Evaluation of in vitro chemosensitivity of vaccine-associated feline sarcoma cell lines to vincristine and paclitaxel

Nilanjana Banerji Department of Veterinary Pathobiology University of Minnesota, St Paul, MN 55108.

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 PhD
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Xia Li Department of Veterinary Pathobiology University of Minnesota, St Paul, MN 55108.

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 MSc
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Jeffrey S. Klausner Department of Small Animal Clinical Sciences University of Minnesota, St Paul, MN 55108.

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Vivek Kapur Department of Veterinary Pathobiology University of Minnesota, St Paul, MN 55108.

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 BVSc, PhD
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Sagarika Kanjilal Department of Veterinary Pathobiology University of Minnesota, St Paul, MN 55108.
College of Veterinary Medicine, and the Department of Dermatology, College of Medicine, University of Minnesota, St Paul, MN 55108.

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 PhD

Abstract

Objective—To determine the in vitro sensitivity of 4 vaccine-associated feline sarcoma (VAFS) cell lines to the chemotherapeutic agents vincristine and paclitaxel.

Sample Population—Cell lines derived from 4 VAFS specimens.

Procedure—Cell lines were cultured in vitro and individually exposed to various concentrations of vincristine and paclitaxel. Survival was estimated after 24 and 72 hours of exposure to each drug, and the drug concentrations that resulted in 50 and 90% reduction in number of viable cells (IC50 and IC90, respectively) were calculated.

Results—Both vincristine and paclitaxel had significant dose-dependent effects on the viability of the VAFS cell lines. After 72 hours of drug exposure, the IC50 and IC90 of vincristine for the 4 cell lines were between 0.005 to 0.039 µg/ml and 0.045 to 1.027 µg/ml, respectively. The IC50 and IC90 values for paclitaxel were between 0.037 to 0.092 µg/ml and 2.450 to 15.413 µg/ml, respectively.

Conclusions—Results of pharmacokinetic studies on vincristine and paclitaxel in other species suggest that concentrations greater than the IC50 values may be possible for both drugs in feline patients as well. The drug concentrations at which viable cell numbers were reduced by 90% may also be attained in vivo for some cases, but detailed information is needed regarding the distribution, concentration, duration of availability, and toxicity of various drugs in cats. Carefully chosen combinations of antineoplastic agents need to be screened to identify treatment protocols that may be further evaluated clinically for the treatment of VAFS. (Am J Vet Res 2002;63:728–732)

Abstract

Objective—To determine the in vitro sensitivity of 4 vaccine-associated feline sarcoma (VAFS) cell lines to the chemotherapeutic agents vincristine and paclitaxel.

Sample Population—Cell lines derived from 4 VAFS specimens.

Procedure—Cell lines were cultured in vitro and individually exposed to various concentrations of vincristine and paclitaxel. Survival was estimated after 24 and 72 hours of exposure to each drug, and the drug concentrations that resulted in 50 and 90% reduction in number of viable cells (IC50 and IC90, respectively) were calculated.

Results—Both vincristine and paclitaxel had significant dose-dependent effects on the viability of the VAFS cell lines. After 72 hours of drug exposure, the IC50 and IC90 of vincristine for the 4 cell lines were between 0.005 to 0.039 µg/ml and 0.045 to 1.027 µg/ml, respectively. The IC50 and IC90 values for paclitaxel were between 0.037 to 0.092 µg/ml and 2.450 to 15.413 µg/ml, respectively.

Conclusions—Results of pharmacokinetic studies on vincristine and paclitaxel in other species suggest that concentrations greater than the IC50 values may be possible for both drugs in feline patients as well. The drug concentrations at which viable cell numbers were reduced by 90% may also be attained in vivo for some cases, but detailed information is needed regarding the distribution, concentration, duration of availability, and toxicity of various drugs in cats. Carefully chosen combinations of antineoplastic agents need to be screened to identify treatment protocols that may be further evaluated clinically for the treatment of VAFS. (Am J Vet Res 2002;63:728–732)

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