Circulating angiogenesis regulators in cancer patients.
OBJECTIVE
To date, numerous studies have demonstrated that several angiogenesis regulators circulate in the blood and may function as endocrine factors in cancer patients. This review aims to give a comprehensive insight into the possible clinical value of circulating angiogenesis regulators, mainly basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF), angiogenin, pleiotrophin, thrombospondin (TSP) and endostatin (ES) in cancer patients.


METHODS
A computerized (MEDLINE) and a manual search based on the reference lists of the publications were performed to identify articles published on this topic.


RESULTS
In a detailed literature search, approximately 100 publications were found up to the end of 1999. Circulating angiogenic factors such as bFGF, VEGF, HGF and angiogenin have been evaluated not only as diagnostic and/or prognostic factors but also as predictive factors in cancer patients. On the other hand, little is known about the clinical significance of negative regulators. Neither the source nor the mechanism of protein externalization has been clarified in detail.


CONCLUSIONS
Although there are no known factors with established clinical utility, circulating angiogenesis regulators may be useful in several situations. They could be used to determine the risk of developing cancer, to screen for early detection, to distinguish benign from malignant disease, and to distinguish between different types of malignancies. In patients with established malignancies such factors might be used to determine prognosis, to predict the response to therapy, and to monitor the clinical course. Further investigations are warranted to assess the specific utility of each factor.
Kuroi
K
K
Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan. kurochan@dd.iij4u.or.jp
Toi
M
M
D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood; D003094:Collagen / Q000097:blood; D016207:Cytokines / Q000097:blood; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D008222:Lymphokines / Q000097:blood; D009369:Neoplasms / Q000097:blood* / Q000098:blood supply* / Q000175:diagnosis; D009389:Neovascularization, Pathologic / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012259:Ribonuclease, Pancreatic / Q000097:blood; D019699:Thrombospondins / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016207:Cytokines; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C066845:pleiotrophin; D017228:Hepatocyte Growth Factor; D003094:Collagen; C046366:angiogenin; D012259:Ribonuclease, Pancreatic