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      1. Author :
        M van Eekelen; LS Sasportas; R Kasmieh; S Yip; J-L Figueiredo; DN Louis; R Weissleder; K Shah
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Oncogene
      6. Products :
      7. Volume :
        29
      8. Issue :
        22
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        brain tumor; glioma; human neural stem cells; TSP-1; endothelial cells; angiogenesis; in vivo imaging
      12. Abstract :
        Novel therapeutic agents combined with innovative modes of delivery and non-invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anticancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that comprises unique regions of three type-I-repeats of TSP-1 and used engineered human neural stem cells (hNSC) to provide sustained on-site delivery of secretable aaTSP-1 to tumor-vasculature. We show that hNSC-aaTSP-1 has anti-angiogenic effect on human brain and dermal microvascular endothelial cells co-cultured with established glioma cells and CD133+ glioma-initiating cells. Using human glioma cells and hNSC engineered with different combinations of fluorescent and bioluminescent marker proteins and employing multi-modality imaging techniques, we show that aaTSP-1 targets the vascular-component of gliomas and a single administration of hNSC-aaTSP-1 markedly reduces tumor vessel-density that results in inhibition of tumor-progression and increased survival in mice bearing highly malignant human gliomas. We also show that therapeutic hNSC do not proliferate and remain in an un-differentiated state in the brains of glioma-bearing mice. This study provides a platform for accelerated development of future cell-based therapies for cancer.
      13. URL :
        http://www.nature.com/onc/journal/v29/n22/abs/onc201075a.html
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4492
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