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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 379 records · Page 21Linked to original sources
PubMed1986

[Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy in the treatment of intracranial malignant germ cell tumors--a preliminary report of a phase II study--The Japanese Intracranial Germ Cell Tumor Study Group].

Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy was undertaken in 30 patients with primary intracranial malignant germ cell tumors in 11 neurosurgical clinics. The response rate of 17 evaluable patients with nonrecurrent tumors was 64.7% (eight CR and three PR), and that in eight patients with recurrent tumors was 50% (two CR and two PR). The one-year and two-year survival rates were 76.2% and 67.7%, respectively, which are better than the treatment results by radiation therapy alone, i.e., 69.8% and 46.5%. These findings suggest that PVB therapy is effective for intracranial malignant germ cell tumors.

Adult↗
PubMed1986

[Cerebral hemodynamics in chronic hypoxic hypoxia].

The effects of chronic-hypoxic hypoxia on cerebral blood flow and its regulating mechanisms were investigated by means of intracardiac injection of radioactively labelled microspheres. In a gas chamber designed and constructed for the purpose, adult cats were exposed to stepwise decreasing inspiratory oxygen concentrations (for 4.5 months with a final O2 concentration of 8 vol%). Using animals adapted to hypoxic hypoxia, responsiveness of cerebral blood flow either to alterations in systemic arterial pressure (SAP) or to alterations in arterial blood oxygen tension (PaO2) were assessed. Flow measurement was done under three different conditions: normoxic normotension (PaO2 greater than 100 mmHg; SAP greater than 100 mmHg), hypoxic normotension (PaO2 = 30 mmHg; SAP greater than 100 mmHg), or normoxic hypotension (PaO2 greater than 100 mmHg; SAP = 60 mmHg). Hematocrit values continuously increased to 56% during the process of adaptation to hypoxia. There was also a remarkable increase in cardiac output of hypoxia-adapted animals subjected to hypoxia and to normoxia. Chronic-hypoxic hypoxia led to increased cerebral blood flow, which persisted even when animals were returned to normoxia. Under hemorrhagic hypotension, cerebral blood flow fell significantly in animals adapted to chronic-hypoxic hypoxia but did not fall short of the absolute values in controls. The relative reduction in cerebral blood flow might be attributable to the decrease in cardiac output and to altered blood viscosity. This implied that, even in animals subjected to long-standing graded hypoxic hypoxia, autoregulatory capacity might be partly preserved.

Adaptation, Physiological↗
PubMed1986

[Efficacy of intracisternal papaverine on symptomatic vasospasm].

This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and decreasing level of consciousness. Bolus injection of 40 mg of 1% papaverine hydrochloride was started on day 6.3 +/- 1.7 and continued for 4.4 +/- 1.6 days. In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm. There was a close correlation between degree of vasospasm and vasodilatation effect (r = 0.88, p less than 0.01). In all but two cases vasodilatation tended to become prominent by repeat doses, twice a day, for two to seven days (r = 0.87, p less than 0.01). Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases (one by high concentration 4% papaverine) during the treatment. Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

Cerebral Angiography↗
PubMed1986

[Treatment modalities for malignant gliomas with reference to their pathophysiology].

The histological classification, pathophysiology, and treatment modalities of malignant gliomas (glioblastoma, malignant astrocytoma) were reviewed with reference to the WHO classification of primary brain tumors and the recent progress made in glioma biology. Patients with glioblastoma and malignant astrocytoma showed, respectively, 10.6% and 22.2 of the five-year survival rate according to the All Japan Brain Tumor Registry. In order to improve the prognosis of malignant glioma patients, many clinical trials have been conducted throughout the world. Malignant gliomas that grow in and invade the brain parenchyma cannot be cured by surgical resection. One should treat the residual tumor with irradiation, chemotherapy and immunotherapy. Radiation therapy alone and radiation therapy plus chemotherapy using nitrosoureas or procarbazine have been proved statistically to be more effective for malignant gliomas than supportive care and radiation therapy alone, respectively. Prospective clinical trials support the view that malignant gliomas should be treated vigorously using a multimodal approach that includes surgical resection, high-dose radiation therapy, and prolonged maintenance chemotherapy.

Antineoplastic Agents↗
PubMed1985

Alterations of the eicosanoid synthetic capacity of rat brain microvessels following ischemia: relevance to ischemic brain edema.

To know the mechanism underlying ischemic brain edema, a time-course analysis of the eicosanoid synthetic capacity of brain microvessels was carried out using unilateral, middle cerebral artery (MCA)-occluded rats. Concomitant with the development of brain edema the synthetic capacity of all products, including cyclooxygenase and lipoxygenase products, increased significantly. Next the effects of 15-hydroperoxyarachidonic acid (15-HPAA) on the synthetic capacity of microvessels were examined. The drug caused a generalized increase of each product, the profile of which was similar to that obtained with ischemic hemispheres, although the ratios of each product differed somewhat among them. The enhanced synthesis of eicosanoids by 15-HPAA was markedly suppressed by radical scavengers such as alpha-tocopherol, hydroquinone, and 1,2-bis(nicotineamide)-propane. Furthermore, the evolution of brain edema was virtually suppressed by the systemic administration of 1,2-bis(nicotineamide)-propane. The above result suggests that the enzyme activity of the arachidonic acid (AA) cascade of microvessels is stimulated by its own products. Such a mechanism will form a vicious cycle that accelerates the accumulation of free radicals within microvessels and thus may play a role in the progressing disruption of the blood-brain barrier (BBB) following ischemia.

Animals↗
PubMed1985

T-cell subsets in patients with gastric cancer.

Peripheral blood T-cell subsets of 70 patients with untreated gastric cancer and 55 age- and sex-matched normal controls were studied by using monoclonal antibodies and flow cytometry. The number of T cells (Leu 4+ cells) was significantly decreased in stage IV patients. Statistically significant decreases in the number of Leu 3a+ cells and in the Leu 3a+/Leu 2a+ ratio were also found in stage IV patients. Stage I-III patients showed no marked imbalance in T-cell subsets. Quantitative changes in T-cell subsets in the advanced stage may be one of the factors responsible for the immunosuppression in advanced gastric cancer.

Adult↗
PubMed1985

The efficacy of radiotherapy for craniopharyngioma.

A series of 125 patients who underwent surgery for craniopharyngiomas was evaluated to assess the efficacy of radiation therapy: 45 patients had received radiotherapy and 80 had not. These patients included all operative survivors (excluding cases with total tumor removal) treated during the 30 years from 1950 to 1979. Median survival time of the irradiated group was greater than 10 years, whereas it was 3.12 years for the nonirradiated (or control) group. The 5- and 10-year survival rates were 88.9% and 76.0% for the irradiated group, and 34.9% and 27.1% for the control group, respectively. Overall comparison, using the Lee-Desu statistical method, revealed that there was a very high statistical significance (at the level of p less than 0.0001) in the difference between the survival times of the irradiated and control groups. The influence of the following factors on the effectiveness of radiotherapy was analyzed: age of the patient at the first operation, sex, date of surgery, the extent of tumor removal, the size of the tumor, the composition of the tumor (cystic or solid), whether the tumor was calcified or not, the histological subtype of the tumor, the presence of intracranial hypertension, the grade of visual failure, and the presence or absence of diabetes insipidus, altered mentation, and adiposogenital syndrome. The results indicated that, when total removal of the tumor is impossible, radiotherapy should be administered.

Adolescent↗
PubMed1985

[Antineoplastic effect of Hu-IFN-beta and other anticancer drugs on malignant brain tumors in athymic nude mice].

We have been studying the therapeutic effect of anticancer drugs such as ACNU and vincristine in human glioma-bearing nude mice models and this time, the effect of interferon was also evaluated. Since 1980, the phase 1, 2 clinical trials on Hu-Interferon (IFN) have been studied in the neurosurgical field and the effect is now regarded to be not as pronounced as previously expected. It is difficult to compare the effect of IFN with other anticancer drugs in an in-vivo study, because of the species specificity of IFN, and only a few studies have so far been reported. With respect to evaluating the therapeutic effect of IFN, the nude mouse model is thought to be useful. The anticancer activity of beta-IFN in nude mice, receiving subcutaneous transplants of human brain tumors (6 strains) was compared with that of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, alpha-IFN, beta-IFN, poly ICLC, the tumor reduction rates were evaluated by Battelle's method. Although in 2 out of 6 glioma strains, the tumor reduction rate (treated/control values) treated with beta-IFN was evaluated as effective, the effectiveness of beta-IFN was inferior to that of ACNU and vincristine. Therefore, further studies are indicated to evaluate the efficiency of the drug at higher dosage levels and to determine its tolerance dose. The combined modality treatment such as chemotherapy and radiation are issues that are still to be settled by further studies.

Animals↗
PubMed1985

[Cerebral blood flow measured by Xenon enhanced CT in brain tumors].

In the management of malignant brain tumors, it is important to know the extent and viability of tumors. However, an ordinary CT scan with iodine enhancement has only a limited ability to distinguish the tumor from surrounding normal tissue. Since the blood flow in tumor tissue was found to be relatively high in a previous experimental report, we have investigated the blood flow in a tumor and the surrounding brain. The Xenon enhanced CT method has several advantages over the conventional isotope method and enables us to evaluate rCBF with the same resolving power as with the CT scan. We evaluated rCBF in 15 brain tumor cases and obtained the following results. Mean rCBF value of the tumor is a little lower than that of gray matter and higher than that of surrounding edema. Our Xe-CT method enables us to distinguish the demarcation between the tumor area and the surrounding edematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumor which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumors. rCBF value and lambda value are important elements to know the uptake rate of anticancer drugs into the brain tumors. And to evaluate these value in each brain tumor is useful in the selection of chemotherapeutic agents.

Adult↗
PubMed1985

[Evaluation of ACNU alone and combined with tegafur as additions to radiotherapy of the treatment of malignant gliomas--a cooperative clinical trial].

Controlled, prospective, randomized studies were performed to evaluate the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and ACNU plus tegafur as additions to radiotherapy for the treatment of malignant gliomas. In the first trial, 105 patients with glioblastoma or anaplastic astrocytoma were randomly divided into two groups after surgery and received radiotherapy (RT, 40 to 60 Gy to the whole brain), or radiotherapy plus concomitant chemotherapy with ACNU (100 mg/m2 on day 1 and 42). Effects of the treatment were compared in 82 evaluable patients from results of CT scans taken before and one month after the completion of radiotherapy. The regression rates more than 50% of the tumor size were observed in 15.0% of patients treated with RT alone and in 47.6% of patients treated with RT plus ACNU. The difference was statistically significant (p less than 0.005). In the second trial, 87 patients were randomly divided into two groups and received RT plus ACNU, or RT plus combined chemotherapy with ACNU and tegafur (400 mg/m2, daily for 8 weeks). Sixty-nine patients were within the valid study group. The regression rates more than 50% of the tumor size were observed in 34.2% of patients treated with RT plus ACNU: and in 41.2% treated with RT, ACNU plus tegafur. No statistical difference was noted in the response rate between the groups. These results indicate that ACNU is an effective agent in conjunction with radiotherapy for patients with malignant gliomas, and that tegafur does not enhance the effectiveness of ACNU.

Adolescent↗
PubMed1985

[The pathomechanism underlying ischemic brain edema: the role of Na+, K+-ATPase of the brain microvessels].

In the present study, the anti-edema effect of AVS [1,2-bis (nicotineamide)-propane] was evaluated using the cat MCA occlusion model with or without recirculation. In the prolonged ischemia (PI) group, cortical edema as assessed by the changes in specific gravity, developed in those cortical areas where the mean 1-CBF was less than 25-30 ml/100 g/min during MCA occlusion (4 hours). In the recirculation group (2 hours' ischemia followed by 2 hours' recirculation: RC group), the ischemic threshold for edema development was almost the same as in the PI group. In both groups, the drop in cortical specific gravity was significantly suppressed by AVS. Regarding the time-course of 1-CBF, there was no difference between the PI-AVS-treated and PI-saline-treated groups. In the RC group, however, the postischemic hypoperfusion was significantly ameliorated by AVS. Based on the present and previous data showing the antiedema effect of AVS, the mechanism of action of AVS was discussed in relation to the pathomechanism underlying ischemic brain edema. Our new concept of ischemic brain edema is briefly stated below. Related in vitro studies have shown the followings: (i) the influx of sodium not of proteins is the principal cause of ischemic brain edema: (ii) the eicosanoid synthetic capacity of the brain microvessel (MV) is increased simultaneous to edema development (iii) an elevation in the level of hydroperoxides enhances the activities of Na+, K+-ATPase as well as the arachidonate cascade of MV. These data suggest that free fatty acids and free radicals liberated following cerebral ischemia stimulate the activity of the MV-Na+, K+-ATPase, which results in increased sodium influx across the BBB. AVS was shown to scavenge hydroxyl radicals and to inhibit the stimulatory effects of a lipid hydroperoxide (15-HPAA) on the activities of Na+, K+-ATPase and the arachidonate cascade of the MV. These actions of AVS may be linked to its antiedema effect.

Animals↗
PubMed1985

[Effects of anticancer drugs on multicellular spheroid of 9L rat brain tumor].

The effects of the anticancer drugs Nimustine (ACNU), Aclacinomycin A (ACR), Adriamycin (ADM), Bleomycin (BLM), Cisplatin (CDDP), and 5-Fluorouracil (5-FU) on the multicellular spheroid of a chemically-induced 9L rat glioma was studied. The multicellular spheroid in which cells grow in vitro as three-dimensional aggregates represents a biological model, which is intermediate between monolayer cells in vitro and solid tumors. Spheroids were initiated in bacteriological grade petri dishes seeded with 10(6) 9L rat glioma cells, cultured for four days and thereafter transferred and further developed in a spinner flask. Spheroids of 200-400 micron diameter were sorted and exposed for 24 hours to 5-FU and one hour for other drugs. After treatment both cytotoxic effect and growth delay were analyzed. Following disaggregation using collagenase, pronase and DNAase, cytotoxic effect on multicellular spheroids was measured by colony forming assay and were compared with those effects on 9L monolayer culture cells in the exponential growth. For growth delay assay, multicellular spheroids were individually transferred to 16 mm well containing 0.4 ml agarose base and 2 ml culture medium. Spheroid size was measured twice a week and growth curves were drawn. The growth delay was determined as the treated group vs. control differences in time required to a size four times that of the initial volume. For cells both in the monolayer culture and the multicellular spheroid, the dose response curve for ADM, BLM and 5-FU was "biphasic" and that for ACNU, ACR and CDDP "shoulder-threshold" type.(ABSTRACT TRUNCATED AT 250 WORDS)

Aclarubicin↗