89 research outputs found
Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma
Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor β, and the late-stage maturity marker α smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this
Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905)
The place of VEGF inhibition in the current management of renal cell carcinoma
Vascular endothelial growth factor (VEGF) is overexpressed in around 80% of patients with clear cell carcinoma of the kidney owing to the inactivation of von Hippel Lindau gene activity. VEGF stimulates angiogenesis and acts as an autocrine growth factor. A number of different agents are now available which target VEGF and its signalling pathways. A significant body of evidence has accumulated demonstrating that antagonism of VEGF and its downstream pathways is clinically useful in a significant proportion of patients with metastatic clear cell carcinoma of the kidney. Enough data is now available to recommend that patients with metastatic clear cell carcinoma of the kidney should at some point during the course of their disease be offered entry into a clinical trial enabling exposure to a targeted inhibitor of VEGF or its signalling pathways. Assuming early clinical trial data is substantiated by ongoing registration studies, efforts should be made to minimise the time taken between licensing and general availability of these active agents
Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications
Genes for components of the chloroplast translational apparatus are conserved in the reduced 73-kb plastid DNA of the nonphotosynthetic euglenoid flagellate Astasia longa
Genes for ribosomal proteins are retained on the 73 kb DNA from Astasia longa that resembles Euglena chloroplast DNA
Under-expression of VHL and over-expression of HDAC-1, HIF-1?, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis
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