Preclinical study on combined chemo- and nonviral gene therapy for sensitization of melanoma using a human TNF-alpha expressing MIDGE DNA vector.

Nonviral gene therapy represents a realistic option for clinical application in cancer treatment. This preclinical study demonstrates the advantage of using the small-size MIDGE(®) DNA vector for improved transgene expression and therapeutic application. This is caused by significant increase in transcription efficiency, but not by increased intracellular vector copy numbers or gene transfer efficiency.

Systemic shRNA mediated knock down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation.

The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients' survival. Inhibition of S100A4 expression in patients might therefore result in decreased metastasis formation and prolonged survival.

Treatment of experimental brain metastasis with MTO-liposomes: impact of fluidity and LRP-targeting on the therapeutic result.

Purpose: To test targeted liposomes in an effort to improve drug transport across cellular barriers into the brain.

Methods: Therefore we prepared Mitoxantrone (MTO) entrapping, rigid and fluid liposomes, equipped with a 19-mer angiopeptide as ligand for LDL lipoprotein receptor related protein (LRP) targeting.

Results: Fluid, ligand bearing liposomes showed in vitro the highest cellular uptake and transcytosis and were significantly better than the corresponding ligand-free liposomes and rigid, ligand-bearing vesicles.

Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer.

Background: Metastasis formation in colon cancer severely reduces the survival rate in patients. S100A4, a calcium-binding protein, is implicated in promoting metastasis formation in colon cancer.

Methods: To identify a transcription inhibitor of S100A4, high-throughput screening of 1280 pharmacologically active compounds was performed using a human colon cancer cell line expressing a S100A4 promoter-driven luciferase (LUC) reporter gene construct (HCT116-S1004p-LUC).

Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis.

Colon cancer metastasis is often associated with activation of the Wnt/β-catenin signaling pathway and high expression of the metastasis mediator S100A4. We previously demonstrated the transcriptional regulation of S100A4 by β-catenin and the importance of the interconnection of these cellular programs for metastasis. Here we probe the hypothesis that the nonsteroidal anti-inflammatory drug sulindac sulfide can inhibit colon cancer metastasis by intervening in β-catenin signaling and thereby interdicting S100A4.

Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model.

The aim of this study was to investigate the effect of liposomal membrane properties on cellular uptake and transcytosis across a tight Madin-Darby canine kidney (MDCK) cell barrier in vitro. More than 25 small vesicles were prepared by lipid film hydration/extrusion to generate small unilamellar vesicles. The fluorescence marker calcein was encapsulated to mimic hydrophilic drug transport.

Anti-proliferative efficacy of icariin on HepG2 hepatoma and its possible mechanism of action.

The aim of the present work was to explore the anti-hepatoma effects of icariin both in vitro and in vivo and to elucidate its potential mechanism of action. The MTT assay was applied to test the anti-proliferative effects of icariin in vitro. HepG2 bearing NMRI nu/nu mice were used to test the anticancer effects of icariin in vivo.

Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor growth and metastases.

The aim of this study was to determine the efficacy of sagopilone (ZK-EPO), a novel epothilone, compared with other anticancer agents in orthotopic models of human primary and secondary brain tumors. Autoradiography and pharmacokinetic analyses were performed on rats and mice to determine passage across the blood-brain barrier and organ distribution of sagopilone. Mice bearing intracerebral human tumors (U373 or U87 glioblastoma, MDA-MB-435 melanoma, or patient-derived non-small-cell lung cancer [NSCLC]) were treated with sagopilone 5-10 mg/kg, paclitaxel 8-12.