In vitro chemosensitivity testing and mechanisms of drug resistance

Tewari, Κ. Κ.; Manetta, Alberto

doi:10.1007/s11912-999-0014-6

Cited by 7 publications

(2 citation statements)

References 42 publications

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“…Quantitative or qualitative changes in these enzyme targets of antineoplastic drugs can compromise drug efficacy. So, an altered drug target is considered to be one of the most important reasons of resistance [7].…”

Section: Introductionmentioning

confidence: 99%

Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells

Saleh

El‐Awady

Alim

et al. 2009

Cell Biochem Biophys

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This study was designed to investigate the molecular changes that may develop during exposure of breast cancer cells to anticancer agents and that may lead to acquired resistance. We used two breast cancer cell lines, a parental (MCF7/WT) and a doxorubicin-resistant (MCF7/DOX) one. Cell survival, cell cycle distribution and RT-PCR expression level of genes involved in DNA damage response, MDR1, GST and TOPOIIalpha were measured. MCF7/DOX cells were five-fold more resistant to doxorubicin (DOX) than the MCF7/WT cells. DOX treatment causes arrest of MCF7/DOX cells in G1 and G2 phases of cell cycle whereas MCF7/WT cells were arrested in S-phase. The molecular changes in both cell lines due to DOX treatment could be classified into: (1) the basal level of p53, p21, BRCA1, GST and TOPOIIalpha mRNA was higher in MCF7/DOX than MCF7/WT. During DOX treatment, the expression level of these genes decreased in both cell lines but the rate of down-regulation was faster in MCF7/WT than MCF7/DOX cells. (2) The expression level of MDR1 was the same in both cell lines but 48 and 72 h of drug treatment, MDR1 disappeared in MCF7/WT but still expressed in MCF7/DOX. (3) There was no change in the expression level of BAX, FAS and BRCA2 in both cell lines. Conclusively, after validation in clinical samples, overexpression of genes like BRCA1, p53, p21, GST, MDR1 and TOPOIIalpha could be used as a prognostic biomarker for detection of acquired resistance in breast cancer and as therapeutic targets for the improvement of breast cancer treatment strategies.

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Section: Introductionmentioning

confidence: 99%

Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells

Saleh

El‐Awady

Alim

et al. 2009

Cell Biochem Biophys

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“…The molecular methods detect the chemosensitivity at the protein or gene level (10,11). Although a single gene may be sufficient for the evaluation, a cytotoxic drug sometimes generates an excessive cellular response (12,13). Cellular methods provide the efficacy results for multiple drugs simultaneously.…”

Section: Introductionmentioning

confidence: 99%

In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading assays

Tatar

Boyraz

Selçuk

et al. 2016

J Turkish German Gynecol Assoc

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Material and Methods:Fresh tumoral tissue samples of 26 newly diagnosed primary ovarian cancer patients were studied with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) and differential staining cytotoxicity (DISC) assays. Chemosensitivity of tumors were studied for paclitaxel, carboplatin, docetaxel, topotecan, gemcitabine, and doxorubicin with each of the three assays. Subgroup analysis was performed for stage, grade, and histologic type. Results:The in vitro chemosensitivity results of MTT, ATP, and DISC assays were found to be similar. The subgroups in which in vitro assays would be more useful were encountered for patients with advanced stage and serous histology ovarian carcinoma. Conclusions:In vitro chemosensitivity can be determined in ovarian carcinoma with ATP, MTT, or DISC assays before the initiation of chemotherapy. These three assays correlate well with each other and are particularly useful for serous and advanced cancers. Large prospective studies comparing standard versus assay-directed therapy with an endpoint of overall survival are required before routine clinical utilization of these assays. (J Turk Ger Gynecol Assoc 2016; 17: 35-40) Keywords: Ovarian cancer, in vitro chemosensitivity, ATP, MTT, DISC Received: 20 January, 2016 Accepted: 22 January, 2016 In vitro chemosensitivity in ovarian carcinoma:Comparison of three leading assays Black and Speer in 1950s (9). The chemosensitivity tests allow detecting the cytotoxic, cytostatic, and apoptotic effects of the chemotherapeutic agent outside the organism. Such an approach is particularly thought to prevent the harmful toxic effects of these agents. Many molecular and cellular assays have been developed to date for the in vitro detection of chemosensitivity. The molecular methods detect the chemosensitivity at the protein or gene level (10,11). Although a single gene may be sufficient for the evaluation, a cytotoxic drug sometimes generates an excessive cellular response (12, 13). Cellular methods provide the efficacy results for multiple drugs simultaneously. Several tests based on cellular methods, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) chemosensitivity assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA), and differential staining cytotoxicity (DISC) assays, have been described in the literature. Despite the logic that any method that predicts the chemosensitivity of a tumor for an individual patient would be helpful for better regimens, no chemosensitivity assay has achieved widespread clinical use to date. In a study from USA with 262 patients, all the patients were treated empirically, but a chemosensitivity assay was also performed concomitantly for all. In addition, in the subgroup of patients treated with assay-sensitive agents, progression-free survival (PFS) and OS are found to be improved, and further analysis has confirmed these results (14,15). Recently, an observational study h...

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Methods and goals for the use of in vitro and in vivo chemosensitivity testing

Blumenthal

Goldenberg

2007

Mol Biotechnol

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Sensitive, specific, and accurate methods to assay chemosensitivity are needed to (1) screen new therapeutic agents, (2) identify patterns of chemosensitivity for different tumor types, (3) establish patterns of cross-resistance and sensitivity in treatment of naïve and relapsing tumors, (4) identify genomic and proteomic profiles associated with sensitivity, (5) correlate in vitro response with preclinical in vivo effects and clinical outcomes for a particular therapeutic agent, and (6) tailor chemotherapy regimens to individual patients. Various methods are available to achieve these end points, including several in vitro clonogenic and proliferation assays, cell metabolic activity assays, molecular assays to monitor expression of markers for responsiveness, drug resistance, and for induction of apoptosis, in vivo tumor growth and survival assays in metastatic and orthotopic models, and in vivo imaging assays. The advantages and disadvantages of the specific assays are discussed. A summary of research questions related to chemosensitivity testing is also included.

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In vitro chemosensitivity testing and mechanisms of drug resistance

Cited by 7 publications

References 42 publications

Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells

Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells

In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading assays

Methods and goals for the use of in vitro and in vivo chemosensitivity testing

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