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      1. Author :
        Ong, Hooi-Tin; Federspiel, Mark J.; Guo, Chang M.; Lucien Ooi, London; Russell, Stephen J.; Peng, Kah-Whye; Hui, Kam M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Journal of Hepatology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Systemic virotherapy; Oncolytic measles virus; Hepatocellular carcinoma; Orthotopically implanted HCC tumor model; Mesenchymal stem cells as cell delivery vehicles; Human neutralizing antibody
      12. Abstract :
        AbstractBackground & aims Although attenuated measles virus (MV) has demonstrated potent oncolytic activities towards human cancers, it has not yet been widely adopted into clinical practice. One of the major hurdles is the presence of pre-existing anti-MV immunity in the recipients. In this study, we have evaluated the combination of the potent oncolytic activity of the attenuated MV with the unique immunoprivileged and tumor-tropic biological properties of human bone marrow-derived mesenchymal stem cells (BM-hMSCs) to combat human hepatocellular carcinoma (HCC) orthotopically implanted in SCID mice passively immunized with human neutralizing antibodies against MV as a preclinical model. Methods SCID mice were orthotopically implanted with patient-derived HCC tissues and established HCC cell lines. SCID mice were passively immunized with human neutralizing anti-measles antibodies. Bioluminescence and fluorescence imaging were employed to monitor the ability of systemically delivered MV-infected BM-hMSCs to infiltrate the implanted tumors and their effects on tumor growth. Results Systemically delivered MV-infected BM-hMSCs homed to the HCC tumors implanted orthotopically in the liver and it was evidenced that BM-hMSCs could transfer MV infectivity to HCC via heterofusion. Furthermore, therapy with MV-infected BM-hMSCs resulted in significantly inhibition of tumor growth in both measles antibody-naïve and passively-immunized SCID mice. In contrast, when cell-free MV viruses were delivered systemically, antitumor activity was evident only in measles antibody-naïve SCID mice. Conclusions
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0168827813004571
      14. Call Number :
        PKI @ catherine.lautenschlager @ 5278
      15. Serial :
        14728