The inhibition of Endostar on the angiogenesis and growth of gastrointestinal stromal tumor xenograft

Wang, Tianbao; Wei, Xiuqing; Lin, Wen‐Cheng; Hanping, Shi; Dong, Wenfeng

doi:10.1007/s10238-011-0143-8

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…As a functional angiogenesis inhibitor, Endostar is at least twice as efficient as endostatin in animal tumor models 20) . It also reduces inoculated tumor growth in mice by substantially inhibiting angiogenesis 21) . In the recent pilot clinical trial, Endostar, combined with chemotherapy, was well tolerated in patients with metastatic colorectal and gastric cancers 22) .…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model

Xu¹,

Mao²,

Chai

et al. 2015

J Atheroscler Thromb

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Aim:Vasa vasorum neovascularization is a key feature of atherosclerosis (AS) and is strongly associated with inflammatory infiltration, lipid deposition, intraplaque hemorrhage, and hemosiderin deposit. Here we investigate the effects of Endostar, a strong anti-angiogenic drug, on vasa vasorum neovascularization in the experimental porcine model of early AS. Methods: Eighteen adult male Ba-Ma mini pigs were randomized into three groups, with six animals in each group. The pigs in the normal (N) group were fed a normal diet for 18 weeks, without balloon injury surgery. The animals in the atherosclerotic (AS) control and AS Endostar groups were fed a hypercholesterolemic diet for 12 weeks after balloon injury surgery; they received either saline or Endostar for an additional six weeks, while continuing the hypercholesterolemic diet. The atherosclerotic abdominal aorta and levels of serum lipids, TNF-alpha, IL-6, and hs-CRP were analyzed at 18 weeks. Results: The AS group had a significantly higher body weight and serum lipid concentration levels than the N group (p 0.05), confirming the success of the hypercholesterolemic diet. However, no statistical differences were noted between the AS and AS Endostar groups. Histopathology results revealed that vasa vasorum density and intima -media thickness (IMT) had also increased in the AS group compared with those in the N group (p 0.05). The Endostar treatment significantly alleviated AS with decreased vasa vasorum density and IMT (AS vs. AS Endostar, p 0.05). Western blot analysis indicated that the expression of VEGF, -catenin, and TNF-alpha in the atherosclerotic abdominal aorta was considerably reduced by the Endostar treatment. In addition, immunohistochemistry results showed that the angiogenesis markers VEGF and -catenin were predominately localized in endothelial cells of the adventitial vasa vasorum. The levels of the serum inflammatory markers TNF-alpha, hs-CRP, and IL-6 were markedly higher in the AS group than in the N group (p 0.05) but showed no marked difference during the Endostar treatment, suggesting that the local inhibition of angiogenesis was not accompanied by a change in serum inflammatory markers and that the inhibitive effect of Endostar on local TNF-alpha expression could be because of the prevention of vasa vasorum neovascularization. Conclusions: Our results demonstrated that the Endostar treatment inhibited vasa vasorum neovascularization and AS progression in the experimental porcine model of early AS, supporting the role of vasa vasorum neovascularization in the development of AS and the therapeutic potential of antiangiogenesis intervention in AS.

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Section: Introductionmentioning

confidence: 99%

Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model

Xu¹,

Mao²,

Chai

et al. 2015

J Atheroscler Thromb

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“…Nevertheless, other mechanisms can also contribute to the combination effect. For example, Endostar may very well contribute to the synergism via anti‐angiogenesis .…”

Section: Discussionmentioning

confidence: 99%

“…To further increase the antitumour activity of Fv-LDP, we explored a new strategy for cancer therapy by combining Fv-LDP and Endostar, which was not related to the cytotoxicity of AE (the active moiety of LDM). Endostar is a known modified recombinant human endostatin and has been approved for clinical use in China [26]. Endostar can also At day 0, 1.5 9 10 6 murine hepatoma 22 cells ascites-passaged were directly transplanted subcutaneously into the right axilla of mice.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, other mechanisms can also contribute to the combination effect. For example, Endostar may very well contribute to the synergism via anti-angiogenesis [26,30]. For the first time, the current study evaluated the antitumour activity of a scFv-based engineered fusion protein, Fv-LDP, that increased the selectivity of LDP via the integration of scFv directed against gelatinases.…”

Section: Discussionmentioning

confidence: 99%

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A Gelatinases‐targeting scFv‐based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma

Gao

Shang

et al. 2015

Basic Clin Pharma Tox

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Gelatinases play important roles in tumour invasion and metastasis and are thus considered promising targets for cancer therapy. In this study, a new single-chain variable fragment (scFv)-based fusion protein Fv-LDP, composed of the anti-gelatinases scFv and lidamycin apoprotein (LDP), was prepared, and its combination with angiogenesis inhibitor Endostar was then investigated. The fusion protein Fv-LDP specifically bound to various tumour cells, and its binding capability to human pulmonary giant cell carcinoma (PG) cells was higher than that of LDP. Fv-LDP inhibited the expression and secretion of gelatinases and could be internalized into tumour cells via endocytosis. Fv-LDP also suppressed the growth of human hepatoma cells and murine hepatoma 22 transplanted in Kunming mice in various degrees. In addition, Endostar could enhance the synergistic or additive inhibition of Fv-LDP on the growth, migration or invasion of human hepatoma cells shown by a colony formation assay and a transwell-based migration or invasion assay, respectively. In vivo, Fv-LDP/Endostar combination showed a significantly synergistic effect on the growth of a human hepatoma xenograft, with an inhibition rate of 80.8% compared with the Fv-LDP (44.1%) or Endostar (8.9%)-treated group. The above-mentioned results indicate that the fusion protein Fv-LDP is effective against transplantable hepatoma in mice and human hepatoma xenografts in athymic mice. Moreover, Endostar can potentiate the inhibition effect of Fv-LDP on the growth of human hepatoma cells and xenografts. These data will provide a new combined strategy for improving the therapeutic efficacy of treatments for hepatoma or other gelatinase-overexpressing tumours.

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“…In the ES group, the majority of lesions subsided, but the fading time was slower than that of the control group. In the DVP graph for the regression of tumour lesions, the extinction process curve was not uniform, which indicated that the microvessel density within the lesions differed (15). In the RT and ES + RT groups, contrast enhancement as a slow in/slow out change was observed, indicating vascular damage and suppression following radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Contrast-enhanced ultrasound analysis of tissue perfusion in tumor-bearing mice following treatment with endostatin combined with radiotherapy

Yang

Tao

2014

Experimental and Therapeutic Medicine

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The aim of this study was to observe the effects of Endostar (recombinant human endostatin) and radiotherapy, singly or in combination, on blood flow in mouse tumour tissue using ultrasound imaging. The ultrasound contrast agent, SonoVue, was used for the contrast-enhanced ultrasound examinations. SonoLiver software was used to analyse dynamic vascular patterns (DVPs) in the contrast process. Blood perfusion data were collected and statistical analysis was performed for data processing. Results were presented as DVP curves and quantitative parameters. Quantitative parameters showed statistically significant (P<0.05) differences in peak strength, rise time, time to peak and mean transit time among the various treatment groups. Changes in tumour blood perfusion were quantified by the assessment of contrast-enhanced ultrasound parameters. The results indirectly reflected the degree of change in angiogenesis in the tumour following experimental intervention. Ultrasound contrast imaging effectively showed the extent of the changes in vascularity and flow state. Therefore, contrast-enhanced ultrasound is suitable for use as an indicator of blood flow changes in an experimental model.

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The inhibition of Endostar on the angiogenesis and growth of gastrointestinal stromal tumor xenograft

Cited by 5 publications

References 35 publications

Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model

Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model

A Gelatinases‐targeting scFv‐based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma

Contrast-enhanced ultrasound analysis of tissue perfusion in tumor-bearing mice following treatment with endostatin combined with radiotherapy

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