PI3K/AKT Signaling Pathway in the Regulation of Non-small Cell Lung Cancer Radiosensitivity After Hypofractionated Radiation Therapy

Wang, P.; Liu, N.; Pang, Qing; Qu, Chao; Wang, B.; Guo, Hua

doi:10.1016/j.ijrobp.2012.07.1790

Cited by 2 publications

(2 citation statements)

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“…Recently, many clinical strategies have been suggested to target PI3K-AKT signaling pathway for clinical treatment of lung cancer [ 38 ], including the novel anticancer reagent sulforaphene [ 39 ]. In addition, Wang et al [ 40 ] reported the role of PI3K/AKT signaling pathway in the regulation of non-small cell lung cancer radiosensitivity after hypo-fractionated radiation therapy.…”

Section: Resultsmentioning

confidence: 99%

Adaptively capturing the heterogeneity of expression for cancer biomarker identification

Xie

Liu

et al. 2018

BMC Bioinformatics

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BackgroundIdentifying cancer biomarkers from transcriptomics data is of importance to cancer research. However, transcriptomics data are often complex and heterogeneous, which complicates the identification of cancer biomarkers in practice. Currently, the heterogeneity still remains a challenge for detecting subtle but consistent changes of gene expression in cancer cells.ResultsIn this paper, we propose to adaptively capture the heterogeneity of expression across samples in a gene regulation space instead of in a gene expression space. Specifically, we transform gene expression profiles into gene regulation profiles and mathematically formulate gene regulation probabilities (GRPs)-based statistics for characterizing differential expression of genes between tumor and normal tissues. Finally, an unbiased estimator (aGRP) of GRPs is devised that can interrogate and adaptively capture the heterogeneity of gene expression. We also derived an asymptotical significance analysis procedure for the new statistic. Since no parameter needs to be preset, aGRP is easy and friendly to use for researchers without computer programming background. We evaluated the proposed method on both simulated data and real-world data and compared with previous methods. Experimental results demonstrated the superior performance of the proposed method in exploring the heterogeneity of expression for capturing subtle but consistent alterations of gene expression in cancer.ConclusionsExpression heterogeneity largely influences the performance of cancer biomarker identification from transcriptomics data. Models are needed that efficiently deal with the expression heterogeneity. The proposed method can be a standalone tool due to its capacity of adaptively capturing the sample heterogeneity and the simplicity in use.Software availabilityThe source code of aGRP can be downloaded from https://github.com/hqwang126/aGRP.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2437-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Adaptively capturing the heterogeneity of expression for cancer biomarker identification

Xie

Liu

et al. 2018

BMC Bioinformatics

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“…The PI3K/Akt signaling pathway is targeted for genomic aberrations including amplification, mutation and rearrangement more frequently than any other signaling pathway in human cancer, with the possible exception of the p53 and retinoblastoma signaling pathways. There is convincing evidence that the alterations of the PI3K/Akt signaling pathway are associated with tumor progression and resistance to radiation and systemic therapies in humans (12,13). LY294002 is an inhibitor of PI3K, which has been used extensively to investigate the role of the PI3K/Akt signaling pathway in normal and transformed cells (14,15).…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

et al. 2017

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Abstract. The aim of the present study was to investigate the synergistic effect of phenylhexyl isothiocyanate (PHI) and LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] on the PI3K/protein kinase B (Akt) signaling pathway, modulating histone acetylation, inhibiting cell viability and inducing apoptosis in HL-60 cells. The inhibition of HL-60 cell viability was monitored using an MTT assay. Cell apoptosis was measured using flow cytometry. Expression of acetylated histone H3 and histone H4, and the Akt signaling pathway proteins phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated ribosomal protein S6 kinase (p-p70 S6K ) was detected using western blotting. The results of the present study identified that PHI and LY294002 were able to inhibit cell viability and induce cell apoptosis in HL-60 cells. The combination exhibited a synergistic effect on cell viability and apoptosis. PHI treatment led to an accumulation of acetylated histone H3 and histone H4, but LY294002 treatment had no effect on histone acetylation. However, LY294002 was identified to enhance the effect of PHI on histone acetylation in HL-60 cells. PHI and/or LY294002 were identified to dephosphorylate proteins in the PI3K/Akt signaling pathway, with a synergistic effect observed when used in combination. The results of the present study indicated that the combination of PHI and LY294002 may offer a novel therapeutic strategy for acute myeloid leukemia.

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PI3K/AKT Signaling Pathway in the Regulation of Non-small Cell Lung Cancer Radiosensitivity After Hypofractionated Radiation Therapy

Cited by 2 publications

References 0 publications

Adaptively capturing the heterogeneity of expression for cancer biomarker identification

Adaptively capturing the heterogeneity of expression for cancer biomarker identification

Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

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