PubMed Health⌕ Search

Biomedical subjects

T Nishidai

Publications and source records attributed to T Nishidai.

At least 19 recordsLinked to original sources
PubMed1990

CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 1. Description of system.

A real time CT-linked 3-D treatment planning system, called a CT simulator, has been developed. The basic system consists of a CT scanner, a multi-image display component, a treatment planning device with real time visual optimization, and a laser beam projecting component. All the components are connected on line. The system can be conveniently used for 3-D planning and simulation for radiation therapy within a reasonably short period of time.

Computer Simulation↗
PubMed1990

CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 2. Clinical application.

We have performed radiotherapy treatment planning (RTP) with a new system called CT simulator in 72 patients. With the system, RTP is performed with the patient lying on the CT couch within a short period of time. All the CT images scanned were immediately transported to the multi-image monitors and to the treatment planning device. Radiotherapy treatment planning could be performed not only at the beam center but also at any CT slice. Using a laser-beam field projector, field outlines were drawn over the patient's skin. In clinical use, the system was useful for cases in which a target lies adjacent to dose limiting organs, cases with a complicated target shape, cases with complicated dose distribution curves, and cases treated with tangential fields. This system enables us to make optimum use of CT information and to make accurate 3-dimensional treatment planning programs.

Computer Simulation↗
PubMed1990

Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation.

We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

Agranulocytosis↗
PubMed1989

Variation in tumor response to fluosol-DA (20%).

The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO2) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C3H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors, only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.

Animals↗
PubMed1987

[Present status of hypoxic cell sensitizers and PLDR inhibitors].

Clinical and basic studies in hypoxic cell radiosensitizers and potentially lethal damage (PLD) repair inhibitors were reviewed. Most clinical trails on misonidazole (MISO) show that the toxicity of MISO is a major reason for failure in the trials and an adequate selection of tumors is needed for the success. Phase III studies on SR-2508 and RO 03-8799, less toxic and more effective sensitizers, are in progress. AK-2123 and RK-28 developed in Japan are drugs with similar clinical applicability of MISO. Thiol depletion of tumors is one of the way to increase the radiosensitization. The measurement of intercapillary distance on histopathological microslide is a valuable method to select the tumors containing much hypoxic cell fractions. Stable and effective chemicals as MISO in hypoxic cell sensitization must be developed to investigate the clinical applicability of PLD repair inhibitors.

Animals↗
PubMed1986

Radiosensitization in vitro and in vivo by 3-nitrotriazoles.

A series of 3-nitro-1,2,4-triazole derivatives bearing various types of side chain (R) at the N1-position (AK-2000 series) were synthesized and their radiosensitizing effect and toxicity in vitro and in vivo were investigated, in comparison with those of Misonidazole (MISO), SR-2508, and RSU-1069. Of the fifteen 3-nitrotriazoles tested, all had sensitizing effects in vitro on hypoxic V79 cells. Also, all but one had definite effects on solid EMT6/KU and SCCVII tumors in vivo. For many of the triazole compounds, the degree of radiosensitization in vitro and in vivo appeared identical. However, they were generally less efficient, both in vitro and in vivo, than the corresponding 2-nitroimidazoles, whereas their aerobic cytotoxicity and toxicity to mice (LD50/7) were comparable to those of the 2-nitroimidazoles. Considering the sensitizing effect and toxicity, AK-2123 (R = CH2CONHC2H4OCH3) may be as useful as MISO, but none of the triazoles have been proved to be superior to SR-2508.

Animals↗
PubMed1986

Chemosensitization by buthionine sulfoximine in vivo.

The in vivo effects of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the cytotoxicity of cyclophosphamide (CYM), cisplatin (CDDP) and bleomycin (BLM), were examined by monitoring the changes of non-protein thiols (NPSH) in normal tissues and in the NFSa fibrosarcoma. We used the lung colony assay as a measure of tumor response and the spleen colony assay as a measure of normal tissue response to CYM. In this study, 5 mmol/kg of BSO was subcutaneously injected four times every 12 hr before administration of the above anti-neoplastic drugs. GSH levels in subcutaneous NFSa tumors decreased to 2% of the control 12 hr after the last administration of BSO, but in the bone marrow, had recovered to 41%. In the colony assays, BSO increased the anti-cancer effects of the three chemotherapeutic agents, but did not modify the bone marrow suppression by CYM. This finding was a result of the differential response of GSH depletion in the tumor and in the bone marrow. Our study demonstrates that BSO is an effective chemosensitizer of these drugs and may be of therapeutic value when used at an optimal interval.

Animals↗
PubMed1986

Radiosensitizing effect of misonidazole in combination with an inhibitor of glutathione synthesis in murine tumors.

The radiosensitizing effects of misonidazole (MISO) in combination with D,L-buthionine-S, R-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, were studied in NFSa tumors of C3H/He mice. The radiation response of tumors was assayed by the tumor growth delay time. The GSH contents in tissues were assayed by high performance liquid chromatography (HPLC). GSH content in the tumors decreased to the minimum level (45% of the control), and then gradually recovered to 75% of the control, respectively, 12 and 24 hr after the intraperitoneal injection of 5 mmole/kg BSO. On the other hand, the maximum non-protein sulfhydryl (NPSH) depletion (29% of the control) in the liver of tumor bearing mice was achieved 6 hr after the administration of the same dose of BSO, but fully recovered 24 hr later. When 5 mmole/kg BSO was injected repeatedly 4 times at an interval of 6 hr, GSH content in the tumors decreased to 19% of the control 24 hr after the first injection of BSO. The radiosensitizing effect of 0.5 mmole/kg MISO was markedly increased by this BSO treatment. The enhancement ratio (ER) of this combined treatment was 1.93. On the other hand, ERs of 1.44 and 1.16 were obtained for MISO (0.5 mmole/kg) and for 4 injections of BSO (5 mmole/kg) in combination with radiation, respectively. Although a considerable increase in the radiosensitizing efficiency of MISO in vivo by the treatment with BSO was found without any notable side effects of the combination, more studies on toxicities are needed to get a definite conclusion on the clinical applicability of the combination.

Animals↗
PubMed1986

The radiosensitizing effects of misonidazole (MISO) in combination with diethyl maleate (DEM) in mouse mammary tumors.

Large radiosensitization of C3H/He mouse mammary tumors was obtained with the combination of a non-protein sulfhydryl (NPSH) depletor, diethyl maleate (DEM), and misonidazole (MISO), compared with MISO alone over a range of MISO dose. The difference in enhancement ratios (ER's) for these two treatments was especially prominent at small MISO doses. ER's of 2.06 and 1.44 were obtained, respectively, by combined treatment with DEM (760 mg/kg) and MISO (100 mg/kg) or treatment with MISO alone. Radiosensitization of tumors by DEM alone was observed for doses over 600 mg/kg. When DEM was combined with MISO (100 mg/kg), ER's of the combination were larger than that of MISO alone, for doses over 400 mg/kg of DEM. Similarly, in case of DEM plus MISO (300 mg/kg), the ER's became larger than MISO alone, for doses over 200 mg/kg of DEM. The NPSH content in untreated tumors was 1.08 mmole/kg on the average and no changes in NPSH content was observed after MISO treatment. DEM treatment markedly reduced the NPSH content of tumors as a function of DEM dose and this decrease in NPSH was not significantly affected by MISO treatment. Tumor NPSH was reduced to 24% or less of control by administration of 760 mg/kg of DEM with or without MISO. These results are consistent with competition theory of NPSH and electron affinic radiosensitizers.

Animals↗
PubMed1986

Combined effect of buthionine sulfoximine and cyclophosphamide upon murine tumours and bone marrow.

Two and four treatments of 5 mmol kg-1 of buthionine sulfoximine (BSO) at an interval of 12 h depleted the glutathione (GSH) content in NFSa tumours of C3H/He mice, respectively, to 24.0 and 1.78 percent of the untreated controls. BSO pre-treatments every 12 h enhanced the cytotoxicity of cyclophosphamide (CYC) towards artificial lung micrometastases of NFSa tumours giving enhancement ratios (ERs) ranging from 1.75 to 1.83 and from 2.41 to 2.73, for two and four BSO pretreatments respectively. Large ERs were obtained at low CYC doses (high cell survival). Four BSO pre-treatments at an interval of 12 h did not increase the cytotoxicity of CYC to bone marrow stem cells. Our results suggest a clinical applicability of the combination of BSO and CYC.

Animals↗
PubMed1986

Chemical competition in target radical reactions: numerical simulation of the theory and comparison with measured oxygen effect on DNA damage in cells.

An intracellular radiation-chemical reaction scheme is tested in which solute and solvent radicals R. react with non-target molecules Sa (scavengers) or with target molecules (presumed to be DNA) to produce target radicals T., which may also be produced by direct ionization of DNA. The rate of target radical decomposition to become 'uncommitted damage' that the cell may repair is affected by the concentration of oxygen (O2), thiols (S) and electronaffinic sensitizers (F), which compete with one another to form, respectively, target products TO2, TS and TF. This uncommitted damage is then subject to biochemical modification, including molecular repair, by the cell. The rate equations for this competing reaction scheme were written and programmed for computer simulations of changes in oxygen, thiol and electronaffinic sensitizer concentrations. A reaction scheme that also includes some non-radical target damage was also simulated. Simulations were made using available experimental data concerning intranuclear concentrations and reaction rate constants, respectively, ko, ks and k1 for the reactions T. + O2----TO2, T. + S----TS and T. + F----TF, which produce uncommitted chemical damage. Experimental data on strand-break induction in glutathione-proficient and glutathione-deficient cells, in cells treated with thiol active agents, and in cells treated with hypoxic sensitizers, along with the computer simulations, generally agree that thiol molecules can react with target radicals to reverse T. in competition with O2 and/or electronaffinic sensitizers. Forward reaction rate constants ko, ks (dithiothreitol), ks (glutathione) and k1 (misonidazole) in the approximate ratio 10:0.3:0.02:0.4 satisfied the above reaction scheme, and approximately 5 per cent non-radical target molecule damage could be included with satisfactory agreement with experimental data.

DNA↗
PubMed1985

Combined effect of misonidazole and glutathione depletion by buthionine sulphoximine on cellular radiation response.

Chinese hamster cells (V79) and glutathione-proficient (GSH+/+) and glutathione-deficient (GSH-/-) human fibroblasts were treated with a glutathione (GSH)-depleting agent buthionine sulphoximine (BSO) and the hypoxic radiosensitizer misonidazole (MISO), separately or in combination. Subsequently, the cells were exposed to X-rays. Determination of the yield of single-strand DNA breaks (ssb) immediately after irradiation indicated no effect of BSO or MISO treatment when radiation exposure was made aerobically. Assuming that ssb determined immediately after irradiation reflects mainly the effect of radical processes, the results obtained with BSO and MISO, singly and in combination, agreed well with the predictions of a modified version of the 'competition model' using V79 and GSH+/+ cells. Some results obtained with GSH-/- cells could not be so explained.

Animals↗
PubMed1985

[Physical dose distribution].

In radiotherapy planning it is essential to compose dose distribution curves on a transverse section of patient. For this purpose we have developed the radiotherapy planning system using a computer (Modulex), in which CT images and CT numbers were input on off-line with a CT magnetic tape, CT numbers were converted into relative electron densities and then, dose distribution curves calculated were output directly on CT images. One of problems lying in this system was that the three-dimensional dose distribution had to be surmised with a couple of two-dimensional ones. Clinical application of this system has been applied to planning of intraoperative radiotherapy that was considered to provide ideal dose distributions, and its effectiveness was discussed.

Computers↗