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)

In this study we purposed an alternative method to study the angiogenic and invasive potential of neuroblastoma cell suspensions implanted on the chick embryo chorioallantoic membrane (CAM) surface. Neuroblastoma cells were seeded in Matrigel and thereafter the suspension was pipetted onto the CAM surface at day 8 of incubation inside a silicon ring previously loaded onto the CAM surface. Four days after implantation, the silicon ring was removed and the angiogenic and invasive response were studied morphologically at macroscopic and microscopic levels and by reverse transcriptase-polymerase chain reaction (RT-PCR) by using human and chicken primers for several angiogenic cytokines, namely vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), hypoxia inducible factor-2alpha (HIF-2alpha), and for an endogenous angiostatic molecule, namely endostatin. Results showed that: (1) Neuroblastoma cells induced an angiogenic response in the CAM assay comparable to that induced by FGF-2; (2) neuroblastoma cells are packed inside Matrigel or are recognizable in the CAM mesenchyme; (3) Angiogenic activity of neuroblastoma cells is associated to an high expression of the transcripts of human VEGF-A, FGF-2, ANG-1 and HIF-2alpha and to a low expression in the transcript of a human endostatin while in the control specimens there is no expression of both angiogenic and angiostatic molecules; and (4) the expression of the transcripts of the same chicken angiogenesis stimulators and inhibitor is unmodified in treated and control specimens. Overall, these data indicate that neuroblastoma cells growth on the chick CAM express characteristics of the human disease. This experimental model could be employed for further research on human tumor progression and anti-angiogenic molecules screening.
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PMID:An alternative in vivo system for testing angiogenic potential of human neuroblastoma cells. 1915 May 83

Neuroblastoma (NB) is one of the most common pediatric solid tumors originating from the neural crest lineage. Despite intensive treatment protocols including megatherapy with hematopoietic stem cell transplantation, the prognosis of NB patients remains poor. More effective therapeutics are required. High vascularity has been described as a feature of aggressive, widely disseminated NB. Our previous work demonstrated the overexpression of vascular endothelial growth factor (VEGF) in NB, and we showed that an anti-VEGF receptor (VEGFR-2) antibody could induce sustained NB tumor suppression and regression. Sunitinib is a kinase inhibitor targeting platelet-derived growth factor receptors and VEGFRs and, therefore, a promising antiangiogenic agent. In this study, we investigated the antitumor activity of sunitinib and its synergistic cytotoxicity with conventional (cyclophosphamide) and novel (rapamycin) therapies. Both NB cell lines and tumor-initiating cells from patient tumor samples were used in our in vitro and in vivo models for these drug testing. We show that sunitinib inhibits tumor cell proliferation and phosphorylation of VEGFRs. It also inhibits tumor growth, angiogenesis, and metastasis in tumor xenograft models. Low-dose sunitinib (20 mg/kg) demonstrates synergistic cytotoxicity with an mTOR inhibitor, rapamycin, which is more effective than the traditional chemotherapeutic drug, cyclophosphamide. These preclinical studies provide the evidence of antitumor activity of sunitinib both in the early stage of tumor formation and in the progressive metastatic disease. These studies also provide the framework for clinical trial of sunitinib, alone and in combination with conventional and novel therapies to increase efficacy and improve patient outcome in NB.
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PMID:In vivo antitumor and antimetastatic activity of sunitinib in preclinical neuroblastoma mouse model. 1941 27