Application of anthracyclines and Vinca alkaloids on the same day represents a hallmark of polychemotherapy protocols for hematopoietic malignancies. Here we show, for the first time, that both drugs might act most efficiently if they are applied on different days. Proof-of-concept studies in 18 cell lines revealed that anthracyclines inhibited cell death by Vinca alkaloids in 83% of cell lines...

OBJECTIVES/HYPOTHESIS Functional recovery after a recurrent laryngeal nerve or facial nerve injury may be impaired due to aberrant reinnervation. Previous work in a rat peripheral nerve injury model found vincristine to be a potent inhibitor of reinnervation, and it has since been used to effectively block neural regeneration in other animal models. However, vincristine's narrow therapeutic ind...

Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, vinblastine, vincristine, and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady state. Although all four derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were dis...

BACKGROUND Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. METHODS We analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adj...

BACKGROUND Peripheral neurotoxicity is a dose-limiting side-effect of a number of effective chemotherapeutic agents. Neuroprotective agents may help to reduce neurotoxicity, thus allowing the intensification of cytostatic therapy in patients. MATERIALS AND METHODS In this in vitro study, using the rat pheochromocytoma cell line PC-12 neurite-outgrowth assay, the potential of amifostine to pro...

We have examined the effects of a 24-h exposure to clinically achiev able concentrations of adriamycin, melphalan, 5-fluorouracil, and vincristine on the estrogen binding capacity of MCF-7 human breast cancer cells using a whole cell binding assay. Adriamycin (0.018 to 1.8 MM), melphalan (0.1 to 5 MM),5-fluorouracil (0.077 to 15.4 MM),and vincristine (0.01 to l nM) reduce the estrogen binding c...

IMPORTANCE With cure rates of childhood acute lymphoblastic leukemia (ALL) exceeding 85%, there is a need to mitigate treatment toxicities that can compromise quality of life, including peripheral neuropathy from vincristine treatment. OBJECTIVE To identify genetic germline variants associated with the occurrence or severity of vincristine-induced peripheral neuropathy in children with ALL. ...

Vincristine is preferentially metabolized to a secondary amine, M1, by CYP3A5 with a 9- to 14-fold higher intrinsic clearance than CYP3A4 using cDNA-expressed enzymes. The genetically polymorphic expression of CYP3A5 may contribute to interindividual variability in vincristine efficacy and toxicity. The current study quantifies the contribution of cytochromes P450 (P450s), including CYP3A4 and ...

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeate...

Patients with hereditary neuropathy at high risk of severe vincristine neurotoxicity are well known. Here, along with a review of the literature, we described two patients with unrecognized hereditary neuropathy who developed foot drop following low dose vincristine therapy. With this report, we wanted to emphasize the importance of detailed neurologic examination and history taking before init...