Pharmacokinetics of monoclonally-purified and recombinant factor VIII in patients with severe von Willebrand disease.

A monoclonally-purified factor VIII (FVIII) concentrate, containing little von Willebrand factor (vWF), was infused to 11 patients with severe von Willebrand disease and unmeasurable levels of plasma vWF. In comparison with the historical data obtained infusing hemophiliacs in the same conditions, monoclonally-purified FVIII had a significantly shorter half-life and faster clearance from plasma but similar in vivo recovery and volume of distribution. Two additional patients with severe von Willebrand disease were also infused with recombinant FVIII totally devoid of vWF. Half-life was very short and in vivo recovery low, with a larger volume of distribution than for monoclonally-purified FVIII. We conclude that in patients with severe von Willebrand disease the small amounts of vWF contained in the monoclonally-purified FVIII concentrate are not sufficient to stabilize infused FVIII, nor to support the normal circulation of endogenous FVIII that these patients produce at a normal rate.

Angiotensin-(1-7): a peptide hormone with anti-cancer activity.

The development of peptides as therapeutic agents has progressed such that these small molecules of less than fifty amino acids are currently in use for the treatment of a variety of pathologies. This review focuses on the pre-clinical studies and clinical trials assessing the anti-cancer properties of angiotensin-(1-7) [Ang-(1-7)], an endogenous heptapeptide hormone of the renin-angiotensin system. Ang-(1-7) mediates biological responses by activating mas, a unique G protein- coupled receptor, thereby providing specific targeted actions when used as a therapeutic agent. Studies in in vitro as well as in vivo mouse models demonstrated that the heptapeptide hormone reduced proliferation of human cancer cells and xenograft tumors. This attenuation was concomitant with decreased angiogenesis, cancer associated fibrosis, osteoclastogenesis, tumor-induced inflammation and metastasis as well as altered regulation of growth promoting cellular signaling pathways. In three clinical trials, Ang-(1-7) was well tolerated with limited toxic or quality-of-life side effects and showed clinical benefit in cancer patients with solid tumors. Taken together, these studies suggest that Ang-(1-7) may serve as a first-in-class peptide chemotherapeutic agent, reducing cancer growth and metastases by pleiotrophic mechanisms as well as targeting the tumor microenvironment.