Introduction Systemic sclerosis (SSc) is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS) is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods Serum levels o...

Proteolytic processing of human plasminogen generates potent antiangiogenic peptides such as angiostatin. The plasminogen kringle 5 (K5) domain, which is distinct from angiostatin, possesses potent antiangiogenic properties on its own, which can be exploited in cancer therapy. It has been recently observed that antiangiogenic agents promote leukocyte-vessel wall interaction as part of their ant...

Immunotherapy of cancer offers great promise, however translation into human studies has yielded relatively poor results to date. The concept of combining cancer vaccination with angiogenesis inhibition is appealing, due to favorable safety profile of both approaches, as well as possible biological synergies. Here we studied the anti-tumor effects of combining plasmid DNA (pDNA) vaccination and...

In light of the involvement of tumor-associated macrophages (TAM) in the promotion of tumor growth and metastasis, strategies to prevent TAM recruitment within the tumor microenvironment are currently under investigation. The recent observation that angiostatin reduces macrophage infiltration in an atherosclerosis model prompted our laboratory to further explore the use of human plasminogen ang...

Osteopontin and MMP9 are implicated in angiogenesis and cancer progression. The objective of this study is to gain insight into the molecular mechanisms underlying angiogenesis, and to elucidate the role of osteopontin in this process. We report here that osteopontin/αvβ3 signaling pathway which involves ERK1/2 phosphorylation regulates the expression of VEGF. An inhibitor to MEK or curcumin si...

Plasmin, a broad spectrum proteinase, is inactivated by an autoproteolytic reaction that results in the destruction of the heavy and light chains of the protein. Recently we demonstrated that a 61-kDa plasmin fragment was one of the major products of this autoproteolytic reaction (Fitzpatrick, S. L., Kassam, G., Choi, K. S., Kang, H. M., Fogg, D. K., and Waisman, D. M. (2000)Biochemistry 39, 10...

Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain (K5) of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeu...

Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-media...