Angiogenesis markers

Fig. 20. Targeting of the endothelial integrin a P3 as a specific angiogenesis marker. The receptor is recognized by a biotinylated antibody that is then bound by an avidin moiety bearing a Gd(III) loaded liposome.

Table 5. Effects of EPA ethylester and EPAD on apoptotic cell number, CD34 (an angiogenesis marker) expression, CDS-, and NK-positive cell numbers in tumors of mice with subcutaneously implanted LLC ...

Reliable markers are needed to monitor the activity of antiangiogenic dtugs. Circulating endothelial cells and their progenitor subset are a potential candidate, as is MRI dynamic measurement of vascular permeability/ flow in response to angiogenesis inhibitors, but neither has been clinically validated. 

Eppenberger U, Kueng W, Schlaeppi JM, et al. Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 1998 16 3129-3136. 

Lockhart AC, Braun RD, DewhirstMW, KlitzmanB, Humphrey JS, Yuan F, etal. Wound angiogenesis as a potential surrogate marker for anti-angiogenesis clinical trials. Proc Am Assoc Cancer Res 2000 41 168 (abstract). 

Lockhart AC, Braun RD, DewhirstMW, Humphrey J, YuanF, Grichnik JM, et al. Wound angiogenesis inhibition as a marker for anti-angiogenic efficacy. Exp Biol 2000 (abstract). 

Cat B is an abundant and ubiquitously expressed cysteine peptidase of the papain family and makes up a major fraction of lysosomal enzymes that is capable of degrading components of the extracellular matrix in various diseases [30-32]. Cat B is also a prognostic marker for several types of cancer [33], and increased expression and secretion of cat B has been shown to be involved in the migration and invasion of various tumours [34—36], The precise role of cat B in solid tumours is not fully understood, but it has been proposed to participate, along with other cysteine cathepsins, in metastasis, angiogenesis, and tumour progression [37], Indeed, cat B inhibitors reduce both tumour cell motility and invasiveness in vitro [38], Recently, metal complexes based on rhenium, gold and palladium were shown to be effective inhibitors of cat B [39-44],... 

In mature tissues, VEGFR3 is primarily localized to lymphatic endothelial cells, where binding of VEGF-C stimulates lymphangiogenesis [25], Some inflamed tissues, such as from arthritic joints, display VEGFR3 colocalized with other blood vessel markers on endothelial cells, although a role in the accelerated blood vessel angiogenesis in this tissue has not been clearly demonstrated [26]. 

Pharmacological neovascular targeting has been technically limited by restricted specificity of presumed neovascular markers. In particular, many markers, such as E-selectin, that are upregulated during angiogenesis may also be upregulated during endothelial cell activation in other contexts, or they may play important protective roles in the host response to injury or infection. 

Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF. Stable expression of angiopoietin-1 and other markers by cultured pericytes Phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest 2002 82 387-401. 

Coradini D, Pellizzaro C, Veneroni S, Ventura L, Daidone M. Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence. Br J Cancer 2002 87 1105-1 111. 

As shown in Table (13) , The reduction of the lymphocyte, CD4 and CD8 T cell numbers in LLC-bearing mice was also inhibited by the oral administration of A-l (30 and/or 300 mg/kg). From the immunohistochemical analysis in tumors, A-l (30, 100 and 300 mg/kg) increased the number of apoptotic cells in the tumors. In the untreated LLC-bearing mice, von Willebrand factor (vWF, a marker of angiogenesis) expression was increased in the tumors. Angiogenesis in the tumors was inhibited by the oral administration of A-l. 

---