[Morphological study on the effects of heat and radiation on mouse mammary carcinoma].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Abe.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have previously defined a human mammary epithelial antigen using a murine monoclonal antibody (MAb), designated DF3, prepared against a membrane-enriched fraction of a human breast carcinoma. MAb DF3 detects a cell surface antigen with a molecular weight (mw) of approximately 300 Kd and a higher mw species also detectable in human milk. These findings and the demonstration that butyric acid (BA) increases DF3 antigen expression suggested that MAb DF3 reacts with a differentiation antigen detectable in human breast carcinoma cells. The results of the present study demonstrate that MAb DF3 reacts with two mucin-like high mw glycoproteins (330 and 450 Kd) present in MCF-7 breast carcinoma cells. The results also demonstrate that the intracellular content and secretion of DF3 antigen is increased by 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-beta-D-arabinofuranosylcytosine (ara-C). Other known inducers of differentiation including retinoic acid (RA), hexamethylene bisacetamide (HMBA), 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and certain polar solvents decrease DF3 antigen expression. Furthermore, the results demonstrate that DF3 antigen is secreted and that the extent coincides with changes in intracellular content. Finally, actinomycin D and cycloheximide inhibit the increases in DF3 antigen expression following TPA treatment thus suggesting that newly synthesized RNA and protein are required for induction of this antigen. Thus, the monitoring of DF3 antigen expression may provide a marker for studying maturation of human breast cancer cells.
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.
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.
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.
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.
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.
Explore the source record for details and available documents.
A new temperate phage, phiBA1, was isolated from Bacillus aneurinolyticus, phiBA1 had an icosahedral head with a diameter of about 70 nm and a tail about 20 nm long and contained a circularly permuted, linear duplex DNA of about 38 x 106 daltons. This phage showed two activities: bacteriocin-like killing activity against five strains of B. aneurinolyticus and normal temperate phage activity against three other strains. phiBA1 killed sensitive cells by a single-hit process. After adsorption of phiBA1 to cells sensitive to killing, the content of intracellular ATP increased for the first 5 min and then gradually decreased. Phage DNA injected into the cell immediately after infection was degraded rapidly. Killing was also caused by heavily UV-irradiated phiBA1. Killing-resistant mutants showed normal adsorption of phiBA1 and normal injection of the DNA with its instantaneous restriction. Our results indicate that the killing action of phiBA1 is different from the phenomenon of abortive infection and suggest that the killing might be caused by a proteinaceous component of phiBA1.
The effects of S-Adenosyl-L-methionine (SAMe) on cerebral monoamine turnover at 60 min of reoxygenation after hypoxia (PaO2, 31-35 mmHg) for 15 min were studied in 44 rats anesthetized with nitrous oxide. The accumulations of monoamine metabolites: 3-methoxy 4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined after probenecid. The accumulations of noradrenaline (NA) and dopamine (DA) were also determined after pargyline. In the non-treated group, there was an impairment of degradation of NA to MHPG and of DA to DOPAC or HVA in the control group (no hypoxia). These changes were accompanied by higher levels of NA and DA in the cerebral cortex, hypothalamus and striatum than those of the control group. In the group treated with 100 mg/kg SAMe plus 38 mg/kg mannitol 3 min after the start of reoxygenation, there were no significant changes in these metabolites and amines. Mannitol alone did not cause significant changes. There were no changes in serotonin and 5-HIAA in any of the groups studied. The effects of SAMe were studied in an additional 16 awake rats. MHPG in all regions measured after probenecid in the rats treated with SAMe was higher than that without SAMe. It appears that SAMe ameliorates perturbation of cerebral catecholamine turnover produced by reoxygenation after hypoxia.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Seventeen patients with moderately severe ophthalmopathy due to Graves' disease were treated by cobalt or supervoltage radiotherapy. All patients complained of diplopia. The mean proptosis value was 21.4 mm. Three patients (18%) showed good response, 7 (41%) moderate and 7 minimal or no response. Improvement was noted mainly in soft tissue changes and diplopia, while proptosis decreased in only 5 patients. All except one patient who had marked extraocular muscle involvement revealed by computed tomography responded to treatment. These data indicate that radiotherapy may be indicated in patients with progressive ophthalmopathy, especially in those who are associated with extraocular muscle enlargement.
A lesion in the left humeral head of a 15-year-old Japanese boy was light-microscopically diagnosed as clear cell chondrosarcoma. Fresh tissues from the lesion were studied ultrastructurally. In most tumor cells, that is, clear cells, paucity of organelles, sparse free ribosomes, and low protein content in cytosol were most striking. Tumor cells had many microvilli characteristic of cartilage cells. Among scanty organelles, vesicles or cisternae of dilated rough endoplasmic reticulum were rather conspicuous, and well-developed Golgi complexes were sparse. Intercellular matrix was scanty. These results suggest that intercellular matrix substance may be synthesized substantially by rough endoplasmic reticulum, whereas the synthesized substance perhaps cannot be transported smoothly into extracellular spaces because of scanty well-developed Golgi complexes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.