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Biomedical subjects

M Matsutani

Publications and source records attributed to M Matsutani.

At least 19 recordsLinked to original sources

Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience.

Among intracranial germ cell tumors, nongerminomatous tumors have proved refractory to conventional treatment with surgery and irradiation. The median survival is less than 2 years. Since 1983, chemotherapy has been delivered in Japan as an adjuvant therapy in patients with intracranial nongerminomatous germ cell tumors. Based on our clinical experience, we undertook a multi-institutional phase II study to establish post-surgical combined chemotherapy and radiation therapy for primary germ cell tumors in the brain. We adopted carboplatin-etoposide (CARB-VP) or cisplatin-etoposide (PE) combination chemotherapy for patients with germinomas and those with tumors that placed them in the intermediate prognosis group, and ifosphamide-cisplatin-etoposide (ICE) for patients with tumors that placed them in the poor prognosis group. One hundred and twelve patients were evaluated. Among patients with germinoma (n = 75), the rate or complete remission after combination therapy was 92.0%; it was 67.8% for patients in the intermediate prognosis group (n = 28). Tumor recurrence was noted in 9 patients with germinoma and 2 patients in the intermediate prognosis group. Of 9 patients with a poor prognosis, 4 experienced disease progression during treatment and died within 10 months. There were no serious complications attributable to the combination therapy. Our treatment protocols are effective for patients with germinomas and those with an intermediate prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

Apocrine adenocarcinoma in a golden hamster.

An apocrine adenocarcinoma was observed in the subcutis of the abdomen of golden hamster. Histologically, the tumor cells irregularly formed multiple layers of cysts and some detached cells were presented in the cystic space. PAS stain with alpha-amylase digestion revealed PAS-positive alpha-amylase-resistant granules in the cytoplasm. Immunohistochemically, cytokeratin was demonstrated in the tumor cells. By electron microscopy, the tumor cells had an oval nucleus with invagination, abundant cytoplasmic organelles and microvilli protruding into the intercellular spaces.

Adenocarcinoma↗

Analysis of the p300/CBP-Associated Factor (PCAF) gene in astrocytic tumors.

The PCAF gene encodes the p300/CBP-Associated Factor (PCAF), a histone acetyltransferase, which regulates p53 by acetylation of Lys320 in the C-terminal portion of p53. While the p53 gene is one of the most frequently mutated tumor suppressor genes in human tumors, such mutations occur in only 30% of astrocytic tumors. Since PCAF can regulate p53 activity, abrogation of PCAF function by PCAF gene mutation could be an alternate mechanism to inactivate the p53 pathway in tumors lacking p53 mutations. To test this hypothesis, we determined the nucleotide sequence of the entire PCAF coding region in 37 astrocytic tumors (17 glioblastomas, 10 anaplastic astrocytomas, 7 low-grade astrocytomas, and 3 pilocytic astrocytomas). We detected two single-nucleotide alterations that represented non-deleterious polymorphisms (GAG > GAA Glu103Glu, AAT > AGT Asn386Ser) but no obvious functional mutations. Moreover, the frequency of the Asn386Ser allele that contained Ser386 in glioma patients was not statistically different from its frequency in individuals without disease, and no significant association was observed between the PCAF polymorphisms and the presence or absence of p53 mutations in the tumors. We conclude that the PCAF gene is not mutated during the development of the astrocytic tumors studied here.

Alleles↗

Suprasellar cystic germinoma.

We report on a germinoma in the suprasellar region, which had multiple large cystic components. A 13-year-old girl with disturbed visual acuity and growth retardation was admitted to our hospital for treatment of an intracranial tumor. The lesion was difficult to diagnose as a germinoma preoperatively, because of its radiographic characteristics. Histopathological examination revealed that the tumor was a germinoma. Surgery, chemotherapy with carboplatin and etoposide, and radiotherapy (30 Gy) were successful in inducing complete remission of the tumor. The patient's endocrine status remained normal, except for a low GH concentration and diabetes insipidus.

Adolescent↗

Germ cell tumors of the CNS in children: recent advances in therapy.

Primary germ cell tumors of the central nervous system are rare neoplasms, accounting for no more than 2% of all malignancies in children and young people under 20 in the Western hemisphere. They have unique features related to age at diagnosis and sites of origin, as well as race and gender predilection. Prognosis has been clearly shown to be strongly related to pathological classification as either pure germinoma or nongerminomatous germ cell tumor, although many of these lesions are comprised of mixed elements. The presence of serum or cerebrospinal fluid tumor marker elevation has been an essential determinant of response to treatment. Because of the deleterious effects of irradiation on the immature nervous system, investigators have used chemotherapeutic strategies that either reduce or eliminate radiation therapy. In this article, we review the most recent advances in therapy for CNS germ cell tumors in the pediatric population and highlight the importance of cooperative trials in this setting.

Brain Neoplasms↗

Common regions of deletion on chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade.

Approximately 30% of human astrocytomas have been reported to display allelic loss of the long arm of chromosome 22, suggesting the presence of a chromosome 22q astrocytoma suppressor gene. To define the most likely location for this putative tumor suppressor, we performed deletion mapping on 141 tumors using 16 chromosome 22q microsatellite markers. Allelic loss of 22q was observed in 2/12 (17%) of astrocytomas, 9/29 (31%) of anaplastic astrocytomas, and 38/100 (38%) of glioblastomas, consistent with a role for chromosome 22q loss in astrocytoma progression as well as formation. Twenty-two tumors exhibited allelic loss at every informative locus, consistent with loss of the entire arm of 22q. Twenty-seven tumors showed partial deletions, with one common region of deletion at 22q12.3-q13.1 between markers D22S280 and D22S282, and a second candidate region at 22q13.2 near the marker D22S1170. For the proximal candidate region, the incidence of allelic loss was similar between grades; for the distal locus, the incidence increased with grade, raising the possibility that the distal locus is involved in a later stage of astrocytoma tumorigenesis.

Alleles↗

High-dose conformal radiotherapy influenced the pattern of failure but did not improve survival in glioblastoma multiforme.

BACKGROUND AND PURPOSE: Although glioblastoma multiforme is clearly radiation-resistant, there is evidence of a dose-dependent response relationship. The purpose of the study was to evaluate the impact of higher dose by rotational multileaf collimator (MLC) conformal radiation therapy. MATERIALS AND METHODS: From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme were treated using the rotational MLC conformal therapy. There were 25 men and 13 women with a median age of 47 years (12-73 years, mean 46.5 years). Median Karnofsky performance score was 80 (30-100, mean 78.2). Median tumor volume was 64 cc (8-800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy in 1, partial resection in 13, subtotal resection in 21, and gross total resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy) in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter. Biweekly i.v. chemotherapy was also administered for both arms. RESULTS: The 1-year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and 15%, respectively. Univariate analysis showed the initial tumor volume, residual tumor volume, and Karnofsky performance score were statistically significant factors for survival. Only the residual tumor volume was statistically significant by multivariate analysis. The 5-year survival rate of patients with residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90-Gy Group appeared inferior to that of the Low-Dose Group, though no statistical difference was seen (the 3-year survival was 40% vs. 22%). Local failure was observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in pattern of failure was statistically significant. Two patients of the High-Dose Group developed radiation necrosis and one died of it. CONCLUSIONS: The high-dose conformal radiotherapy did not improve survival in the disease, but did change the pattern of failure.

Adolescent↗

Expression of vascular endothelial growth factor in human brain tumors.

Compared to normal brain an increased expression of vascular endothelial growth factor (VEGF) has been reported in many types of brain tumors. However, the numbers of samples analyzed and information about the cellular distribution of VEGF have been limited. Here we used novel monoclonal antibodies against VEGF to analyze, using immunohistochemistry, Western blotting and enzyme-linked immunosorbent assay, its expression in 108 human brain tumors that included astrocytic tumors, meningiomas, pituitary adenomas, primary intracranial germ cell tumors and neuronal tumors. The results showed that 37 of 48 astrocytic tumors (77%) and 15 of 19 meningiomas (79%) were immunoreactive for VEGF, consistent with previous reports. However, in contrast to a previous report that analyzed only VEGF mRNA; all of our 15 pituitary adenomas showed specific immunoreactivity for VEGF. We also extended the studies to previously unanalyzed neoplasms: 13 of 15 primary intracranial germ cell tumors (82%), and 7 of 10 neuronal tumors (70%) were immunoreactive for VEGF. Direct protein analysis by Western blotting confirmed the expression of VEGF in those tumors, and showed differential expression of the isoforms of VEGF protein; a pituitary adenoma expressed both VEGF165 and VEGF189 proteins, a central neurocytoma expressed only VEGF165, while an immature teratoma expressed only VEGF189. The data herein show that VEGF is expressed in a wide spectrum of brain tumors and suggest differences among tumor entities in the mechanisms of VEGF up-regulation as well as their employment of distinct VEGF isoforms for neovascularization.

Adenoma↗

Effect of cilostazol in preventing restenosis after percutaneous transluminal coronary angioplasty.

This study sought to evaluate the effect of cilostazol in preventing restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) in 68 patients: 35 patients received cilostazol immediately after PTCA and 33 patients received aspirin or ticlopidine. Repeat coronary angiography was performed 4 to 6 months after PTCA and the incidence of restenosis was significantly lower (17%) in the cilostazol group than in the non-cilostazol group (40%) (p < 0.05), which indicates that cilostazol has the potential to prevent restenosis after PTCA.

Aged↗

Proliferative activity of central neurocytoma: measurement of tumor volume doubling time, MIB-1 staining index and bromodeoxyuridine labeling index.

Central neurocytoma is considered to be a benign intracranial neoplasm, but little is known about the biological behavior of this type of tumor. Proliferative activity of central neurocytoma was measured in 10 cases using MIB-1 staining for Ki-67 antigen. The MIB-1 staining value varied from < 0.1% to 5.6%, to indicating that some of these tumors have proliferative potential similar to that of anaplastic astrocytoma or malignant meningioma. The bromodeoxyuridine labeling index (BUdR LI, BrdU LI) was measured in 2 cases and the results correlated well with those of the MIB-1 analysis. Tumor volume doubling time (Td) measured in one case was 358 days which is similar to that of malignant meningioma. In one case, the MIB-1 value taken before and after 58 Gy of radiation treatment decreased markedly from 5.6% to 0.2%. The other 9 cases were also treated by radiation therapy (50-60 Gy) and no tumor recurrence was observed during follow-up periods ranging from 23 to 160 months. Another two patients with partially removed and 3 with subtotally removed tumors showing relatively high MIB-1 values might also have benefited from radiation therapy.

Adult↗

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases.

The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

Adolescent↗

[Recurrent hypertensive intracerebral hemorrhage: characteristics and risk factors].

From January 1978 to December 1995, a total of 269 patients with hypertensive intracerebral hemorrhage were treated in our institution. We reviewed 23 patients with recurrence to analyze their characteristics and risk factors. RECURRENCE RATE: The recurrence rate was 8.6%, showing it is not so rare. HEMORRHAGIC SITE: In the first hypertensive intracerebral hemorrhage, the hemorrhagic site was putaminal in 60.9%, subcortex in 13.0%, thalamic in 8.7% and cerebellar in 8.7%. In the second episode, the site was putaminal in 39.1%, thalamic in 34.8%, cerebellar in 13.0%, and subcortex in 8.7%. Therefore, during recurrence, hemorrhage occurred relatively more frequently in the thalamus than in the initial site. INTERVAL TO REBLEEDING: The Interval between the first and second hemorrhage ranged from 2 months to 15 years (average 4 years and 7 months). BLOOD PRESSURE AND RECURRENCE: In patients in whom hypertensive intracerebral hemorrhage recurred in less than 3 years from the initial hemorrhage, blood pressure was well controlled by antihypertensive drugs during the interval. This indicates that factors other than blood pressure control are concerned in the prevention of recurrence. In patients in whom hemorrhage recurred 3 years or more after the initial episode, blood pressure was poorly controlled, indicating that strict antihypertensive therapy is necessary to prevent recurrence after a long interval. RISK FACTORS FOR RECURRENCE: The following risk factors for recurrence of hypertensive intracerebral hemorrhage have been reported in the literature: diastolic blood pressure > or = 100 mmHg; unstable-hypertension (blood pressure abruptly rising from the normal range) : uncontrollable hypertension; and hypoproteinemia. Of these, we emphasize that unstable hypertension is the most important risk factor, as illustrated in our series of patients.

Adult↗

[Chemoradiation for malignant brain tumors].

The author reviewed treatment results of chemoradiation therapy for malignant brain tumors. For astrocytic tumors, radiation therapy combined with radiosensitizing chemotherapeutic agents, mainly nitrosourea compounds (BCNU or ACNU), has been a standard treatment modality for a long time. The therapy is more effective for anaplastic astrocytoma than glioblastoma. The chemoradiation therapy is now applied for medulloblastoma; it prolonged 5-year survival up to 70%. Metastatic brain tumors are frequently treated by radiation therapy alone. When combined with cisplatin, radiation therapy shows a more excellent antitumor effect.

Antineoplastic Agents↗

Solitary metastasis to the choroid plexus of the lateral ventricle. Report of three cases and a review of the literature.

Three cases of cancer metastasis to the choroid plexus of the lateral ventricle are reported. The metastases were from sigmoid colon cancer, renal cell carcinoma and pulmonary cancer, and were located in the trigone in two cases and the right inferior horn in one. Total removal was accomplished in all cases without any complications. In addition, eight reported cases of single brain metastasis to the choroid plexus of the lateral ventricle, including clinical and radiological features, are discussed. Peritumoral edema on computed tomographic (CT) scan or magnetic resonance (MR) imagining was found to be an important feature of metastasis developing at this site.

Aged↗

Comparison of whole brain radiation therapy and locally limited radiation therapy in the treatment of solitary brain metastases from non-small cell lung cancer.

The benefit and risk of whole brain radiation therapy (WBRT) compared to locally limited radiation therapy was assessed in 61 patients with solitary brain metastases from non-small cell lung cancer without an unresectable active primary lesion or systemic dissemination in the other organs. Twenty-three patients received local irradiation (Group A), and 38 patients received whole brain irradiation with or without local irradiation (Group B). The survival was significantly better in Group A than in Group B (p < 0.05), with median survivals of 83.1 and 30.7 weeks, respectively. One-year local recurrence rates were 7% in Group A and 21% in Group B, but the difference was not statistically significant. The 1-year distant recurrence rate was similar at 18%. Radiation-induced dementia occurred in two patients in Group A (8.7%) and seven in Group B (18.4%), but was not statistically significant (p = 0.30). There is no obvious benefit and possible disadvantages of WBRT compared to local irradiation for the population of patients investigated in this study. Intraoperative radiation therapy or stereotactic radiosurgery without WBRT should be considered in the patients with solitary brain metastases.

Adult↗