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      Differentially expressed gene profile and relevant pathways of the traditional Chinese medicine cinobufotalin on MCF-7 breast cancer cells

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          Abstract

          Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF-7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalin-related pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC proto-oncogene non-receptor tyrosine kinase and cyclin-dependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the ‘neuroactive ligand-receptor interaction’ and ‘calcium signaling’ pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor-2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF-7 cells.

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          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            From traditional Chinese medicine to rational cancer therapy.

            Many natural products and derivatives thereof belong to the standard repertoire of cancer chemotherapy. Examples are Vinca alkaloids, taxanes and camptothecins. In recent years, the potential of natural products from plants, notably from medicinal plants used in traditional Chinese medicine (TCM), has been recognized by the scientific community in the Western world. To provide an example of the most recent developments in this field, we have selected several compounds, namely artesunate, homoharringtonine, arsenic trioxide and cantharidin, that are found in natural TCM products and that have the potential for use in cancer therapy. Controlled clinical studies have shown that homoharringtonine and arsenic trioxide can exert profound activity against leukaemia. Increased knowledge of the molecular mechanisms of TCM-derived drugs and recent developments in their applications demonstrate that the combination of TCM with modern cutting-edge technologies provides an attractive strategy for the development of novel and improved cancer therapeutics.
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              Primary and secondary prevention of breast cancer

              Breast cancer is the most common cancer among women and is the second cancer frequently occurring worldwide of newly-diagnosed cancers. There is much evidence showing the influence of life style and environmental factors on the development of mammary gland cancer (high-fat diet, alcohol consumption, lack of physical exercise), the elimination of which (primary prevention) may contribute to a decrease in morbidity and mortality. Secondary prevention, comprising diagnostic tests (e.g. mammography, ultrasonography, magnetic resonance imaging, breast self-examination, as well as modern and more precise imaging methods) help the early detection of tumours or lesions predisposing to tumours.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                May 2019
                19 March 2019
                19 March 2019
                : 19
                : 5
                : 4256-4270
                Affiliations
                [1 ]Department of Spleen and Stomach Diseases, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region 530023, P.R. China
                [2 ]Research Department, The Affiliated Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [3 ]Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [4 ]Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [5 ]Ultrasonics Division of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [6 ]PET-CT, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                Author notes
                Correspondence to: Professor Jie Li, Department of Spleen and Stomach Diseases, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, 89-9 Dongge Road, Nanning, Guangxi Zhuang Autonomous Region 530023, P.R. China, E-mail: 254926526@ 123456qq.com
                Article
                mmr-19-05-4256
                10.3892/mmr.2019.10062
                6471831
                30896874
                6054ee2e-601a-4c76-965e-d5bec96a1eba
                Copyright: © Li et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 April 2018
                : 01 January 2019
                Categories
                Articles

                gene profile,pathways,traditional chinese medicine,cinobufotalin,breast cancer

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