monastrol and Triple-Negative-Breast-Neoplasms

monastrol has been researched along with Triple-Negative-Breast-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for monastrol and Triple-Negative-Breast-Neoplasms

Article	Year
Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer. Molecular oncology, 2014, Volume: 8, Issue:8 An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers. Topics: Animals; Apoptosis; Benzamides; Cell Line, Tumor; Drug Synergism; Female; Humans; Kinesins; Mice; Mice, Inbred BALB C; Mitosis; Pyrimidines; Quinazolines; Thiones; Triple Negative Breast Neoplasms; Vinblastine; Xenograft Model Antitumor Assays	2014

Article

Year

Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.

Molecular oncology, 2014, Volume: 8, Issue:8

An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.

Topics: Animals; Apoptosis; Benzamides; Cell Line, Tumor; Drug Synergism; Female; Humans; Kinesins; Mice; Mice, Inbred BALB C; Mitosis; Pyrimidines; Quinazolines; Thiones; Triple Negative Breast Neoplasms; Vinblastine; Xenograft Model Antitumor Assays

2014