|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation.
|
10353251 |
1999 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here we show that the product of the von Hippel-Lindau (VHL) tumor suppressor gene mediated ubiquitylation and proteasomal degradation of HIF-1 alpha under normoxic conditions via interaction with the core of the oxygen-dependent degradation domain of HIF-1 alpha.
|
10944113 |
2000 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These studies define a new class of HIF-1-responsive gene, the activation of which has implications for the understanding of hypoxic tumor metabolism and which may provide endogenous markers for tumor hypoxia.
|
11156414 |
2000 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Under hypoxic conditions, immunohistochemical analysis of tumor cell lines revealed elevated levels of AM and HIF-1alpha as compared with normoxia, and we also found an increase of immunoreactive AM in the conditioned medium of tumor cells analyzed by RIA.
|
10847587 |
2000 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The tumor suppressors VHL (von Hippel-Lindau protein) and p53 target HIF-1alpha for ubiquitination such that their inactivation in tumor cells increases the half-life of HIF-1alpha.
|
11359907 |
2001 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The level of HIF-1alpha mRNA was not different between tumors and adjacent kidney tissue.
|
11431362 |
2001 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
ER-alpha expression (both its proportion and intensity) was significantly lower in nuclear HIF-1 alpha-positive tumors than in negative tumors.
|
11676860 |
2001 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors.
|
11410504 |
2001 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
This was not related to vascular parameters that were identical to those found in HIF-1 wild-type tumours.
|
11803471 |
2002 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The tumor strongly expressed EPO messenger RNA and the 2 regulatory subunits HIF-1alpha and HIF-2alpha.
|
11986208 |
2002 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here we demonstrate that both nonselective (indomethacin) and COX-2-selective (NS-398) NSAIDs inhibit hypoxia-induced in vitro angiogenesis in gastric microvascular endothelial cells via coordinated sequential events: 1) increased expression of the von Hippel-Lindau (VHL) tumor suppressor, which targets proteins for ubiquitination leading to 2) reduced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) and, as a result, 3) reduced expression of vascular endothelial growth factor (VEGF) and its specific receptor Flt-1.
|
11772947 |
2002 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Analysis of the DNA extracted from a benign or tumorous region of one of these specimens showed that only the wildtype (nonmutated) form of the HIF-1alpha gene was amplified from the normal DNA whereas only the mutated form of the HIF-1alpha gene was amplified from the tumor.
|
12136249 |
2002 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Accumulation of HIF-1 alpha caused by mutant VHL protein in tumor cells may result in VEGF over expression, which has been used to explain the increased vascularity of RCC.
|
12853836 |
2003 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
HIF-1 controls cellular and systemic responses to oxygen availability and coordinates up-regulation of genes involved in many pathways concerned with tumour growth and metabolism including angiogenesis, glucose and energy metabolism, cellular proliferation, differentiation and viability, apoptosis, pH regulation and matrix metabolism.
|
12558074 |
2003 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
As the inducible overexpression of HIF-1alpha did not increase the rate of apoptosis, it provides a helpful new tool in drug discovery and tumor research to differentiate between hypoxia-dependent and hypoxia-independent pathways during HIF-1alpha-dependent gene regulation and HIF-1alpha-dependent effects on apoptosis.
|
12928580 |
2003 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Among the five cases without VHL mutations, staining for ubiquitin or HIF-1alpha was not present in three cases but was present in two tumors, both of which had 3p deletions.
|
12781449 |
2003 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Subsequent xenograft generations have conserved immunohistochemical and ultrastructural properties typical for malignant renal epithelium-derived neoplasia (vimentin+, CK-19+, CA IX+ with hypoxia-inducible factor (HIF)-1 alpha constitutive expression) and have demonstrated extensive proliferation, lack of apoptosis, severe genetic alterations, and molecular expression alterations; transforming growth factor beta 1 (TGF-beta 1), hepatocyte growth factor (HGF), proto-oncogene (c-met), matrix metalloproteinase (MMP)-1, and vascular endothelial growth factor (VEGF) C and D were overexpressed, whereas human epidermal growth factor receptor (HER)-2, MMP-2 and MMP-9, VEGF-R3, p53, and p27 were severely down-regulated, suggesting a proangiogenic environment, local invasiveness, and facilitated lymphatic metastasis.
|
12941820 |
2003 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
These data demonstrate that inhibition of hypoxia-induced activation of HIF-1alpha through activation of HIF-hydroxylase can provide a novel therapeutic strategy for inhibition of tumor growth and neovascularization and support the development of gene transfer approaches based on the activation of HIF-prolyl hydroxylases.
|
14695194 |
2003 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia-inducible factor 1alpha (HIF-1alpha) and mediates its ubiquitination and proteosomal degradation.
|
12393546 |
2003 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Although there was a tendency for poorer prognosis in patients with high HIF-1alpha-expressing tumors, this correlation was not statistically significant.
|
12673675 |
2003 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We conclude that HIF-1 is the regulatory link between tumor hypoxia and VEGF production in pancreatic cancer, thus establishing a biochemical pathway between tumor hypoxia and neoangiogenesis in this highly aggressive neoplasm.
|
12499918 |
2003 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth.
|
13130303 |
2003 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The transcription factor hypoxia-inducible factor 1 (HIF-1) is a major regulator of tumor cell adaptation to hypoxic stress.
|
15591418 |
2004 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Expression of the von Hippel-Lindau (VHL) tumor suppressor factor blocked the expression of both FECH mRNA and HIF-1alpha protein during normoxic culture of renal carcinoma cell line (RCC4).
|
15312748 |
2004 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These results imply that HIF-1alpha(785) may play an important role in tumor promotion mediated by the Ras oncogene, phorbol ester or tumor growth factors.
|
15543236 |
2004 |