High Level of Vascular Endothelial Growth Factor in Hemorrhagic Pleural Effusion of Cancer

Ishimoto, Osamu; Saijo, Yasuo; Narumi, Kunihiro; Kimura, Yuichiro; Ebina, Masahito; Matsubara, N.; Asou, Noboru; Nakai, Yushi; Nukiwa, Toshihiro

doi:10.1159/000065723

Cited by 48 publications

(44 citation statements)

References 14 publications

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“…In addition a VEGF blockade has been identified to lead to marked reductions in ascites formation (1,5,8,19). Cancer-associated effusions contain significantly more VEGF than those resulting from inflammatory diseases, which suggests that VEGF levels are an independent and statistically significant prognostic indicator of survival (20,21). The results of a previous study revealed that hemorrhagic malignant effusions (RBC count, >1x10 4 /µl) exhibit significantly higher VEGF levels (1,942 pg/ml) compared with non-hemorrhagic effusions (202 pg/ml) (P= 0.016) in malignant patients (21).…”

Section: Discussionmentioning

confidence: 95%

“…VEGF has an important role in increasing vascular permeability during malignant ascites formation (1)(2)(3)(4)(5). Previous studies have revealed that high concentrations of VEGF are detected in the hydrothorax and ascites fluid of cancer patients (20)(21)(22). The vascular permeabilizing activity of VEGF has been reported to be 50,000 times more potent than histamine.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer-associated effusions contain significantly more VEGF than those resulting from inflammatory diseases, which suggests that VEGF levels are an independent and statistically significant prognostic indicator of survival (20,21). The results of a previous study revealed that hemorrhagic malignant effusions (RBC count, >1x10 4 /µl) exhibit significantly higher VEGF levels (1,942 pg/ml) compared with non-hemorrhagic effusions (202 pg/ml) (P= 0.016) in malignant patients (21). In addition, malignant patients with large volumes of effusion (>1 liter) demonstrate higher concentrations of VEGF in the (21).…”

Section: Discussionmentioning

confidence: 99%

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Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

et al. 2015

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Abstract. Endostar, a modified recombinant human endostatin, inhibits the growth of a variety of tumors by suppressing neovascularization. Vascular endothelial growth factor (VEGF) has an important role in malignant ascites formation. In order to determine whether Endostar can suppress the formation of ascites and prolong survival times, mouse models of malignant ascites were established using S180 and H22 tumor cells. The experimental mice were randomly divided into four groups: The three treatment groups received different doses of Endostar (4, 8 and 16 mg/kg), and the control group received 0.9% w/v NaCl. The volume of ascites, and the tumor cell, red blood cell (RBC), VEGF protein and mRNA content of the ascites was measured alongside the peritoneal permeability and the mouse survival time. In vitro analysis of cultured Endostar-treated S180 and H22 cells was also performed in order to examine cellular proliferation and the level of VEGF secreted protein and mRNA. The results revealed that Endostar suppressed the ascites volume, decreased the level of tumor cells, RBCs and VEGF in the ascites fluid, and lowered the permeability of the peritoneum. The tumor cells collected from the ascites in the Endostar-treated mice demonstrated a decrease in the expression of VEGF mRNA. The survival rates of the 8 and 16 mg/ kg Endostar-treated mice were longer than those of the controls. The in vitro experiments revealed a significant inhibition of VEGF protein secretion and VEGF mRNA by Endostar, but no effect on cellular proliferation. In conclusion, Endostar lowers ascites production by downregulating VEGF expression, and may therefore be effective for the treatment of malignant ascites. IntroductionMalignant ascites is caused by the accumulation of fluid in the peritoneal cavity following the intraperitoneal (i.p.) spread of tumor cells. Ascites can occur in a variety of cancers, including ovarian (37%), pancreaticobiliary (21%), gastric (18%), esophageal (4%), colorectal (4%) and breast (3%) cancer (1-3). Ascites may result in a poor quality of life due to symptoms of abdominal distention, pain, nausea, vomiting, anorexia, dyspnea, limb edema, insomnia and fatigue (1-3).Chemotherapy is a common first-line treatment for patients with ascites. However, limited evidence exists concerning its efficacy in patients with recurrent ascites. The i.p. administration of radioisotopes, or chemotherapy and peritoneovenous shunting procedures, has also been used (3,4). However, data regarding these approaches is also lacking. These methods are able to relieve the symptoms of recurrent ascites, but do not prolong survival (4). Repeated paracentesis is associated with regular hospital admissions and can lead to a number of problems, including pain, protein loss, hypovolemia, infection, peritonitis and bowel perforation (3,4). The preclinical and clinical evidence concerning anti-angiogenic agents, such as vascular endothelial growth factor (VEGF) antagonists and matrix metalloproteinase inhibitors, suggest that these agents may have...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

et al. 2015

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“…As mentioned above, VEGF is a multifunctional cytokine with critical roles in vasculogenesis and in both pathological and physiological angiogenesis and lymphangiogenesis [19]. Excluding malignancy, some other pathological conditions, such as hypoxia, pulmonary embolism, hemorrhagic effusions and empyema, could also lead to or present with heightened levels of VEGF [15,16,20]. VEGF also has a central role in wound healing and inflammation [11].…”

Section: Discussionmentioning

confidence: 99%

Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions

2007

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“…Angiogenesis is regulated by a number of angiogenic and antiangiogenic cytokines.Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis and vascular permeability.It stimulates capillary formation and has specific mitogenic and chemotactic effects on vascular endothelial cells (Zebrowski et al, 1999). VEGF contributes to the formation of MPE because of their involvement in the induction of neovascularization, in vascular permeability, and in hemorrhage (Ishimoto et al, 2002). Endostatin is one of the better-characterised endogenously produced angiogenesis inhibitors, it can activate tyrosine kinase and induce endothelial cells to form various signaling complexes, thereby inducing tumor vascular endothelial cell into the process of apoptosis and inhibiting microvascular generation (O'Reilly et al, 1997;Skovseth et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Yu¹,

Lu²,

Xia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro-and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro-and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

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High Level of Vascular Endothelial Growth Factor in Hemorrhagic Pleural Effusion of Cancer

Cited by 48 publications

References 14 publications

Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

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