Tomoyoshi Hosokawa

The University of Tokyo, 白山, Tōkyō, Japan

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Publications (17)34.57 Total impact

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    ABSTRACT: Ascofuranone demonstrated antitumor activity against FM3A murine mammary carcinoma, implanted in the peritoneal cavity of syngeneic mice, C3H/He. It was more effective by treatment prior to implantation than by that after implantation. Treatment with ascofuranone also increased splenic cytotoxicity and phagocytic activity of host animal cells. Moreover, ascofuranone induced inflammatory cells in the peritoneal cavity which are mainly composed of polymorphonuclear leukocytes and macrophages. These cells are more potent in cytotoxicity against FM3A cells than with resident peritoneal cells. The antitumor activity of ascofuranone was suppressed by ip administration of silica, just prior to tumor implantation. These results suggest that the prophylactic antitumor activity of ascofuranone is expressed through the activation of phagocytes. Ascofuranone also suppressed pulmonary metastasis of B16 melanoma and Lewis lung carcinoma. Treatment after tumor implantation failed to suppress the metastasis. Single treatment of ascofuranone 4 days prior to implantation decreased the metastasis of Lewis lung carcinoma but not that of B16, whereas single treatment of ascofuranone 24 hours prior to the tumor implantation decreased the metastasis of B16 but not that of Lewis lung carcinoma.
    The Journal of Antibiotics 08/1988; 41(7):959-65. DOI:10.7164/antibiotics.41.959 · 1.73 Impact Factor
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    J Magae · T Hosokawa · Y Matsuda · M Hotta · J Hayasaki · K Nagai · K Ando · M Yamasaki · G Tamura ·
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    ABSTRACT: Ehrlich ascites carcinoma-bearing mice exhibit hypertriglyceridemia. An antitumor antibiotic, ascofuranone, suppressed tumor-induced hypertriglyceridemia when administered i.p. even when no evident antitumor activity was observed without affecting the levels of free fatty acids, phospholipids, cholesterol, glucose, and total protein in plasma. Ascofuranone did not reduce plasma triglycerides of normal mice. Insulin and clofibrate, known modifiers of lipid metabolism, showed no significant suppression. Ascofuranone is also effective on solid tumor-induced hypertriglyceridemia. Another notable change of metabolism affected by tumor-bearing in the early stage where hypertriglyceridemia has not yet fully progressed is hypoglycemia. Although ascofuranone did not affect hypoglycemia, the suppressive effect on hypertriglyceridemia was more evident when ascofuranone was administered in the early stage than in the later stage. These results suggest that ascofuranone suppresses hypertriglyceridemia by specifically affecting the changes of host metabolism which is induced in the early stage of tumor bearing.
    Cancer Research 02/1987; 47(1):96-9. · 9.33 Impact Factor
  • Tomoyoshi Hosokawa · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: Male 12-week-old C57BL/KsJ db/db mice were treated for 1 week with a dietary admixture of an experimental antidiabetic agent, AS-6 (4-O-carboxymethylascochlorin, 0.1%). The fatty acid composition of the adipose tissue and its plasma membranes in the treated mice was compared with that in untreated db/db mice and their lean littermates. The results indicate that, when compared with the lean, the db/db adipose tissue and its plasma membrane are extremely rich in nonessential fatty acids, and AS-6 treatment modifies the fatty acyl composition only in the membranes in which 16:1 and 18:1 increase and C18 decreases.
    Biochimica et Biophysica Acta 04/1985; 834(1):130-3. DOI:10.1016/0005-2760(85)90185-7 · 4.66 Impact Factor
  • Tomoyoshi Hosokawa · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: Genetically obese diabetic mice (db/db) have greatly diminished 45Ca2+ binding on the plasma membranes of the adipocytes (45-55%) compared with their lean littermates. Treatment for 1 week with a diet admixture of AS-6 (0.1% in the diet) significantly restored the binding to a level comparable to the lean littermates. The addition of AS-6 in vitro had no effect on the binding, which eliminates the possibility that AS-6 is a Ca2+ ionophore. The results suggest that AS-6 treatment enhances the Ca2+ binding by causing structural alteration(s) in the membranes.
    Biochemical and Biophysical Research Communications 03/1985; 127(1):247-53. DOI:10.1016/S0006-291X(85)80151-0 · 2.30 Impact Factor
  • Tomoyoshi Hosokawa · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: The mechanism of a new hypoglycemic agent, AS-6, was comparatively studied using the adipocytes from AS-6 treated and untreated genetically obese diabetic mice, db/db. the db/db mice were treated for 1 week with a diet admixture of AS-6 (0.1%). The treatment resulted in the following alterations in metabolic activities; AS-6 treatment increased 125I-insulin binding by 1.4-3.3 fold over the insulin range of 1-1000 microU/ml, the treatment increased the basal activities in 2-deoxyglucose uptake, and in CO2 generation and lipogenesis from U-(14C)-glucose compared with the db/db controls, the treatment partially restored insulin responsiveness in 2-DG uptake and CO2 generation, and 1 mU/ml of insulin greatly stimulated lipogenesis by 5.6 fold above the basal in the control adipocytes while AS-6 treatment changed the lipogenic response less stimulative to the insulin. The results suggest that AS-6 treatment significantly increases insulin binding to the adipocytes associating with an enhancement in glucose metabolism under basal and physiological concentrations of insulin.
    Biochemical and Biophysical Research Communications 02/1985; 126(1):471-6. DOI:10.1016/0006-291X(85)90629-1 · 2.30 Impact Factor
  • Tomoyoshi Hosokawa · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: The protein bands of adipocyte plasma membranes from the genetically obese diabetic mice C57BL/KsJ db/db (db/db mice) showed slight but significant changes compared with their lean littermates. The treatment for 1 week with a new antidiabetic agent, AS-6, caused the changes to revert toward the condition in the lean littermates. In the absence of insulin, the plasma membrane and mitochondria mixture (P3 fraction) of the lean littermates densely labeled 55000 and 57000 dalton protein bands by phosphorylating with (a-32P)-ATP, whereas the labeling was less in the P3 from AS-6 treated and untreated db/db mice. Insulin inhibited phosphorylation of these bands in P3 from the lean littermates and untreated db/db mice, while the hormone enhanced the labeling in AS-6 treated db/db mice compared with the basal condition without insulin. Ca2+ greatly enhanced the labeling in all three groups, whereas Mg2+ mimicked the insulin action diminishing the labeling of these bands in the lean and untreated db/db groups. However, Mg2+ enhanced the phosphorylation in the P3 from AS-6 treated db/db mice compared with the basal condition.
    Biochemical and Biophysical Research Communications 12/1984; 125(1):64-9. DOI:10.1016/S0006-291X(84)80334-4 · 2.30 Impact Factor
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    ABSTRACT: Ascofuranone (AF) showed an antitumor protective effect on L-1210 leukemia when AF was administered once 7 days before tumor challenge. However, effect was not elicited when host mice were treated with AF simultaneously with tumor challenge. AF pretreatment on day 7, 5 and 3 before tumor challenge protected the host from the ascites form of S-180. AF also retarded tumor growth when administered once daily for 5 consecutive days 24 hours after transplantation, but antitumor effect was not seen with combined treatments before and after the transplantation. Similar results were noted with Ehrlich ascites carcinoma. AF treatment of normal mice enlarged the solid lymphoid organs without affecting body weight gain. The splenocytes derived from AF-treated mice lowered mitogenic response to phytohemagglutinin, while the mitogenic response to concanavalin A and lipopolysaccharide was unaffected.
    The Journal of Antibiotics 12/1982; 35(11):1547-52. DOI:10.7164/antibiotics.35.1547 · 1.73 Impact Factor
  • Tomoyoshi Hosokawa · Mikio Sawada · Kunio Ando · Gakuzo Tamura ·

    Agricultural and biological chemistry 01/1982; 46(3):775-781. DOI:10.1271/bbb1961.46.775
  • Tomoyoshi Hosokawa · Kunio Ando · Gakuzo Tamura ·

    Agricultural and biological chemistry 01/1982; 46(11):2865-2869. DOI:10.1271/bbb1961.46.2865
  • Tomoyoshi Hosokawa · Mikio Sawada · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: The effect of 4-O-methylascochlorin (MAC), an experimental hypocholesterolemic agent, on cholesterol metabolism was investigated in rats in two separate experiments. The administration of MAC for 2 and 6 consecutive weeks at daily doses of 100-135 mg/kg resulted in reduction in serum cholesterol levels of 16% after 2 weeks of treatment in the first experiment, and 13% after 6 weeks in the second experiment in comparison to the corresponding controls. MAC administered at a daily dose of 100 mg/kg for 2 weeks showed a significant increase in the biliary excretion of bile acids and cholesterol in bile-duct cannulated rats with or without the administration of taurocholate. In the second experiment, MAC treatment for 6 weeks produced a marked increase in the fecal output of acidic sterols during a 2 to 6-week period. MAC treatment also further enhanced hepatic cholesterol 7 alpha-hydroxylase in the rats. Therefore, it appears that the mechanism of serum cholesterol lowering due to MAC is related to the enhancement of hepatic bile acid synthesis and the increase in biliary and fecal excretion of bile acids.
    Lipids 07/1981; 16(6):433-8. DOI:10.1007/BF02535011 · 1.85 Impact Factor
  • Tomoyoshi Hosokawa · Tsuneo Okutomi · Mikio Sawada · Kunio Ando · Gakuzo Tamura ·
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    ABSTRACT: When deoxycorticosterone acetate (DOCA)-loaded uninephrectomized rats were fed on standard laboratory pellet diet and 1% saline for 5 weeks, caloric homeostasis became abnormal resulting in (a) hyperlipidemia, (b) cholesterol deposit in the heart, (c) significant reduction of triglycerides in the aorta, heart and liver and (d) a 60% increase in the cardiac free fatty acids (FFA) on one hand and a 50% reduction of the hepatic FFA on the other. These facts suggest that the hypertension severely reduces hepatic lipogenesis, whereas the cardiovascular system depends much more on FFA as a metabolic fuel than on glucose. This idea is supported by the deficiency in total body potassium (K) and decrease in serum immunoreactive insulin (IRI) which occur in the hypertension. These alterations were attenuated by the fungal prenylphenols, 4-0-methylascochlorin (MAC) and ascofuranone (AF). The protective effect seems to be partly attributable to the counteraction to DOCA. In addition, the agents caused a specific increase of renal water reabsorption. MAC treatment resulted in a particularly marked reduction of saline intake and excretion of unusually thick urine with 2.8 times higher sodium (Na) concentration than in the DOCA/saline control rats.
    European Journal of Pharmacology 03/1981; 69(4):429-38. DOI:10.1016/0014-2999(81)90446-5 · 2.53 Impact Factor
  • Tomoyoshi Hosokawa · Mikio Sawada · Kunio Ando · Gakuzo Tamura ·

    Agricultural and biological chemistry 01/1980; 44(10):2461-2468. DOI:10.1271/bbb1961.44.2461
  • Kunio Ando · Hiroshi Sasaki · Tomoyoshi Hosokawa · Yoshiharu Nawata · Yoichi Iitaka ·

    Tetrahedron Letters 12/1975; 16(11):887–890. DOI:10.1016/S0040-4039(00)72011-9 · 2.38 Impact Factor
  • Tomoyoshi HOSOKAWA · Koji SUZUKI · Tsuneo OKUTOMI · Mikio SAWADA · Kunio ANDO ·

    The Japanese Journal of Pharmacology 01/1975; 25(1):35-39. DOI:10.1254/jjp.25.35
  • Hiroshi Sasaki · Tomoyoshi Hosokawa · Yoshiharu Nawata · Kunio Ando ·

    Agricultural and biological chemistry 01/1974; 38(8):1463-1466. DOI:10.1271/bbb1961.38.1463
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    ABSTRACT: Ascofuranone significantly reduced serum lipid levels of rats fed with normal diet 6 hr after a single oral administration of 108 mg/kg. When the antibiotic was orally given for 10 consecutive days to normolipidemic rats, the treatment resulted in marked reduction of serum cholesterol, triglycerides, phospholipids and free fatty acids without affecting organ weight gain, serum total protein, albumin/globulin ratio and serum transaminases. Reduction was also noted with cardiac cholesterol content but liver total sterol and fecal sterol excretion were unchanged. Acute toxicity of ascofuranone is weak to mice and rats and the antibiotic did not induce hepatomegaly which is the main side effect of a positive control agent, ethyl p chlorophenoxyisobutyrate.
    The Journal of Antibiotics 12/1973; 26(11):681-6. DOI:10.7164/antibiotics.26.681 · 1.73 Impact Factor
  • Hiroshi Sasaki · Tomoyoshi Hosokawa · Mikio Sawada · Kunio Ando ·
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    ABSTRACT: A new antibiotic with hypolipidemic activity, ascofuranone, C23H29ClO5, and a related substance, ascofuranol, C23H31ClO5, were isolated from the filter cake of the fermented broth of Ascochyta viciae Libert, an ascochlorin producing fungus, and their structures were elucidated. They possess 3 substituted 5 chloro orcylaldehyde moiety with novel sesquiterpenyl side chains.
    The Journal of Antibiotics 12/1973; 26(11):676-80. DOI:10.7164/antibiotics.26.676 · 1.73 Impact Factor
  • Hideo OISHI · Tomoyoshi HOSOKAWA · Tsuneo OKUTOMI · Koji SUZUKI · Kunio ANDO ·

    Agricultural and biological chemistry 01/1969; 33(12):1790-1791. DOI:10.1271/bbb1961.33.1790