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In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs

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  • 1 Small Animal Clinic, Hannover School of Veterinary Medicine; D-30173 Hannover, Germany.
  • | 2 Institute for Experimental Pathology, Hannover Medical School, D-30625 Hannover, Germany.
  • | 3 Institute for Veterinary Pathology, Justus-Liebig-University, D-35392 Giessen, Germany.
  • | 4 Institute for Experimental Pathology, Hannover Medical School, D-30625 Hannover, Germany.
  • | 5 Small Animal Clinic, Hannover School of Veterinary Medicine; D-30173 Hannover, Germany.
  • | 6 Small Animal Clinic, Hannover School of Veterinary Medicine; D-30173 Hannover, Germany.

Abstract

Objective—To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations.

Sample Population—30 mammary gland tumors excised from dogs.

Procedure—Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation.

Results—Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor).

Conclusion and Clinical Relevance—The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors. (Am J Vet Res 2001;62:1825–1830)

Abstract

Objective—To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations.

Sample Population—30 mammary gland tumors excised from dogs.

Procedure—Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation.

Results—Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor).

Conclusion and Clinical Relevance—The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors. (Am J Vet Res 2001;62:1825–1830)