Publications [#168938] of Mark W. Dewhirst

Papers Published

1. X Zhang, T Kon, H Wang, F Li, Q Huang, ZN Rabbani, JP Kirkpatrick, Z Vujaskovic, MW Dewhirst, CY Li, Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha., Cancer research, United States, vol. 64 no. 22 (November, 2004), pp. 8139-42, ISSN 0008-5472
   (last updated on 2009/12/31)

   Abstract:
   Hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, we examined the idea of down-regulating HIF-1alpha in tumor cells for therapeutic gain. We show that the expression levels of HIF-1alpha can be significantly attenuated by use of the recently established small interfering RNA technology in combination with adenovirus-mediated gene transfer. Down-regulation of the HIF-1alpha protein enhanced hypoxia-mediated tumor cell apoptosis in vitro. Subcutaneous tumor growth was also prevented from cells with attenuated HIF-1alpha expression. In addition, intratumoral injection of adenovirus encoding the HIF-1alpha-targeted small interfering RNA had a small but significant effect on tumor growth when combined with ionizing radiation. Therefore, our results provide proof of HIF-1alpha as an effective target for anticancer therapy. They also suggest that an adenovirus-based small interfering RNA gene transfer approach may be a potentially effective adjuvant strategy for cancer treatment.

   Keywords:
   Apoptosis • Base Sequence • Cell Hypoxia* • Cell Line • Cell Line, Tumor • DNA Primers • Humans • Hypoxia-Inducible Factor 1, alpha Subunit • Polymerase Chain Reaction • RNA, Small Interfering* • Radiotherapy* • Transcription Factors • genetics* • physiology*