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)

The relationship between non-small cell lung cancer and platelet counts, serum levels of vascular endothelial growth factor (VEGF) and endostatin, is unclear. Platelet counts and serum VEGF and endostatin levels were measured preoperatively in 99 patients with non-small cell lung cancer, and the relationship between these factors and clinicopathological features, including prognosis, was examined. Mean serum VEGF level was slightly higher in patients than in healthy subjects (P=0.23). Mean serum endostatin level was 42.4+/-40.4 ng/ml in patients compared to 16.3+/-10.3 ng/ml in healthy subjects (P=0.0003). Serum endostatin levels were significantly higher in patients with involvement greater than T2 or stage IB, compared to other patients. Platelet count and serum endostatin level greater than the median were associated with poor prognosis. Our results suggested that platelet count and serum endostatin level may be useful markers for non-small cell lung cancer.
Lung Cancer 2002 Jan
PMID:Serum endostatin correlates with progression and prognosis of non-small cell lung cancer. 1175 Jul 10

The use of tumor angiogenesis as a therapeutic target is based on extensive literature showing the dependence of tumors on the process of angiogenesis for growth, invasion, and metastasis. Seminal work performed by Folkman three decades ago determined that tumors beyond the size of approximately 2 mm require angiogenesis for subsequent growth and development. This basic hypothesis stimulated research in the field of angiogenesis and has resulted in the identification of factors that both enhance and inhibit this "angiogenic switch." The intent of this article is to present data on several angiogenesis inhibitors that are currently undergoing clinical evaluation in cancer patients. These agents may be particularly useful in the treatment of lung cancer, both as adjunctive therapy in early-stage or locally advanced disease, as well as in combination strategies with platinum-based therapy in metastatic disease. Although angiogenesis inhibitors have been in clinical trials for the past decade, there has been a shift in recent years towards the development of more mechanism-based and receptor-targeted agents. Interestingly, no antiangiogenic agent has been approved as such for use in cancer, perhaps because of the challenges involved in the clinical development of these novel agents. These include the potential requirement for long-term administration, difficulties in deriving biologically efficacious doses in early clinical trials, and the inability to use tumor regression as a primary endpoint in phase II trials.
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PMID:Angiogenesis inhibitors in clinical development for lung cancer. 1189 16

We previously reported a novel in situ observation model for microcirculation of lung metastasis from subcutaneously implanted Lewis lung cancer into mouse. Using this model, we studied the correlation of blood flow and the size of lung metastasis. It was revealed that metastatic growth and its angiogenesis are suppressed by circulating angiogenesis inhibitors, such as angiostatin or endostatin, released from primary tumor. When we removed the primary tumor, the metastasized lung cancer significantly grew faster and larger. But the blood flow per area did not increase either inside or outside of the metastatic tumor. This suggests that the growth of metastatic tumor is directly regulated not by blood flow increase but by the other effects of the circulating factors.
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PMID:Blood flow does not correlate with the size of metastasis in our new intravital observation model of Lewis lung cancer. 1207 28

Thalidomide, an angiogenesis inhibitor is currently used in clinical trials in the US and Europe in combination with chemotherapy for the treatment of various solid tumors. The prognosis of patients suffering from small-cell lung cancer (SCLC) is poor. A 73-year-old female with extensive disease of SCLC was given six courses of chemotherapy with adriamycine, cyclophasphamide and oncovine, which led to complete remission of the disease. Following written informed consent, the patient has been treated with thalidomide 200 mg orally on a daily basis for 2 years and 5 months. There has been no sign of tumor recurrence during the follow-up. This case underlines the possible role of additional treatment with angiogenesis inhibitors in combination with traditional chemotherapy in the therapy of SCLC. Although there is no proof that thalidomide contributed to this good outcome and no conclusions can be drawn from this treatment in a single patient, further studies may determine the role of thalidomide as an adjuvant antiangiogenic agent in the therapy of SCLC.
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PMID:Long-term survival of a patient with small-cell lung cancer (SCLC) following treatment with thalidomide and combination chemotherapy. 1254 55

It has now been almost 30 years since Dr J. Folkman first proposed that inhibition of angiogenesis could play a key role in treating cancer; however, it is only recently that anti-angiogenesis agents have entered the clinical setting. The search for novel therapies is particularly important in lung cancer, where the majority of patients succumb to their disease despite aggressive treatments. Several classes of agents now exist that target the different steps involved in angiogenesis. These include drugs inhibiting matrix breakdown, the matrix metalloproteinase inhibitors (MMPIs), such as marimastat, prinomastat, BMS275291, BAY12-9566, and neovastat drugs that block endothelial cell signaling via vascular endothelial growth factor (VEGF) and its receptor (VEGFR) including rhuMAb VEGF, SU5416, SU6668, ZD6474, CP-547,632 and ZD4190. Drugs that are similar to endogenous inhibitors of angiogenesis including endostatin, angiostatin and interferons. There has also been renewed interest in thalidomide. Drugs such as squalamine, celecoxib, ZD6126, TNP-470 and those targeting the integrins are also being evaluated in lung cancer. Despite early enthusiasm for many of these agents, Phase III trials have not yet demonstrated significant increases in overall survival and toxicity remains an issue. It is hoped that as our understanding of the complex process of angiogenesis increases, so will our ability to design more effective targeted therapies.
Lung Cancer 2003 Dec
PMID:Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. 1461 19

Patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis and high mortality. The therapeutic improvement caused by the new generation of cytotoxic agents seems to have reached a plateau. The main categories of targeted therapeutics applicable for NSCLC include receptor-targeted therapy, signal transduction or cell-cycle inhibition, angiogenesis inhibitors, gene therapy, and vaccines. Several major classes of agents directed at specific cellular mechanisms exist for the treatment of NSCLC. The anti-epidermal growth factor receptor (EGFR) group contains trastuzumab and IMC-C225, monoclonal antibodies against EGFRs that are overexpressed in many cancers. OSI-774 and ZD1839 are inhibitors of EGFR tyrosine kinase, a key enzyme of the signaling pathway. Farnesyl transferase inhibitors, such as SCH66336, and protein kinase C inhibitors, such as ISIS 3521, have also shown antitumor activity. Antiangiogenesis agents that have shown promise include TNP-470, recombinant endostatin, and angiostatin. Antibodies to vascular endothelial growth factor (VEGF) also seem to control tumor progression and may prolong survival. LY317615, an inhibitor of protein kinase Cb, augmented the tumor growth delay produced by cytotoxic drugs. All of these agents are in different phases of clinical testing and have shown encouraging activity as single agents or in combination with chemotherapy drugs. These new agents are more target specific, less toxic, easier to administer, and may lead to enhanced safety and survival for patients with advanced NSCLC.
Clin Lung Cancer 2002 Mar
PMID:Targeted therapy using novel agents in the treatment of non-small-cell lung cancer. 1472 Mar 53

Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Although serum levels of endostatin have extensively been studied in patients with malignant diseases, endostatin in pleural effusion has not been fully evaluated. In order to determine whether endostatin is present in pleural effusion, and to determine whether endostatin levels vary in pleural effusion of different etiology, we measured levels of endostatin in 38 malignant pleural effusion due to lung cancer patients and 29 patients with non-malignant disease using an ELISA kit. Free form of endostatin was measurable (> 11.2 pg/ml) in 26 of 38 malignant and 13 of 29 non-malignant pleural effusion. Endostatin levels in the 38 malignant pleural effusion were significantly higher than those in patients with the 29 patients with non-malignant diseases ( p = 0.0131). However, there was not statistically significant difference between the patients with pleuropneumonia and those with tuberculous pleurisy ( p = 0.2194). In malignant pleural effusion due to lung cancer, the pleural effusion endostatin levels did not differ when the histological types of lung cancer were considered ( p = 0.0674). Endostatin was present in both malignant and non-malignant pleural effusion, and elevated levels of endostatin were observed in malignant pleural effusion. Although the mechanisms are unclear, elevated levels of endostatin in pleural effusion may represent the local productions of endostatin in pleural space.
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PMID:Endostatin levels in exudative pleural effusions. 1474 37

Targeting cells that support tumor growth by administering potent angiogenesis inhibitors is currently an area of intense interest. In the present study, a unique plasmid vector for the mouse endostatin gene, pXLG-mEndo, was constructed and evaluated with and without radiation using the Lewis lung carcinoma (LLC) cell line. The physical properties of the expressed endostatin protein were validated by PCR, gel electrophoresis, and Western blot. Enzyme-linked immunosorbent and immunocytochemical analyses for the therapeutic gene demonstrated that transfected LLC cells secreted the protein into the medium. Exposure of the cells to 2 gray (Gy) gamma-rays reduced the time to reach the maximum expression level of the endostatin gene and also increased the amount of secreted endostatin protein (P<0.001). Biological activity of the endostatin was demonstrated by the inhibition of tube formation by human umbilical vein endothelial cells (HUVEC). Based on (3)H-thymidine incorporation, endostatin expression significantly depressed DNA synthesis in HUVEC and LLC cells compared to controls transfected with parental vector or no vector (P<0.005). In addition, radiation increased the efficiency of endostatin-mediated inhibition of both cell types over a 3-day period post-exposure (P<0.05 or less). Intratumoral injection of 100 small mu g pXLG-mEndo combined with 10 Gy radiation significantly delayed LLC tumor growth, especially when each modality was delivered twice (P<0.05 or less compared to all other groups). No toxicity was observed. These findings are very promising and suggest that endostatin therapy with a plasmid vector, such as pXLG-mEndo, may enhance the efficacy of radiotherapy for lung cancer.
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PMID:Radiation-enhanced endostatin gene expression and effects of combination treatment. 1577 88

Endostatin is an important endogenous inhibitor of neovascularization, which has been widely used in anti-angiogenesis therapy for cancer. To fully explore the potential of endostatin, we evaluated the anti-tumor efficacy of the combination of recombinant human endostatin adenovirus and low-dose gemcitabine in nude mice. We injected recombinant human endostatin adenovirus intratumorally plus a low dose of gemcitabine i.p. routinely. The combination treatment produced no side-effects, and resulted in marked suppression in tumor formation and growth of established human lung carcinoma xenografts in nude mice, with decreased microvessel density and increased apoptosis percentage. Our data support the idea of synergistic anti-tumor properties of endostatin plus low-dose chemotherapy against human lung cancer in vivo.
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PMID:Synergistic anti-tumor effect of recombinant human endostatin adenovirus combined with gemcitabine. 1584 21

Endostatin (ED) is a carboxyl-terminal fragment of type XVIII collagen with a strong anti-angiogenic activity. The purpose of this study is to determine the effect of ED gene transfer into lung cancer cells on in vivo tumor growth in a murine model. The murine lung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ED gene to express and secrete ED. After clones were selected to secrete ED, several stable transfectants with ED gene (LLC/ED) and control transfectants (LLC/Mock) were established. In vitro proliferation of these transfectants demonstrated similar growth speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LCC/ED transfectants was significantly greater than that of LLC/Mock transfectants. Immunohistochemical staining analysis demonstrated that ED gene transfer induced angiogenesis, suggesting coinduction of another gene implicated for neovascularization. As expected, LLC/ED transfectants secreted not only ED but also vascular endothelial growth factor (VEGF) to a much greater degree than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ED cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to a much greater degree than those of LLC/Mock cells. These results indicate that ED gene transfer in murine lung carcinoma cells induces VEGF secretion, resulting in enhancement of in vivo tumorigenecity in the murine model. More attention should be paid for ED gene therapy into lung cancer cells since it may influence other proteins secretion, which upregulates angiogenesis.
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PMID:Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity. 1587 83


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