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  • miR mimics are also currently under Phase I clinical

    2018-11-14

    miR-16 mimics are also currently under Phase I clinical trials for patients with Malignant Pleural Mesothelioma (MPM) and Advanced Non-Small Cell Lung Cancer (NSCLC) that have failed standard therapy. These miR-16 mimics were delivered intravenously, using EnGeneIC Delivery Vehicle (EDV)-Packaging, and were conjugated with an EGFR-targeting antibody. Preliminary data presented by Van Zandwijk et al. (Van Zandwijk et al., 2015) show manageable safety profile in 5 patients. In addition, MIRagen Therapeutics recently announced phase I clinical trials for two candidate miRNA-based candidates: MRG-201, a synthetic microRNA mimic to microRNA-29b, will be tested for patients with scleroderma, and MRG-106, a synthetic microRNA antagonist of microRNA-155, will be tested for patients with cutaneous T-cell lymphoma of the mycosis fungoides (MF) sub-type. The estimated primary completion date for both the studies is late 2016.
    Conclusion
    Outstanding Questions miRNA-based therapeutics hold great promise as highly specific, targeted therapies for cancer treatment. However, to achieve superior sensitivity and specificity, and accelerate their adoption in the clinic, there still exists the need to improve their chemical designs, develop better delivery options, show prolonged therapeutic efficiency, and evaluate the long-term safety of these agents in vivo. Furthermore, it is imperative to understand the underlying intricate network of interactions between miRNAs and the human genome, transcriptome and proteome before their transition into clinical use. In addition, a full assessment of their toxicities need to be performed, and low-toxicity strategies such as combining miRNAs and siRNAs at low doses, or using miRNA therapy as an additive to established chemotherapy regimens, should be evaluated. Overall, miRNA-based therapy can potentially bring an exciting new facet to personalized medicine for cancer treatment; however, a deeper and clearer understanding of its biology is required.
    Search Strategy and alk5 Criteria
    Author Contribution
    Acknowledgements
    Introduction
    Bone Graft Prefabrication Following the IVB Principle: Basic Considerations
    Literature Review To analyze the current state of the art, we searched the PubMed Medline databases for articles published between Jan. 1, 1991, and Jan. 1, 2016, using the search terms “in vivo bioreactor”, “in vivo tissue engineering”, “bone tissue engineering”, “bone graft prefabrication”, and “bone regeneration”. We included 110 publications regarding bone graft prefabrication following the IVB principle (Fig. 4). We categorized all the publications into small animal models, large animal models, and clinical studies to evaluate the safety, efficacy, and cost effectiveness of the IVB strategies. The studies published within the last 5years are summarized in Tables 1–3.
    Discussion: Future Trends and Challenges
    Conclusion
    Acknowledgments This research was supported by grants from the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (Grant No. 2012BA/11B03), the State Key Program of the National Natural Science Foundation of China (Grant No. 81230042), and the National Natural Science Foundation of China (Grant No. 81501679).
    Introduction Hepatocellular carcinoma (HCC) is listed as the fifth and seventh most alk5 frequently diagnosed cancer in men and women, respectively, across the globe, and the most common primary liver tumor with increasing incidence in the United States and elsewhere. With a dismal outcome largely due to postsurgical recurrence and/or metastasis, HCC is the third most common cause of cancer-related death worldwide (Jemal et al., 2011; Siegel et al., 2012). Although targeted chemotherapy with special target(s) has experienced a rapid progress in the recent decade, the management of patients with advanced HCC, who become unqualified for liver transplantation or liver resection, is still far from satisfactory. Indeed, even patients who have received liver resection often have a high frequency of metastasis/recurrence (Maluccio and Covey, 2012). While clinical trials demonstrated that Sorafenib prolonged the median overall survival time for 2.3–3months in advanced HCC patients (Cheng et al., 2009), limited efficacy with side effects demanded improvement of autotrophs therapy.