As with any anticancer therapeutic

As with any anticancer therapeutic BTB06584? agent, there is clinical ambiguity regarding individual patient response. Some agents directly target VEGF, such as bevacizumab, a humanized monoclonal antibody, while others indirectly target receptors and downstream regulators, such as sunitinib and rituximab. While the regulation and metabolism are unique in vivo, the protein expression lev els produced by individual patient cells may provide information on how each patient will Inhibitors,Modulators,Libraries respond clinically to a given anticancer agent. The heterogeneity of protein expression demonstrated in this study may provide infor mation to enable the prediction of the efficacy of anti ang iogenic factors. Further studies correlating the in vitro expression levels with patient outcome are warranted.

Conclusion Linear correlations exist between expression levels of ang iogenesis related factors under normoxic and hypoxic conditions. This suggests the behaviour of primary cells derived from patient tumors grown under in vitro nor moxic conditions may provide a correlation to the in vivo hypoxic environment. Differential expression for Inhibitors,Modulators,Libraries each sample across all factors suggests predictive value for ang iogenesis related anti cancer agents, using not only VEGF, but an array of angiogenesis related proteins. These Inhibitors,Modulators,Libraries data suggest further studies should be considered to correlate in vitro expression of these proteins with in vivo patient response to anti angiogenesis therapeutics. Background Renal cell carcinoma is the most lethal urologic tumor and the sixth leading cause of cancer deaths in Western countries.

Each year, around 200,000 patients are diagnozed with this malignancy resulting in approxi mately Inhibitors,Modulators,Libraries 100,000 deaths, and its incidence is increasing steadily. RCC is represented by 80% by clear cell RCC, originating from the renal proximal tubule. RCC is resistant to radio, hormono, and chemotherapy, and immunotherapy is effective in only 15% of selected patients. The recent development of anti angiogenic strategies based on small molecule tyrosine kinase recep tor inhibitors lead to the approval of sunitinib or soraf enib as first line therapy for RCC. So far the best known oncogenic signal in human CRCC is constituted by the von Hippel Lindau tumor suppressor gene and hypoxia induced factors. Inhibitors,Modulators,Libraries Inherited and sporadic forms of CRCC are associated with inactivation of the VHL gene.

In hypoxic conditions, or when the VHL gene is defectuous as it is the case in 60% of CRCC, HIFs are stabilized allowing the expression of a large panel of target genes involved in growth, motility, metabolism and angiogenesis such as vascular endothe lium growth factor, tumor growth factors, parathyroid hormone related protein, namely glucose transporters and transferrin, all shown to contribute to CRCC tumorigenesis.

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