Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

MicroRNAs in non-small cell lung cancer: Gene regulation, impact on cancer cellular processes, and therapeutic potential.

Lung cancer remains the most lethal cancer among men and women in the United States and worldwide. The majority of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Developing new therapeutics on the basis of better understanding of NSCLC biology is critical to improve the treatment of NSCLC. MicroRNAs (miRNAs or miRs) are a superfamily of genome-derived, small noncoding RNAs that govern posttranscriptional gene expression in cells. Functional miRNAs are commonly dysregulated in NSCLC, caused by genomic deletion, methylation, or altered processing, which may lead to the changes of many cancer-related pathways and processes, such as growth and death signaling, metabolism, angiogenesis, cell cycle, and epithelial to mesenchymal transition, as well as sensitivity to current therapies. With the understanding of miRNA biology in NSCLC, there are growing interests in developing new therapeutic strategies, namely restoration of tumor suppressive miRNAs and inhibition of tumor promotive miRNAs, to combat against NSCLC. In this article, we provide an overview on the molecular features of NSCLC and current treatment options with a focus on pharmacotherapy and personalized medicine. By illustrating the roles of miRNAs in the control of NSCLC tumorigenesis and progression, we highlight the latest efforts in assessing miRNA-based therapies in animal models and discuss some critical challenges in developing RNA therapeutics

Nonreciprocal conversion between microwave and optical photons in electro-optomechanical systems

We propose to demonstrate nonreciprocal conversion between microwave and optical photons in an electro-optomechanical system where a microwave mode and an optical mode are coupled indirectly via two non-degenerate mechanical modes. The nonreciprocal conversion is obtained in the broken time-reversal symmetry regime, where the conversion of photons from one frequency to the other is enhanced for constructive quantum interference while the conversion in the reversal direction is suppressed due to destructive quantum interference. It is interesting that the nonreciprocal response between the microwave and optical modes in the electro-optomechanical system appears at two different frequencies with opposite directions. The proposal can be used to realize nonreciprocal conversion between photons of any two distinctive modes with different frequencies. Moreover, the electro-optomechanical system can also be used to construct a three-port circulator for three optical modes with distinctively different frequencies by adding an auxiliary optical mode coupled to one of the mechanical modes.Comment: 10 pages, 4 figure

The role of Intellectual Capital Reporting (ICR) in organisational transformation: A discursive practice perspective

Intellectual Capital Reporting (ICR) has garnered increasing attention as a new accounting technology that can engender significant organisational changes. However, when ICR was first recognised as a management fashion, the intended change it heralded in stable environments was criticised for having limited impact on the state of practice. Conceiving ICR through a lens predicated on the notion of discursive practice, we argue that ICR can enable substantive change in emergent conditions. We empirically demonstrate this process by following the implementation of ICR in one organisation through interviews, documents and observations over 30 months. The qualitative analysis of the data corpus shows how situated change, subtle but no less significant, can take place in the name of intellectual capital as actors appropriate ICR into their everyday work practices while improvising variations to accommodate different logics of action. The paper opens up a new avenue to examine the specific roles of ICR in relation to the types of change enacted. It thus demonstrates when and how ICR may transcend a mere management fashion and the intended change it sets in motion through altering organisational actors’ ways of thinking and doing within the confines of their organisation