Mechanotransduction of mesenchymal melanoma cell invasion into 3D collagen lattices: filopod-mediated extension-relaxation cycles and force anisotropy.

Mesenchymal cell migration in interstitial tissue is a cyclic process of coordinated leading edge protrusion, adhesive interaction with extracellular matrix (ECM) ligands, cell contraction followed by retraction and movement of the cell rear. During migration through 3D tissue, the force fields generated by moving cells are non-isotropic and polarized between leading and trailing edge, however the integration of protrusion formation, cell-substrate adhesion, traction force generation and cell translocation in time and space remain unclear. Using high-resolution 3D confocal reflectance and fluorescence microscopy in GFP/actin expressing melanoma cells, we here employ time-resolved subcellular coregistration of cell morphology, interaction and alignment of actin-rich protrusions engaged with individual collagen fibrils.

Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens.

Information on the carcinogenic potential of chemicals is primarily available for High Production Volume (HPV) products. Because of the limited knowledge gain from routine cancer bioassays and the fact that HPV chemicals are tested only, there is the need for more cost-effective and informative testing strategies. Here we report the application of advanced genomics to a cellular transformation assay to identify toxicity pathways and gene signatures predictive for carcinogenicity.

A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators.

Expression of the epithelial cell adhesion molecule EpCAM is upregulated in a variety of carcinomas. This antigen is therefore explored in tumour diagnosis, and clinical trials have been initiated to examine EpCAM-based therapies. Notably, the possible intracellular effects and signalling pathways triggered by EpCAM-specific antibodies are unknown.

Analysis of neuroendocrine differentiation and the p53/BAX pathway in UICC stage III colorectal carcinoma identifies patients with good prognosis.

Background And Aims: Neuroendocrine differentiation is an independent prognostic factor in colorectal cancer. Moreover, an altered p53/BAX pathway is associated with a poor clinical outcome in Union Internationale Contre le Cancer (UICC) stage III disease. Because these markers are involved in different genetic events disrupted in colorectal cancer, we investigated the prognostic power of a multimarker analysis.

Targeting the epidermal growth factor receptor by erlotinib (Tarceva) for the treatment of esophageal cancer.

Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Because of very poor 5-year survival new therapeutic approaches are mandatory. Erlotinib (Tarceva), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored.