HIF-1 and total HIF pathway activation scores were decreased with higher ascorbate in pRCC tumors (Spearman <i>r</i> = -0.38, <i>p</i> < 0.05 and <i>r</i> = -0.35, <i>p</i> < 0.05).This was not evident for ccRCC tumors.
We found that the anti-angiogenic TKI sunitinib disrupted the balance between HIF-1α and HIF-2α in RCCs and led to a protective effect on HUVECs against sunitinib treatment when cultured with conditioned medium.
Serum Ang-2 and MMP-2 and tumor HIF-1α were identified as relevant baseline biomarkers of sunitinib activity in advanced RCC, warranting further research into their prognostic versus predictive value.
Although 24% of Xp11 translocation RCC expressed HIF-1alpha (like CCRCC), unlike CCRCC CA IX expression was characteristically only focal (mean 6% cell labeling) in Xp11 translocation RCC.
Most RCCs result from inactivation of the von Hippel Lindau (VHL) tumor suppressor, leading to stable expression of Hypoxia-Inducible Factor-alpha (HIF-1alpha, -2alpha, -3alpha) and the induction of downstream target genes, including those responsible for angiogenesis and metastasis.
However, quantitative analyses of VEGF production and its correlation with VHL mutations and HIF-1 alpha expression in authentic tissues from patients with RCC are lacking.