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

Angiogenesis inhibition, which has been extensively studied for the treatment of various malignancies, is beginning to emerge as a new potential therapy for proliferative synovitis, particularly rheumatoid arthritis (RA). The rheumatoid pannus, the site of inflammation and joint destruction in the rheumatoid synovium, relies on the development of new vasculature to sustain its growth. A host of mediators have been shown to induce angiogenesis at the site of the inflamed synovium; these include vascular endothelial growth factor, fibroblast growth factor, integrin alpha(V)beta3, angiopoietin, prosta-glandin E1 and prostaglandin E2, and matrix metalloproteinases. In addition, hypoxia at the site of synovial inflammation contributes to angiogenesis stimulation. Several naturally-occurring inhibitors exist, such angiostatin and endostatin. There are a number of drugs undergoing study in the treatment of proliferative synovitis, which capitalise on the correlation between angiogenesis inhibition and the reduction of signs and symptoms of RA. Paclitaxel and an anti-integrin alpha(V)beta3 antibody, LM-609, are currently in clinical trials. Other drugs that may inhibit angiogenesis in RA include TNP-470 (formerly called AGM-1470), PPI-2458, PTK-787, bevacizumab and thalidomide. Many of these drugs have shown promise for the treatment of oncologic disorders, and are now being evaluated for the treatment of proliferative synovitis.
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PMID:New antiangiogenic strategies for the treatment of proliferative synovitis. 1570 17

Low-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and lower side effects, especially in combination with other antiangiogenic agents. This study aims to investigate whether LDM chemotherapy of paclitaxel could synergize with cetuximab, an antiangiogenic agent to suppress HT-29 human colon tumors in BALB/c nude mice. To explore its possible mechanism, the tumor vascular status was detected by staining with anti-CD31 Ab and the tumoral expression of thrombospondin-1 was examined by immunohistochemistry, western blot analysis, and real-time PCR. Our results showed that empirical metronomic paclitaxel regimens in combination with cetuximab induces significant and durable antitumor responses without overt toxicity. Paclitaxel LDM chemotherapy displayed stronger antiangiogenic activity than maximum tolerable dose (MTD) chemotherapy, whereas MTD chemotherapy induced more apoptotic cells. The combinational therapy with LDM and cetuximab showed the strongest antiangiogenic activity among all the groups. Paclitaxel LDM chemotherapy also dramatically upregulated the expression of thrombospondin-1, but MTD chemotherapy did not. These results suggest that the combination of paclitaxel LDM chemotherapy and cetuximab represents a potent strategy to combat colon cancers.
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PMID:Low-dose metronomic chemotherapy of paclitaxel synergizes with cetuximab to suppress human colon cancer xenografts. 1931 12

Several phase III trials have shown that the addition of an antiangiogenic agent to conventional chemotherapy can improve clinical benefit in patients with advanced solid tumors. This study examined the feasibility of combining pazopanib (Votrient), an oral antiangiogenic agent, with paclitaxel and carboplatin. This 3 + 3 dose-escalation phase I study evaluated the maximum-tolerated regimen (MTR) of daily pazopanib in combination with paclitaxel 175 mg/m(2) and carboplatin [dosed at area under the curve (AUC) 5 or 6] given every 21 days in patients with advanced solid tumors. Plasma samples were collected to evaluate the effect of pazopanib on the pharmacokinetics of paclitaxel and carboplatin. Thirty-four patients were enrolled. The MTR was paclitaxel 175 mg/m(2) and carboplatin AUC5 with pazopanib 200 mg. The most common dose-limiting toxicities were neutropenia and thrombocytopenia. Two patients with esophageal cancer had a complete response and four patients, one each with breast, small-cell lung, pancreatic, and gastroesophageal junction cancer, had partial responses. Pazopanib at 200 mg increased paclitaxel maximal concentration (C(max)) by 43% and carboplatin (AUC5 or AUC6) C(max) by 54%. Paclitaxel and carboplatin given every 21 days at standard doses was not feasible in combination with the monotherapy pazopanib dose of 800 mg daily because of dose-limiting myelosuppression. Coadministration of pazopanib increased exposure to paclitaxel and carboplatin and likely contributed to this effect. Given the antitumor activity of this regimen, further studies are underway to determine a clinically tolerable schedule of pazopanib with paclitaxel and carboplatin.
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PMID:Phase I study of pazopanib in combination with paclitaxel and carboplatin given every 21 days in patients with advanced solid tumors. 2267 11