Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is the leading cause of cancer death in the U.S. with survival restricted to a subset of those patients able to undergo surgical resection. However, even with surgery, recurrence rates range from 30% to 60%, depending on the pathologic stage. With the advent of partially effective, but potentially toxic adjuvant chemotherapy, it has become increasingly important to discover biomarkers that will identify those patients who have the highest likelihood of recurrence and who thus might benefit most from adjuvant chemotherapy. Hundreds of papers have appeared over the past several decades proposing a variety of molecular markers or proteins that may have prognostic significance in non-small cell lung cancer. This review analyzes the largest and most rigorous of these studies with the aim of compiling the most important prognostic markers in early stage non-small cell lung cancer. In this review, we focused on biomarkers primarily involved in one of three major pathways: cell cycle regulation, apoptosis, and angiogenesis. Although no single marker has yet been shown to be perfect in predicting patient outcome, a profile based on the best of these markers may prove useful in directing patient therapy. The markers with the strongest evidence as independent predictors of patient outcome include cyclin E, cyclin B1, p21, p27, p16, survivin, collagen XVIII, and vascular endothelial cell growth factor.
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PMID:Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. 1593 Mar 32

Lung cancer is the leading cause of cancer deaths in the USA. Despite the development of new chemotherapy regimens, the prognosis remains poor. Several studies comparing various platinum-based regimens failed to produce a significant impact in the outcomes for patients with non-small cell lung cancer and this therapeutic modality appears to be reaching a plateau. It has become clear that further advances will require the addition of agents with a different mechanism of action. Bevacizumab is the antiangiogenic agent at the most advanced stage of development in the treatment of cancer. Bevacizumab is synergistic with chemotherapy and usually well tolerated. The addition of bevacizumab to chemotherapy improved survival in patients with metastatic non-small cell lung cancer in a randomized clinical trial. Several small molecule antiangiogenic agents are in development. In this article, currently available data from clinical trials of antiangiogenic compounds in advanced non-small cell lung cancer are reviewed.
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PMID:Clinical trials of antiangiogenic therapy in non-small cell lung cancer: focus on bevacizumab and ZD6474. 1661 42

Endostatin (ED) is a carboxyl-terminal fragment of collagen XVIII with strong antiangiogenic activity. ED has been considered as a highly specific inhibitor of endothelial cell proliferation and migration through interaction with its receptor on the surface of endothelial cells. Recently, direct antitumor effects of ED in colon cancer cells and head and neck squamous cell carcinoma cells has been reported. However, its effect on lung cancer cells has not been clarified. The purpose of the present study was to determine the effect of ED on in vitro lung cancer cell function and to identify its receptor on lung cancer cells. We revealed that alpha5 integrin is capable of being a functional ED receptor among several integrins that are expressed on murine lung cancer (Lewis lung cancer [LLC]) cells. We further demonstrated that the ED-integrin interaction modulates various in vitro biological functions of LLC cells as we revealed that immobilized ED helps in LLC cell adhesion and migration in an integrin-dependent manner. Furthermore, ED inhibited LLC cell proliferation and induced apoptosis. Interestingly, ED did not demonstrate any antiproliferative activity against the other murine lung cancer cell line, KLN205, that lacks alpha5 integrin but binds to immobilized ED through the beta1 integrin. In addition, the binding of ED to alpha5 integrin on LLC cells induced phosphorylation of focal adhesion kinase. Taken together, these results suggest that the interaction between ED and alpha5 integrin may play an important role in lung cancer cell function.
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PMID:Signal transduction mediated by endostatin directly modulates cellular function of lung cancer cells in vitro. 1741 9

Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar in vitro and in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Endostar blocked microvessel sprouting from rat aortic rings in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar.
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PMID:Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. 1764 65

Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence forming another his-tag structure, was approved by the State Food and Drug Administration of China (SFDA) in 2005 for the treatment of non-small-cell lung cancer. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we examined the anti-invasive activities of endostar in vitro. The results showed that endostar suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a concentration-dependent manner. It could inhibit the wound healing migration of MDA-MB-435 cells and invasion of MDA-MB-435 cells through reconstituted ECM (matrigel). Zymography revealed that endostar decreased the secretion of MMP-2 and MMP-9. Endostar could also inhibit the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells. Additionally, endostar exerted an inhibitory effect on the phosphorylation of ERK1/2. Collectively, these data provided a molecular basis for the anti-invasive effects of endostar.
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PMID:Endostar suppresses invasion through downregulating the expression of matrix metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells. 1848 Apr 15

Angiogenesis plays an important role in the growth of solid tumors. To date, no information has been acquired on the effectiveness of gene therapy in the orthotopic lung cancer model of syngeneic immunocompetent mice treated with an angiogenesis inhibitor. Here, we report the establishment of such a model in which Lewis lung carcinoma (LL/2) cell suspensions were orthotopically inoculated into the lung parenchyma of C57BL/6 mice, which were also injected with a recombinant adenoviral vector delivering the human endostatin gene (Ad-hE). We found that orthotopic implantation of LL/2 cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by remote mediastinal lymph node metastasis. Conditioned medium from Ad-hE-transfected LL/2 cells apparently inhibited proliferation of human umbilical vein endothelial cells (HUVECs). The level of endostatin protein in serum could be identified by enzyme-linked immunosorbent assay. Treatment with Ad-hE resulted in inhibition of tumor growth and prolongation of survival time of tumor-bearing mice. Immunohistochemical analysis revealed that intratumoral angiogenesis was significantly suppressed. Furthermore, the finding of angiogenesis inhibition was also supported by measuring the number of circulating endothelial cells (CECs). Apoptotic cells were found to be increased within tumor tissues from mice treated with Ad-hE. In addition, treatment with Ad-hE combined with cis-diamminedichloroplatinum(II) (cisplatin) enhanced antitumor activity. These observations provide further evidence of the antitumor effect of endostatin gene therapy, and may be of importance for further exploration of potential application of this combined approach in the treatment of human lung cancer as well as other solid tumors.
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PMID:Gene therapy with the angiogenesis inhibitor endostatin in an orthotopic lung cancer murine model. 1893 2

The purpose of this work was to develop an effective delivery system for antiangiogenic therapy. Endostatin was microencapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by using a w/o/o multiple emulsification-evaporation technique. Endostatin microspheres showed the encapsulation efficiency 100% with mean particle size about 25 microm. Endostatin released in vitro from PLGA microspheres were biologically active and significantly inhibited the migration of endothelial cells. In rats, endostatin microspheres produced a sustained release process in which the steady-state concentration was reached from day 5 to day 27 with the steady-state levels of endostatin between 174.8+/-33.3 and 351.3+/-126.3 ng/ml. In Lewis lung cancer model, a dose of 10 mg/kg endostatin microspheres was just as effective in suppressing tumor growth as a dose of 2 mg/kg/day free endostatin for 35 days (total dose 70 mg/kg). These results indicated PLGA microspheres further reduced the amount of endostatin needed to achieve significant tumor inhibition in mice when compared with systemic administration.
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PMID:Sustained delivery of endostatin improves the efficacy of therapy in Lewis lung cancer model. 1908 38

Lung cancer is the leading cause of cancer-related mortality in the United States. Patients treated with adjuvant chemotherapy have a 5-year survival rate of 25% to 70% depending on stage, whereas those with advanced disease have a median survival of approximately 8 months when treated with standard platinum-based therapy. Improvements in our understanding of cancer biology have led to the development of novel agents that more precisely affect the target of interest, allowing for a more rational approach to clinical trial design. Angiogenesis, the growth of new vessels from preexisting vessels, is a fundamental step in tumor growth and progression. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is the most studied antiangiogenic agent in patients with non-small-cell lung cancer (NSCLC). There was an improvement in overall survival when bevacizumab was combined with paclitaxel and carboplatin in patients with advanced NSCLC that was not seen when bevacizumab was combined with cisplatin and gemcitabine. Studies with bevacizumab in the adjuvant and advanced setting are ongoing in patients with NSCLC. Small-molecule inhibitors targeting the VEGF receptor and the tyrosine kinase receptor have also shown promise when combined with standard chemotherapy, but their role in the treatment of patients with NSCLC remains to be determined. This article reviews clinical trials that have incorporated antiangiogenic agents in the treatment of patients with NSCLC.
Clin Lung Cancer 2009 Mar
PMID:Emerging data with antiangiogenic therapies in early and advanced non-small-cell lung cancer. 1936 48

The essential role of angiogenesis in tumor growth and metastasis is well established. The key mediator of angiogenesis, vascular endothelial growth factor (VEGF), is a rational target for novel therapy. High VEGF levels correlate positively with reduced overall survival (OS) and relapse-free survival. Several molecular targeted agents that inhibit VEGF or its receptors are currently in late-stage development or available for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody against VEGF that has proven efficacy when combined with different chemotherapy regimens. In the pivotal US phase III trial (E4599) combining bevacizumab with carboplatin/paclitaxel, significantly improved clinical outcomes were observed in terms of OS, progression-free survival (PFS), and response rate (RRs). Although the phase III AVAiL (Avastin in Lung Cancer) trial (BO17704) combining bevacizumab with cisplatin/gemcitabine also showed improved outcomes in terms of PFS and RR, OS data is immature. Bevacizumab is the first agent to improve clinical outcomes when combined with doublet chemotherapy and administered until disease progression. Herein, key clinical data from trials of antiangiogenic agents in the first-line treatment of NSCLC are discussed, with a focus on bevacizumab, currently the only approved antiangiogenic agent for the treatment of NSCLC. The optimal integration of these agents into current and future first-line treatment regimens will be discussed, stressing the importance of therapeutic administration until disease progression. The promising activity of antiangiogenic agents in the advanced disease setting, allied with growing understanding of their novel modes of action, holds therapeutic promise for their future application in early-stage disease.
Clin Lung Cancer 2008
PMID:New options for integrating antiangiogenic therapy and platinum-based first-line chemotherapy for advanced non-small-cell lung cancer. 1941 23

The hallmark radiological finding in metastatic brain disease is multiple enhancing lesions. We report a case of metastatic lung cancer to the brain with a lack of contrast enhancement. We believe that this unusual finding is due to inadvertent "treatment" of the metastases with the antiangiogenic agent bevacizumab (Avastin).
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PMID:Nonenhancing brain metastases. 1949 Apr 1


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