In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours

Dietel, Manfred; U, Bals; Schaefer, Birgit M.; Herzig, Ingrid; Arps, H; Zabel, Maciej

doi:10.1016/0959-8049(93)90398-y

Cited by 20 publications

(17 citation statements)

References 20 publications

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“…Clinically relevant concentrations of 5-FU (0.05 lg/ml) and cisplatin (0.5 lg/ml) (Dietel et al 1993) showed no effect on cell viability in either cell line. Therefore, a fivefold increased concentration of the combination chemotherapy was used.…”

Section: Cetuximab Responsiveness Of Gastric Cancer Cell Linesmentioning

confidence: 89%

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

Heindl

Eggenstein

Keller

et al. 2012

J Cancer Res Clin Oncol

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Section: Cetuximab Responsiveness Of Gastric Cancer Cell Linesmentioning

confidence: 89%

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

Heindl

Eggenstein

Keller

et al. 2012

J Cancer Res Clin Oncol

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“…), we decided to measure the resistance at a pre-defined concentration, which is equivalent to the clinically achievable concentration as discussed previously. 16 Furthermore, additionally to the selection of clinically achievable concentrations, chemotherapeutic antineoplastic agents that are commonly included in clinical therapy protocols as a stand-alone agent or in at least one combination protocol were chosen (Table I).…”

Section: Discussionmentioning

confidence: 99%

“…C1 5 10 21 3 C2 and C3 5 10 3 C2. Concentration C2 was deduced from levels assessed to be clinically achievable in tumor tissue, 15 as discussed previously 16 (Table I). In each experiment, 500 cells/microtiter dish were seeded onto 96-well plates.…”

Section: Resistance Testsmentioning

confidence: 99%

Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations

Győrffy

Surowiak

Kiesslich

et al. 2005

Intl Journal of Cancer

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140

119

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Cancer patients with tumors of similar grading, staging and histogenesis can have markedly different treatment responses to different chemotherapy agents. So far, individual markers have failed to correctly predict resistance against anticancer agents. We tested 30 cancer cell lines for sensitivity to 5-fluorouracil, cisplatin, cyclophosphamide, doxorubicin, etoposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, topotecan and vinblastine at drug concentrations that can be systemically achieved in patients. The resistance index was determined to designate the cell lines as sensitive or resistant, and then, the subset of resistant vs. sensitive cell lines for each drug was compared. Gene expression signatures for all cell lines were obtained by interrogating Affymetrix U133A arrays. Prediction Analysis of Microarrays was applied for feature selection. An individual prediction profile for the resistance against each chemotherapy agent was constructed, containing 42-297 genes. The overall accuracy of the predictions in a leave-oneout cross validation was 86%. A list of the top 67 multidrug resistance candidate genes that were associated with the resistance against at least 4 anticancer agents was identified. Moreover, the differential expressions of 46 selected genes were also measured by quantitative RT-PCR using a TaqMan micro fluidic card system. As a single gene can be correlated with resistance against several agents, associations with resistance were detected all together for 76 genes and resistance phenotypes, respectively. This study focuses on the resistance at the in vivo concentrations, making future clinical cancer response prediction feasible. The TaqManvalidated gene expression patterns provide new gene candidates for multidrug resistance. Supplementary material for this article can be found on the International Journal of Cancer website at

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“…After the completion of three cycles of drug, the dose was doubled, and the procedure was repeated until the final drug levels were achieved. The final concentration of each drug was MTX 28 ng/mL, CIS 1000 ng/mL, DOX 100 ng/mL, WIN 10 ng/mL, TOP 24 ng/mL, and PAC 1100 ng/mL according to Dietel et al (1993) [29]. These consternations were twofold greater than the concentration in the plasma 2 hours after intravenous administration [29].…”

Section: Methodsmentioning

confidence: 99%

MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines

Januchowski

Wójtowicz

Sujka-Kordowska

et al. 2013

BioMed Research International

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118

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Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.

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In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours

Cited by 20 publications

References 20 publications

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations

MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines

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