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T Kunimoto

Publications and source records attributed to T Kunimoto.

At least 19 recordsLinked to original sources
PubMed1991

Antitumor activity of polymorphonuclear leukocytes activated by a beta-1,3-D-glucan.

The antitumor activity of mouse polymorphonuclear leukocyte (PMN) treated with a beta-1,3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK-N) and its carboxymethylated derivative (CM-TAK) was investigated in vitro and in vivo. ICR mouse PMN showed strong cytotoxicity against sarcoma 180 cells and inhibition of the growth of the tumor cells in vitro in the presence of TAK-N but not in the presence of CM-TAK. Since the cytotoxicity induced by TAK-N was almost completely inhibited by catalase, it seems to be mediated by H2O2 production by PMN. On the other hand, TAK-N induced no cytotoxicity in macrophages and neither did CM-TAK in PMN or in macrophage. Intraperitoneal injection of TAK-N into ICR mice induced a large number of PMN and macrophages in the peritoneal cavity. The peritoneal exudate PMN which were harvested at 10 to 72 h after TAK-N injection showed cytotoxicity against sarcoma 180 cells, but the peritoneal exudate macrophages did not. Treatment of sarcoma 180 ascites tumor-bearing ICR mice with TAK-N at a dose of 100 mg/kg prolonged significantly the survival time over that of the control. These results indicate that TAK-N induces PMN cytotoxicity against sarcoma 180 cells not only in vitro but also in vivo. The antitumor effect of TAK-N on sarcoma 180 ascites tumor seems to be derived from PMN stimulated with TAK-N.

Animals↗
PubMed1990

[Tumor-regressing factor induced by antitumor polysaccharide in the serum of tumor-bearing mice].

A potent tumor-regressing activity was found in the serum of mice with S180 tumor undergoing rapid regression caused by antitumor polysaccharides. Beta (1-3) glucan including CM-TAK and lentinan and mannoglucan MGA induced such activity. It causes a rapid decrease in the number of tumor cells accompanied with a marked increase in neutrophiles in solid tumors. The entity of the activity was named as tumor-regressing factor (TRF) and was partially purified revealing a proteinaceous nature with an approximate molecular weight of 250,000. The factor was induced in a serum of tumor-bearing mice in various host-tumor combinations after the tumor growth had been established but only weakly in normal mice. The sensitivity of tumors to the factor was also dependent on the stage of tumor growth. The serum of normal mice or tumor-bearing mice without polysaccharide treatment exhibited similar activity as TRF after definite chromatographic step. The chromatographic behavior of the revealed activity was closely similar to that of the induced factor. It was postulated that a TRF-like activity exists in normal serum in a inactivated form being bound by antagonist(s) and the appropriate chromatography might remove the antagonist resulting in the active form of the factor. The concept was confirmed by reconstituting the chromatographic fractions, the revealed activity was again obscured after mixing with a certain fraction.

Animals↗
PubMed1987

Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.

Animals↗
PubMed1987

Antitumor activity of a new camptothecin derivative, SN-22, against various murine tumors.

The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.

Animals↗
PubMed1987

[Antitumor activity of new derivatives of camptothecin].

With the purpose of obtaining more potent and less toxic camptothecin (CPT) analogs, we prepared many derivatives of CPT. Among them, 7-ethyl-CPT (SN 22) and 7-ethyl-10-hydroxy-CPT (SN 38) showed strong antitumor activity with less toxicity. They were, however, insoluble and when they were made soluble, their activity was markedly diminished, as a result of cleavage of the delta-lactone ring. We therefore attempted to make soluble derivatives without breaking the delta-lactone ring and obtained 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-CPT (CPT-11), which showed very strong antitumor activity by i.p., i.v. or p.o. administration against the ascites type of L1210 leukemia, P388 leukemia, sarcoma 180, Meth A fibrosarcoma, B16 melanoma, Ehrlich carcinoma and MH134 hepatoma and the solid type of sarcoma 180, Meth A fibrosarcoma, Lewis lung carcinoma, C3H/HeN mammary carcinoma, Ehrlich carcinoma and MH134 hepatoma. The antileukemic activity of CPT-11 against L1210 was much higher than that of adriamycin. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration, the LD50 being 765.3 mg/kg, 22 times greater than that of CPT-Na.

Animals↗
PubMed1986

Rapid tumor regression and induction of tumor-regressing activity in serum by various immune-modulating agents.

A rapid decrease in the number of tumor cells from S180 tumors was caused by several antitumor polysaccharides including the beta (1-3)glucans lentinan and TAK-N and a mannoglucan MGA, but not by those lacking antitumor activity. MGA was demonstrated to induce potent tumor-regressing activity in the serum of tumor-bearing mice similar to that reported previously to be induced after an injection of CM-TAK, a carboxymethylated beta (1-3)glucan. It is probable that the induction of rapid regression of established tumors is a phenomenon common to antitumor polysaccharides and some microbiological products and that the tumor-regressing factor in the serum underlies a common mechanism.

Animals↗
PubMed1986

Antitumor polysaccharide-induced tumor-regressing factor in the serum of tumor-bearing mice: purification and characterization.

Marked tumor-regressing activity was induced in the serum of S180 tumor-bearing mice by injection of an antitumor polysaccharide, CM-TAK [carboxymethylated beta(1-3)glucan]. Maximal activity was induced 7-14 days after the tumor transplantation and 10-12 h after CM-TAK treatment. A quantitative assay for the activity was established on the basis of the initial decrease in the number of the tumor cells within 24 h. The factor with tumor-regressing activity was purified 10,000-fold by the series of hydroxylapatite chromatography, ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, and boronate-mediated affinity chromatography. The molecular weight was estimated to be 250,000 by gel filtration. The activity was proteinase K sensitive, but relatively resistant to trypsin. Neuraminidase did not affect the activity. It is believed that the tumor-regressing factor is different from the tumor necrosis factor.

Alcaligenes↗
PubMed1986

Rapid tumor regression caused by antitumor polysaccharide and induction of tumor-regressing factor in the serum of tumor-bearing mice.

The antitumor polysaccharide CM-TAK [carboxymethylated beta(1-3)glucan] caused immediate and rapid loss of viable tumor cells from S180 solid tumors in ICR mice if it was given after a week of tumor growth. We found marked tumor-regressing activity in the serum of mice with S180 tumors undergoing CM-TAK-induced regression. When injected intravenously into S180-bearing mice, 0.1 ml of serum/mouse induced complete regression of day-14 tumors. However, in vitro cytotoxic activity against L929 and S180 cells was not detected. After the injection of CM-TAK or serum, along with the rapid decrease in tumor cells there was a marked increase in polymorphonuclear leukocytes. The serum was also active against fibrosarcoma Meth A in BALB/c mice, inducing partial regression or significant decrease in growth of the tumor. The properties of the factor in the serum seem to be different from those reported for tumor-necrotizing factor and other endogenous cytotoxic substances.

Animals↗
PubMed1985

The therapeutic effects of orally administered 5'-deoxy-5-fluorouridine, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil on experimental murine tumors.

The antitumor effects of three 5-fluorouracil-related compounds, 5'-deoxy-5-fluorouridine (5'-DFUR), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-fluorouracil (5-FU) itself, on several experimental murine tumors were compared after oral administration. 5'-DFUR showed strong antitumor activity against the solid type of four kinds of tumors tested with a wide range of effective doses, and also showed moderate antitumor activity against three kinds of solid tumors with a narrow range of effective doses. 5'-DFUR was effective against a few kinds of ascites tumors. In general, the antitumor activity of FT-207 was not very strong, with narrow ranges of effective doses under the present conditions. 5-FU showed strong toxicity but at lower doses its antitumor effectiveness was almost the same as that of FT-207. When the doses were divided into three and the divided dose was given orally three times a day for five consecutive days to mice bearing L1210 leukemia, this modality (with any of the three drugs) enhanced the ILS of the mice by two to three times in the case of the ascites type but not the solid type of L1210. The chemotherapeutic index in oral treatment of the solid type of tumors was higher for 5'-DFUR than for FT-207 or 5-FU. The minimum lethal doses in oral administration for five consecutive days were about 3, 1.5 and 0.5 mmol/kg/day for 5'-DFUR, FT-207 and 5-FU, respectively. In conclusion, 5'-DFUR appeared to have stronger antitumor activity and less toxicity than FT-207 and 5-FU, and it is therefore expected to be clinically useful.

Animals↗
PubMed1984

Separation of macrophages from mouse peritoneal exudate cells with substrata coated with chemically modified collagens.

A cell-separation technique was designed on the basis of specific interaction between macrophages and chemically modified collagens in the presence of serum. When unseparated mouse peritoneal exudate cells containing approximately 50% macrophages and 50% lymphocytes were incubated in dishes coated with unmodified and chemically modified collagens, only macrophages adhered more rapidly and in greater numbers to succinylated and methylated collagen than to unmodified collagen. The adherent macrophages could be easily detached from the substrata by divalent cation chelating agents. The purity and recovery of macrophages separated by this method were approximately 92-94% and 41-48%, respectively.

Animals↗
PubMed1982

Superoxide anion production from mouse peritoneal macrophages stimulated with surface-bound IgG and immune complexes: adsorption characteristics of IgG in relationship to biological activity.

The bridging of IgG antibody molecules by either multivalent antigen or protein A adsorbed to a polymer surface triggers superoxide anion (O-2) generation from mouse peritoneal macrophages. Macrophages, upon stimulation with IgG adsorbed to a hydrophobic polymer, polystyrene, also significantly generated O-2. In contrast, soluble IgG did not stimulate macrophages. From these results we speculated that IgG adsorbed to polystyrene produces the same kind of a conformational change in its Fc region as seen in immune complexes, and leads to enhancement of the ability of the Fc region to bind macrophage Fc receptors, acting as a multivalent cross-linking agent to aggregate the Fc receptors. The surface charge density of the immunosorbent did not affect the antigen recognition function of antibody, but markedly affected its effector function. These findings suggest that activation of the Fc receptor-mediated function of macrophages requires, on the one hand, optimal conformational change and orientation of IgG and immune complexes adsorbed to the polymer surface and, on the other hand, the bridging of IgG molecules by multivalent agents.

Adsorption↗
PubMed1982

Action of a new antibiotic, neo-enactin, on the cell membrane and its application to combination treatment in a cultured tumor cell system.

Neo-enactin, a new antibiotic obtained from a Streptoverticillium, was found to act on the eukaryotic cell membrane and induce changes in the transport of molecules across the cell membrane. Neo-enactin markedly potentiated the action of the antitumor agents bleomycin and vincristine in vitro. The uptake of [14C]vincristine by HeLa cells was enhanced 3.4-fold in the presence of neo-enactin. It is suggested that the potentiation of a second drug by neo-enactin may result from enhanced permeation of that drug.

Animals↗