title: Prediction of cell kill kinetics of anticancer agents using the collagen gel droplet embedded-culture drug sensitivity test.
abstract: A vital component of chemotherapy is selecting effective anticancer agents for the patient and determining an appropriate dose and administration regimen. Prediction of the drug sensitivity of each patient and cell kill kinetics of the drug may improve the outcome of treatment and avoid unnecessary dosing of the drug. For this reason, the development and clinical application of anticancer drug sensitivity tests and cell kill kinetics tests which successfully reflect clinical outcomes are required. In the present study, we tried to establish a cell kill kinetics test through the use of new anticancer agents: paclitaxel, docetaxel, SN-38, vinorelbine, and gemcitabine. These agents were studied at concentrations close to their clinical doses using a collagen gel droplet embedded-culture drug sensitivity test (CD-DST). It is thought that the mechanism, by which the anticancer agents used in this study exert their effects is dependent on the cell cycle; however, the cell kill kinetics of these agents at clinical concentrations has not yet been clarified in vitro. We investigated the drug sensitivity and cell kill kinetics of these new anticancer agents against a human colon cancer strain. Results of this study suggest that the test method established by us can predict drug sensitivity and cell kill kinetics of the agents, and can be a useful tool in deciding appropriate treatment regimen for individual patients.
authors.affiliation: Department of Hospital Pharmacy, Aichi Medical University, School of Medicine, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan. 100019@gk.amu.aichi-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Megumi
authors.initials: M
authors.lastname: Komiyama
authors.forename: Arisa
authors.initials: A
authors.lastname: Tsutsui
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yabushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okada
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D003094:Collagen; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000077146:Irinotecan; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D000077146:Irinotecan; D003094:Collagen; D012264:Ribonucleotide Reductases; D017239:Paclitaxel; D000077235:Vinorelbine; D002166:Camptothecin; D000093542:Gemcitabine