Chemotherapy-induced peripheral neuropathy

Malik, Bushra; Stillman, Mark J.

doi:10.1007/s11910-008-0010-5

Cited by 34 publications

(28 citation statements)

References 48 publications

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“…Impairment of axonal transport has been implicated in chemotherapeutic druginduced peripheral neuropathy, but the causal relationship and the mechanism of axonal transport in drug-associated neurological toxicity remain largely unknown (28). In the present study, several anti-cancer drugs, including paclitaxel, vincristine, cisplatin, and oxaliplatin, suppressed axonal transport at the effective concentrations for inhibiting tumor cell growth (20 -22).…”

Section: Discussionmentioning

confidence: 69%

“…In the present study, several anti-cancer drugs, including paclitaxel, vincristine, cisplatin, and oxaliplatin, suppressed axonal transport at the effective concentrations for inhibiting tumor cell growth (20 -22). This suppression of axonal transport might be commonly shared by these anti-neoplastic agents that cause neurological toxicity (28).…”

Section: Discussionmentioning

confidence: 96%

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Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

et al. 2010

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Abstract. Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 96%

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

et al. 2010

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“…However, a consequence of this progress is the increased incidence of toxicity-related symptoms affecting nervous system, especially the peripheral nervous system 1 . Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological syndrome secondary to anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy: review for clinical practice

Simão¹,

Murad²,

Martins³

et al. 2015

Revista Dor

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“…Despite the clinical successes of several antitubulin agents including vinca alkaloids and taxane analogs, toxicity and drug resistance have limited the effectiveness of antimitotic agents in clinical use (Dumontet and Sikic, 1999;Verrills and Kavallaris, 2005;Malik and Stillman, 2008). We identified a novel compound, I-387, that inhibits the in vitro growth of a number of human cancer cell lines with nanomolar IC 50 values.…”

Section: Discussionmentioning

confidence: 99%

Biotransformation of a Novel Antimitotic Agent, I-387, by Mouse, Rat, Dog, Monkey, and Human Liver Microsomes and In Vivo Pharmacokinetics in Mice

Ahn¹,

Kearbey²,

Li³

et al. 2011

Drug Metab Dispos

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ABSTRACT:3-(1H-Indol-2-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone (I-387) is a novel indole compound with antitubulin action and potent antitumor activity in various preclinical models. I-387 avoids drug resistance mediated by P-glycoprotein and showed less neurotoxicity than vinca alkaloids during in vivo studies. We examined the pharmacokinetics and metabolism of I-387 in mice as a component of our preclinical development of this compound and continued interest in structure-activity relationships for antitubulin agents. After a 1 mg/kg intravenous dose, noncompartmental pharmacokinetic analysis in plasma showed that clearance (CL), volume of distribution at steady state (Vd ss ), and terminal half-life (t 1/2 ) of I-387 were 27 ml per min/kg, 5.3 l/kg, and 7 h, respectively. In the in vitro metabolic stability study, half-lives of I-387 were between 10 and 54 min by mouse, rat, dog, monkey, and human liver microsomes in the presence of NADPH, demonstrating interspecies variability. I-387 was most stable in rat liver microsomes and degraded quickly in monkey liver microsomes. Liquid chromatography-tandem mass spectrometry was used to identify phase I metabolites. Hydroxylation, reduction of a ketone group, and O-demethylation were the major metabolites formed by the liver microsomes of the five species. The carbonyl group of I-387 was reduced and identified as the most labile site in human liver microsomes. The results of these drug metabolism and pharmacokinetic studies provide the foundation for future structural modification of this pharmacophore to improve stability of drugs with potent anticancer effects in cancer patients.

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Chemotherapy-induced peripheral neuropathy

Cited by 34 publications

References 48 publications

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

Chemotherapy-induced peripheral neuropathy: review for clinical practice

Biotransformation of a Novel Antimitotic Agent, I-387, by Mouse, Rat, Dog, Monkey, and Human Liver Microsomes and In Vivo Pharmacokinetics in Mice

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