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Antitumor effects of the MIG and IP-10 genes transferred with poly [D,L-2,4-diaminobutyric acid] on murine neuroblastoma.

Abstract
The number of tumor-infiltrating lymphocytes is known to be related to outcomes in patients with a variety of malignancies. Interferon (IFN) gamma-inducible protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic effects on activated T lymphocytes and natural killer (NK) cells. The aim of this study was to evaluate the antitumor effects of exogenous expression of the MIG and IP-10 genes delivered to solid tumors by poly [D,L-2,4-diaminobutyric acid] (PDBA). The murine MIG and IP-10 genes were transfected into mouse neuroblastoma cells with PDBA. MIG and IP-10 levels in supernatants of transfected cells were measured by enzyme-linked immunosorbent assay. The chemotactic activities of MIG and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay. Tumors were injected in vivo with PDBA/pmMIGColon, two colonsIP-10 complexes to evaluate the effects of these genes on tumor volume and survival time of mice. Transfected PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10 protein in vitro. MIG and IP-10 proteins secreted into the culture medium showed chemotactic activity. MIG and IP-10 gene therapy with the PDBA system in vivo significantly inhibited tumor growth and prolonged survival time of mice. In conclusion, PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment of solid tumors.
AuthorsM Tominaga, Y Iwashita, M Ohta, K Shibata, T Ishio, N Ohmori, T Goto, S Sato, S Kitano
JournalCancer gene therapy (Cancer Gene Ther) Vol. 14 Issue 8 Pg. 696-705 (Aug 2007) ISSN: 0929-1903 [Print] England
PMID17514193 (Publication Type: Journal Article)
Chemical References
  • Aminobutyrates
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Cxcl9 protein, mouse
  • Polymers
  • 2,4-diaminobutyric acid
Topics
  • Aminobutyrates
  • Animals
  • Cell Line, Tumor
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC (genetics)
  • Female
  • Gene Transfer Techniques
  • Lymphocytes, Tumor-Infiltrating (immunology)
  • Mice
  • Mice, Inbred A
  • Neuroblastoma (genetics, immunology, therapy)
  • Polymers

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