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Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review.

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Taxol, a diterpene alkaloid isolated from the bark of Taxus brevifolia, has a unique mechanism of action. The drug promotes the formation of microtubule polymers in a cell, by reversibly and specifically binding the beta-subunit of tubulin. Taxol is administered intravenously by a 3-24-hour infusion

Effect of deuterium oxide (D2O) on the IgE-mediated Ca2+ influx, arachidonic acid and histamine release in rat basophilic leukemia cells.

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Deuterium oxide (D2O), which is known to stimulate microtubule aggregation, enhanced the IgE-mediated 45Ca2+ influx, (14C)-arachidonic acid and histamine release in rat basophilic leukemia cells (RBL-2H3) in the same dose-dependent manner (up to 90% (v/v]. We compared the interaction between D2O and

Phase I and pharmacodynamic study of taxol in refractory acute leukemias.

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Taxol, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered to adults with refractory leukemias as a 24-h i.v. infusion in a Phase I study. The primary objectives were to determine the maximum tolerated dose of taxol administered on this

Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocytic leukaemia cells associated with changes in Bcl-2 phosphorylation and expression.

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Microtubule active drugs are used in the treatment of malignancies and their mechanism of action in cycling cells is to produce mitotic arrest followed by apoptosis. In this study, we investigate in detail the specificity and mechanism by which a microtubule de-polymerising agent, nocodazole,

Taxol: a review of its preclinical in vivo antitumor activity.

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Taxol has been demonstrated in numerous laboratories worldwide to have broad-spectrum antitumor activity against many tumor models. The susceptible tumors include murine leukemias and solid tumors, and human solid tumor xenografts. The initial findings of taxol's ineffectiveness against most distal

Taxol: a promising new drug of the '90s.

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Taxol (paclitaxel, Bristol-Myers Squibb Company, Princeton, NJ), a drug extracted from the stem bark of the western yew, shows great promise as an antineoplastic agent for ovarian, breast, nonsmall cell lung, and head and neck cancers; melanoma; and leukemia. Although Taxol first was isolated in

Restoration of taxol sensitivity of multidrug-resistant cells by the cyclosporine SDZ PSC 833 and the cyclopeptolide SDZ 280-446.

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BACKGROUND Taxol, a promising agent for the treatment of cancer, has entered phase II clinical trials. Nevertheless, it belongs to the class of compounds that show impaired retention in multidrug-resistant cells expressing P-glycoprotein (Pgp), a drug efflux pump. Chemosensitizers like verapamil

Synergistic interaction of lovastatin and paclitaxel in human cancer cells.

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The hydroxymethylglutaryl-CoA reductase inhibitor lovastatin is used widely to treat hypercholesterolemia and has been shown to have cell cycle-specific effects. In these studies, we have examined the effects of combining lovastatin and paclitaxel (Taxol), a microtubule-stabilizing agent, in the

Phase II study of taxol in patients with untreated advanced non-small-cell lung cancer.

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BACKGROUND Taxol, a complex plant product (a diterpene) extracted from the bark of Taxus brevifolia, has demonstrated substantial anticancer activity in ovarian and breast cancers, malignant melanoma, and acute myelogenous leukemia. Due to allergic reactions in phase I and early phase II studies,

Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome.

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Deficiencies in the SBDS gene result in Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome associated with leukemia predisposition. SBDS encodes a highly conserved protein previously implicated in ribosome biogenesis. Using human primary bone marrow stromal cells (BMSCs),

Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol.

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Taxol, a diterpenoid plant product that enhances the polymerization of tubulin, is currently entering clinical trials in the treatment of human leukemia. In order to develop an in vitro assay to predict tumor sensitivity to taxol, human leukemic cell lines were exposed to clinically achievable

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