Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.

Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage.

Iterative Design and in Vivo Evaluation of an Oncolytic Antilymphoma Peptide.

Oncolytic peptides represent a promising new strategy within the field of cancer immunotherapy. Here we describe the systematic design and evaluation of short antilymphoma peptides within this paradigm. The peptides were tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic immunotherapeutic.

Improved anticancer potency by head-to-tail cyclization of short cationic anticancer peptides containing a lipophilic β(2,2) -amino acid.

We have recently reported a series of synthetic anticancer heptapeptides (H-KKWβ(2,2) WKK-NH(2) ) containing a central achiral and lipophilic β(2,2) -amino acid that display low toxicity against non-malignant cells and high proteolytic stability. In the present study, we have further investigated the effects of increasing the rigidity and amphipathicity of two of our lead heptapeptides by preparing a series of seven to five residue cyclic peptides containing the two most promising β(2,2) -amino acid derivatives as part of the central lipophilic core. The peptides were tested for anticancer activity against human Burkitt's lymphoma (Ramos cells), haemolytic activity against human red blood cells (RBC) and cytotoxicity against healthy human lung fibroblast cells (MRC-5).

Synthesis of anticancer heptapeptides containing a unique lipophilic β(2,2) -amino acid building block.

We report a series of synthetic anticancer heptapeptides (H-KKWβ(2,2) WKK-NH(2)) containing eight different central lipophilic β(2,2) -amino acid building blocks, which have demonstrated high efficiency when used as scaffolds in small cationic antimicrobial peptides and peptidomimetics. The most potent peptides in the present study had IC(50) values of 9-23 µm against human Burkitt's lymphoma and murine B-cell lymphoma and were all nonhaemolytic (EC(50)  > 200 µm). The most promising peptide 10e also demonstrated low toxicity against human embryonic lung fibroblast cells and peripheral blood mononuclear cells and exceptional proteolytic stability.