Subcellular CXCR4 and HIF-1α expression levels were independent adverse prognostic factors and could be combined with TNM stage to generate a predictive nomogram of the clinical outcome of patients with RCC.
Inactivation of <i>VHL</i> causes the accumulation of hypoxia-inducible factor-1 (HIF-1), and in turn, accumulation of HIF-1 induces overexpression of vascular endothelial growth factor (VEGF); the increase in VEGF expression makes RCC a highly vascularized tumor, and forms the rationale for antiVEGF treatment.
HIF-1α expression was linked to shorter OS in the digestive tract, epithelial ovarian, breast, non-small cell lung, and clear cell renal cell carcinomas.
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.
Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC).
In immunoblot assays, the expression of HIF-1α was lowly detected in whole and nuclear lysates of RCC cell lines even under normoxia (20% O<sub>2</sub>), and their expression in whole lysates was increased under hypoxia (1% O<sub>2</sub>).
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.
In this study, the expression of LimD1, VHL and HIF1α was analyzed in primary renal cell carcinoma (RCC) samples to understand their association with development of the disease.
In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 α and its targets, the tyrosine kinase receptors, promoting RCC development and progression.
In conclusion, these results suggest that HOTAIR promotes Rcc tumorigenesis via miR-217/HIF-1α/AXL signaling, which may provide a new target for the diagnosis and therapy of Rcc disease.
New treatment modalities targeted to HIF-1α and HIF-2α might be planned as well as VEGF-targeted therapies in the management of clear cell renal cell carcinomas.
This study evaluated the associations of the HIF1A+1772C/T (rs11549465) polymorphism with clinicopathologic prognostic factors, recurrence/progression, and survival in a cohort of 179 patients with RCC treated at Portuguese Oncology Institute of Porto.
Collectively, we propose that concurrent activation of p53 and HIF1α may effectively result in cancer-cell apoptosis, and that combined MDM2 antagonists and mTOR inhibitors may be useful in RCC therapy.
Taken together, these data suggest that PIG3 was involved in HIF-1α regulation, and reveal a novel signaling pathway of PIG3/HIF-1α in the regulation of cell migration in renal cell carcinoma.
The elucidation of the VHL-HIF-1α (hypoxia inducible factor-1α)-VEGF (vascular endothelial growth factor) pathway has led to the development of targeted therapy in renal cell carcinoma (RCC).
In this study, we investigated the effect of SF1126 on hypoxic HIF-1α/HIF-2α stability as well as on antitumor and/or antiangiogenic activity in renal cell carcinoma (RCC) models in vitro and in vivo.
MOTIF analysis of aberrantly hypermethylated regions revealed enrichment for binding sites of AP2a, AHR, HAIRY, ARNT, and HIF1 transcription factors, reflecting contributions of dysregulated hypoxia signaling pathways in RCC.