16-16-dimethylprostaglandin-e2 and Melanoma

We investigated the effect on in vivo administration of 16,16-dimethyl-prostaglandin E2 (di-M-PGE2) alone and in combined treatment with alpha-beta interferon (IFN) on NK activity in normal, cyclophosphamide (CY)-treated, tumor bearing or irradiated and bone marrow reconstituted mice and on B-16 melanoma growth. Normal mice inoculated with IFN (30,000 U/mouse, 24 hr before testing) showed a significant increase in NK activity, while those treated with di-M-PGE2 (10 micrograms/mouse daily X 4 days) showed a suppressed NK response. No difference was observed between mice treated with di-M-PGE2 alone and those treated with di-M-PGE2 associated with IFN. In immunosuppressed animals single treatments were slightly (di-M-PGE2) or not (IFN) effective, while the combined administration of di-M-PGE2 and IFN caused a marked increase in NK activity. Moreover, di-M-PGE2 was able to accelerate the recovery rate of NK activity in bone marrow-reconstituted murine chimeras, suggesting that the synergistic effect of prostaglandins and IFN could derive from the action of di-M-PGE2 on progenitor pre-NK cells and of IFN on effector cells. Finally, we observed a good correlation between the enhancement of the NK activity and the tumor growth inhibition.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Chimera; Cyclophosphamide; Immunosuppression Therapy; Interferon Type I; Killer Cells, Natural; Male; Melanoma; Mice; Mice, Inbred C57BL; Prostaglandins E, Synthetic

Topics: 16,16-Dimethylprostaglandin E2; Animals; Antibody Formation; Antibody-Producing Cells; Antilymphocyte Serum; Cell Count; Cell Transformation, Neoplastic; Doxorubicin; Female; Hemagglutinins; Immunity, Cellular; Immunosuppression Therapy; Melanoma; Mice; Mice, Inbred C57BL; Prostaglandins E, Synthetic; Rabbits; Splenectomy; T-Lymphocytes; Thymectomy

Two hundred seventy-one B-16 melanoma-bearing mice were randomized and treated for 4 days with either control diluent, 10 micrograms of 16,16-dimethyl-PGE2-methyl-ester (di-M-PGE2), chemotherapy, or chemotherapy plus di-M-PGE2. The chemotherapeutic regimens included adriamycin (7.5 mg/kg), 5-fluorouracil (250 mg/kg), nitrogen mustard (5 mg/kg), and vincristine (0.5 mg/kg). The number of plaque-forming cells and hemagglutinin titers in response to sheep erythrocytes were used as measures of humoral immunity while cellular immunity was assessed by evaluation of delayed hypersensitivity. As we previously reported, the presence of subcutaneous B-16 tumors induced substantial immunosuppression and this suppression was reversed by treatment with di-M-PGE2. Treatment with all four chemotherapeutic agents induced profound immunosuppression. Similarly, the addition of di-M-PGE2 to the chemotherapy protocols resulted in significant augmentation of cellular and humoral immunity.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Antibody Formation; Doxorubicin; Drug Therapy, Combination; Immunity, Cellular; Immunosuppression Therapy; Mechlorethamine; Melanoma; Mice; Mice, Inbred C57BL; Prostaglandins E, Synthetic; Vincristine

Topics: 16,16-Dimethylprostaglandin E2; Adjuvants, Immunologic; Animals; Female; Immune Sera; Immunity; Immunosuppression Therapy; Melanoma; Mice; Mice, Inbred C57BL; Prostaglandins E, Synthetic; Thymectomy; Thymus Gland

Topics: 16,16-Dimethylprostaglandin E2; Carcinoma; Cells, Cultured; DNA, Neoplasm; Dose-Response Relationship, Drug; Drug Synergism; Melanoma; Neoplasms, Experimental; Prostaglandins A, Synthetic; Prostaglandins E, Synthetic; Structure-Activity Relationship; Time Factors

We have compared the effects of indomethacin alone (100 microgram/mouse/day) with those of indomethacin plus adriamycin, 5-FU, nitrogen mustard, thioTEPA, and vincristine on B-16 tumor cell proliferation in vivo. As we have previously described, after four days of treatment with indomethacin, subcutaneous tumors were slightly smaller and lighter in weight, but contained more melanoma cells. Addition of indomethacin to cytotoxic regimens resulted in either no change or a decrease in the effectiveness of the chemotherapy. In previous studies we demonstrated that treatment of tumor-bearing mice with a long-acting synthetic analogue of PGE2 (di-M-PGE2) stimulated the synthesis of endogenous prostaglandins. In order to evaluate if these endogenously synthesized prostaglandins were responsible for the inhibition of B-16 growth in vivo, mice were treated with di-M-PGE2 or di-M-PGE2 plus indomethacin. Addition of indomethacin did not alter the tumor inhibitory effects of di-M-PGE2.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Cell Count; Cell Division; Doxorubicin; Female; Fluorouracil; Indomethacin; Mechlorethamine; Melanoma; Mice; Thiotepa; Vincristine

Topics: 16,16-Dimethylprostaglandin E2; Animals; Female; Immunity, Cellular; Immunologic Deficiency Syndromes; Melanoma; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Prostaglandins E, Synthetic; Time Factors