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Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis.

Stoeltzing O, Ahmad SA, Liu W, McCarty MF, Parikh AA, Fan F, Reinmuth N, Bucana CD, Ellis LM - Br. J. Cancer (2002)

Bottom Line: Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours.Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05).Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

ABSTRACT
Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3+/-0.5 ml (mean+/-s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

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Impact of Ang-1 expression on ascites formation in peritoneal carcinomatosis. Thirty days after tumour cell inoculation, ascites volumes were measured in each mouse. Seven of the nine mice in the pcDNA group developed detectable ascites, with a median ascites volume of 1.3 ml. In contrast, none of the 10 mice in the Ang-1 group developed ascites (P<0.01, Fisher's Exact test). Bars: median.
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fig2: Impact of Ang-1 expression on ascites formation in peritoneal carcinomatosis. Thirty days after tumour cell inoculation, ascites volumes were measured in each mouse. Seven of the nine mice in the pcDNA group developed detectable ascites, with a median ascites volume of 1.3 ml. In contrast, none of the 10 mice in the Ang-1 group developed ascites (P<0.01, Fisher's Exact test). Bars: median.

Mentions: The incidence of ascites formation was significantly higher in mice injected with pcDNA-transfected KM12L4 cells (7 out of 9, 78%) than in mice injected with Ang-1-overexpressing KM12L4 cells (0 out of 10) (P<0.01, Fisher's exact test). The ascites volumes in peritoneal metastases–bearing mice in the pcDNA group ranged from 0.3 ml to 5 ml, with a median ascites volume of 1.3 ml (haemorrhagic ascites in all cases). The median ascites volume was significantly higher in the pcDNA group (P<0.01) than in the Ang-1 group as none of the Ang-1 mice developed ascites even though three of them had peritoneal tumours (Figure 2Figure 2


Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis.

Stoeltzing O, Ahmad SA, Liu W, McCarty MF, Parikh AA, Fan F, Reinmuth N, Bucana CD, Ellis LM - Br. J. Cancer (2002)

Impact of Ang-1 expression on ascites formation in peritoneal carcinomatosis. Thirty days after tumour cell inoculation, ascites volumes were measured in each mouse. Seven of the nine mice in the pcDNA group developed detectable ascites, with a median ascites volume of 1.3 ml. In contrast, none of the 10 mice in the Ang-1 group developed ascites (P<0.01, Fisher's Exact test). Bars: median.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376191&req=5

fig2: Impact of Ang-1 expression on ascites formation in peritoneal carcinomatosis. Thirty days after tumour cell inoculation, ascites volumes were measured in each mouse. Seven of the nine mice in the pcDNA group developed detectable ascites, with a median ascites volume of 1.3 ml. In contrast, none of the 10 mice in the Ang-1 group developed ascites (P<0.01, Fisher's Exact test). Bars: median.
Mentions: The incidence of ascites formation was significantly higher in mice injected with pcDNA-transfected KM12L4 cells (7 out of 9, 78%) than in mice injected with Ang-1-overexpressing KM12L4 cells (0 out of 10) (P<0.01, Fisher's exact test). The ascites volumes in peritoneal metastases–bearing mice in the pcDNA group ranged from 0.3 ml to 5 ml, with a median ascites volume of 1.3 ml (haemorrhagic ascites in all cases). The median ascites volume was significantly higher in the pcDNA group (P<0.01) than in the Ang-1 group as none of the Ang-1 mice developed ascites even though three of them had peritoneal tumours (Figure 2Figure 2

Bottom Line: Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours.Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05).Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

ABSTRACT
Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3+/-0.5 ml (mean+/-s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

Show MeSH
Related in: MedlinePlus