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N Shitara

Publications and source records attributed to N Shitara.

At least 55 records · Page 3Linked to original sources
PubMed1988

Insulin binds to specific receptors and stimulates macromolecular synthesis in C6 glioma cells.

The existence of insulin receptors and biological responses to insulin on macromolecular synthesis have been studied in C6 glioma cells. Binding of 125I-insulin to C6 glioma cells was specific, time- and PH-dependent. Porcine insulin competed for 125I-insulin binding in a dose-dependent manner. Unlabeled polypeptides, including glucagon, bovine growth hormone, bovine prolactin did not compete for 125I-insulin binding. Scatchard analysis of the binding data gave a curvilinear plot which may indicate negative co-operativity or the existence of both high and low affinity (Ka = 7.55 x 10(10) - 4.25 x 10(9] sites. Incubation of cultures with insulin caused a time and dose-dependent stimulation of DNA, RNA and protein synthesis in C6 glioma cells (measured by 3H-thymidine, 3H-uridine or 3H-leucine incorporation into DNA, RNA, or protein respectively). The increase of macromolecular synthesis was admitted at more than 2 nM concentration of insulin. Maximal stimulation of DNA synthesis (142% of control) occurred 6 hours after incubation with 167 nM insulin. The same concentration of insulin caused a 45% increase in 1 hour on RNA synthesis, a 37% increase in 2 hour on protein synthesis. These results indicate that C6 glioma cells have specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis. Insulin in the brain and even blood may be an important growth factor in the glioma cells of the patients with disrupted blood-brain-barrier.

Cells, Cultured↗
PubMed1988

Factors possibly influencing the prognosis of oligodendroglioma.

Fifty-seven cases of oligodendroglioma (including eight cases of malignant oligodendroglioma) treated at the University of Tokyo Hospital between 1961 and 1985 were analyzed for factors influencing the survival rate. Factors related to a poor outcome were findings of malignancy and symptoms of dementia. Survival rate and postoperative survival period were not influenced significantly by radiation therapy, extent of resection, tumor characteristics, or ABO blood groups.

Adolescent↗
PubMed1988

[Treatment of recurrent craniopharyngioma].

Treatment results on 48 patients with "recurrent" craniopharyngioma treated by surgery or/and radiation are analyzed. Median relapse-free survival time was 43.6 months in patients treated initially with radiation and 22.2 months without. Operative death occurred in 17% of all patients and in 3 out of six patients after total removal. The five- and ten-year survival rates were 91.7% and 66.8%, respectively, for 14 patients treated with combined surgery and radiation therapy. For 26 patients treated with surgery, the survival rates were 20.3% and 10.1%. All of 6 patients, who had received both initial and later radiotherapy, were well 1/2 to 18 years later without clinical evidence of radiation injury. These results lead us to the following conclusions: 1) A radical surgery in recurrent cases has the higher risks of mortality and morbidity than that of the first radical surgery. 2) Radiation therapy improved the survival rate of patients with "recurrent" craniopharyngioma. 3) After initial radiation therapy, additional irradiation was allowed based on the scale of nominal standard dosage and the estimation of "decay factor".

Adolescent↗
PubMed1987

Cell cycle perturbation of cultured C6 glioma cells following short-term contact with a low dose of ACNU.

The purpose of this study was to investigate the cell cycle perturbation of cultured C6 rat glioma cells induced by 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3-(2-chloroethyl)3-nitrosourea hydrochloride (ACNU) using simultaneous flow cytometric measurements of DNA and bromodeoxyuridine (BrdU) content. A new graphic computer program permitted the quantification of cell density in hexagonal subareas and allowed the fraction of BrdU-labeled cells with mid-S phase DNA content (FLS) to be defined in a narrow window. The cell kinetic parameters such as cell cycle time (Tc) and S phase time (Ts) were estimated from a manually plotted FLS curve at 18 and 6 hr, respectively. The major effect of ACNU on the cell cycle was an accumulation of the cells in the G2M phase 12 to 24 hr posttreatment when compared to G2M traverse of untreated cells. For the two-dimensional analysis, cells were labeled with BrdU and then treated with ACNU, or treated with ACNU and then labeled with BrdU. It was concluded that the cells in the S and G2M phases at the time of ACNU administration progressed to mitosis but that the G1 phase cells accumulated in the subsequent G2M phase. Two-dimensional FCM analysis using BrdU provided a useful tool in studying cell cycle perturbation.

Animals↗
PubMed1987

[Treatment of autochthonous rat brain tumors with chemotherapy and radiotherapy].

The authors tried to establish a model of primary, autochthonous avian sarcoma virus-induced rat glioma for experimental chemotherapy and radiotherapy. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of an infectious cells-free homogeneous sub-group D Schmidt-Ruppin avian sarcoma virus into 3-day-old inbred Fischer rats induced brain tumors in all rats. The mean survival time of the inoculated rats was 58.7 +/- 12 days. With regard to the classification of the induced brain tumors in Fischer rats, astrocytoma accounted for 70%. This ASV-induced tumor in rats fulfills the following criteria for a desirable animal model. Spontaneously arising. Glial origin. Intraparenchymal growth. Uniformly fatal within a reasonable time period. In the present study, the therapeutic effects of anticancer drugs, such as ACNU and vincristine were evaluated and additionally, the effect of ACNU used in conjunction with radiation was also evaluated in this model. The mean survival time of rats was prolonged significantly with ACNU (20 mg/kg) or radiation therapy (1,000 rads), respectively, and in cases where ACNU was used together with radiation, the mean survival time was prolonged further still, but not very significantly, in comparison with radiation therapy alone. In conclusion, the ASV-induced rat glioma model was considered to be closely akin to a spontaneous brain tumor in terms of morphology, blood supply and kinetics of the primary tumor. Moreover, the therapeutic sensitivity of this model to anticancer drugs was fairly similar to that of human anaplastic astrocytoma. Considering these observations, this model seems to be an excellent experimental brain tumor model which is useful for evaluating the effect of new therapies against malignant brain tumors.

Animals↗
PubMed1987

[Efficacy of interferon-beta and interleukin-2 as cytokines for malignant brain tumor treatment].

The role of Interferon-beta (IFN-beta) as maintenance therapy for malignant gliomas and medulloblastomas was described. The low dose but continuous long-term administration of IFN-beta as a maintenance treatment for malignant gliomas after the induction therapy with surgery and chemoradiotherapy demonstrated the complete remission of the tumor in six cases of malignant gliomas. Such method of IFN-beta administration did not induce any serious side effects and might be useful for treatment of malignant gliomas. In addition, recent advance of adoptive immunotherapy using lymphokine activated killer cells (LAK) was briefly reviewed.

Adolescent↗
PubMed1984

The beta-adrenergic receptor system in human glioma-derived cell lines: the mode of phosphodiesterase induction and the macromolecules phosphorylated by cyclic AMP-dependent protein kinase.

beta-Adrenergic receptors and the activities of adenylate cyclase, phosphodiesterase and protein kinase were examined in two human glioma cell lines, U 251 and LM, as well as in rat C6 glioma. [3H]Dihydroalprenolol binding to beta-adrenergic receptors was specific, saturable and of high affinity in each cell line. The dissociation constant (Kd) and maximal binding (Bmax) extrapolated from Scatchard curves were Kd = 17.4 +/- 3.2 nM and Bmax = 1110 +/- 197 fmol/mg protein for the U-251 cells; Kd = 14.4 +/- 2.2 nM and Bmax = 655 +/- 105 fmol/mg protein for the LM cells; and Kd = 5.6 +/- 1.1 nM and Bmax = 454 +/- 80 fmol/mg protein for the C6 glioma cells. L-Isoproterenol stimulated cyclic AMP formation in all 3 cell lines. beta-Adrenergic agonists also increased calcium-dependent and calcium non-dependent phosphodiesterase activity in these tumor cells. Cytosolic protein kinase in the 3 cell lines phosphorylated exogenous histone as a substrate. The phosphorylation was enhanced by cyclic AMP. Cytosolic protein kinase also phosphorylated endogenous cytosolic macromolecules. The phosphorylated proteins had molecular weights of 30,000, 51,000 and 90,000 in the two human glioma cell lines. The present results indicate that human glioma cell lines have functional beta-adrenergic receptors linked to adenylate cyclase. These beta-receptors can also regulate phosphodiesterase activity and cyclic AMP in human glioma cells can activate protein kinase and induce the phosphorylation of specific proteins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

[Synchronization chemoradiotherapy for malignant gliomas].

Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines.

Human glioma-derived cell lines previously determined by a microtiter chemotherapy assay to be either 'sensitive' or 'resistant' to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were treated with BCNU (1-80 micrograms/ml) and observed using microcinematography, scanning electron microscopy, and transmission electron microscopy. Striking bleb formation and cell retraction were observed to occur in a dose-dependent relationship within minutes in the cells known to be BCNU-sensitive. At 15 micrograms/ml, 69% of cells showed blebs by 30 min, 87% by 90 min, and 100% by 4 hr. This activity was not seen in BCNU-resistant cells. These morphological changes occur at a time too early to be accounted for by the known BCNU mechanism of DNA alkylation and cross-link formation and suggest that cytoplasmic and/or membrane events may be significant initial events in the cytotoxic actions of BCNU.

Adult↗
PubMed1983

Flowcytometric and cytogenetic analysis of human cultured cell lines derived from high- and low-grade astrocytomas.

Five human cell lines cultured from high- and low-grade astrocytomas in cerebral hemisphere have been analyzed for DNA and protein distribution by flowcytometric (FCM) and correlated with cytogenetic profiles. Simultaneous calibration with chicken erythrocytes as a co-running standard provided an estimate of chromosomal number of predominate stem cells of each cell line by the ratio of the DNA content of the major peak (G1) to that of chicken erythrocyte (T/E ratio) of FCM. Various lines had different distributions of chromosomal number, ranging from near diploid to tetraploid. Each line had a stem-cell population and chromosomal markers indicative of clonal selection, but no common marker specific to astrocytomas. The histogram of DNA distribution obtained by FCM correlated well with the chromosomal distribution by cytogenetic analysis. In addition, simultaneous measurement of protein and DNA content in multidimensional FCM demonstrated a sigmoid configuration of the profiles, which indicated a gradual increase of protein content associated with an increase of chromosomal number or with progression of cell cycle. To avoid confusion of a bimodal chromosomal distribution with the G2/M phase of the cell cycle, and to determine chromosomal numbers associated with a DNA histogram, simultaneous cytogenetic and FCM study are required. More rapid than cytogenetic analysis, the T/E ratio allows estimation of chromosomal number of the stem-cell population associated with DNA histograms of cultured glioma-derived cell lines.

Astrocytoma↗
PubMed1983

[Adjuvant immunotherapy with levamisole for malignant glioma].

The long-term therapeutic results in patients with glioblastoma multiforme and malignant astrocytoma were compared between 15 cases of levamisole treated group and 18 cases of control group similar in method and time of treatment to the levamisole treated group. As the result, it was found that the prolongation of life was noted in the levamisole treated group compared with the control. In adult patients, the levamisole treated group survived significantly longer than the control group (p less than 0.05). There is, however, no significant difference of prolongation of the survival time between the levamisole treated (8 cases) and control (8 cases) groups, both which were pretreated by chemoradiotherapy using ACNU and vincristine. This paper refers also to side effects of levamisole.

Adolescent↗
PubMed1982

Phase I-II trials of poly(ICLC) in malignant brain tumor patients.

Poly(ICLC) preparation, containing poly-L-lysine and poly(I) . poly(C) at a weight ratio of 1:2, was given intravenously at a dose of 0.05 to 0.2 mg/kg to 7 patients with malignant brain tumor. Poly(ICLC) induced significant serum interferon (more than 100 reference units/ml) in all patients. The highest interferon titer induced was 875 reference units/ml. Severe side effect was not observed except fever. Hypotension, leukopenia and elevation of liver enzyme levels were observed as side effects in a few cases.

Adult↗
PubMed1982

Products of cultured neuroglial cells. III. Release of an 85,000 molecular weight glycoprotein by C6 glioma cells in vitro.

With [3H]fucose as a marker, C6 glioma cells in culture released an 85,000 molecular weight molecule into the medium as the major extracellular glycoprotein. The quantity and extracellular/cytoplasmic ratio of this glycoprotein suggest that its cellular processing is different from that of five other released glycoproteins of molecular weights 55,000, 115,000, 130,000, 150,000, and 170,000. Nearly 40% of newly synthesized glycoproteins in the cells was released into the culture medium. Major glycoproteins retained by the cells migrated electrophoretically to molecular weight positions of 82,000, 110,000, 120,000, 140,000, and 160,000, and approximately one-third of these returned glycoproteins were labile to trypsinization. Both synthesis and release of these macromolecules were inhibited more than 95% with cycloheximide treatment, demonstrating that nearly all fucosylation was linked to protein synthesis. Since 40% of all glycoproteins was released under conditions of more than 99% cellular viability, it is likely that these extracellular glycoproteins are physiological products of membrane turnover and secretion, but not of cell lysis. The results provide a basis for the further study of glial differentiation and of shed glioma antigens.

Animals↗
PubMed1982

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)].

Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.

Adult↗