Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human neuroblastoma (NB) is a highly heterogeneous childhood cancer secreting a high level of vascular endothelial growth factor (VEGF). Its vascularization has been clearly correlated with metastatic progression and poor outcome. Thus, molecules that target the vascular endothelium are regarded as new therapeutics of clinical interest. Angiostatin, an internal fragment of plasminogen containing the first four kringle structures, has been described as a powerful angiogenic inhibitor. We used a recombinant adenovirus encoding the human angiostatin kringle 1-3 directly fused to human serum albumin HSA (AdK3-HSA). Coupling to HSA has been previously shown to increase the in vivo half-life of this angiostatic factor, and to lead to tumor growth inhibition in the MDA-MB-231 carcinoma model. For the assessment of antiangiogenic gene therapy in the human NB IGR-N835 tumor model, 5 x 10(9) PFU of AdK3-HSA were intravenously injected in tumor-bearing athymic mice presenting either of the following experimental settings: early stage, established, and minimal residual tumors. No delay in tumor growth was observed in animals treated with AdK3-HSA as compared to those treated with the empty virus AdCO1. In early-stage tumors, kinetics of tumor occurrence and tumor growth were similar in AdK3-HSA- and AdCO1-treated animals. K3-HSA was found to be expressed at high levels (the mean value for the three experiments being 19.4+/-15.9 microg/ml) in the circulation of all animals up to 21-35 days after virus injection. In addition, IGR-N835 tumors were found to be highly vascularized and to release high amounts of angiogenic factors, in particular VEGF (665+/-370 pg/mg total protein). Thus, in spite of high circulating levels, K3-HSA may be unable to displace the NB proangiogenic switch. In this regard, a more promising target to inhibit NB angiogenesis seems to be the VEGF/VEGFR system.
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PMID:High level of stabilized angiostatin mediated by adenovirus delivery does not impair the growth of human neuroblastoma xenografts. 1460 72

We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF) receptors 1 and 2, CD31, CD146, and alpha(v)beta(3) integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL)-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.
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PMID:Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcoma xenograft model. 1514 Mar 99

Advanced glycation end-products (AGEs) inhibit ischemia-induced angiogenesis but are potential triggers of neoangiogenesis that occurs in peritoneal dialysis (PD) patients. We investigated whether the effect of glucose and AGEs on human peritoneal mesothelial cells (HPMCs) might alter the release of vascular endothelial growth factor (VEGF) and subsequently the formation of capillary tubes by human umbilical vein endothelial cells (HUVECs). HPMCs were exposed to glucose and the glycated protein Nvarepsilon-(carboxymethyl)lysine-human serum albumin (CML-HSA) and VEGF production was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Capillary tube formation by HUVECs in presence of HPMC supernatant or co-cultured with HPMC was investigated. AGE and VEGF levels in PD effluents from 11 patients were measured. CML-HSA stimulated VEGF production by HPMCs, P<0.001. Glucose and AGE inhibited capillary tube formation by HUVECs, P<0.001. HPMC supernatant potentiated capillary tube formation, P<0.001. In co-culture with HPMC capillary tube formation was increased, especially by HPMCs stimulated by CML-HSA, P<0.001. Anti-VEGF antibody limited this effect, P<0.001. Preincubation of HPMCs with anti-receptor for AGEs (RAGE) antibody reduced capillary tube formation, P<0.001. AGE and VEGF levels in PD effluents were increased during long dwell time, P<0.05 and P<0.001, respectively. In a co-culture system, we showed that VEGF production by HPMC favors capillary tube formation through mesothelial RAGE activation and could explain neoangiogenesis in PD patient.
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PMID:Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation. 1714 74

Kaposi sarcoma (KS) is associated with human herpesvirus (HHV)-8 and is dependent on the induction of vascular endothelial growth factors (VEGFs). VEGF regulates genes that provide arterial or venous identity to endothelial cells, such as the induction of EphrinB2, which phenotypically defines arterial endothelial cells and pericytes, and represses EphB4, which defines venous endothelial cells. We conducted a comprehensive analysis of the Eph receptor tyrosine kinases to determine which members are expressed and therefore contribute to KS pathogenesis. We demonstrated limited Eph/Ephrin expression; notably, the only ligand highly expressed is EphrinB2. We next studied the biologic effects of blocking EphrinB2 using the extracellular domain of EphB4 fused with human serum albumin (sEphB4-HSA). sEphB4-HSA inhibited migration and invasion of the KS cells in vitro in response to various growth factors. Finally, we determined the biologic effects of combining sEphB4-HSA and an antibody to VEGF. sEphB4-HSA was more active than the VEGF antibody, and combination of the 2 had at least additive activity. sEphB4-HSA reduced blood vessel density, pericyte recruitment, vessel perfusion, and increased hypoxia, with an associated increase in VEGF and DLL4 expression. The combination of sEphB4-HSA and VEGF antibody is a rational treatment combination for further investigation.
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PMID:The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade. 1883 96