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  • Colcemid br Moreover we followed up these

    2020-08-30


    Moreover, we followed up these 216 patients with BC after surgery, and analyzed their survival data by Cox regression. Univariate analysis showed that the CD155 Colcemid level, primary tumor size, lymph node metastasis status, and TNM stage were the risk factors for OS. Multivariate analysis further confirmed that the CD155 expression level and TNM stage were independent risks factors for OS. In other words, the CD155 expression level, like the TNM stage, should also be Colcemid an in-dependent prognostic indicator for postoperative patients with BC.
    In summary, in many common malignant tumors, the CD155 gene and its expression are involved in cancer cell proliferation and metas-tasis by regulating the immune cells. CD155 may become a promising therapeutic target if we can block or inhibit the functions exhibited by CD155.
    Conflict of interest
    None.
    Acknowledgments
    This project was supported by the Youth Medical Talent Program of Jiangsu Province (QNRC2016425). We thank LetPub (www.letpub. com) for its linguistic assistance during the preparation of this manu-script.
    References
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    R.K. Brookland, L. Meyer, D.M. Gress, D.R. Byrd, D.P. Winchester, The eighth edition AJCC Cancer Staging Manual: continuing to build a bridge from a popula-tion-based to a more “personalized” approach to cancer staging, CA Cancer J. Clin. 67 (2017) 93–99.
    A. Moretta, Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction, Cancer Res. 64 (2004) 9180–9184. [24] H. Ochiai, S.A. Moore, G.E. Archer, T. Okamura, T.A. Chewning, J.R. Marks, J.H. Sampson, M. Gromeier, Treatment of intracerebral neoplasia and neoplastic meningitis with regional delivery of oncolytic recombinant poliovirus, Clin. Cancer Res. 10 (2004) 4831–4838. [25] A.K. Wagner, N. Kadri, J. Snall, P. Brodin, S. Gilfillan, M. Colonna, G. Bernhardt,
    Contents lists available at ScienceDirect
    International Journal of Pharmaceutics
    journal homepage: www.elsevier.com/locate/ijpharm
    CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies T for KRAS silencing in cancer treatment
    a Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PL, United Kingdom b NorthWest Centre for Advanced Drug Delivery (NoWCADD), Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom c Tecrea Ltd. 2 Royal College Street, London NW1 0NH, United Kingdom d Department of Pathology and Population Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, United Kingdom e Advanced Drug Delivery, Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom f Laboratory of Polymers and Biomaterials, Fondazione Istituto Italiano di Tecnologia, 16163 Genova, Italy
    Keywords:
    Hyaluronan
    Polymer therapeutics
    siRNA
    KRAS 
    KRAS is a small GTPase that regulates cell proliferation and survival. In tumors, the KRAS gene is mutated, and leading to unregulated tumor growth. Despite the recognized importance of KRAS in cancer, attempts to develop small molecule inhibitors have proved unsuccessful. An alternative strategy is gene silencing and the use of small nucleic acid sequences (e.g. siRNA, shRNA), has been reported to successfully downregulate KRAS. In this study we developed ternary nanocomplexes to deliver an anti-KRAS siRNA to colorectal cancer cells, exploiting the interaction of hyaluronic acid (HA) with CD44 as a means to achieve selective targeting of CD44-positive cancer cells. Two different polycations, poly(hexamethylene biguanide) and chitosan, were complexed with siRNA and coated with HA. Physico-chemical properties and stability of nanoparticles were characterized, including size, surface charge, and degree of siRNA protection. We demonstrate nanoparticle internalization (flow cytometry), siRNA cytosolic release (confocal microscopy) and KRAS silencing (RT-qPCR) in CD44+/KRAS+ colorectal cancer cell line, HCT-116. Further we demonstrate that the uptake of HA-decorated nanoparticles in cancer cells is higher when co-cultured with fibroblasts.
    1. Introduction