Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid

Senger, Donald R.; Galli, Stephen J.; Dvorak, Ann M.; Perruzzi, Carole; Harvey, V S; Dvorak, Harold F.

doi:10.1126/science.6823562

Cited by 3,505 publications

(2,158 citation statements)

References 7 publications

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“…CEP03 significantly increased EC proliferation by 27±19% in normoxic condition and by 27±18% in hypoxic conditions ( P <0.05). These relative increases were comparable to those caused by VEGFA22, 23, 24 (32±19% and 22±10% under normoxic and hypoxic conditions, respectively; P <0.05; Figure 3). In addition, the enhancement in proliferation was not observed when CEP03 was incubated with fibroblast under the same conditions (Figure 4).…”

Section: Resultssupporting

confidence: 61%

Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease

Hou

Yang

Tang

et al. 2018

JAHA

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BackgroundCEP (ω‐[2‐carboxyethyl]pyrrole) protein adducts are the end products of lipid oxidation associated with inflammation and have been implicated in the induction of angiogenesis in pathological conditions such as tissue ischemia. We synthesized small molecules derived from CEP protein adducts and evaluated the angiogenic effect of the CEP analog CEP03 in the setting of peripheral arterial disease.Methods and ResultsThe angiogenic effect of CEP03 was assessed by in vitro analysis of primary human microvascular endothelial cell proliferation and tubelike formation in Matrigel (Corning). In the presence of CEP03, proliferation of endothelial cells in vitro increased by 27±18% under hypoxic (1% O2) conditions, reaching similar levels to that of VEGFA (vascular endothelial growth factor A) stimulation (22±10%), relative to the vehicle control treatment. A similar effect of CEP03 was demonstrated in the increased number of tubelike branches in Matrigel, reaching >70% induction in hypoxia, compared with the vehicle control. The therapeutic potential of CEP03 was further evaluated in a mouse model of peripheral arterial disease by quantification of blood perfusion recovery and capillary density. In the ischemic hind limb, treatment of CEP03 encapsulated within Matrigel significantly enhanced blood perfusion by 2‐fold after 14 days compared with those treated with Matrigel alone. Moreover, these results concurred with histological finding that treatment of CEP03 in Matrigel resulted in a significant increase in microvessel density compared with Matrigel alone.ConclusionsOur data suggest that CEP03 has a profound positive effect on angiogenesis and neovessel formation and thus has therapeutic potential for treatment of peripheral arterial disease.

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Section: Resultssupporting

confidence: 61%

Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease

Hou

Yang

Tang

et al. 2018

JAHA

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“…3 Increased local expression of vascular endothelial growth factor (VEGF) has drawn much attention relating to the pathogenesis of diabetic retinopathy. Evidences suggest that VEGF, a cytokine that acts as an endothelial cell mitogen, 4,5 and induces increased microvascular permeability, 6 is causally involved in the development of diabetic retinopathy. 7,8 Although intraocular levels of VEGF have been studied extensively, systemic vasculogenic factors have not been fully evaluated in previous studies.…”

Section: Introductionmentioning

confidence: 99%

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Lee

Chae

Kim

2005

Eye

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“…While a variety of growth factors exhibit angiogenic activity, there is strong evidence for a pivotal role of VEGF in tumour angiogenesis. Vascular endothelial growth factor (VEGF), which is also known as vascular permeability factor (VPF), stimulates angiogenesis by increasing vascular permeability (Senger et al, 1983) and by acting as an endothelial cell mitogen (Ferrara and Heinzel, 1989). VEGF is a dimeric glycoprotein with four spliced variants consisting of 121, 165, 189 and 206 amino acid residues expressing almost identical biological activities by binding to specific class III receptor tyrosine kinases (flt-l and KDR) (Neufeld et al, 1996;Terman and Dougher-Vermazen, 1996).…”

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confidence: 99%

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

Obermair

Tempfer²,

Hefler³

et al. 1998

Br J Cancer

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Summary As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml-', VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.

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Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid

Cited by 3,505 publications

References 7 publications

Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease

Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

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