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Biomedical subjects

S Tsukagoshi

Publications and source records attributed to S Tsukagoshi.

At least 199 records · Page 11Linked to original sources
PubMed1980

Lymph node metastasis and effects of 1-beta-D-arabinofuranosylcytosine, 5-fluorouracil, and their lipophilic derivatives in an experimental model system using P388 leukemia.

Mouse P388 leukemic cells inoculated into the right forefootpad metastasized primarily to the right axillary lymph node. No significant metastasis to other lymph nodes or organs was detected on Day 12 after the inoculation of 10(6) P388 cells in the forefootpad, except that a lesser extent of metastasis was observed in some cases in the right inguinal lymph node, liver, and spleen. A quantitative estimation of metastasis in the axillary lymph node was accomplished by transferring the lymph node i.p. to the recipient mice (bioassay method). The metastasis of P388 cells to the axillary lymph node occurred linearly depending on the elapse of time after inoculation. In studying the chemotherapeutic effect on lymph node metastasis, two experimental models were established. Model 1, 10(6) P388 cells were inoculated into the right forefootpad, and drug was administered thereafter. The right axillary lymph node was removed on Day 8, and the extent of inhibition of lymph node metastasis was estimated by the bioassay method. In Model 2, P388 cells were inoculated, and the right forelimb including original tumor was amputated on Day 6 when the metastasis had already been established. The drug was given thereafter, and the extent of inhibition of metastasis was estimated on Day 12 by the bioassay method. In this experimental system, a lipophilic derivative N4-behenoyl-1-beta-D-arabinofuranosylcytosine was more effective than its parent compound 1-beta-D-arabinofuranosylcytosine; however, 5-fluorouracil was found to be more potent than its lipophilic derivative ftorafur for the inhibition of lymph node metastasis, suggesting an existence of various pharmacokinetic factors for the inhibition of lymph node metastasis.

Animals↗
PubMed1979

Potentiation of L1210 murine leukemia vaccine in vivo by levamisole.

Intraperitoneal inoculation of either levamisole or 2 x 10(6) cells of concanavalin-A (Con-A)-bound L1210 leukemia vaccine produced no cured mice after subsequent ip inoculation of 10(3) live L1210 cells. Combined inocluation of levamisole and Con-A-bound vaccine produced about 20% cure incidence but no prolongation of life span of tumor-bearing mice after inoculation of live L1210 cells. Combined inoculation of levamisole and Con A-free vaccine did not induce detectable immune resistance in mice. These results suggest that levamisole enhanced host response to cell-bound Con-A associated with immunogenic potency of the vaccine. Levamisole given intravenously and orally was as effective as that inoculated intraperitoneally in enhancing the induction of resistance in mice by Con-A-bound vaccine. Dose of levamisole was very critical for this enhancement, being effective at 0.38 mg/kg but not either at 0.75 or 0.19 mg/kg. Furthermore, levamisole restored immune resistance induced by a larger inoculum of Con-A-bound vaccine cells (10(7)) and impaired by cyclophosphamide.

Adjuvants, Immunologic↗
PubMed1978

Effect of combined use of anticancer drugs with a polysaccharide preparation, Krestin, on mouse leukemia P388.

When CDF1 mice inoculated intraperitoneally with leukemia P388 were treated intraperitoneally with mitomycin-C, of which dose was not so effective, on day 1 and given intraperitoneally polysaccharide preparation, Krestin, on day 2, 5, or 8 after tumor inoculation, best therapeutic results judged from 60-day survivors were obtained by combined use of mitomycin-C on day 1 and Krestin on day 5. Besides mitomycin-C, none of anticancer drugs such as cyclophosphamide, 5-fluorouracil, and 6-mercaptopurine was effective in this system. From these results, it was concluded that in this system, enhancement of anti-tumor effect of mitomycin-C by Krestin depends on the time of Krestin administration and that the combination effect is observed with mitomycin-C but not with cyclophosphamide, 5-fluorouracil, or 6-mercaptopurine.

Animals↗
PubMed1978

Antitumor activity of water-soluble platinum(II) complexes of 1,2-cyclohexanediamine isomers.

Dichloroplatinum(II) complexes of 1,2-cyclohexanediamine isomers were reported to have high antitumor activity against leukemia L-1210 and P-388, but they were hardly soluble in water and, therefore, dibromo- and diiodo-platinum(II) complexes of 1,2-cyclohexanediamine isomers were prepared. They were not soluble in water but showed high antitumor activity. When the chloride ions are replaced with sulfate ions, they become soluble and also they are anti-tumor active. Bismonobromoacetatoplatinum (II) complexes were synthesized and tested. Mono- and bis-(D-glucuronato)platinum(II) complexes of 1,2-cyclohexanediamine isomers were newly synthesized. All of them were freely soluble in water and showed high antitumor activity with low toxicity. The chelated mono(D-glucuronato)platinum(II) was found to be more effective than the monodentate bis(D-glucuronato)platinum (II) complexes.

Animals↗
PubMed1977

Enhancement of anti-tumor activity of 1-beta-D-arabinofuranosylcytosine by encapsulation in liposomes.

1-beta-D-Arabinofuranosylcytosine (ara-C) was encapsulated in four different types of unsonicated artificial vesicles of phospholipid (liposomes) to compare the anti-tumor effect on mouse leukemia L1210 inoculated in CD2F, mice with that of free ara-C. The anti-tumor activity of ara-C was markedly enhanced by encapsulation in liposomes when given in a single IP injection. Among the four types of liposomes, a physically stable and positively charged liposome consisting of sphingomyelin, stearylamine and cholesterol (20:2:15 molar ratio) most effectively enhanced the effect of ara-C. A single IP dose of 50 mg/kg of ara-C, encapsulated in this kind of liposome exhibited high activity, producing a survival rate of 60% of the treated mice at 60 days. This enhanced effect of ara-C encapsulated in liposomes was also demonstrated when the drug was administered either IV or SC, and the range between the minimum effective and the maximum tolerable doses was wide enough to allow the safe use of the encapsulated ara-C. Intraperitoneal administration of encapsulated ara-C induced a more prolonged survival of mice inocualted with L1210 than did free ara-C, regardless of whether it was given in single or multiple doses.

Administration, Oral↗
PubMed1977

Induction of resistance to L1210 leukemia in BALB/c X DBA/2Cr F1 mice, with L1210 cells treated with glutaraldehyde and concanavalin A.

Immunization with L1210 mouse leukemia cells treated with glutaraldehyde and concanavalin A resulted in the induction of leukemia-specific immune resistance in BALB/c X DBA/2Cr F1 mice. This was measured by survival of the mice after challenge either with the intact cells or with modified leukemia cells of less malignancy. Factors involved in the induction of immunoprophylaxis were analyzed. To produce an immune response against L1210 cells, preincubation with both glutaraldehyde and concanavalin A was required. Repeated sensitization with this combination produced higher incidences of survivors upon subsequent challenge with L1210 cells than did a single sensitization by equivalent or larger doses. However, the sensitization was rendered less effective by repetition of the immunization process five times.

Aldehydes↗
PubMed1977

Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity.

New anthracycline antibiotics have been isolated from the culture of Streptomyces galilaeus MA144-M1. Among 14 anthracycline compounds, aclacinomycin-A showed the strongest activity in inhibiting leukemia L-1210 and had lower toxicity than others. Antitumor activity of aclacinomycin-A against leukemia L-1210 and P-388, solid sarcoma-180, and lymphosarcoma 6C3HED was examined in comparison with adriamycin and daunomycin. Aclacinomycin-A showed the same degree of activity against leukemia L-1210 and P-388, when administered intraperitoneally, as daunomycin and somewhat less than adriamycin. In oral administration, aclacinomycin-A also exhibited a significant activity on leukemia L-1210. The degree of inhibition of the growth of sarcoma-180 and 6C3HED lymphosarcoma transplanted subcutaneously by aclacinomycin-A was almost the same as that of adriamycin and daunomycin, although the optimal dose was about twice more than adriamycin. Acute cardiotoxicity of aclacinomycin-A by a test using hamsters was more than 10 times lower than that of adriamycin.

Aclarubicin↗
PubMed1977

N4-Behenoyl-1-beta-D-arabinofuranosylcytosine as a potential new antitumor agent.

N4-Acyl-1-beta-D-arabinofuranosylcytosines, which are lipophilic antitumor analogs of 1-beta-D-arabinofuranosylcytosine, were dissolved by the use of a detergent, HCO-60, and the differences in the antitumor activities when the drugs were administered in the forms of solution or suspension were compared. N4-Stearoyl-1-beta-D-arabinofuranosylcytosine (NSC 201290), which was the most active compound when administered as an aqueous suspension, diminished in its activities after it had been dissolved into a clear solution, whereas N4-behenoyl-1-beta-D-arabinofuranosylcytosine (NSC 239336) exhibited activities superior to those of the parent compound 1-beta-D-arabinofuranosylcytosine when administered as a solution. Moreover, the high efficacy of this compound was long lasting in the host animal, regardless of the treatment schedules or the presence of the 1-beta-D-arabinofuranosylcytosine-inactivating enzyme, cytidine deaminase.

Animals↗
PubMed1977

Enhanced induction of immune resistance by concanavalin A-bound L1210 vaccine and an immunopotentiator prepared from Coriolus versicolor.

Combined administration of a vaccine consisting of a small number (2 X 10(6)) of L1210 murine leukemic cells treated with glutaraldehyde and concanavalin A and a protein-bound polysaccharide preparation of Coriolus versicolor induced synergistic resistance to L1210 leukemia in BALB/c X DBA/2CrF1 mice. This effect was dependent on the dose and timing of the administration of the protein-bound polysaccharide preparation, being most effective at the time of or 1 day after the second vaccination. Induced resistance was not cross-reactive with P388 murine leukemia, indicating specificity of resistance. This immunopotentiation by the protein-bound polysaccharide did not occur when L1210 cells treated with glutaraldehyde, but not with concanavalin A, were used as a vaccine.

Animals↗
PubMed1976

Antitumor activities of newly synthesized N4-acyl-1-beta-D-arabinofuranosylcytosine.

New derivatives of 1-beta-D-arabinofuranosylcytosine were synthesized and their antitumor activities were tested against mouse leukemia L1210. Among the 50 compounds investigated, a series of N4-acyl derivatives with long-chain saturated fatty acids were found to be highly active. The most active derivatives were N4-stearoly-1-beta-D-arabinofuranosylcytosine, which was administered in the form of suspension, and N4-behenoyl-1-beta-D-arabinofuranosylcytosine given in the form of solution. They were superior to the parent compound, 1-beta-D-arabinofuranosylcytosine, in that smaller dosages exhibited strong activities regardless of the treatment schedule, and they were also resistant to cytidine deaminase.

Acylation↗
PubMed1976

Effect of drug combination of antitumor activity and myelotoxicity.

Relationship between the survival time of L-1210-bearing mice and myelosuppression of normal mice after combination chemotherapy was studied. In a variety of combinations of 6-mercaptopurine, 6-thioguanine, and cyclophosphamide, a combination of cyclophosphamide and 6-thioguanine produced the highest increase in life span (ILS) and the highest number of 60-day survivors of all. In contrast, a combination of 6-mercaptopurine and 6-thioguanine showed as low as ILS as did single agents. A combination of 6-mercaptopurine, cyclophosphamide, and 6-thioguanine exhibited the second best effect on survival time of leukemic mice. However, in myelosuppression as measured by changes in the total number of nucleated cells, in the number of hematopoietic colony-forming cell, and in peroxidase level of femoral bone-marrow, the combination of 6-mercaptopurine and 6-thioguanine showed no more toxicity than the other 2-drug combinations. In addition to these findings, the presence of a striking difference in the cell number in ascitic fluid of leukemic mice among the animals given 6-thioguanine, and those given other 2- or 3-drug combinations may suggest that the difference in the antileukemic activity is not due to the difference in the toxicity against the host, but due to the difference in the activity of direct action of combined drugs on leukemic cells in the peritoneal cavity or in other sites.

Animals↗