Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis.

Background: Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro.

Inhibition of urokinase plasminogen activator with a novel enzyme inhibitor, WXC-340, ameliorates endotoxin and surgery-accelerated growth of murine metastases.

The urokinase plasminogen activator (u-PA) is intimately associated with tumour invasion and metastases. Surgery facilitates accelerated metastatic tumour growth in murine models, a phenomenon related to elevated perioperative bacterial lipopolysaccaride (LPS) and inflammatory cytokine levels. The objectives of the study were to examine the role of u-PA in cytokine-enhanced tumour cell invasion in vitro and surgery-induced accelerated metastatic tumour growth in vivo and to assess the potential benefit of a novel selective u-PA inhibitor WXC-340 in this setting.

Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1.

The serine protease uPA (urokinase-type plasminogen activator) and its receptor uPAR (CD87) are often elevated in malignant tumours, hence, inhibition of this tumour-associated plasminogen activation system provides an attractive target for therapeutic strategies. WX-UK1, a derivative of 3-aminophenylalanine in the L-conformation with inhibitory antiproteolytic properties, was tested for its specificity spectrum using specific chromogenic paranitroanilide peptide substrates. The corresponding D-enantiomer of WX-UK1 was used as a control.

Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system.

The overall survival rate of patients suffering from carcinomas has remained poor and nearly unchanged over the last decades. This is mainly due to the so-called minimal residual disease, i.e.

Protein expression of MMP-13, uPA, and PAI-1 in pseudocapsular and interface tissue around implants of loose artificial hip joints and in osteoarthritis.

Matrix metalloproteinase 13 (MMP-13), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1) have been reported to be involved in aseptic loosening of artificial hip joints. This study for the first time presents the protein levels of all of these factors in synovial-like interfaces between bone and prosthesis and in pseudocapsular tissues surrounding the artificial joint in patients with aseptic loosening (n=17) measured by ELISA. No differences were observed in the antigen expression of MMP-13, uPA, and PAI-1, comparing interface and pseudocapsular tissue.