Dataset Information

Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.

ABSTRACT: In-vitro chemo-sensitivity experiments are an essential step in the early stages of cancer therapy development, but existing data analysis methods suffer from problems with fitting, do not permit assessment of uncertainty, and can give misleading estimates of cell growth inhibition. We present an approach (bdChemo) based on a mechanistic model of cell division and death that permits rigorous statistical analyses of chemo-sensitivity experiment data by simultaneous estimation of cell division and apoptosis rates as functions of dose, without making strong assumptions about the shape of the dose-response curve. We demonstrate the utility of this method using a large-scale NCI-DREAM challenge dataset. We developed an R package "bdChemo" implementing this method, available at https://github.com/YiyiLiu1/bdChemo .

SUBMITTER: Liu Y

PROVIDER: S-EPMC5807362 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.

Liu Yiyi Y Crawford Forrest W FW

Scientific reports 20180209 1

In-vitro chemo-sensitivity experiments are an essential step in the early stages of cancer therapy development, but existing data analysis methods suffer from problems with fitting, do not permit assessment of uncertainty, and can give misleading estimates of cell growth inhibition. We present an approach (bdChemo) based on a mechanistic model of cell division and death that permits rigorous statistical analyses of chemo-sensitivity experiment data by simultaneous estimation of cell division and ...[more]

PMID: 29426887

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Project description:BACKGROUND: MicroRNA is a naturally occurring class of non-coding RNA molecules that mediate posttranscriptional gene regulation and are strongly implicated in cellular processes such as cell proliferation, carcinogenesis, cell survival and apoptosis. Consequently there is increasing focus on miRNA expression as prognostic factors for outcome and chemotherapy response. Only approximately 50% of patients with bladder cancer respond to chemotherapy. Therefore, predictive markers, such as miRNAs, that can identify subgroups of patients who will benefit from chemotherapy will have great value for treatment guidance. METHODS: We profiled the expression of 671 miRNAs in formalin fixed paraffin embedded tumors from patients with advanced bladder cancer treated with cisplatin based chemotherapy. We delineated differentially expressed miRNAs in tumors from patients with complete response vs. patients with progressive disease and in tumors form patients with short and long overall survival time. Furthermore, we studied the effect of up- and down regulation of key miRNAs on the cisplatin sensitivity in eight bladder cancer cell lines with different sensitivities to cisplatin. RESULTS: miRNA expression profiling identified 15 miRNAs that correlated with response to chemotherapy and 5 miRNAs that correlated with survival time. Three miRNAs were associated with both response and survival (886-3p, 923, 944). By changing the cellular level of the response-identified miRNAs in eight bladder cell lines with different cisplatin sensitivity we found that down-regulation of miR-27a, miR296-5p and miR-642 generally reduced the cell viability, whereas up-regulation of miR-138 and miR-886-3p reduced the viability of more than half of the cell lines. Decreasing miR-138 increased the cisplatin sensitivity in half of the cell lines and increasing miR-27a and miR-642 generally increased cisplatin sensitivity. CONCLUSIONS: MiRNAs seem to be involved in cisplatin based chemo response and may form a new target for therapy and serve as biomarkers for treatment response.

Dataset Information

Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.

Publications

Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.

Similar Datasets

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