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Biomedical subjects

K Kawamoto

Publications and source records attributed to K Kawamoto.

At least 181 records · Page 10Linked to original sources
PubMed1991

Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation.

Three ACNU-resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross-resistance to vinblastine, adriamycin, and VP-16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels in these sublines were elevated 2- to 3-fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cysteine, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X-ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator.

Animals↗
PubMed1991

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light.

This is the first report on the use of photodynamic therapy (PDT) for rat pituitary tumor in vivo. Rat pituitary tumor (GH3) cells were cultured, GH3 tumor was subcutaneously implanted in nude mice, and pheophorbide-a (Ph-a) and white light were prepared. Photocytotoxicity proportional to Ph-a concentration, intensity of irradiation, and incubation time was observed in vitro. Despite the delay in the disappearance of Ph-a from the tumor, Ph-a in the pituitary gland rapidly decreased after intravenous administration in vivo. Through PDT, the tumor grossly disappeared, the plasma levels of rat growth hormone secreted from the tumor also remarkably decreased, and the development of giantism was inhibited. These results indicate that PDT is effective against rat pituitary tumor.

Animals↗
PubMed1991

Flow cytometric analysis of antineoplastic effects of interferon-alpha, beta and gamma labelled with fluorescein isothiocyanate on cultured brain tumors.

Antineoplastic effects of interferons (IFNs) on brain tumors have often been reported in the literature, however, so far as we know, there are no reports of the study on the antineoplastic effect of IFNs (alpha, beta, and gamma) labelled with fluorescein isothiocyanate (FITC) using flow cytometry (FCM). Three established glioma cell lines and 11 cultured cells of brain tumor from surgical specimens were exposed to IFN-alpha, beta, and gamma at the concentrations of 10(2)-10(5) IU/ml for 24 h, respectively. Using FCM, the viability of the cells was evaluated with fluorescein diacetate stain and the cell cycle was analyzed from the DNA-histogram with propidium iodide stain. Furthermore, FITC-labelled IFN-alpha, beta and gamma were also contacted with each cell to calculate respective positive cells. The viability decreased about 60% on day 1 and day 3, indicating the effect of IFN-alpha and beta on U373MG cells and on some cultured glioma cells from surgical materials, whereas, IFN-gamma had no effects. Antineoplastic effect of each IFN well correlated with FITC-positive rates, demonstrating S phase block in the cell cycle. IFN-gamma had no antineoplastic effects, whereas IFN-alpha and beta showed antineoplastic effects, which fact suggested that IFN-gamma receptor be different from those of IFN-alpha and beta. The method of FITC-labelling for IFNs with the aid of FCM has the advantages as follows: 1) Antineoplasticity of IFN can be simply evaluated with FCM; 2) It is easy to analyze the action mechanism of IFN; 3) Information on the receptor is obtainable; and 4) Sensitivity can be evaluated prior to administration of IFN, suggesting possibilities of clinical application of this method.

Antineoplastic Agents↗
PubMed1991

Central neurocytoma: immunohistochemical and ultrastructural study.

Eight cases of central neurocytomas were studied by immunohistochemistry and electron microscopy. Seven tumors were located in the lateral ventricles and one in the subependymal region. All but one patient had a favorable postoperative course. The tumors were composed of small uniform cells possessing amitotic round nuclei with frequent perinuclear halos, a few Homer Wright rosettes and no ganglion cells; an appearance resembling that of oligodendroglioma. Immunohistochemical studies disclosed neuron-specific enolase and Leu-7 positivity in all tumors, S-100 protein-positive cells were found in six, while glial fibrillary acidic protein--and vimentin-positive cells were confined to the blood vessels. Myelin basic protein as well as neurofilament were not detected in the tumors. Synaptophysin-positive areas were seen in one tumor. Ultrastructural examination showed distinctive neuronal tumor cells which had a cytoplasm with sparse dense-core vesicles and thin cell processes containing parallel microtubules. They were classified into three different types of tumor cells according to the extent of differentiation. The most consistent finding for histological diagnosis was the presence of typical or abortive synapses with clear and dense-core vesicles. Additionally, synaptophysin may be a specific marker for some central neurocytomas.

Adult↗
PubMed1991

A case report of juvenile polyposis with adenomatous change and a review of 34 cases reported in Japan.

It has recently come to be thought that cases of juvenile polyposis have a natural tendency to develop adenoma and/or carcinoma. Here we present a case of juvenile polyposis coli with adenomatous change in a 21-year-old male, with a review of 34 cases of juvenile polyposis in the Japanese literature, and discuss the pathogenetic development of the polyps and their malignant potential. In this case, focal or entire adenomatous areas were found in large part of the polyps in the resected sigmoid colon and rectum, though these findings had not been recognized in 23 polypectomy specimens from the rectum 10 months prior to the operation. It was suggested that adenomatous change developed quickly in a very short time.

Adenocarcinoma↗
PubMed1991

A case report of hepatocellular carcinoma within adenomatous hyperplasia: is adenomatous hyperplasia a precancerous lesion or not?

It is controversial whether adenomatous hyperplasia (AH) of the liver progresses to hepatocellular carcinoma. We experienced two hepatic lesions in a patient (73-yr-old male) with cirrhotic liver. One was diagnosed as HCC and the other was AH including a small HCC histologically. To investigate cell kinetics and the ploidy pattern of these lesions, Feulgen DNA-cytofluorometry analysis was performed. The result of this analysis suggested that AH developed into extremely well-differentiated HCC composed of mononuclear diploid cells at first and then was further transformed into clear cell type HCC composed of mononuclear tetraploid cells. The development of human HCC, at least in cirrhotic liver, may therefore be a multi-step process.

Aged↗
PubMed1991

A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH).

The authors report a very rare case of pituitary adenoma producing both GH and ACTH. A 29-year-old female was admitted with obesity, amenorrhea, acromegaly, hirsutism, excessive pigmentation, acne, and diabetes mellitus. Computed tomography revealed an intrasellar tumor 16 mm in height, with a destroyed sellar floor. The blood concentrations of GH, ACTH and cortisol were increased (GH: 92 ng/ml, ACTH: 94 pg/ml, cortisol: 18.3 micrograms/dl). No diurnal variation in the amount of cortisol was observed. The urinary 17-OHCS was suppressed by 8 mg but not by 2 mg of dexamethasone. A subtotal adenomectomy was then performed through the transsphenoidal approach, which led to a sufficient reduction of both blood GH and ACTH (cortisol). Histologically the tumor was an acidophilic pituitary adenoma. Immunoperoxidase staining showed diffuse GH and sporadic ACTH producing cells, but failed to show any cells producing both hormones. The electron micrograms of neoplastic cells showed the ultrastructural characteristics of respective GH and ACTH cells. Another increase in both GH and cortisol, which occurred 19 months after the operation, has been controlled by bromocriptine administration. This case may be the first reported case of a pituitary adenoma producing both GH and ACTH, not accompanied by prolactin (PRL) hypersecretion, which has been fully confirmed endocrinologically and histopathologically.

Adenoma↗
PubMed1991

[Establishment of ACNU-resistant rat gliosarcoma cell lines and their characteristics].

One of the most serious problems in cancer chemotherapy is the acquired drug resistance of tumor cells. In order to investigate the mechanism of acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), nine resistant cells were isolated from rat gliosarcoma 9L cells and characterized. ACNU-resistant cells were easily isolated after a single treatment even with low-dose ACNU (5 micrograms/ml). However, in spite of repeatedly high-pressure dose of ACNU, more than 30 fold increase to parental 9L cell resistance was not achieved. At this time, further increase in selection pressure resulted in cell death. The resistant ratios of these resistant cells were stable in the absence of ACNU for more than 1 year. Luria and Delbrück's fluctuation test indicated that the appearance of ACNU-resistant cells occurred spontaneously at a rate of (4.40-8.02) x 10(-7)/cell/generation. In karyotypic analysis, the mode was higher in the resistant cells than in 9L cells, but a homogeneously staining region or double minute chromosome, which was considered to be a result of gene amplification, was not observed. In growth kinetics, all the resistant cells except R1 and R12 cells had higher saturation density and plating efficacy than parental 9L cells. These findings seemed to be due to cellular modification associated with ACNU resistance.

Animals↗
PubMed1991

Cross-resistance patterns in ACNU-resistant glioma sublines in culture.

Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance.

Animals↗
PubMed1991

Hypersensitivity of rat glioma sublines with acquired ACNU resistance to L-asparaginase.

Cell lines resistant to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) show a high degree of collateral sensitivity to L-asparaginase. The mechanism for this phenomenon was investigated by comparing the nutritional requirements and asparagine synthetase activity of the resistant sublines to those of parent cells. Nine ACNU-resistant sublines were isolated from rat glioma 9L cells after incubation with various concentrations of ACNU in Ham's F-12 medium. The 9L cells grew independently of asparagine, developing well in asparagine-deficient Dulbecco's modified Eagle's medium. In contrast, the growth rates of all nine ACNU-resistant sublines decreased under the same conditions and required the addition of 10(-4) M asparagine for maximum growth. Asparagine synthetase activity in the ACNU-resistant cells was much lower than in the 9L cells, suggesting that the requirement for asparagine in the resistant sublines was due to reduced activity of this enzyme. A growth-inhibition assay showed that the ACNU-resistant sublines were more sensitive to L-asparaginase than 9L cells by up to 2 x 10(5)-fold. These results suggest that L-asparaginase therapy has the potential to become a new approach for treating acquired ACNU resistance.

Animals↗
PubMed1991

[Multidisciplinary therapy using interferon and immunological evaluation for glioma patients: two-color analysis of T cell subsets].

We have employed IAR therapy [combination of postirradiation, chemotherapy and interferon (IFN)] for malignant glioma patients. Changes of lymphocyte fractions in patients were evaluated before and after IAR therapy, using a recently developed two-color analysis. Eight malignant glioma patients received irradiation, chemotherapy (ACNU) and immunotherapy (OK-432 and IFN-beta). Peripheral blood lymphocytes taken during hospitalization with IAR therapy (first half and latter half), and every 3 to 6 months for 2 years at the longest after IAR therapy were double-stained with FITC- and PI-labelled antibodies and two-color analysis was conducted by a FACS Analyzer. Six patients out of 8 survived for 6 months to 2 years, 2 died after 3 and 6 months, respectively. Leu-2a (suppressor/cytotoxic T), especially Leu-2a+ 15- (cytotoxic T) showed a high value. Leu-2a level decreased during treatment, and both Leu-2a+ 15- and Leu-2a+ 15+ (suppressor T) values decreased. Two thirds of the patients showing an increased Leu-2a+ 15+ level died. Leu 3a (helper/inducer T), especially Leu-3a+ 8+ (inducer T) level decreased, but Leu-3a+ 8- (helper T) level increased during treatment. The level decreased in the worse patients. Leu-3a/Leu-2a ratio was low, but it increased during treatment as compared with the results of conventional therapy. Leu-7, Leu-11a, NK activity, and gamma-IFN productivity were further studied. Treatment combined with IFN revealed an influence on the T cells resulting in an increase of helper T level and suppression of suppressor T level.

Adult↗
PubMed1991

[Regeneration of peripheral nerves and intracerebral transplantation].

Axoplasmic flow is essential to the regeneration of peripheral nerves. We observed a mean of 12 mm/day for the slow axoplasmic flow and a mean of 410mm/day for the fast axoplasmic flow. In the process of regeneration of peripheral nerves, however, slow transport increased to 14.7mm/day and fast transport to 572mm/day on day 7. We reviewed the relevant literature on the axoplasmic flow and described the topics in this report. Some central nerves may show poor regeneration but it has been confirmed that nerve cells grow and survive by intracerebral nerve transplantation, and this technique has been applied to the treatment of Parkinson's disease. Further development can be expected for the regeneration of central nerves through transplantation.

Animals↗
PubMed1991

Establishment and characterization of human medulloblastoma xenograft line.

A new xenotransplantable tumor line, MED-FU, was derived from a 6-year-old female patient with cerebellar medulloblastoma. This tumor was grown in nude mice as serially transplantable subcutaneous xenografts composed of small round cells with hyperchromatic nuclei and scant cytoplasm. Many rosettes and mitoses were observed. Immunohistochemically, glial fibrillary acidic protein (GFAP), S-100 protein, and neuron specific enolase (NSE) were not detected. The doubling time of the subcutaneous tumors was 6.8 days. Highly concentrated polyamines were detected in the tumor tissue and serum of tumor-bearing mice. This xenotransplanted tumor line, MED-FU, is considered to provide an available experimental model for the study of human medulloblastoma.

Animals↗
PubMed1991

Antineoplastic effects of natural killer cells sorted with flow cytometry on brain tumors.

For the purpose of FCM, we have developed a new method of sterile sorting of NK cells by negative selection using FITC-labelled monoclonal antibodies. In this method, over 95% lymphocytes with large granular lymphocytes (NK cells) were obtained by exclusion of Leu-1 and HLA-DR positive cells from human peripheral blood. From the results of cytotoxicity test of NK cells against 4 types of glioma cell lines and 6 kinds of cultured cells from surgical materials, the antineoplastic effect was recognized in 4 out of 6 surgical materials. Administration of NK cells through an Ommaya tube in 2 brain tumor patients caused no side effects. This technique is clinically applicable because 1) NK cells are easy to obtain, 2) NK cells show antineoplastic effect on brain tumors, and 3) the sensitivity can be evaluated in individual patients.

Antibodies, Monoclonal↗
PubMed1990

Multiple oligodendroglioma--case report.

A 32-year-old male was hospitalized with headache and disturbance of consciousness. Computed tomography (CT) revealed a tumor and an intracranial hematoma in the right frontal lobe. The tumor was totally removed, and postoperative radiation therapy was administrated locally at 50 Gy. Five years later, he experienced sudden onset of headache and vertigo. CT demonstrated a mass lesion with a hematoma in the cerebellar vermis. The tumor was subtotally removed and he underwent postoperative local irradiation at 50 Gy as well as ventriculoperitoneal shunting. Four years later, he complained of visual and gait disturbances, and CT disclosed a tumor in the suprasellar region. Following partial removal of the tumor, local brain irradiation was given at 40 Gy. Histological examination proved all three tumors to be oligodendrogliomas with no evidence of malignant change.

Adult↗