Publications [#169041] of Mark W. Dewhirst

Papers Published

1. F Siddiqui, EJ Ehrhart, B Charles, L Chubb, CY Li, X Zhang, SM Larue, PR Avery, MW Dewhirst, RL Ullrich, Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct., International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, England, vol. 22 no. 7 (November, 2006), pp. 587-606, ISSN 0265-6736
   (last updated on 2009/12/31)

   Abstract:
   PURPOSE: Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under control of a heat shock promoter. This approach limits systemic toxicity by restricting IL-12 delivery locally to the tumour. The kinetics of the downstream cytokines interferon-gamma (IFN-gamma) and interferon inducible protein-10 (IP-10) and other molecules affecting angiogenesis, vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were also studied. MATERIALS AND METHODS: 4T1 tumours were grown in Balb/C mice and the AdhspmIL-12 construct was injected intra-tumourally. The tumours were heated after 24 h using a water bath. At various time points post-heating the tumours were collected and quantitatively assessed for cytokine production and vascularity. RESULTS: A significant reduction was seen in the tumour vasculature of the treated group vs. the control group mice. Systemic effects of IL-12 were limited to generalized immunostimulation. No hepatoxicity was noted. CONCLUSIONS: This study suggests that IL-12 can be effectively delivered using a gene-based approach with a heat shock promoter. This results in quantitatively measurable anti-angiogenesis and general immunostimulation. The complex inter-play of other pro- and anti-angiogenic factors (IFN-gamma, IP-10, VEGF and PAI-1) was also studied.

   Keywords:
   Adenoviridae • Angiogenesis Inhibitors • Animals • Chemokine CXCL10 • Chemokines, CXC • Gene Therapy • Genetic Vectors • Hyperthermia, Induced* • Interferon-gamma • Interleukin-12 • Lung Neoplasms • Mammary Neoplasms, Animal • Mice • Mice, Inbred BALB C • Neoplasm Metastasis • Plasminogen Activator Inhibitor 1 • Reverse Transcriptase Polymerase Chain Reaction • Vascular Endothelial Growth Factor A • administration & dosage* • biosynthesis • drug therapy* • methods* • pathology • prevention & control • secondary • therapeutic use