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  • br Conclusions br This study was the first attempt to

    2019-10-07


    5. Conclusions
    This study was the first attempt to develop nomogram using miRNAs for prognostic evaluation in GC. Five significant miRNAs were identified associated with prognosis and the constructed five-miRNA signature was an independent prognostic factor for patients with GC.  Gene 699 (2019) 125–134
    The proposed nomogram provides accurate prognosis prediction for post-surgery patients with GC. However, its applicability to patients with other types of cancer still remains to be investigated.
    Declaration of interest
    None.
    Funding
    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
    Acknowledgements
    The authors wish to thank Yanfang Liao for her help in data pro-cessing in this work.
    References
    Hausser, J., Zavolan, M., 2014. Identification and consequences of miRNA-target inter-actions—beyond repression of gene expression. Nat Rev Genet 15, 599–612.
    motes proliferation of gastric cancer Tigecycline by targeting miR-145. Cell. Physiol.
    Kupcinskas, J., Wex, T., Link, A., Leja, M., Bruzaite, I., Steponaitiene, R., Juzenas, S., Gyvyte, U., Ivanauskas, A., Ancans, G., Petrenkiene, V., Skieceviciene, J., Kupcinskas, L., Malfertheiner, P., 2014. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS One 9, e87467.
    progression via targeting transcription factor Sp1 in gastric cancer. FEBS Lett. 588, 1168–1177.
    microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11, 228–234.
    Zhang, L., Sun, Z.J., Bian, Y., Kulkarni, A.B., 2013. MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett. 331, 230–238.
    Contents lists available at ScienceDirect
    Journal of Biotechnology
    journal homepage: www.elsevier.com/locate/jbiotec
    A fluorescent 3D cell culture assay for high throughput screening of cancer T drugs down-regulating survivin
    Xin Xin, Yongqi Wu, Ru Zang, Shang-Tian Yang
    William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 West Woodruff Ave., Columbus, Ohio, 43210, USA
    Keywords:
    Cancer
    Drug discovery
    3D cell culture
    High throughput screening
    Survivin 
    Survivin, a member of inhibitor of apoptosis family, is currently undergoing intensive investigations as a pro-mising cancer marker due to its overexpression in multiple tumor tissues and close relationship with che-motherapy resistance. In this study, a novel 3D survivin promoter assay was developed, using enhanced green fluorescent protein (EGFP) as the reporter to assess survivin promoter activity for cancer drug screening. Breast cancer MCF-7 cells were engineered to express EGFP controlled by a human survivin promoter and a CMV promoter, respectively. These cells were cultured in three-dimensional (3D) polymer-based scaffolds on a 40-microbioreactor platform (40-MBR) with real-time monitoring of EGFP signals. The EGFP production driven by the survivin promoter was strongly correlated with survivin transcriptional level in MCF-7 cells treated with YM155, a small-molecule survivin promoter suppressant. Moreover, the potential inhibition effects of doxor-ubicin and cisplatin on survivin and their cytotoxicity were also evaluated in this system. This study demon-strated the potential application of the novel 3D survivin promoter-EGFP reporter assay for high-throughput screening of chemicals down-regulating survivin as a molecular target for cancer therapy.
    1. Introduction
    Survivin, as a member of inhibitor of apoptosis (IAP) family, has garnered great interests over the past decade. Its primary functions include apoptosis inhibition, cell division regulation and angiogenesis enhancement (Wheatley and McNeish, 2005). Although survivin is rarely expressed in normal adult tissues, survivin expression is in-variably up regulated at high levels in vast majority of human tumors (Lv et al., 2010; Jaiswal et al., 2015). There are clear correlations Tigecycline of survivin overexpression with aggressiveness, prognosis and treatment efficacy of diverse types of cancer (Ismail, 2018). To date, the potential of using survivin as a diagnostic, prognostic or predictive tumor marker has been confirmed by detecting its level in multiple tumor tissues (Duffy et al., 2007; Lv et al., 2010; Khan et al., 2017). For example, emerging data showed that nuclear staining of survivin antigen in breast carcinoma would be a promising diagnostic method to evaluate the degree of neoplasia (Adamkov et al., 2010). Furthermore, various strategies including anti-sense oligonucleotides, ribozymes, RNA in-terference, and small-molecule antagonists have been developed to inhibit survivin expression in tumor cells. These potential anti-cancer therapies can significantly improve the effectiveness of chemother-apeutic agents such as cisplatin, paclitaxel, and 5-fluorouracil (Al Shamaileh et al., 2017; Chen et al., 2017; Kar et al., 2015; Ueno et al.,