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Biomedical subjects

H Mogami

Publications and source records attributed to H Mogami.

At least 163 records · Page 9Linked to original sources
PubMed1986

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) against peritoneal dissemination of intracranial germ cell tumor.

We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram. Our results suggest that combined PVB therapy is effective in the treatment of extraneural metastasis from intracranial germ cell tumors.

Adult↗
PubMed1986

Effects of ACNU and radiotherapy on malignant glioma.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Adolescent↗
PubMed1986

Development of experimental meningeal gliomatosis models in rats.

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of rat C6 and 9L glioma cells into Wistar and Fischer 344 rats, respectively. Tumor growth was steady and rapid in both MG models when more than 10(6) tumor cells were implanted. The median survival time of the rats inoculated with tumor cells was inversely related to the number of the cells inoculated. The clinicopathological features observed in both MG models were similar to those seen in diffuse leptomeningeal involvement of gliomas in humans. The models may be useful for investigating the pathophysiology of MG and for the determination of the efficacy of chemotherapeutic agents in brain-tumor chemotherapy.

Animals↗
PubMed1986

[The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma].

We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1986

[Overcoming of ACNU resistance in a subline of rat glioma in vitro and in vivo by reserpine].

Reserpine was shown to enhance the cytotoxicity of ACNU in both C6 and C6/ACNU rat glioma cells in vitro and also to enhance the chemotherapeutic effect of ACNU in C6/ACNU-bearing rats (C6/ACNU meningeal gliomatosis rats), in which ACNU resistance could be partially overcome by reserpine. When reserpine was added to the culture at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. Intracellular uptake of ACNU in C6/ACNU cells increased and the efflux from the cells decreased when 20 microM reserpine was added to the culture. In in vivo experiments, combined ACNU (1 mg/kg) and reserpine (250 micrograms/kg) therapy by intrathecal injection of these drugs improved % ILS (increased life span) with statistical significance compared with that after treatment with ACNU alone. The probable explanation of the enhanced cytotoxic-effect of ACNU in ACNU-resistant glioma cells presented in in vitro and in vivo is increased intracellular ACNU concentration resulting from inhibition of the efflux of ACNU from the resistant cells.

Animals↗
PubMed1986

[Mechanism and overcoming of resistance in ACNU-resistant sublines of rat brain tumors].

One of the most serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of such resistance to ACNU and the means to overcome it, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU were selected in vivo. Uptake and retention of ACNU in these resistant cells were studied with [14C] ACNU. The results indicated that the resistance exhibited by both sublines of C6/ACNU and 9L/ACNU were due to both reduced uptake and retention of the drug. In an attempt to clarify the more detailed biochemical mechanism of resistance in these cells, we surveyed various membrane-modifying agents which potentiate the sensitivity of these resistant cells to ACNU. Among a number of membrane-modifying agents, calcium antagonists, especially nicardipine and verapamil, were found to cause retention of ACNU in the resistant cells and to enhance the effect of ACNU on these resistant cell lines. It might therefore be concluded that ACNU resistance can be overcome by membrane-modifying agents, such as nicardipine and verapamil.

Animals↗
PubMed1986

[Studies on the mechanism of ACNU resistance in sublines of rat C6 glioma and 9L gliosarcoma in vitro].

One of the serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of this resistance against chemotherapeutic agents, especially ACNU, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] were selected previously in vivo from rat C6 glioma and 9L gliosarcoma, respectively. Uptake and retention of ACNU in these resistant cells were studied with [14C]ACNU. The result indicated that the resistance exhibited by both sublines of C6/ACNU and 9L/ACNU cells were due to the reduced uptake and retention of the drug. The study of the effects of oxidative phosphorylation inhibitor, DNP (2, 4-dinitrophenol), on the uptake and retention of ACNU suggested that there is an active outward transport mechanism for ACNU in 9L/ACNU cells. It might be concluded that ACNU-resistant brain tumor cells are resistant to ACNU by virtue of both the reduced uptake of the drug and the increased active efflux.

Animals↗
PubMed1986

[Possibility of overcoming of ACNU resistance in an ACNU-resistant subline of C6 rat glioma].

Membrane-modifying agents such as reserpine, calcium antagonists (nicardipine, verapamil) and calmodulin inhibitor (trifluoperazine) were found to enhance the cytotoxicity of ACNU in vitro and in vivo in ACNU-resistant C 6 (C 6/ACNU) glioma. In in vitro experiments, uptake and retention studies with [14C] ACNU revealed that intracellular uptake and retention of ACNU in C 6 cells were larger than those in C 6/ACNU cells, and that these membrane-modifying agents increased the cellular uptake and retention of ACNU in C 6, especially in C 6/ACNU cells. The amount of ACNU in C 6/ACNU cells reached the same level as that detected in C 6/ACNU cells. When these drugs were added along with ACNU at the concentration of 10 to 20 microM to the culture in vitro, ACNU resistance was completely overcome. In in vivo experiment, reserpine, nicardipine, verapamil and trifluoperazine in doses 250 to 500 micrograms/kg intrathecally administered with 1 mg/kg ACNU 1 day after the tumor inoculation significantly enhanced the chemotherapeutic effect of ACNU in C 6/ACNU bearing (C 6/ACNU-MG) rats. It might be concluded that the mechanism of enhancement of ACNU cytotoxicity presented in in vitro and in vivo is explained by the enhanced accumulation of ACNU by these membrane-modifying agents in C 6, especially in ACNU-resistant (C 6/ACNU) cells, and, furthermore, that combination chemotherapy with ACNU and such membrane interacting drugs as reserpine, calcium antagonists (nicardipine, verapamil) and calmodulin inhibitor (trifluoperazine) could lead to the capability of overcoming resistance to ACNU in glioma.

Animals↗
PubMed1986

[Intrathecal ACNU against malignant leptomeningeal tumors--toxicity and therapeutic effect in experimental animals].

Leptomeningeal dissemination is one of the major causes which increase the morbidity and mortality of the patients with malignant brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and therapeutic effect of intrathecal ACNU (nimustine hydrochloride) using experimental animals. Systemic and local toxicity was tested in normal rats that received ACNU intracisternally. The animals given ACNU more than 3.0 mg/kg progressively lost their body weight, and ACNU 6.0 mg/kg was fatal in 80% of animals. Animals given ACNU less than 1.5 mg/kg gained weight in the same rate as in control animals. Increased capillary permeability to intravenous Evans blue was observed in the subpial region of the brain in the rats given ACNU 6.0 mg/kg intracisternally. The increase of capillary permeability was dominant along the ambient cistern, hypocampal fissure, and at the base of the brain. Demyelinization and loss of neurons were seen in the same areas as well. These changes were not observed in the animal given ACNU less than 1.5 mg/kg. Therapeutic effect of intrathecal ACNU against the leptomeningeal tumor was studied in rats with meningeal carcinomatosis which was induced by intracisternal inoculation of 1 X 10(4) cells of Walker 256 carcinosarcoma. The median survival times of the animal given ACNU 1.5 mg/kg intrathecally on day 2 or 5 after tumor inoculation were prolonged by 55 to 64%, and 64 to 145%, respectively, as compared to those of untreated control animals (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2].

We have studied the in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2 (rIL-2). LAK cells were generated by placing 5 X 10(7) fresh C 57 BL/6 splenocytes (erythrocytes were lysed osmotically) in 10-cm (diameter) dishes (Falcon) containing 10 ml of complete medium (CM). The CM consisted of RPMI 1640 with 0.1 mM non-essential amino acids, 1 microM sodium pyruvate, 5 X 10(-5)M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine, 10% heat-inactivated fetal calf serum (FCS) and 10 units/ml of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd). The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hr. The LAK cells were then harvested, washed three times, and resuspended in RPMI 1640 with 5% heat-inactivated FCS for the in vitro cytotoxicity assay. The antitumor cytotoxic activity of LAK cells was estimated in triplicate by 4 hr 51Cr release assays. The cytotoxic activity of LAK cells against syngeneic 203 glioma and normal syngeneic glioblasts was approximately 50% and a few %, respectively. The in vitro cytotoxicity of LAK cells against syngeneic EL-4 thymoma, allogeneic YAC-1 lymphoma and P-815 mastocytoma was 72%, 87% and 43%, respectively. Thus LAK cells have apparent tumor specificity in vitro and are easily generated. Fresh splenocytes of CBA/J mice were markedly lytic for natural killer (NK)-sensitive YAC-1 cells, but not for 203-glioma cells or NK-resistant P-815 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Lumbosacral lipoma: computed tomographic scan findings and surgical correction].

Display of the specific anatomic derangements by high-resolution computed tomographic (= CT) scan provides an important basis for planning corrective surgery of lumbosacral lipoma. In this paper, analysis of four infants and a child with lumbosacral lipoma revealed following discrepancy between the image by CT scan and operative finding. Most of lipoma showed a sharply outlined area of low density (approximately -100 H.U.) in the CT scan. Lipoma in the spinal cord parenchym represented intermingled fatty and neural tissue. There were also relatively high density areas in some cases and correspondingly, there were very fibrous lipomas, which could be identified by microscopic histological examination. Although there was a general correlation between the site of lumbosacral skin abnormality and underlying intraspinal lesion, some case does not match perfectly. In conclusion, a removal of the lumbosacral lipoma for the tethering effect always preferable to a total extirpation even though with technological advances in operative magnification and surgical instrumentation and a removal of the compressing lamina is necessary for adequate decompression.

Child↗