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Biomedical subjects

T Inada

Publications and source records attributed to T Inada.

At least 217 records · Page 12Linked to original sources

Pharmacodynamic aspects of in vitro and in vivo chemosensitivity tests.

To determine the optimal conditions for clonogenic assay, the antitumor activities of 5-fluorouracil (5-FU) in vitro and in vivo were compared from a pharmacodynamic viewpoint in a human carcinoma xenograft-nude mouse system. In the clonogenic assay, tumor cells were exposed to 5-FU continuously for 2 weeks, and the results of the assay were evaluated in terms of colony survival rates (T/C). Tumor-bearing BALB/c male nude mice were treated with 5-FU, and the results were evaluated in terms of the lowest values of relative mean tumor weights (T/C). To compute the area under the curve (AUC) after administration of 5-FU in vitro and in vivo, agar and serum levels of 5-FU were measured by bioassay. Antitumor activities in terms of T/Cs against a gastric carcinoma strain (H-111) depended highly on the AUCs in vitro and in vivo. The T/C in vitro (z) was correlated with the AUC in vitro (w), z = 58.4 x 0.99331w, and the T/C in vivo (y) was also correlated with the AUC in vivo (x), y = 52.1 x 0.88552x. On the assumption that the T/Cs of these two regression equations were equivalent (y = z), a correlation between w and x was derived. To predict the T/C at the maximum tolerated dose of 5-FU in mice, the optimal drug concentration in vitro was calculated to be 2.7 micrograms/ml, which also proved to be suitable for seven other carcinoma strains. Our experimental system was thought to be adequate for selecting the optimal drug concentration in the clonogenic assay.

Animals↗

[Long-term survival in an elderly patient with acute myeloblastic leukemia].

A 79-year-old patient with acute myeloblastic leukemia (M2 type in FAB), who has survived more than 5 years, is reported. She was admitted because of fever and anemia. Her white blood cell count was 6200/mm3 with 58% blasts. Bone marrow aspiration showed a nucleated cell count of 26 X 10(4)/mm with 84% blasts, Complete remission was achieved within one month by DCMP two-step method therapy. She relapsed in the third and fifth years after initial therapy. Because leukemic change is atypical, she was treated with a low dose of Ara-C therapy, resulting in complete remission. In cases of acute myelobastic leukemia in elderly patients, long-term survival is rare. However in this case, follow-up has succeeded for 5 years. This patient is the oldest case of acute myeloblastic leukemia ever reported in Japan.

Age Factors↗

Infection of mice with lactic dehydrogenase virus prevents development of experimental allergic encephalomyelitis.

A significant reduction in the incidence of experimental allergic encephalomyelitis (EAE) in SJL/J mice was observed when mice were infected with lactic dehydrogenase virus (LDV) 14 days before, on day 0, or 3 days after immunization with spinal cord homogenate. These results are discussed in terms of the selective infection by LDV of I-region-associated antigen- (Ia) positive macrophages.

Animals↗

Protective effect of zinc against lethality in irradiated mice.

The protective effect of zinc against radiation hazard was observed by comparing LD50(30) values of irradiated mice with and without the administration of zinc before irradiation. Two hundred male mice, 7 weeks old, were irradiated with an intestinal dose at 5.62, 6.31, 7.08, 7.94, 8.91, or 10.00 Gy, with or without oral administration of zinc from 10 days prior to gamma irradiation until the end of the study. The reduction of mortalities in zinc-administered mice in comparison to controls was most prominent at the dose of 7.94 Gy, i.e., the mortality rate in the zinc-administered group was 0.44 and that in the control group was 1.00. At a dose of 8.91 Gy, zinc-administered mice survived significantly longer than controls. The LD50(30) of zinc-administered mice was 7.70 Gy, while that of the control was 6.90 Gy. In zinc-administered mice the acceleration of turnover and elevated excretion of radioactive zinc were observed, while the concentration of stable zinc in organs remained constant. The effect of zinc was not observed in experiments in vitro using human melanoma cells. Therefore it can be assumed that the protective effect of zinc against radiation would correlate with the homeostatic mechanism of zinc which exists in the whole body of mammalians.

Animals↗

Live lactate dehydrogenase-elevating virus (LDV) induces suppressor T cells that inhibit the development of delayed hypersensitivity to LDV.

A strong delayed-type hypersensitivity (DTH) response to lactate dehydrogenase-elevating virus (LDV) in mice was induced by immunization with u.v.- or heat-inactivated virus by the intravenous, intraperitoneal and especially the subcutaneous route. The peak DTH response was seen 7 days after immunization. Live virus, in contrast, did not induce a DTH response in young (1- to 3-month-old) mice irrespective of inoculation route, except after pretreatment with cyclophosphamide (CY), when the response peaked at 14 days. Live virus, however, induced a significant DTH response in old mice (greater than 8 months) without CY. The DTH response to inactivated virus was reduced when live virus was given intraperitoneally at the same time, but was partially restored when Ia-positive peritoneal cells were also given intravenously. The DTH response induced in infected mice pretreated with CY was suppressed by injection of spleen cells from infected or from normal 1- to 3-month-old mice. Suppression by normal spleen cells was abolished by treatment with anti-Thy1.2, anti-Lyt1 and anti-Lyt2 plus complement, whereas suppression by spleen cells from infected mice was prevented by anti-Thy1.2 and anti-Lyt2 plus complement. It is concluded that suppression of the DTH response was associated with induction of suppressor T cells and that severe depletion of Ia-positive cells may also have played a part.

Animals↗

[Clinical investigation of indications in proton therapy].

The indications for curative treatment with proton therapy were investigated by the clinical results of 31 cancer patients treated with proton beams between 1983 and 1985 at the Particle Radiation Medical Science Center of Tsukuba University. Many locally extended, radioresistant lesions, lesions with large volume and small radiocurable lesions in this series revealed sufficient improvement without definite late damage in the surrounding normal tissues. This clinical result suggests that proton beam treatment could be applied to lesions in a much wider range for curative purposes as compared with conventional radiotherapy. This study is to be continued further.

Adult↗

Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice.

Six human carcinoma xenografts serially transplanted into nude mice were used for the study of chemosensitivity and cell kinetics. Three gastric carcinomas (St-4, St-40 and H-111), two colon carcinomas (Co-3 and Co-4) and one breast carcinoma (MX-1) were inoculated into the subcutaneous tissue of BALB/cA nude mice. The maximum tolerable doses of mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPA) and 5-fluorouracil (5-FU) were administered when the tumor weights reached 100-300 mg. The response rates of the tumor to these drugs were found to be 3/6 for MMC, 2/6 for 5-FU and 1/6 for ADM and CPA. Percent labeled mitosis curves obtained from 3H-thymidine pulse labeling were analyzed by the method of Quastler and Sherman. It was found that the antitumor effect of MMC was closely correlated with the growth fractions of the tumors (r = -0.98, P less than 0.001), and it appeared that the tumor cells were more sensitive to MMC in the resting stages during the proliferating phase than in the other cell cycle phases. Cell kinetics is considered to be an important factor in determining chemosensitivity, and the system of human tumor xenografts-nude mice seems to be a suitable experimental model for investigating the correlation between cell kinetics and chemosensitivity in vivo.

Animals↗