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Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression

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Abstract

Interruption of the tumor metastatic process is a new, thought provoking molecular target for the treatment of cancer. The Nm23-H1 metastasis suppressor gene stands as a validated molecular target owing to its reduced expression in many aggressive human tumors, and the reduction in metastatic potential in vivo upon re-expression in multiple cell lines. Several compounds have been identified which elevate Nm23-H1 expression in vitro including indomethacin, γ Linolenic Acid, trichostatin A, 5-aza-deoxycytidine, and high dose medroxyprogesterone acetate. Using a model of lung metastatic colonization by MDA-MB-231 human breast carcinoma cells, we demonstrated that high dose MPA reduced the formation of overt lung metastases by 37–46% and those metastases that formed were statistically smaller. A Phase II clinical trial of high dose MPA, alone or in combination with metronomic chemotherapy has recently opened.

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  1. Patricia S. Steeg

    Present address: , 37 Convent Drive, Room 1122, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Women’s Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Jean-Claude Marshall, Jong Heun Lee & Patricia S. Steeg

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  1. Jean-Claude Marshall
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  2. Jong Heun Lee
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  3. Patricia S. Steeg
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Correspondence to Patricia S. Steeg.

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Marshall, JC., Lee, J.H. & Steeg, P.S. Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression. Mol Cell Biochem 329, 115–120 (2009). https://doi.org/10.1007/s11010-009-0116-3

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  • DOI: https://doi.org/10.1007/s11010-009-0116-3

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