Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clotting activation occurs frequently in cancer. Tissue factor (TF), the most potent initiator of coagulation, is expressed aberrantly in many types of malignancy and is involved not only in tumor-associated hypercoagulability but also in promoting tumor angiogenesis and metastasis via coagulation-dependent and coagulation-independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) is the natural inhibitor of TF coagulant and signaling activities. Studies have shown that TFPI exhibits antiangiogenic and antimetastatic effects in vitro and in vivo. In animal models of experimental metastasis, both circulating and tumor cell-associated TFPI are shown to significantly reduce tumor cell-induced coagulation activation and lung metastasis. Heparins and heparin derivatives, which induce the release of TFPI from the vascular endothelium, also exhibit antitumor effects, and TFPI may contribute significantly to those effects. Indeed, a non-anticoagulant low-molecular-weight heparin with intact TFPI-releasing capacity has been shown to have significant antimetastatic effect in a similar experimental mouse model. The evidence supporting the dual inhibitory functions on TF-driven coagulation and signaling strengthen the rationale for considering TFPI as a potential anticancer agent. This article primarily summarizes the evidence for antiangiogenic and antimetastatic effects of TFPI and describes its potential mechanisms of action. The possible application of TFPI and other inhibitors of TF as potential anticancer agents is described, and information regarding potential antitumor properties of TFPI-2 (which has structural similarities to TFPI) is also included.
 ...
PMID:The role of tissue factor pathway inhibitor in tumor growth and metastasis. 1800 Jul 90

Matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 are known to influence tumor angiogenesis and progression. This work aimed to describe the levels of MMP-2 and TFPI-2 expression associated with tumor angiogenesis and early postoperative recurrence in patients with pancreatic carcinoma. Expression of MMP-2 and TFPI-2 in carcinoma tissues and paracarcinomatous tissues was assayed by immunostaining. Expression of vascular endothelial growth factor (VEGF) and CD34 in tumor tissues was also assayed by immunostaining. The correlations of MMP-2 and TFPI-2 with VEGF, microvessel density (MVD), and early postoperative recurrence were analyzed. The results showed that MMP-2 expression was significantly increased (P < 0.05) and TFPI-2 expression was significantly decreased (P < 0.001) in carcinoma tissues compared with paracarcinomatous tissues. MMP-2 expression was positively correlated with VEGF (r = 0.594, P < 0.001) and MVD (r = 0.432, P < 0.001) in carcinoma tissues. TFPI-2 expression was negatively correlated with VEGF (r = -0.654, P < 0.001) and MVD (r = -0.360, P < 0.001) in carcinoma tissues. Multivariate logistic regression analysis showed that up-regulated MMP-2 and down-regulated TFPI-2 were independent predictors of early postoperative recurrence of pancreatic carcinoma. Receiver operating characteristic curve analysis showed that the combination of MMP-2 and TFPI-2 was a reliable predictive model of early recurrence. We conclude that increased MMP-2 expression and reduced TFPI-2 expression are closely linked to angiogenesis and early postoperative recurrence of pancreatic carcinoma. Immunohistochemical assay of MMP-2 and TFPI-2 may be useful for predicting early relapse of pancreatic carcinoma after surgery.
...
PMID:Increased matrix metalloproteinase-2 expression and reduced tissue factor pathway inhibitor-2 expression correlate with angiogenesis and early postoperative recurrence of pancreatic carcinoma. 2680 87