.

Brain↗

Intracranial extracerebral neuroblastoma originating from the convexity dura mater.

A 19-year-old female presented with an unusual intracranial extracerebral neuroblastoma originating from the dura mater. The tumor was located in the right frontal convexity, and had adhered neither to the underlining arachnoid membrane nor the cerebral cortex. The tumor feeders were meningeal arteries. Light microscopy showed the tumor consisted of small compact cells, forming numerous Homer-Wright rosettes. Immunohistochemical examination and electron micrography confirmed the diagnosis of neuroblastoma. Intracranial extracerebral neuroblastoma is extremely rare, especially originating from the dura mater. This neuroblastoma probably originated from heterotopic neuroglial nest cells in the meninges.

Adult↗

Venous hemangioma of the temporalis muscle.

A 14-year-old girl presented with a diffuse venous hemangioma of the right temporalis muscle. The muscle had become swollen, thinning the underlying zygomatic and temporal bones. Magnetic resonance (MR) imaging demonstrated a diffuse isointense area containing high intensity foci on the T1-weighted images, and a serpiginous high intensity pattern on the T2-weighted images. A biopsy specimen revealed irregularly dilated veins in the fibrous stroma of the muscle. Diffuse abnormal signals on MR images may be a pathognomonic feature of intramuscular venous hemangiomas.

Adolescent↗

Phase II study of DTIC, ACNU, and vincristine combination chemotherapy for supratentorial malignant astrocytomas.

This phase II clinical study evaluated the use of 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) pretreatment to reduce cellular resistance and enhance the antitumor effects of chloroethyl nitrosoureas in 32 patients with supratentorial malignant gliomas, including 13 anaplastic astrocytoma and 19 glioblastoma multiforme. All patients received a total dose of 50-65 Gy radiation therapy after surgery. Chemotherapy consisted of DTIC (1 mg/kg) on days 1-5, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (2 mg/kg) on day 5, and vincristine (0.02 mg/kg) on days 1 and 15 every 5 weeks. One patient achieved complete response and 12 patients showed partial response. Median survival time was 18 months and median time-to-progression was 11 months. No significant toxicity was encountered. There was no significant benefit of this pretreatment to combination chemotherapy when compared with previous results. This study does not support a further role for DTIC as a depleter of O6-alkylguanine deoxyribonucleic acid alkyltransferase activity preceding chloroethyl nitrosourea-based chemotherapy.

Adolescent↗

Combined irradiation and chemotherapy using ifosfamide, cisplatin, and etoposide for children with medulloblastoma/posterior fossa primitive neuroectodermal tumor--results of a pilot study.

Ten children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor of the posterior fossa were treated with total surgical resection, radiation therapy, and ICE chemotherapy regimen with ifosfamide (900 mg/m2, days 1-5), cisplatin (20 mg/m2, days 1-5), and etoposide (60 mg/m2, days 1-5) every 4 weeks for eight cycles. Four children under 2 years old were at first treated with eight cycles of ICE chemotherapy, and then irradiated. The ICE regimen was well tolerated by all children, with no irreversible adverse effects. However, dose reductions during the eight cycles were inevitable mainly due to myelosuppression. Complete remissions were achieved in eight of 10 patients at 1 month after completion of the treatment. One child showed recurrence 21 months after complete remission. The disease-free survival rate was 70% with a mean observation period of 24 months after surgery. The ICE regimen is a useful treatment modality for children with medulloblastoma. Further study is warranted to clarify long-term outcome in a number of patients.

Antineoplastic Combined Chemotherapy Protocols↗

Long-term evaluation of radiation-induced brain damage by serial magnetic resonance imaging.

The long-term changes during late delayed radiation-induced brain damage were investigated by serial magnetic resonance (MR) imaging of eight patients over a mean follow-up period of 45 months after irradiation. The radiation damage appeared as an enhanced lesion on T1-weighted MR images with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) at 3 to 30 months after radiotherapy (mean 12.8 months). In all patients, an abnormal high signal intensity area on T2-weighted imaging preceded the enhanced lesion. The volume and number of enhanced lesions continued to increase for 3 to 23 months (mean 10.3 months). The high signal intensity area on T2-weighted imaging simultaneously expanded. The lesions were subsequently stabilized, and in four long-term survivors, the Gd-DTPA-enhanced lesions then decreased in size, the intervals from onset to regression were 12, 13, 17, and 35 months (mean 19.3 months), respectively. However, two patients showed a relapse of the enhanced lesion with latent periods of 8 and 9 months, respectively. Finally, the radiation-damaged brain became atrophic including the high signal intensity area on T2-weighted images. Late delayed radiation-induced brain damage continues to progress for over a year and then regresses, but thereafter a relapse may occur.

Adolescent↗

[The relation of dental examination results at corporation offices to occupation, subjective symptoms of fatigue and daily lifestyle--an investigation based on the number of missing teeth].

Our investigation was intended to find a relationship between the dental health of labourers and, their jobs, subjective symptoms of fatigue and daily lifestyle. Dentists checked the dental health of 2,565 corporation employees (790 male and 775 female) of small to medium-sized enterprises in Hiroshima prefecture. At the same time they examined the employees' occupation, subjective symptoms of fatigue and their health maintenance behavior according to Breslow's criteria. The data were divided into age groups spanning 10 years. Among males in their 30s, those engaged in transport/driving and engineering/production had more missing teeth than others. We found a relationship between the number of missing teeth and subjective symptoms of fatigue among men in their 30s. This suggests that the greater the number of missing teeth, the greater their subjective symptoms of fatigue. The results suggest that missing teeth cause malocclusion which leads to subjective symptoms of fatigue.

Adult↗

[Stereotactic irradiation for brain metastases using linear accelerator].

A stereotactic irradiation (STI) system using a linear accelerator was developed and its effectiveness for brain metastasis was investigated. The system consisted of a conventional linear accelerator, invasive fixation head frame (RADFRAME, Mizuho Ika Kogyo), and a tungsten collimator. The RADFRAME was developed to be used with any linear accelerators and with any dose planning systems. The accuracy of the irradiation was assured to be within +/-1.5mm. Fifty-one patients with metastatic brain tumors were treated using the system. The overall median survival time was 10 months. No difference in survival was observed between patients with a single lesion and patients with two or three lesions. Complete, partial, and minimal responses were obtained in 16 (39%), 18 (41%), and 7 (16%) lesions. These were comparable to the reported results of gamma knife treatment. A maximum dose of 25 Gy was suggested to be more effective than lower doses. Local control rate was higher in tumors with a diameter of less than 2.0cm (87.5%) than in larger tumors (60%). No difference in tumor response was observed among various histopathologic types. In a patient with a 25mm cerebellar metastasis from an adenocarcinoma of the lung, autopsy at 5 months after STI showed fibrinoid degeneration and hyaline deposition without residual tumor at the Gd-enhanced region on MRI. The efficacy of linac stereotactic irradiation was equal to that of gamma knife radiotherapy for metastatic brain tumors.

Adenocarcinoma↗

Clinicopathological study of choroid plexus tumors: immunohistochemical features and evaluation of proliferative potential by PCNA and Ki-67 immunostaining.

This report concerns the retrospective immunohistochemical characterization and evaluation of the proliferative potential of eight choroid plexus tumors (CPTs) that included six cases of choroid plexus papilloma (CPP), one of whom had a recurrence, and two cases of choroid plexus carcinoma (CPC). Antibodies to prealbumin, glial fibrillary acidic protein (GFAP), vimentin, keratin, and carcinoembryonic antigen (CEA) were used to determine the immunohistochemical features of interest. The proliferative potential was evaluated with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. Antibody binding was visualized by the avidin-biotin-peroxidase complex (ABC) method. Immunoreactivity was scored on a-to 4+ scale, and in the case of PCNA and Ki-67, expected as staining index (SI). All seven CPP specimens were immunostained for prealbumin, but not for CEA. Expression of GFAP, vimentin and keratin varied from one CPP case to another. Both CPCs expressed CEA, but not prealbumin, GFAP and keratin; one of them was vimentin-positive. As determined by immunostaining for Ki-67, the proliferative potential was lower in the CPPs than in the CPCs. Among the former, the highest Ki-67 SI was seen in the primary lesion of a recurring papilloma. On the other hand, immunostaining for PCNA gave less consistent SI values. Our results show that immunohistochemical assays for prealbumin and CEA expression are of significant value for the differential diagnosis of CPPs and CPCs, and that high Ki-67 SI values may serve as an indicator of CPP recurrence, even if the primary lesion is benign.

Adult↗

Successful chemoradiation therapy for high-grade skull base chondrosarcoma in a child.

High-grade chondrosarcoma in the skull base has been known to be extremely refractory to adjuvant therapy. We report successful chemoradiation therapy for skull base chondrosarcoma in a child. The patient was a 6-year-old boy with an invasive skull base tumor. In spite of gross total removal of the tumor, it recurred 1 month after surgery. Following an intra-arterial injection of adriamycin (10 mg), the second gross total removal was carried out. At the end of the operation, cisplatin (20 mg) was locally injected into the surgical cavity. The patient was further given a total of six courses of systemic chemotherapy in combination with adriamycin (30 mg/m2) and cisplatin (100 mg/m2) and 55 Gy focal irradiation. One year after the most recent surgery, the patient is in complete remission. The efficacy of adjuvant therapy of this rare tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Proton magnetic resonance spectroscopy (1H-MRS) for the evaluation of treatment of brain tumours.

We investigated metabolic changes in brain tumours following treatment, using proton magnetic resonance spectroscopy. In meningiomas, effective therapeutic embolisation led to an acute increase in lactate. In radiosensitive tumours such as malignant lymphoma, a decrease in lactate and in increase in N-acetyl-aspartate occurred after radiotherapy, which preceded changes observed on magnetic resonance imaging. On the other hand, no significant changes in spectral patterns were observed in malignant gliomas resistant to therapy. Tissue characterisation of brain tumours by spectral patterns on proton magnetic resonance spectroscopy remains controversial. However, we have shown it to be sensitive to metabolic changes following treatment, which may reflect the efficacy of the therapy.

Astrocytoma↗

Trigeminal neuralgia caused by a cerebellopontine-angle lipoma: case report.

This report describes the surgical management of a rare trigeminal neuralgia caused by a cerebellopontine (CP)-angle lipoma. A 13-year-old girl presented with typical trigeminal neuralgia in the right mandibular area. Magnetic resonance imaging (MRI) disclosed a lipoma in the right CP angle. A suboccipital craniectomy revealed a lipoma around the 7th and 8th cranial nerves, but there was no apparent lipoma on the surface of the trigeminal nerve. Since the trigeminal nerve swelled only by infiltration of the lipoma, a partial rhizotomy of the involved sensory root was inevitable. The surgery relieved her neuralgia. She remained analgesic in the mandibular area.

Adolescent↗