bryostatin-5 has been researched along with bryostatin-1* in 3 studies
3 other study(ies) available for bryostatin-5 and bryostatin-1
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Comparison of the antitumor activity of bryostatins 1, 5, and 8.
Bryostatin 1, a macrocyclic natural lactone isolated from a marine Bryozoan, has undergone phase I testing in humans. Side effects of treatment have included muscle pain and joint aches, a transient decrease in platelets, and the release of tumor necrosis factor alpha (TNF alpha) and IL-6 into the blood stream. In animals, anticancer activity has been demonstrated against murine leukemias, lymphomas, melanomas, and sarcomas. The mechanism of action of this compound depends in part on its ability to activate protein kinase C. To determine the biologic activity and toxicity of other members of the family of bryostatin compounds, we studied the ability of bryostatins 5 and 8 to inhibit the growth of murine melanoma K1735-M2. Bryostatins 1, 5, and 8 induced equivalent inhibition of melanoma growth, but bryostatins 5 and 8 induced less weight loss than bryostatin 1 (P < 0.001). Neither the injection of an antimurine TNF alpha antibody nor an adenovirus, which produces a mutated TNF receptor inhibiting TNF alpha activity, into mice had any effect on either bryostatin-induced weight loss or melanoma tumor growth inhibition. Using a novel competition assay, the levels of bryostatin in the plasma were measured. The approximate half-life (t1/2) of bryostatin was 8.62 min, the clearance (Cl) 3.53 ml/min and the AUC 322.20 nmol/l min. A similar result was obtained with each bryostatin analog. These results suggest that human testing of additional bryostatin analogs may yield compounds with similar antitumor activity but decreased side effects. A novel assay to measure the level of all bryostatins in the plasma of patients undergoing treatment is described. Topics: Animals; Antineoplastic Agents; Biological Assay; Bryostatins; Lactones; Macrolides; Melanoma, Experimental; Mice; Protein Kinase C; Tumor Necrosis Factor-alpha; Weight Loss | 1996 |
The antineoplastic bryostatins affect human basophils and mast cells differently.
Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multi-potential stimulators of immune cells. We have examined the effects of bryostatins on mediator release from human basophilic leukocytes and human tissue mast cells. Bryostatins 1, 2, and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and unpurified peripheral blood basophils, whereas they caused no release of peptide-leukotriene C4 from these cells. The rate of histamine release caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/- SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37 degrees C, approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4 degrees C). The addition of increasing concentrations of extracellular Ca2+ to the medium caused histamine release in the presence of bryostatins. Subeffective concentrations of bryostatins and anti-IgE produced a synergistic effect on histamine release from basophils. Staurosporine, chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein kinase C inhibitors, inhibited the histamine secretion activated by bryostatin 1 and tetradecanoylphorbol-acetate (TPA). Preincubation with granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human basophils induced by bryostatin 1. Neither bryostatin 1 nor bryostatin 2 induced the release of histamine from mast cells isolated from human lung or skin tissues. However, brief (10 minutes) preincubation with bryostatin 1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by anti-IgE from skin or lung mast cells. Bryostatin 1 was a more potent (by approximately 30 times) inhibitor of IgE-mediated histamine release than was TPA. The heterogeneous effects exerted by bryostatins on human basophils and mast cells can be of interest for those designing therapeutic trials using these agents. Topics: Antibodies, Anti-Idiotypic; Basophils; Bryostatins; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine Release; Interleukin-3; Interleukin-5; Lactones; Leukotriene C4; Lung; Macrolides; Mast Cells; Protein Kinase C; Skin; Tetradecanoylphorbol Acetate | 1995 |
Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells.
Nimesulide (NIM) is a sulfonanilide nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of various inflammatory diseases and chemically unrelated to other acidic NSAIDs, such as acetylsalicylic acid (ASA) and indomethacin (INDO). We investigated the effects of NIM and of its in vivo metabolite, 4-hydroxy-NIM (OH-NIM), on the release of performed (histamine) and de novo synthesized mediators (sulfidopeptide leukotriene C4 [LTC4] and prostaglandin D2 [PGD2]) from human basophils and mast cells isolated from lung parenchyma (HLMC) and skin (HSMC). Histamine release from basophils challenged with rabbit anti-human IgE antibody (anti-IgE) was enhanced by preincubation with ASA or INDO (92.2 +/- 7.1% at 10(-3) M and 61.1 +/- 6.7% at 3 x 10(-6) M, respectively; P < .001). In contrast, NIM and its metabolite, OH-NIM (10(-6) to 10(-3) M), caused concentration-dependent inhibition (2.9 to approximately 60% and 3.7 to approximately 90%, respectively) of IgE-mediated histamine release from basophils. NIM and OH-NIM also inhibited histamine release from basophils induced by the Ca++ ionophore A23187 and different protein kinase C activators, such as 12-O-tetradecanoyl-phorbol-13-acetate, bryostatin 1 and bryostatin 5. NIM and OH-NIM also inhibited the IgE-mediated histamine release from HLMC (52.3 +/- 9.6% and 66.1 +/- 12.1% at 10(-3) M, respectively; P < .0001) and HSMC (67.3 +/- 3.7% and 77.7 +/- 12.0% at 10(-3) M, respectively; P < .0001) but had little or no effect on HLMC and HSMC activated by A23187. NIM (10(-6) to 10(-3) M) markedly inhibited the de novo synthesis of LTC4 from basophils, LTC4 and PGD2 from HLMC and PGD2 from HSMC. NIM and OH-NIM potentiated, whereas ASA and INDO reversed, the inhibitory effect of adenylate cyclase agonists, such as prostaglandin E1 and forskolin. In addition, NIM and OH-NIM reversed the enhancing effects of ASA and INDO on IgE-mediated histamine release from basophils. Topics: Adolescent; Adult; Alprostadil; Amino Acid Sequence; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Basophils; Bryostatins; Calcimycin; Colforsin; Complement C5a; Histamine Release; Humans; Immunoglobulin E; Indomethacin; Lactones; Leukotriene C4; Lung; Macrolides; Mast Cells; Middle Aged; Molecular Sequence Data; N-Formylmethionine Leucyl-Phenylalanine; Prostaglandin D2; Skin; Sulfonamides; Tetradecanoylphorbol Acetate | 1993 |