Hypoxia-Inducible Factor 1α in Clear Cell Renal Cell Carcinoma

Klatte, Tobias; Seligson, David B.; Riggs, Stephen B.; Leppert, John T.; Berkman, Maria K; Kleid, Mark D.; Hong, Yuling; Kabbinavar, Fairooz; Pantuck, Allan J.; Belldegrun, Arie S.

doi:10.1158/1078-0432.ccr-07-0411

Cited by 175 publications

(138 citation statements)

References 40 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Hypoxia-inducible factor has been shown to play a major role in the angiogenesis and growth of various tumours, including breast (Leek et al, 2002), bladder (Palit et al, 2005), renal (Klatte et al, 2007), pancreatic (Shibaji et al, 2003) and cervical (Birner et al, 2000) cancers. Indeed, overexpression of, in particular, HIF-1a, has been correlated with unfavourable prognosis in a number of malignancies (Theodoropoulos et al, 2005;Maynard and Ohh, 2007;Trastour et al, 2007).…”

mentioning

confidence: 99%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

View full text Add to dashboard Cite

The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1a (HIF-1a) and HIF-2a protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n ¼ 90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1a and HIF-2a expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1a and HIF-2a, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (Po0.001) and associated with poor survival (hazard ratio (HR) ¼ 8.7, Po0.005) and decreased disease-free survival (HR ¼ 4.7, Po0.005). hypoxia-inducible factor-1a and -2a were expressed in 450% of rectal cancers (HIF-1a, 54%, 48/90; HIF-2a, 64%, 58/90). HIF-1a positivity was associated with both TNM stage (Po0.05) and vascular invasion (Po0.005). In contrast, no associations were shown between HIF-2a expression and any pathological features, and HIF-1a positivity had no effect on outcome. The study showed an independent association between HIF-1a expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1a, but not HIF-2a, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.

show abstract

mentioning

confidence: 99%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Klatte et al [51] recently investigated the association between tissue microarray-based HIF-1␣ nuclear expression and outcome to determine the prognostic value of this biomarker. HIF-1␣ was overexpressed across all RCC subtypes, with clear cell RCC exhibiting the highest expression.…”

Section: Prognostication/predicting Response To Therapymentioning

confidence: 99%

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

2011

Self Cite

View full text Add to dashboard Cite

In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed. The Oncologist 2011;16(suppl 2):4 -13

show abstract

“…Previous studies have implicated a role of RhoA in RCC carcinogenesis. For instance, active RhoA was required for the accumulation of HIF1a, one of the most important regulators for RCC (Klatte et al, 2007), in trophoblast (Hayashi et al, 2005) and RCC cells (Turcotte et al, 2003) under hypoxia condition. By promoting RhoA activation, overexpressed plasma membrane associated sialidase could increase RCC cell motility (Ueno et al, 2006).…”

Section: Involvement Of Cbp In Renal Cell Carcinogenesis X Feng Et Almentioning

confidence: 99%

“…RCC is one of the most challenging malignancies because of its resistance to cytotoxic chemotherapeutic agents and radiation therapy (D'Hondt et al, 2005). Recent investigations have been focused on the molecular mechanisms of potential targets such as von HippelLindau protein and hypoxia-inducible factors (HIFs) and their roles in oncogenesis and progression of RCC (Bratslavsky et al, 2007;Klatte et al, 2007;Rathmell and Chen, 2008). Despite these efforts, the precise molecular mechanisms of carcinogenesis, progression and metastasis of RCC remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%