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Biomedical subjects

A Ishida

Publications and source records attributed to A Ishida.

At least 325 records · Page 18Linked to original sources

Effects of hyperthermia and ethanol on the cytotoxicity of bleomycin, adriamycin, cis-diamminedichloroplatinum(II) and macromomycin toward hela cells.

The cytotoxic effect of bleomycin on HeLa S3 cells is greatly enhanced when the cells are exposed to ethanol before drug treatment or treated with the drug at 43 degrees (hyperthermic temperature). On the other hand, the cytotoxic effects of adriamycin, cis-diamminedichloroplatinum(II) and macromomycin are not enhanced by ethanol exposure, but are potentiated by 43 degrees hyperthermia. This effect of ethanol suggests a unique mode of action in sensitizing cells to bleomycin.

Anti-Bacterial Agents↗

Selective enhancement of the cytotoxicity of the bleomycin derivative, peplomycin, by local anesthetics alone and combined with hyperthermia.

The effect of local anesthetics alone and combined with hyperthermia on the cytotoxic effect of the bleomycin derivative, peplomycin, was studied in FM3A and HeLa cells. Noncytotoxic doses of the local anesthetics procaine, lidocaine, butacaine, tetracaine, and dibucaine enhanced peplomycin cytotoxicity. This enhancement correlated with the reported anesthetic potency of these agents. Combination of lidocaine (3 to 6 mM) and moderate hyperthermia (40 and 41 degrees) greatly enhanced peplomycin cytotoxicity, although these doses of lidocaine alone were ineffective at 37 degrees, and the temperatures alone enhanced the cytotoxicity only slightly. Cell sensitization to peplomycin cytotoxicity induced by lidocaine combined with 41 degrees hyperthermia produced a decrease in cell survival that depended on the dose of lidocaine and the dose and duration of peplomycin treatment. Lidocaine at 37 or 41 degrees did not enhance the cytotoxicity of Adriamycin, mitomycin C, and cis-diamminedichloroplatinum(II), suggesting a unique interaction with peplomycin. The enhancing effect of lidocaine on peplomycin-induced cell killing was found to increase as pH increased within the range of 7.0 to 8.0.

Anesthetics, Local↗

Potentiation of bleomycin cytotoxicity toward cultured mouse cells by hyperthermia and ethanol.

The effects of hyperthermia and ethanol on bleomycin cytotoxicity toward mouse mammary carcinoma FM3A cells in culture were followed in terms of clonal growth in a soft agar medium. Heating the cells at 43 degrees during or before bleomycin treatment sensitized them to bleomycin. Heat treatment after drug treatment was less effective. Bleomycin cytotoxicity was also greatly potentiated by exposing the cells to ethanol at a concentration of more than 4% (v/v) at 37 degrees before or after drug treatment. However, when the cells were exposed to ethanol during bleomycin treatment, the potentiation of cytotoxicity was reduced, and a higher concentration of ethanol was required for inducing equivalent sensitization. The cytoxicity of pepleomycin, a potent antitumor agent derived from bleomycin, was also greatly potentiated by hyperthermia and ethanol. The cellular uptake of 3H-pepleomycin was not increased by either treatment, and thus the increased cytotoxicity was not correlated with a change in membrane permeability to the drug. The sensitizing effect of hyperthermia or ethanol was maximum when the drug treatment was carried out immediately after the cells were exposed to heat or ethanol. Sensitization decreased linearly as the time interval between the two treatments was increased, and after a 6 hr interval the sensitizing effect of either agent disappeared. This recovery from the sensitized state was not inhibited by cycloheximide or by incubation in phosphate-buffered saline instead of complete growth medium, but it was reversibly inhibited at 0 degrees. It is suggested that the modes of action of hyperthermia and ethanol in inducing cell sensitization of bleomycin are similar.

Animals↗

Synergistic enhancement of bleomycin cytotoxicity toward tumor cells in culture by a combination of ethanol and moderate hyperthermia.

Bleomycin cytotoxicity toward mouse mammary carcinoma FM3A cells and human carcinoma HeLa S3 cells in culture was greatly potentiated by exposing the cells to a combination of a low concentration of ethanol and moderate hyperthermia. For example, the exposure of FM3A cells to a combination of 4.3% ethanol and 39 degrees, 2.4% ethanol and 41 degrees or 1.5% ethanol and 42 degrees induced a marked sensitization which was almost equivalent to that induced by exposure to 6% ethanol at 37 degrees and was greater than that induced by exposure to 43 degrees hyperthermia alone. However, when the cells were exposed to 3% ethanol at 37 degrees and then treated with bleomycin at 41 degrees, sensitization was hardly induced, indicating a requirement for simultaneous exposure to ethanol and hyperthermia to produce a synergistic increase in bleomycin cytoxicity. A possible application of these findings to cancer treatment with bleomycin is discussed.

Animals↗

Ca binding of isolated cardiac nexus membranes related to intercellular uncoupling.

Nexus membranes were isolated from cardiac muscles of guinea pig or ox. It was confirmed by autoradiography that Ca2+ was actually bound with the nexus, and by atomic absorption spectroscopy that bound Ca increased extensively at [Ca2+] higher than 10(-6) to 10(-5) M and showed the dose-response relationship against [Ca2+].

Adenosine Triphosphatases↗

Synergistic cell killing by antitumor agents and hyperthermia in cultured cells.

The effects of treatment with several antitumor agents in combination with hyperthermia (42 degrees and 43 degrees) on the cell survival of cultured mouse leukemia L5178Y and mammary carcinoma FM3A cells were studied by following clonal growth in a soft-agar medium. L5178Y cells were more heat-sensitive than FM3A cells. The cytotoxicity of bleomycin was markedly increased when the cells were treated with the drug in combination with hyperthermia or were preheated prior to drug treatment. The sensitization of FM3A cells to bleomycin was much more pronounced at 43 degrees than 42 degrees. The action of adriamycin was also potentiated at the elevated temperatures, but that of daunomycin was not. The sensitization of FM3A cells to adriamycin at 43 degrees, however, was limited to short times of heat exposure; the cells becoming resistant to further killing by adriamycin after heat exposure times of more than 30 min. The two cell lines were resistant to the cytotoxic action of low concentrations of aclacinomycin A at 37 degrees, but they became sensitized at 42 degrees and 43 degrees. The cytotoxicity of actinomycin D was also markedly potentiated at 42 degrees. The cytotoxic effects of mitomycin C, neocarzinostatin, carboquone and 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) were also appreciably potentiated at 42 degrees but those of cytosine arabinoside, 5-fluorouracil and vincristine were not.

Animals↗