In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioryactors using mammalian cells engineered for genomic containment of mUltiple copies of defined target genes for genotoxic assessment. The Rat 2A fibroblasts (Stratagene, Inc.) were genetically engineered to contain high-density target genes for mutagenesis. Stable t...

We have investigated the hypoxia Inducibility of vascular endothelial growth factor (VEGF) in multicellular tumor spheroids of HT29 cells using a monoclonal antibody to a fluorinated bioreductive drug, EFS [2-(2-nitro-lJI-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamidel, a chemical probe for hypoxia. We have shown that VEGF expression is predominantly localized in interior spheroid cell...

Malignant pleural mesothelioma is a highly chemoresistant solid tumor. We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/mTOR inhibitors. Here, we investigate the activity of GDC-0980, a novel dual PI3K/mTOR inhibitor, which has been proposed to be effective in mesothelioma. In...

Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix-free spheroids from breast MCF-7 and pancreati...

Although electroporation is gaining increased attention as a technology to enhance clinical chemotherapy and gene therapy of tissues, direct measurements of electroporation-mediated transport in multicellular environments are lacking. In this study, we used multicellular tumor spheroids of DU145 prostate cancer cells as a model tissue to measure the levels and distribution of molecular uptake i...

The culture of EMT6/Ro multicellular tumor spheroids in a 20-fold range of glucose concentrations and a 4-fold range of oxygen tensions had profound effects on the cell subpopulations which developed in the spheroids. As the spheroids increased in diameter the rate of accumulation of cells with a G1-phase DNA content was much greater for those spheroids cultured in the lower oxygen and glucose ...

Multicellular cancer spheroids (MCSs) have emerged as a promising in vitro model that recaptures many features of solid tumours vivo. To generate spheroids, cells are encapsulated microgels with high throughput. While the biophysical properties spheroid and biomaterial influence function behavior cells, characterization these remains largely unexplored. In addition, existing techniques lack con...