Browsing by Author "Chen, Lu"

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    OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers
    (Springer Nature, 2018) Monroig-Bosque, Paloma del C.; Shah, Maitri Y.; Fu, Xiao; Fuentes-Mattei, Enrique; Ling, Hui; Ivan, Cristina; Nouraee, Nazila; Huang, Beibei; Chen, Lu; Pileczki, Valentina; Redis, Roxana S.; Jung, Eun-Jung; Zhang, Xin; Lehrer, Michael; Nagvekar, Rahul; Mafra, Ana Carolina P.; Monroig-Bosque, Maria del Mar; Irimie, Alexandra; Rivera, Carlos; Dumitru, Calin Dan; Berindan-Neagoe, Ioana; Nikonowicz, Edward P.; Zhang, Shuxing; Calin, George A.
    The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can "hijack" the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.
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    Screw and Edge Dislocations in Cement Phases: Atomic Modeling
    (2013-10-09) Chen, Lu; Shahsavari, Rouzbeh; Nagarajaiah, Satish; Duenas-Osorio, Leonardo
    Cement is the key strengthening and the most energy-intensive ingredient in concrete. With increasing pressure for reducing energy consumption in cement manufacturing, there is an urgent need to understand the basic deformation mechanisms of cement. In this thesis, we develop a computational framework based on molecular dynamics to study two common types of defects, namely screw and edge dislocations, in complex, anisotropic crystalline polymorphs of cement clinkers and cement hydration products. We found the likelihood of these defects in regions with higher Young moduli. We also found the preferred cement polymorphs that require less energy for grinding via analysis of Peierls stresses. Together, the results provide a detailed understanding of the role and type of defects in cement phases, which impact the rate of hydration, crystal growth and grinding energy. To our knowledge, this is the first study with atomic-resolution on deformation-based mechanisms in cement crystalline phases.