Biomedical subjects

Xinghua Wang

Publications and source records attributed to Xinghua Wang.

6 recordsLinked to original sources

PubMed2006

Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus.

PURPOSE: A dual-regulated adenovirus variant CNHK500, in which human telomerase reverse transcriptase promoter drove the adenovirus 5 (Ad5) E1a gene and hypoxia-response promoter controlled the E1b gene, was engineered. This virus has broad anticancer spectrum and higher specificity compared with mono-regulated adenovirus CNHK300. The objective of the current study is to show its antitumor selectivity and therapeutic potential. EXPERIMENTAL DESIGN: The antitumor specificity of human telomerase reverse transcriptase and hypoxia response promoters was evaluated in a panel of tumor and normal cells. Under the control of these promoters, the tumor-selective expression of E1a and E1b genes was evaluated. Further in vitro antitumor specificity and potency of this virus were characterized by viral replication and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, hepatocellular carcinoma xenografts were established to evaluate CNHK500 antitumor efficacy in vivo by different routes of virus administration and different dosages. RESULTS: Human telomerase reverse transcriptase and hypoxia response promoters were activated in a tumor-selective manner or under hypoxia treatment in a broad panel of cells. Selective adenoviral early gene expression, efficient viral replication, and oncolysis were observed in all tested cancer cells with more attenuated replication capacity in normal cells. Significant regression of hepatocellular carcinoma xenografts and prolonged survival were observed by either i.t. or i.v. administration. CONCLUSIONS: CNHK500 greatly reduced side effects in normal cells via dual control of adenoviral essential genes while still preserving potent antitumor efficacy on broad-spectrum cancer cells in vitro and in vivo. It can be used as a powerful therapeutic agent not only for liver cancers but also for other solid tumors.

Adenoviridae↗

PubMed2006

Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.

Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) of interferon-gamma (IFN-gamma) may be useful because of the possibility that it will yield IFN-gamma-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a human TERT promoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or human IFN-gamma gene to generate novel immune gene-viral therapeutic systems, CNHK300-mIFN-gamma and CNHK300-hIFN-gamma, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-gamma induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.

Adenoviridae↗

PubMed2005

Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of mice: comparison between commercially available microbubble contrast agents.

PURPOSE: To compare three commercial microbubble contrast agents (Optison, SonoVue, and Levovist) for their effect on gene delivery in skeletal muscle in conjunction with the use of therapeutic ultrasound. MATERIALS AND METHODS: The study was approved by the Animal Care and Use Committee. Plasmid DNA (10 microg) encoding green fluorescent protein (GFP) was mixed with microbubbles (or saline control) and injected into the tibialis anterior muscle of mice with and without adjunct ultrasound (1 MHz, 2 W/cm2, 30 seconds, 20% duty cycle). The efficiencies of GFP transgene expression were determined with four experimental conditions: (a) plasmid and saline as control (six mice), (b) plasmid and Optison (six mice), (c) plasmid and SonoVue (four mice), and (d) plasmid and Levovist (air based, four mice). The right legs were exposed to ultrasound, while the left legs were unexposed. Transfection efficiency was assessed by counting the number of GFP-positive fibers. Tissue damage was assessed by measuring the maximal-damage area on serial sections. RESULTS: When ultrasound was applied, both SonoVue and Optison significantly improved (P < .05) gene transfection efficiency. Optison was also effective (P < .05) even when no ultrasound was applied, which is consistent with previous studies. Levovist without ultrasound decreased the level of transfection (P < .05), with increased tissue damage. CONCLUSION: Both non-air-based agents show promise in gene delivery in skeletal muscle with undetectable tissue damage. Enhanced gene transfer with additional ultrasound was achieved only with SonoVue.

Albumins↗

PubMed2005

Grey-scale contrast enhancement in rabbit liver with SonoVue at different doses.

To evaluate the dose of ultrasound (US) contrast agent (UCA) in relation to the contrast-enhancement effect, an in vivo model of perfusion was studied using SonoVue, a second-generation UCA, and low mechanical index (MI) grey-scale harmonic imaging. SonoVue, at eight different doses (0.02, 0.04, 0.06, 0.08, 0.10, 0.12, 0.14 and 0.16 mL/kg BW), was applied in five normal rabbits. Flow-related parameters obtained from time-intensity curves were calculated and plotted over the contrast agent doses, and nonlinear curve fitting was performed. Results showed that, along with an increase of the administrated contrast agent dose, the enhancement duration (ED) and the area under the curve (AUC) increased logarithmically, and the time to enhancement (ET) decreased logarithmically. There was a progressive increase of the peak signal intensity (PSI) following an increase of SonoVue dose only in the dose range of 0.02 up to 0.10 mL/kg body weight (BW) in the portal vein and in the dose range of 0.02 up to 0.12 mL/kg BW in the liver parenchyma. Moreover, a good correlation was observed between the parameters obtained from liver parenchyma and those obtained from the portal vein. The results indicated that SonoVue in conjunction with continuous harmonic low-MI grey-scale imaging has the capability of flow quantification on both vessels and parenchyma. The parameters of time-intensity curve were influenced intensely by different contrast agent doses.

Animals↗

PubMed2005

Finite-difference time-domain simulation of a liquid-crystal optical phased array.

Accurate modeling of a high-resolution, liquid-crystal-based, optical phased array (OPA) is demonstrated. The modeling method is extendable to cases where the array element size is close to the wavelength of light. This is accomplished through calculating an equilibrium liquid-crystal (LC) director field that takes into account the fringing electric fields in LC OPAs with small array elements and by calculating the light transmission with a finite-difference time-domain method that has been extended for use in birefringent materials. The diffraction efficiency for a test device is calculated and compared with the simulation.

Journal Article↗

PubMed2004

Finite-difference time-domain calculations of a liquid-crystal-based switchable Bragg grating.

A polymer-wall-confined transmissive switchable liquid crystal grating is proposed and investigated by two-dimensional finite-difference time-domain optical calculation and liquid-crystal-director calculation, to our knowledge for the first time. The results show how to obtain optimized conditions for high diffraction efficiency by adjusting the liquid crystal parameters, grating geometric structure, and applied voltages. The light propagation direction and efficiency can be accurately calculated and visualized concurrently.

Journal Article↗