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13-Cis retinoic acid can enhance the antitumor activity of non-replicating Sendai virus particle against neuroblastoma.

Abstract
Hemagglutinating virus of Japan-envelope (HVJ-E) is a drug delivery vector based on inactivated Sendai virus. Recently, antitumor activities were found for HVJ-E itself and clinical trials of HVJ-E for some malignant tumors are now ongoing. We investigated the in vitro and in vivo antitumor effects of HVJ-E against neuroblastoma, which is one of the most common malignant solid tumors in childhood. The sensitivity of human neuroblastoma cell lines to HVJ-E correlated with the expression level of gangliosides, Sialylparagloboside (SPG) and GD1a, receptors for HVJ. Among the cell lines, SK-N-SH was the most sensitive to HVJ-E in vitro and total SPG and GD1a expression was the highest. Complete eradication of subcutaneous tumors derived from SK-N-SH cells was achieved by intratumoral injection of HVJ-E in SCID mice and no recurrence was observed for more than 300 days after HVJ-E inoculation. In contrast, NB1 cells expressed the lowest amount of GD1a and SPG and were resistant to HVJ-E in vitro. The expression of GD1a increased by 13-cis retinoic acid (13cRA), which is a therapeutic drug for high risk neuroblastoma, thus leading to an improved sensitivity to HVJ-E in vitro. Only growth inhibition of the subcutaneous tumors derived from NB1 cells was achieved by HVJ-E in the SCID mice, but the combination of 13cRA and HVJ-E could achieve partial eradication of the xenograft and also lead to an improved prognosis. In conclusion, HVJ-E is a promising therapeutic modality for neuroblastoma and 13cRA can be used as an adjuvant to HVJ-E.
AuthorsMotonari Nomura, Takashi Shimbo, Yasuhide Miyamoto, Masahiro Fukuzawa, Yasufumi Kaneda
JournalCancer science (Cancer Sci) Vol. 104 Issue 2 Pg. 238-44 (Feb 2013) ISSN: 1349-7006 [Electronic] England
PMID23134437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 Japanese Cancer Association.
Chemical References
  • Antineoplastic Agents
  • Gangliosides
  • Viral Envelope Proteins
  • ganglioside GD1alpha
  • G(M1) Ganglioside
  • Isotretinoin
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant (methods)
  • Female
  • G(M1) Ganglioside (analogs & derivatives, genetics, metabolism)
  • Gangliosides (genetics, metabolism)
  • Genetic Vectors (pharmacology)
  • Humans
  • Isotretinoin (pharmacology)
  • Mice
  • Mice, SCID
  • Neuroblastoma (drug therapy, genetics, therapy, virology)
  • Oncolytic Virotherapy (methods)
  • Sendai virus (physiology)
  • Viral Envelope Proteins (pharmacology)

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