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/ZeitungSCORING: ZeitschriftenaufsätzeForschungBegutachtung

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@article{34005ef2c377477983bb4c03cf9a092f,
title = "Separating Response of Tumor and non-Tumor Cells to Drug In Vitro by Quantifying a Mutation",
abstract = "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.",
keywords = "Antineoplastic Agents/pharmacology, Biomarkers, Tumor/antagonists & inhibitors, Cell Line, Tumor, Cell Survival/drug effects, DNA Mutational Analysis/methods, Dose-Response Relationship, Drug, Feasibility Studies, Humans, Melanoma/drug therapy, Mutation, Polymerase Chain Reaction, Proto-Oncogene Proteins B-raf/antagonists & inhibitors, Skin Neoplasms/drug therapy, Vemurafenib/pharmacology",
author = "Markus Kleinpoppen and Christoph Moebius and Katharina Grupp and Lan Kluwe and Marco Blessmann",
note = "Copyright{\textcopyright} 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.",
year = "2019",
month = apr,
doi = "10.21873/anticanres.13284",
language = "English",
volume = "39",
pages = "1777--1783",
journal = "ANTICANCER RES",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "4",

}

RIS

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 -