Evidence map›Paper›PMID 11556841›Full record

ArticleBritish journal of cancer2001

Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival.

A Giatromanolaki, M I Koukourakis, E Sivridis, H Turley, K Talks, F Pezzella, K C Gatter, A L Harris

Open access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 5 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 5 syntheses or guidelines pooled it, 472 citations in OpenAlex.

  1. Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026
    Pooled it
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  5. Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016
    Pooled it
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  11. Prognostic value of combining clinical factors,Annals of nuclear medicine · 2024
    Article
  12. Article
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  14. [Tumor-associated Macrophage: 
Emerging Targets for Modulating the Tumor Microenvironment].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024
    Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

A GiatromanolakiDepartment of Pathology, Democritus University of Thrace, P.O.Box 128, Alexandroupolis 68100, Greece.
M I Koukourakis
E Sivridis
H Turley
K Talks
F Pezzella
K C Gatter
A L Harris
John Radcliffe Hospital · GBDemocritus University of Thrace · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia inducible factors HIF1alpha and HIF2alpha are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1alpha and 2alpha protein levels, as a consequence of a redox-sensitive stabilization. The HIFalphas enter the nucleus, heterodimerize with the HIF1beta protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1alpha and HIF2alpha expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2alpha expression with HIF1alpha expression showed a significant association (P< 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P< 0.004), PD-ECGF (P< 0.003) and bFGF (P< 0.04) was noted. HIF1alpha correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2alpha was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2alpha protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2alpha expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1alpha expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2alpha expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1alpha and HIF2alpha overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting the HIF pathway may prove of importance in the treatment of NSCLC.

Indexed as

Transcription FactorsAdenocarcinomaAdultAgedBasic Helix-Loop-Helix ProteinsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDNA-Binding ProteinsEndothelial Growth FactorsEndothelial PAS Domain-Containing Protein 1Erb-b2 Receptor Tyrosine KinasesFemaleHumansHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsEndothelial Growth FactorsEndothelial PAS Domain-Containing Protein 1Erb-b2 Receptor Tyrosine KinasesHIF1A protein, humanHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitKi-67 AntigenNuclear ProteinsProto-Oncogene Proteins c-bcl-2Thymidine PhosphorylaseTrans-ActivatorsTranscription Factors

Identifiers

PMID11556841
PMCPMC2375073
OpenAlexW2085650758

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.