ABSTRACT
As a potential cancer therapy, we developed a recombinant adenovirus named Ad-VT, which was designed to express the apoptosis-inducing gene (apoptin) and selectively replicate in cancer cells via E1a manipulation. However, how it performs in bladder cancer remains unclear. We examined the antitumor efficacy of Ad-VT in bladder cancers using CCK-8 assays and xenograft models. Autophagy levels were evaluated by western blotting, MDC staining, and RFP-GFP-LC3 aggregates' analyses. Here, we report the selective replication and antitumor efficacy (viability inhibition and apoptosis induction) of Ad-VT in bladder cancer cells. Using xenograft tumor models, we demonstrate that its effects are tumor specific resulting in the inhibition of tumor growth and improvement of the survival of mice models. Most Importantly, Ad-VT induced a complete autophagy flux leading to autophagic cancer cell death through a signaling pathway involving AMPK, raptor and mTOR. Finally, we suggest that treatment combination of Ad-VT and rapamycin results in a synergistic improvement of tumor control and survival compared to monotherapy. This study suggests that Ad-VT can induce selective autophagic antitumor activities in bladder cancer through the AMPK-Raptor-mTOR pathway, which can be further improved by rapamycin.
Subject(s)
Adenoviridae/genetics , Autophagy/genetics , Oncolytic Virotherapy/methods , Urinary Bladder Neoplasms/therapy , AMP-Activated Protein Kinases/metabolism , Animals , Capsid Proteins/genetics , Cell Line, Tumor , Female , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Regulatory-Associated Protein of mTOR/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Urinary Bladder Neoplasms/genetics , Xenograft Model Antitumor AssaysABSTRACT
A class of linear polarization conversion coding metasurfaces (MSs) based on a metal cut-wire structure is proposed, which can be applied to the reduction properties of radar cross section (RCS). We firstly present a hypothesis based on the principle of planar array theory, and then verify the RCS reduction characteristics using linear polarization conversion coding MSs by simulations and experiments. The simulated results show that in the frequency range of 6â»14 GHz, the linear polarization conversion ratio reaches a maximum value of 90%, which is in good agreement with the theoretical predictions. For normal incident x- and y-polarized waves, RCS reduction of designed coding MSs 01/01 and 01/10 is essentially more than 10 dB in the above-mentioned frequency range. We prepare and measure the 01/10 coding MS sample, and find that the experimental results in terms of reflectance and RCS reduction are in good agreement with the simulated ones under normal incidence. In addition, under oblique incidence, RCS reduction is suppressed as the angle of incidence increases, but still exhibits RCS reduction effects in a certain frequency range. The designed MS is expected to have valuable potential in applications for stealth field technology.
