Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells

Ling, Yun; Yang, Yong; Lu, Na; Qin, You; Wang, Sen; Gao, Ying; Chen, Yan; Guo, Qinglong

doi:10.1016/j.bbrc.2007.06.155

Cited by 223 publications

(199 citation statements)

References 27 publications

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“…The results revealed a downregulation of VEGF mRNA in the tumor cells obtained from the peritoneal cavity of the Endostar-treated mice. Certain studies have indicated that the effects of endostatin are associated with VEGF, a crucial regulator in angiogenesis (23,24). Previous data have revealed that Endostar may exert anti-angiogenic effects via a similar mechanism to endostatin.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 2015

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“…Results of univariate and multivariate proportional hazard analysis for predictors of overall survival time among the study population. Investigators have previously reported that endostatin exerts antiangiogenic effects by blocking vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells (21). Dong et al (22) and Brideau et al (23) found that endostatin inhibits lymphangiogenesis by downregulating the tumor expression of VEGF-C. By contrast, the osteopontin-related mechanism may be mediated in endostatin antitumor activity (24).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of serum and tumor tissue endostatin evaluation in operable non-small cell lung cancer

Zhang

et al. 2014

Biomedical Reports

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Abstract. Endostatin, as the most potential antiangiogenic factor, is a naturally occurring fragment of collagen XVIII in bloodstream capable of inhibiting tumor growth and metastasis. This study was conducted to explore the clinical value of endostatin in serum and tumor tissue in patients with operable non-small cell lung cancer (NSCLC). ELISA and immunohistochemistry were applied to detect the expression of endostatin in serum and tumor tissue in 105 patient-matched operable NSCLC patients. The serum level of endostatin was significantly higher in NSCLC patients than healthy individuals (P=0.0018). Cases with poorer differentiation showed a higher endostatin serum level (P=0.008). There was no significant correlation between tumor tissue expression and clinical parameters, such as TNM stage, differentiation degree, histological type and lymph node invasion status. A stronger expression of endostain in tumor tissue was associated with a higher serum level (r=0.223). The univariate and multivariate analyses with Cox proportional hazards model for overall survival showed that tumor stage and node status were independent prognostic factors, whereas neither endostatin levels in serum nor in tumor tissue showed potential in predicting the long-term survival of operable NSCLC patients. In conclusion, the results observed in the present study did not support the prediction of overall survival in operable NSCLC based on the expression levels of endostatin in serum and tumor tissue.

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“…Antiangiogenesis is a useful strategy for anticancer treatment, and it has been shown that the antiangiogenesis effect can inhibit the growth of tumors, increase the efficacy of chemotherapy and prolong the overall survival in several types of somatic tumors. endostar is a new recombinant human endostatin which is designed and manufactured in china, and its antiangiogenesis effect has been shown in preclinical studies (42)(43)(44). A phase III randomized clinical trial conducted in china compared vinorelbine (nVB) plus endostar vs. nVB alone patients with metastatic non-small cell lung cancer (45), and the results indicated that the addition of Endostar improved the efficacy of chemotherapy and significantly increased the time to progression and overall survival.…”

Section: Target Therapy For Patients With Metastatic Gastric Cancermentioning

confidence: 99%

Gastric carcinoma in China: Current status and future perspectives (Review)

Zhu

Li²

2010

Oncology Letters

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Abstract. gastric cancer is one of the most frequently occurring cancers in china, with an estimated 380,000 new cases each year, accounting for more than 40% of the worldwide annual cancer incidence. there is geographical clustering of the distribution of gastric cancer in china, with most of the high-risk areas being rural. D2 resection is the standard lymphadenectomy for curative resection in china, but more extensive lymphadenectomy is conducted for selected patients. Perioperative chemotherapy, postoperative chemotherapy or chemoradiotherapy can be combined with surgery. It remains uncertain which option is best, but if surgery is insufficient, adjuvant chemoradiotherapy is recommended. In the palliative setting, although there is no standard first-line chemotherapy, regimens based on taxane, oxaliplatin or capecitabine, or the epirubicin, cisplatin, 5-fluorouracil regimen and its modifications are the most common options selected by chinese oncologists. several studies to evaluate target therapy are ongoing, but it is too early to draw any conclusions. However, the development of target therapy is likely to become a milestone in the treatment of gastric cancer. Contents1. epidemiology of gastric carcinoma in china 2. Methods of staging gastric cancer 3. surgery for gastric cancer 4. Perioperative chemotherapy and new adjuvant therapy 5. Adjuvant chemotherapy or chemoradiotherapy after surgery 6. Palliative and salvage chemotherapy for metastatic patients 7. target therapy for patients with metastatic gastric cancer 8. Future treatment for metastatic gastric cancer

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Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells

Cited by 223 publications

References 27 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 significance of serum and tumor tissue endostatin evaluation in operable non-small cell lung cancer

Gastric carcinoma in China: Current status and future perspectives (Review)

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