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Biomedical subjects

K Kohda

Publications and source records attributed to K Kohda.

156 records · Page 9Linked to original sources

Hyperthermic potentiation of bleomycin cytotoxicity in the presence of Bacillus thuringiensis subsp. israelenis delta-endotoxin.

We previously reported that a 25-kDa Bacillus thuringiensis subsp. israelensis (BTI) delta-endotoxin potentiated the antitumor activity of bleomycin (BLM) in both in vitro and in vivo systems. We report here a characteristic hyperthermic synergy toward the cytocidal activity of BLM in the presence of BTI endotoxin in cultured L1210 cells. Cytocidal gain, i.e., the ratio of the IC50 of BLM in the absence versus the presence of BTI delta-endotoxin, reached ca. 20 at 40 degrees C, suggesting that a more effective heat-BLM combination treatment may be achieved in the presence of BTI delta-endotoxin.

Animals↗

Potentiation of bleomycin cytotoxicity by polyhydric alcohols.

The cytotoxicity of bleomycin (BLM) toward Chinese Hamster V79 and murine leukemia L1210 was extraordinarily potentiated in the presence of glycerol. The synergistic effect of glycerol emerged in combinations with BLM analogs (peplomycin and libromycin) as well, but not with other cytotoxic drugs such as adriamycin, neocarzinostatin, paraquat, hydrogen peroxide, and N-methyl-N-nitrosourea. The cytotoxicity of BLM and its analogs was potentiated by some polyhydric alcohols as intensely as by glycerol. Polyhydric alcohols containing more than two hydroxyl groups in the molecule were effective in V79 cells, and those containing more than three hydroxyl groups were effective in L1210 cells. The cellular uptake of [3H] peplomycin was not affected by glycerol. For antitumor activity, when 0.5 ml of glycerol (10%) and erythritol (10%) were combined with 2.0 mg/kg/day of BLM, the 5-day treatment of Ehrlich cell-bearing (i.p.) mice prolonged the life span by 244% and 282% (T/C), respectively. When a low dose of BLM (0.2 mg/kg/day) was combined with 0.5 ml of glycerol (20%) and erythritol (30%), the therapeutic gains were 1.82 and 1.88, respectively. These results suggest the possibility that the adjuvant treatment of BLM with polyhydric alcohols might be applied to the clinical treatment of cancerous peritonitis and pleuritis.

Alcohols↗

Potentiation of bleomycin cytotoxicity by high molecular weight polyacrylic acid. II. Involvement of rapid conformational change of polyacrylate.

We report that bleomycin (BLM) cytotoxicity is dramatically potentiated in the presence of high molecular weight polyacrylic acid (A119). For potentiation, an appropriate amount of divalent cations such as Ca++, Mg++, or Ba++ was required, in addition to vortex - stirring of the reaction mixture. There was no potentiation when A119 alone was pre-stirred or left standing for several days in the presence of divalent cations prior to use. Taking into account of kinematic viscosity of A119 observed during the treatment, a rapid conformational change of A119 in the presence of divalent cations might be involved in the potentiation mechanism.

Acrylic Resins↗

Potentiation of bleomycin cytotoxicity in cultured mammalian cells by polyacrylic acid. III. Induction of DNA strand breakage and suppression of cellular heat production.

The 2E cytotoxicity of bleomycin toward cultured mammalian cells was synergistically enhanced by vortex-stirring in the presence of a low dose of high molecular weight polyacrylic acid. Cellular DNA isolated immediately after the above treatment suffered from severe single strand breaks. Heat production of the treated cells also decreased sharply immediately after the treatment, indicating that some functional disorder was probably induced on the cell membrane leading to cell death, possibly resulting from enhanced DNA strand breaks.

Acrylic Resins↗

Potentiation of antitumor activity of bleomycin towards solid tumors in mice by Bacillus thuringiensis subsp. israelensis toxin.

We previously reported that a 25-kDa Bacillus thuringiensis subsp. israelensis (BTI) toxin is cytotoxic to cultured tumor cells and can also potentiate the cytotoxic effect of some antitumor agents in vitro. In this study, we examined the in vivo effect of BTI toxin on the potentiation of antitumor activity of bleomycin (BLM) against solid tumor-bearing mice. Three tumor cell lines, Ehrlich carcinoma, B16 melanoma and Meth A fibrosarcoma, were employed. It was shown that dose of BTI toxin, ineffective alone, potentiated the antitumor activity of BLM when used in combination.

Animals↗

Lignified materials as potential medicinal resources. II. Prevention of pathogenic bacterial infections in mice.

Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E. coli or P. aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi. Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection.

Animals↗

Enhanced cytotoxicity caused by increased DNA strand breakage resulting from synergistic potentiation of bleomycin with Bacillus thuringiensis subsp. israelensis delta-endotoxin.

We previously reported that a 25 kDa Bacillus thuringiensis subsp. israelensis (BTI) delta-endotoxin potentiates the cytotoxicity of bleomycin (BLM) in cultured cells. In order to clarify the mechanism involved, we examined the induction of DNA strand breakage by BLM in the presence of BTI toxin. Results showed that the increase in strand breakage resulted in enhanced cytotoxicity through the synergistic potentiation of BLM with BTI toxin.

Animals↗

Cytotoxicity of antitumor agents toward cultured murine leukemia L1210 cells under a serum-deprived apoptotic condition.

Apoptosis is known to be induced in L1210 cells that are cultured in serum-deprived medium. In this study, inhibitory effects of some antitumor agents on the growth of L1210 cells cultured in a normal and a serum-deprived medium were compared. All the antitumor agents examined were equally cytotoxic to cells in both media, indicating that the cytotoxic effects of these agents were not coupled with programmed apoptosis so as to induce synergistic cell death. The single cell-gel electrophoresis assay (comet assay) revealed that antitumor agents induced DNA strand breakage in a dose-dependent manner under either normal or serum-deprived culture conditions without any synergistic increases in DNA strand breakage.

Animals↗

Growth inhibition of cultured human leukemia cells by 3-aminothymidine and its analogue.

In a previous report, we demonstrated that 3-aminothymidine (1) strongly inhibits the growth of the human T-cell acute lymphoblastoid leukemia cell line CCRF-HSB-2. In order to further study cell growth inhibition by this compound, several of its derivatives and analogues were synthesized and their growth inhibition activities examined using various cultured cell lines. Compound 1 was the most active among the compounds tested and the most effective against cells of the human T-cell acute lymphoblastoid leukemia cell line CCRF-CEM. 3-Methylthymidine (2) also inhibited the growth of CCRF-CEM cells but at a level about one thirtieth that of 1. Introduction of a methyl or acetyl group at the 3-amino group of 1 resulted in the loss of growth inhibition activity. 3-Amino- and 3-methyl-5-bromo-2'-deoxyuridines (6 and 7), the analogues of 1 and 2 both exhibited an ability to inhibit cell growth and their levels of activity were similar in extent, in spite of the difference in their 3-amino and 3-methyl groups, however, these levels were less than that of 1. Compounds 1, 2, 6 and 7 all showed evidence of growth inhibition in every human leukemia cell line examined.

Antineoplastic Agents↗