Vinca alkaloids, vinblastine and vincristine sulfate, have a variety of effects on cells in vivo and in vitro (1-10) . In low sublethal doses, vinblastine and vincristine arrest cells in mitosis (1-3) and prevent the formation and organization of the spindle microtubules (2, 3) . Accumulation of large proteinaceous crystals in platelets (7), in tissue culture cells (8, 10), and in cells of the ...

In this study, Monte Carlo statistical mechanical simulations for vinblastine and vincristine werecarried out in standard manner using the Metropolis sampling technique in canonical (T, V, N)ensemble., Geometrical optimizations of vinblastine and vincristine were carried out with the HFmethod coupled to 6-31G(d) basis sets for all atoms. Simulation was done by four force fields ofMM+, BIO+, AMB...

Vinblastine is an antimitotic plant alkaloid with an elimination half-life of about 24 h. The cytotoxicity of vinblastine against solid tumor cell lines in vitro is markedly increased with prolonged exposure. Therefore, 24 patients with advanced malignancy were treated with a prolonged continuous i.v. infusion of vinblastine given via an implantable pump. The patients received vinblastine for a...

P-Glycoprotein, the plasma membrane protein responsible for the multidrug resistance of some tumour cells, is an active transporter of a number of structurally unrelated hydrophobic drugs. We have characterized the modulation of its ATPase activity by a multidrug-resistance-related cytotoxic drug, vinblastine, and different multidrug-resistance-reversing agents, verapamil and the dihydropyridin...

Previous ultrastructural studies appear to indicate that the lacinate appendages (highly elaborated laminar structures which cover the surface of moth spermatozoa) may be intracellular derivatives of transient microtobules found in the elongating spermatids of these insects. Additional support for this theory is supplied by the present study in which testes of the warehouse moth Ephestia cautel...

The Vinca alkaloids differ in their chemotherapeutic effectiveness and their toxicities. To determine whether differences are due to a differential effect on the assembly of tubulin into microtubules, we examined the effects of vincristine, vinblastine, and a newer alkaloid, desacetyl vinblastine amide, on the assembly of bovine brain tubulin in vitro. The three compounds block bovine tubulin p...

Brain-derived neurotrophic factor (BDNF) and its receptors are necessary for the survival and development of many neuronal cells. Because BDNF and TrkB are expressed in many poor-prognosis neuroblastoma (NB) tumors, we evaluated the role of BDNF in affecting sensitivity to chemotherapeutic agents. We investigated the effects of activation of the BDNF-TrkB signal transduction pathway in two NB c...

Vincristine and vinblastine exhibit differential activity against tumors and normal tissues. In this work, a number of cultured cell lines were assayed for their sensitivity to the antiproliferative and cytotoxic effects of the two drugs following short-term (4 hr) or during continuous exposures. Differential activity was not seen when cells were subjected to continuous exposures. The concentra...

P-Glycoprotein-mediated drug efflux can yield a multidrug-resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. Pervilleine A, a novel tropane alkaloid obtained from a chloroform extract of Erythroxylum pervillei as the result of bioactivityguided fractionation, was found to restore the vinblastine sensitivity of cultured multidrug-resistant KB-V1 and CEM/VL...

A question of broad importance in cellular neurobiology has been, how is microtubule cytoskeleton of the axon organized? It is of particular interest because of the history of conflicting results concerning the form in which tubulin is transported in the axon. While many studies indicate a stationary nature of axonal microtubules, a recent series of experiments reports that microtubules are rec...