RESUMO
The magnetic velocity induction system (MAVIS) is commonly used for velocimetry in shock compression experiment. Due to some discrepancies, the variation in induced voltage amplitude is ambiguous, which makes the simulation of this experiment particularly significant. In this work, we have designed a MAVIS, which was used to determine the induced voltage amplitude and flyer velocity. We built a three-dimensional model of MAVIS and performed the simulations using the Analysis System Electromagnetics Suite. Additionally, we performed some experiments and compared the results of both studies on the basis of flyer thickness, radius, and velocity. It was established that the flyer velocity influenced the induced electromotive force (EMF) in the pick-up coils. The increase in flyer radius led to the increase in the induced EMF. The cut-off radius for flyers was also discussed in detail by computing the lowest induced EMFs at discrete flyer velocities and radii. Due to the eddy current loss, experimental data laid slightly lower than simulations. The simulation data have proved its accuracy within the experimental error range. Thus, it can be applied as an economical framework to calculate projectile velocity precisely, regardless of its geometry, and to estimate the trigger level of the oscilloscope before performing the experiments. In order to enhance the quality of induced voltage, we also proposed a new design consisting of three pick-up coils. This redesigned MAVIS contributed significantly in signal narrowing as well as controlled the loss in amplitude peaks that reduced the experimental uncertainty in flyer velocity <0.4%.
RESUMO
Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We have previously identified a subset of cancers harbouring homozygous deletion of the glycolytic enzyme enolase (ENO1) that have exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small-molecule enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low-nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumours in mice at doses well-tolerated in non-human primates. Our data provide an in vivo proof of principle of the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential use across a range of therapeutic settings.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Inibidores Enzimáticos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Fosfopiruvato Hidratase/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Animais , Linhagem Celular Tumoral , Feminino , Glioma/tratamento farmacológico , Glicólise/efeitos dos fármacos , Humanos , Macaca fascicularis , Masculino , Camundongos , Camundongos SCID , Fosfopiruvato Hidratase/genética , Medicina de Precisão , Deleção de Sequência , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent evidences highlight the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. LncRNA CASC7 is a â¼9.3kb lncRNA whose function is currently unknown. The present study aimed to investigate the expression of CASC7 in patients with colorectal cancer (CRC) and its effect on CRC cells. The expression levels of CASC7, miR-21 and ING3 were estimated by reverse transcription-quantitative polymerase chain reaction (RT-PCR) or western blot in CRC tissues and CRC cell lines (SW480 and HCT-116). The relationship between miR-21 and CASC7 or ING3 was analyzed by RNA immunoprecipitation (RIP), RNA pull-down and luciferase reporter assay. In addition, the biological roles of CASC7 were examined using cell counting kit-8 assay, flow cytometry, and migration and invasion assays following the downregulation or upregulation of CASC7 by small interfering RNA or pcDNA-CASC7, respectively. In this study, CASC7 expression was significantly decreased in CRC tissues and CRC cell lines. Further functional experiments suggested that CASC7 overexpression could inhibit cell viability, migration and invasion, and promote apoptosis in CRC cells. CASC7 and ING3 were both a target of miR-21 in CRC cells, and CASC7 could control ING3 expression by regulating miR-21. Moreover, we have found that CASC7 inhibited colon cancer cell proliferation and migration via miR-21/ING3 axis. These observations suggested that CASC7 played an important role in CRC pathogenesis and may be considered as a novel diagnostic marker of CRC.