A novel non-parametric method for uncertainty evaluation of correlation-based molecular signatures: its application on PAM50 algorithm.

Motivation: The PAM50 classifier is used to assign patients to the highest correlated breast cancer subtype irrespectively of the obtained value. Nonetheless, all subtype correlations are required to build the risk of recurrence (ROR) score, currently used in therapeutic decisions. Present subtype uncertainty estimations are not accurate, seldom considered or require a population-based approach for this context.

The tumor microenvironment: characterization, redox considerations, and novel approaches for reactive oxygen species-targeted gene therapy.

The tumor microenvironment is a complex system that involves the interaction between malignant and neighbor stromal cells embedded in a mesh of extracellular matrix (ECM) components. Stromal cells (fibroblasts, endothelial, and inflammatory cells) are co-opted at different stages to help malignant cells invade the surrounding ECM and disseminate. Malignant cells have developed adaptive mechanisms to survive under the extreme conditions of the tumor microenvironment such as restricted oxygen supply (hypoxia), nutrient deprivation, and a prooxidant state among others.

Matricellular proteins and inflammatory cells: a task force to promote or defeat cancer?

In the last years it became clear that the tumor microenvironment plays a major role in neoplastic growth. Proteins secreted either by the malignant cells or by the tumor-associated stromal cells act as extracellular signal transductors, orchestrating tumor progression. Sentinel cells of the innate immune system patrol the different organs and have proven either to promote tumor growth or induce tumor suppression.

Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells.

Secreted protein, acidic and rich in cysteines (SPARC) is a secreted protein associated with increased aggressiveness of different human cancer types. In order to identify downstream mediators of SPARC activity, we performed a 2-DE proteomic analysis of human melanoma cells following antisense-mediated downregulation of SPARC expression. We found 23/504 differential spots, 15 of which were identified by peptide fingerprinting analysis.