Yao Huang

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

Are you Yao Huang?

Claim your profile

Publications (6)16.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cirrhosis is the long‑term outcome of chronic hepatic injury and no effective therapy is currently available for this disease. Mesenchymal stromal cells (MSCs) are multipotent cells that are easily acquired and amplified, and may be potential candidates for cell therapy against cirrhosis. This study aimed to determine the therapeutic effects of human umbilical cord‑derived MSCs (hUCMSCs) for the treatment of liver cirrhosis and identify an effective method for engrafting MSCs. The model of liver cirrhosis was established by induction of diethylnitrosamine (DEN) in rats. The isolated hUCMSCs were identified by morphology, flow cytometry and multilineage differentiation; they were injected into the vein of DEN‑induced rats at varied cell doses and infusion times. Biochemical analyses of the serum and histopathological analysis of the liver tissues were performed to evaluate the therapeutic effects of hUCMSCs in all treatment groups. The results indicated that isolated hUCMSCs were capable of self‑replication and differentiated into multiple lineages, including osteoblast‑, adipocyte‑ and hepatocyte‑like cells. Compared with the control group, administration of hUCMSCs at different cell doses and infusion times relieved DEN‑induced cirrhosis to varying degrees. The therapeutic effects of hUCMSCs on liver cirrhosis gradually improved with increased cell dose and infusion times. The improvement of cirrhosis was due to the capacity of hUCMSCs to breakdown collagen fibers in the liver. It was demonstrated that infusion of hUCMSCs effectively relieved liver cirrhosis by facilitating the breakdown of collagen fibers in a dose‑dependent manner and multiple infusions caused a relatively greater improvement in cirrhosis compared with a single infusion of hUCMSCs.
    Molecular Medicine Reports 01/2014; · 1.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011(let7T), by introducing eight copies of let-7 target sites (let7T) into the 3' untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011(let7T) was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011(let7T) was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011(let7T) to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011(let7T)in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011(let7T) may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated.
    PLoS ONE 01/2011; 6(7):e21307. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oncolytic adenovirus is capable of infecting, replicating in and lysing cancer cells. In adenovirus infection and replication, the wild type E1a gene (wE1a) mediates various genetic events to facilitate viral replication and exert antitumor effect. To enhance its antitumor efficacy and optimize its safety, we manipulated the wE1a gene and designed a 720-bp truncated minimal-E1a (mE1a) by deletions and mutations of amino acid residues. The mE1a gene was incorporated in an adenovirus under the control of hTERT promoter, giving the vector AdDC315-mE1a. A variety of cancer cell lines infected with the virus expressed the mE1a protein and showed considerable down-regulation in Neu protein expression as compared to normal cell lines. mE1a also had a lower binding affinity to the Rb protein, preserving the Rb tumor suppressive function. The mE1a expression allowed efficient adenovirus replication with high and stable replication ratios in cancer cells (about 125- to 8500-fold higher at 48 h and 180- to 10,900-fold higher at 96 h post-infection). Further, the mE1a-supported oncolytic adenovirus induced higher cancer cell apoptosis, stronger cell cycle arrest and more effective antitumor efficacy in hepatocarcinoma xenografts in nude mice. In conclusion, the truncated minimal mE1a can act as a tumor inhibitor gene, and may be used to construct oncolytic adenovirus vectors for use in gene therapy of a variety of cancers.
    Chemico-biological interactions 07/2009; 181(1):1-7. · 2.46 Impact Factor
  • Digestive Diseases and Sciences 06/2009; · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Replication-competent adenovirus (RCAd) constitutes an alternative in cancer therapy. For obtaining advanced RCAd generations with high oncolytic capability and a good safety profile, we constructed an E2F promoter-regulated RCAd carrying p16 gene, AdE2F-p16, in which the E1a gene was controlled by the E2F promoter. The experimental data showed that the E2F promoter endowed AdE2F-p16 with high specificity in cancer cells. While rarely replicating in normal cells, AdE2F-p16 could replicate in p16-deficient cancer cells, with 2,937- to 160,000-fold increased replicative capability in different cancer cell lines. AdE2F-p16 expressed p16 within cancer cells and led to potent antitumor efficacy in gastric cancer xenografts in nude mice, with a tumor inhibition rate of 59.14%. Due to the combined effects of cancer cell apoptosis induced by p16 expression and oncolysis by virus replication, the E2F promoter-regulated, p16-armed RCAd provides a promising strategy for cancer gene therapy.
    Digestive Diseases and Sciences 12/2008; 54(7):1425-31. · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Conditionally replicating adenovirus (CRAd) has demonstrated to be safe in clinical studies. We generated a triple-regulated p53-armed CRAd, SG600-p53, in which the partially deleted E1a and E1b genes are regulated under the human telomerase reverse transcriptase promoter and the hypoxia response element. SG600-p53 was proven to be effective both in vitro and in vivo. In this study, the preclinical safety profiles of SG600-p53 in animal models were investigated. SG600-p53 had no adverse effects on mouse behavioral and nervous systems at 1.0 x 10(11) viral particles (VP)/kg, 2.0 x 10(11) VP/kg and 4.0 x 10(11) VP/kg doses, and on cat cardiovascular and respiratory systems at 2.0 x 10(10) VP/kg, 4.0 x 10(10) VP/kg, and 8.0 x 10(10) VP/kg doses. In acute toxicity test in mice, the maximum tolerated dose (2.5 x 10(13) VP/kg) induced cachexia, decreased activity, and eye closure in 9/20 mice which could be self-resolved within 30 min. Sensitized by five repeated ip injections at 1.0 x 10(10) VP/kg each ip and excitated by one iv injection at 1.0 x 10(11) VP/kg, guinea pigs did not show any sign of systemic anaphylaxis. In repeat-dose toxicological studies, the no-observable-adverse-effect levels of SG600-p53 in rats (1.0 x 10(11) VP/kg) and cynomolgus monkeys (5.0 x 10(11) VP/kg) were 12-fold and 60-fold of the proposed clinical dose, respectively. Intramuscular injections of SG600-p53 in cynomolgus monkeys caused inflammation at injection sites, which was alleviative at the end of observation period. The anti-virus antibody was produced in animal sera and decreased gradually 4 weeks later. No histopathological changes were found by bone marrow examination. Our data in different animal models suggest that SG600-p53 is a safe antitumor therapeutic agent.
    Toxicological Sciences 09/2008; 106(1):242-50. · 4.33 Impact Factor

Publication Stats

38 Citations
16.21 Total Impact Points

Institutions

  • 2008–2011
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
  • 2009
    • Nanjing Normal University
      • Jiangsu Key Laboratory for Molecular and Medical Biotechnology
      Nan-ching, Jiangsu Sheng, China
  • 2008–2009
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China