The translation initiation factor eIF4E is a novel protooncogene found over expressed in most breast carcinomas (Kerekatte et al., 1995), but the pathology where this elevation is initially manifested and its possible role in cancer progression are unknown. We report that eIF4E is markedly increased in vascularized malignant ductules of invasive carcinomas, whereas necrotic and avascular ductal carcinomas in situ display signi®cantly lower levels. eIF4E facilitates the synthesis of FGF-2, a powerful tumor angiogenic factor. Conversely, reducing eIF4E with antisense RNA in MDA-435 cells suppresses their tumorigenic and angiogenic properties, consistent with loss of FGF-2 synthesis. These ®ndings suggest a causal role for eIF4E in tumor vascularization.
A new method of nanoparticle formulation for low water-soluble materials was demonstrated on the example of curcumin. The drug was dissolved in organic solvent that is miscible with water (ethanol) and drug nucleation was initiated by gradual worsening the solution with addition of aqueous polyelectrolyte assisted by ultrasonication. Curcumin crystals of 60-100 nm size were obtained depending on the component concentrations, sonication power, and an initial solvent. A layer-bylayer shell assembly with biocompatible polyelectrolytes was used to provide particle coating with high surface potential and stabilization of drug nanocolloids. Polyelectrolyte layer-by-layer encapsulation allowed sustained drug release from nanoparticles over the range of 10-20 hours.Many anticancer drugs are poorly soluble in water (curcumin, paclitaxel, tamoxifen, etc). Currently there is no established nanoscale delivery system for the continuous slow release of such drugs other than micelles, although micelles contain a very small percentage of the desired drugs 1-3 . Other approaches for drug nanoformulation include ultrasonicated decomposition of drug powder 4 and drug loading to polymeric (often gelatin or polysaccharide) coacervates [5][6][7][8] . For such formulations, a usual size of drug carriers is 200-300 nm, which is not small enough for the most efficient medical applications.Natural polyphenolic compounds are interesting as substances with variety of biological activity. High antioxidant, antiviral, and anticancer activities have been proven for plant extracts and polymeric tannins including their isolated individual compounds (such as curcumin) [9][10][11][12] . In this paper we describe a new approach for the preparation of drug nanocolloids with diameters less than 100 nm which is based on sonication assisted nucleation of drug particles from their solutions in organic solvents. An aggregation of the formed nanoparticles was avoided by polycation adsorption onto particles followed by the polyelectrolyte layer-by-layer (LbL) nanoshell formation [13][14][15][16][17][18] . The following procedure was used for formation stable curcumin nanocolloids through controlled crystallization initiated by worsening saturated curcumin alcohol solutions (Scheme 1). Curcumin powder was dissolved in 60 % ethanol / water solution (curcumin was obtained from Sabinsa and all other chemicals were purchased from Sigma-Aldrich). After curcumin been completely dissolved, we added aqueous polycations, poly(allylamine hydrochloride), PAH, or biodegradable protomine sulfate, (PS) and started ultrasonication with UIP1000, Hielscher instrument, at 100 Wt per mL of solution. During the sonication, water was slowly added into the solution. Because of the adding water, solvent becomes more polar, causing decrease of curcumin solubility, and Correspondence to: Yuri Lvov, ylvov@latech.edu.
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Author ManuscriptLangmuir. Author manuscript; available in PMC 2011 June 1.
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4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentiates its possible role in angiogenesis.
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