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Sialic Acid-blocking glycomimetics

R Gupta, Q Yang, S K Dogra, N Wajapeyee
High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples...
July 13, 2017: Oncogene
Christian Büll, Thomas Jan Boltje, Eric A W van Dinther, Timo Peters, Annemarie M A de Graaf, Jeanette H W Leusen, Martin Kreutz, Carl G Figdor, Martijn H den Brok, Gosse J Adema
Sialic acid sugars are overexpressed by cancer cells and contribute to the metastatic cascade at multiple levels. Therapeutic interference of sialic acids, however, has been difficult to pursue because of the absence of dedicated tools. Here we show that a rationally designed sialic acid-blocking glycomimetic (P-3F(ax)-Neu5Ac) successfully prevents cancer metastasis. Formulation of P-3F(ax)--Neu5Ac into poly(lactic-co-glycolic acid nanoparticles coated with antityrosinase-related protein-1 antibodies allowed targeted delivery of P-3F(ax)--Neu5Ac into melanoma cells, slow release, and long-term sialic acid blockade...
January 27, 2015: ACS Nano
Christian Büll, Thomas J Boltje, Melissa Wassink, Annemarie M A de Graaf, Floris L van Delft, Martijn H den Brok, Gosse J Adema
Cancer cells decorate their surface with a dense layer of sialylated glycans by upregulating the expression of sialyltransferases and other glycogenes. Although sialic acids play a vital role in many biologic processes, hypersialylation in particular has been shown to contribute to cancer cell progression and metastasis. Accordingly, selective strategies to interfere with sialic acid synthesis might offer a powerful approach in cancer therapy. In the present study, we assessed the potential of a recently developed fluorinated sialic acid analogue (P-3F(ax)-Neu5Ac) to block the synthesis of sialoglycans in murine melanoma cells and the consequences on cell adhesion, migration, and in vivo growth...
October 2013: Molecular Cancer Therapeutics
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