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Antitumor effects of combined carboplatin and gemcitabine in canine transitional cell carcinoma

De Brito Galvao, Joao Felipe
http://rave.ohiolink.edu/etdc/view?acc_num=osu1305257807

Abstract Details

2011, Master of Science, Ohio State University, Veterinary Clinical Sciences.
Gemcitabine has demonstrated synergistic antitumor activity in a variety of human cancer cells when combined with carboplatin. The purpose of this study was to evaluate the antitumor activity of gemcitabine in canine TCC cell lines alone and in combination with carboplatin. We hypothesized that combined gemcitabine and carboplatin would have synergistic effects in vitro in canine TCC. Demonstration of synergistic antitumor activity in canine TCC cell lines would provide a rationale for effective treatment of canine TCC with this combination of drugs. Five TCC cell lines were treated with gemcitabine, carboplatin, and the combination. Cell proliferation was assessed using CyQUANT® cell proliferation assay, cell cycle was evaluated using propidium iodide staining, and apoptosis was assessed by measuring caspase-3/7 enzymatic activity. Synergy was quantified by combination index analysis using CompuSyn software. Treatment of canine TCC cell lines with carboplatin or gemcitabine decreased cell proliferation, increased apoptosis, and induced cell cycle arrest. When TCC cell lines were treated with gemcitabine and carboplatin in combination at therapeutically relevant concentrations, a significant decrease in cell proliferation was observed compared to gemcitabine or carboplatin alone and the drug combination was synergistic in 3 of 5 cell lines and additive in the other two. Drug sequence did not reliably affect cell proliferation amongst cell lines during combination treatment. We conclude, gemcitabine exhibits biologic activity against canine TCC cells and when combined with carboplatin the two exhibit synergistic activity. Our results support further evaluation of this drug combination in dogs with TCC to determine its clinical efficacy.
Nongnuch Inpanbutr, DVM, PhD (Advisor)
William Kisseberth, DVM, PhD (Advisor)
Dennis Chew, DVM (Committee Member)
46 p.
Veterinary Services
cell proliferation; combination index; apoptosis; cell cycle; cancer; in vitro; cell culture

Recommended Citations

Citations

  • De Brito Galvao, J. F. (2011). Antitumor effects of combined carboplatin and gemcitabine in canine transitional cell carcinoma [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1305257807

    APA Style (7th edition)

  • De Brito Galvao, Joao Felipe. Antitumor effects of combined carboplatin and gemcitabine in canine transitional cell carcinoma. 2011. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1305257807.

    MLA Style (8th edition)

  • De Brito Galvao, Joao Felipe. "Antitumor effects of combined carboplatin and gemcitabine in canine transitional cell carcinoma." Master's thesis, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1305257807

    Chicago Manual of Style (17th edition)

osu1305257807
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© 2011, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.