Giornale italiano di nefrologia, 2008-05, Vol.25 (3), p.297-305
2008
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Details
- Autor(en) / Beteiligte
- Titel
- The role of angiogenesis in renal carcinoma
- Ist Teil von
- Giornale italiano di nefrologia, 2008-05, Vol.25 (3), p.297-305
- Ort / Verlag
- Italy
- Erscheinungsjahr
- 2008
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Renal cell carcinoma is characterized by intense angiogenesis associated with the inactivation of the von Hippel-Lindau oncosuppressor gene with consequent hyperexpression of proangiogenic factors. Functional and molecular characterization of renal tumor endothelial cells has demonstrated an increase in angiogenesis and cell survival. The proangiogenic phenotype was due to hyperactivation of the PI3K/Akt/mTor pathway, which downregulates the synthesis of the antiangiogenic factor thrombospondin-1. Moreover, renal tumor endothelial cells presented an immature and embryonic phenotype with expression of the embryonic kidney-specific gene PAX-2. It is conceivable that the endothelium present in renal carcinoma is heterogeneous, with a possible origin from adjacent vessels, resident or circulating stem cells, or from the tumor cells themselves. The relevance of the angiogenic process in renal carcinoma is underlined by the therapeutic effect of antiangiogenic drugs. Different drugs against VEGF, such as the anti-VEGF monoclonal antibody bevacizumab, and small molecule tyrosine-kinase inhibitors, such as sunitinib and sorafenib, showed a clinical effect in patients with metastatic carcinoma. However, antiangiogenic therapy, although beneficial, is not sufficient per se. These studies suggest a role for the angiogenic program in the growth and dissemination of renal carcinoma and indicate the need for new therapeutic strategies.
- Sprache
- Italienisch
- Identifikatoren
- ISSN: 0393-5590Titel-ID: cdi_proquest_miscellaneous_69206664
- Format
- –
- Schlagworte
- Angiogenesis Inhibitors - therapeutic use, Antibodies, Monoclonal - therapeutic use, Antibodies, Monoclonal, Humanized, Benzenesulfonates - therapeutic use, Bevacizumab, Carcinoma, Renal Cell - blood supply, Carcinoma, Renal Cell - drug therapy, Carcinoma, Renal Cell - genetics, Carcinoma, Renal Cell - metabolism, Drug Therapy, Combination, Endothelial Growth Factors - biosynthesis, Endothelial Growth Factors - genetics, Endothelial Growth Factors - metabolism, Endothelium, Vascular - metabolism, Endothelium, Vascular - pathology, Humans, Indoles - therapeutic use, Kidney Neoplasms - blood supply, Kidney Neoplasms - drug therapy, Kidney Neoplasms - genetics, Kidney Neoplasms - metabolism, Neovascularization, Pathologic - drug therapy, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - metabolism, Niacinamide - analogs & derivatives, PAX2 Transcription Factor - metabolism, Phenotype, Phenylurea Compounds, Protein Kinase Inhibitors - therapeutic use, Proto-Oncogene Proteins c-akt - metabolism, Pyridines - therapeutic use, Pyrroles - therapeutic use, Thrombospondin 1 - metabolism, Vascular Endothelial Growth Factor Receptor-1 - metabolism