Separating Response of Tumor and non-Tumor Cells to Drug In Vitro by Quantifying a Mutation
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Separating Response of Tumor and non-Tumor Cells to Drug In Vitro by Quantifying a Mutation. / Kleinpoppen, Markus; Moebius, Christoph; Grupp, Katharina; Kluwe, Lan; Blessmann, Marco.
in: ANTICANCER RES, Jahrgang 39, Nr. 4, 04.2019, S. 1777-1783.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsätze › Forschung › Begutachtung
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TY - JOUR
T1 - Separating Response of Tumor and non-Tumor Cells to Drug In Vitro by Quantifying a Mutation
AU - Kleinpoppen, Markus
AU - Moebius, Christoph
AU - Grupp, Katharina
AU - Kluwe, Lan
AU - Blessmann, Marco
N1 - Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - BACKGROUND/AIM: Conventional in vitro assays measure the effect of drugs on total cells, while separating the effect to those on tumor and non-tumor cells is important for assessing drug specificity. Our aim was to evaluate the feasibility of separating the efficacy of vemurafenib on tumor and non-tumor cells in a mixed culture.MATERIALS AND METHODS: Melanoma A2058 cells and CCD18Co non-tumor cells were mixed and treated with vemurafenib. DNA was subjected to digital PCR to determine the ratio of the mutant 1799A to the wild-type 1799T alleles and viabilities of total cells were subsequently calculated as percentages of tumor and non-tumor cells.RESULTS: The set-up proportion of tumor cells correlated well with the calculated one. The calculated viability of tumor cells decreased with increasing doses of vemurafenib while that of the non-tumor cells remained rather constant. Variability of digital PCR data was high.CONCLUSION: Using the BRAF mutation 1799T>A to separate the response of tumor and non-tumor cells to a drug, such as vemurafenib, is feasible, supporting a foundation for a genetic in vitro tool for testing drug efficacy and specificity.
AB - BACKGROUND/AIM: Conventional in vitro assays measure the effect of drugs on total cells, while separating the effect to those on tumor and non-tumor cells is important for assessing drug specificity. Our aim was to evaluate the feasibility of separating the efficacy of vemurafenib on tumor and non-tumor cells in a mixed culture.MATERIALS AND METHODS: Melanoma A2058 cells and CCD18Co non-tumor cells were mixed and treated with vemurafenib. DNA was subjected to digital PCR to determine the ratio of the mutant 1799A to the wild-type 1799T alleles and viabilities of total cells were subsequently calculated as percentages of tumor and non-tumor cells.RESULTS: The set-up proportion of tumor cells correlated well with the calculated one. The calculated viability of tumor cells decreased with increasing doses of vemurafenib while that of the non-tumor cells remained rather constant. Variability of digital PCR data was high.CONCLUSION: Using the BRAF mutation 1799T>A to separate the response of tumor and non-tumor cells to a drug, such as vemurafenib, is feasible, supporting a foundation for a genetic in vitro tool for testing drug efficacy and specificity.
KW - Antineoplastic Agents/pharmacology
KW - Biomarkers, Tumor/antagonists & inhibitors
KW - Cell Line, Tumor
KW - Cell Survival/drug effects
KW - DNA Mutational Analysis/methods
KW - Dose-Response Relationship, Drug
KW - Feasibility Studies
KW - Humans
KW - Melanoma/drug therapy
KW - Mutation
KW - Polymerase Chain Reaction
KW - Proto-Oncogene Proteins B-raf/antagonists & inhibitors
KW - Skin Neoplasms/drug therapy
KW - Vemurafenib/pharmacology
U2 - 10.21873/anticanres.13284
DO - 10.21873/anticanres.13284
M3 - SCORING: Journal articles
C2 - 30952717
VL - 39
SP - 1777
EP - 1783
JO - ANTICANCER RES
JF - ANTICANCER RES
SN - 0250-7005
IS - 4
ER -
