Evidence map›Paper›PMID 24551189›Full record

ArticlePloS one2014

HIF-1α and HIF-2α: siblings in promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation.

Lun Wu, Zhihao Fu, Shiji Zhou, Jianping Gong, Chang An Liu, Zhengrong Qiao, Shengwei Li

RetractedAbstract readRetracted Publication
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

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  19. Hypoxia-inducible factors as molecular targets for liver diseases.Journal of molecular medicine (Berlin, Germany) · 2016
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Lun WuThe Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Hepatobiliary Surgery, Chongqing, China.
Zhihao FuThe Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Hepatobiliary Surgery, Chongqing, China.
Shiji ZhouThe Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jianping GongThe Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Hepatobiliary Surgery, Chongqing, China.
Chang An LiuThe Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Hepatobiliary Surgery, Chongqing, China.
Zhengrong QiaoThe Department of General Surgery, The People's Five Hospital of Chongqing, Chongqing, China.
Shengwei LiThe Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Hepatobiliary Surgery, Chongqing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-intensity focused ultrasound (HIFU) is a widely applied to treatment for unresectable hepatocellular carcinoma. However, insufficient HIFU can result in rapid progression of the residual tumor. The mechanism of such rapid growth of the residual tumor after HIFU ablation is poorly understood.

objectiveThe aim of this study was to investigate the dynamic angiogenesis of residual tumor, and the temporal effect and mechanism of the HIF-1, 2α in the residual tumor angiogenesis.

methodsXenograft tumors of HepG2 cells were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with hepatoma cells. About thirty days after inoculation, all mice (except control group) were treated by HIFU and assigned randomly to 7 groups according to various time intervals (1st, 3rd, 5th day (d) and 1st, 2nd, 3rd, 4th week (w)). The residual tumor tissues were obtained from the experimental groups at various time points. Protein levels of HIF-1α, HIF-2α, VEGF-A, and EphA2 were quantified by immunohistochemistry analysis and Western Blot assays, and mRNA levels measured by Q-PCR. Microvascular density was calculated with counting of CD31 positive vascular endothelial cells by immunohistochemical staining.

resultsCompared with the control group, protein and mRNA levels of HIF-1α reached their highest levels on the 3rd day (P<0.01), then decreased (P<0.05). HIF-2α expression reached its highest level on the 2nd week compared with control group (P<0.01), then decreased (2 w-4 w) (P<0.05). The protein and mRNA levels of VEGF-A and EphA2 in the residual tumor tissues group that received HIFU were significantly decreased until 1 week compared with the control group (P<0.01). However, the levels increased compared to controls in 2-4 weeks (P<0.05). Similar results were obtained for MVD expression (P<0.05).

conclusionInsufficient HIFU ablation promotes the angiogenesis in residual carcinoma tissue over time. The data indicate that the HIF-1, 2α/VEGFA/EphA2 pathway is involved.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsBasic Helix-Loop-Helix ProteinsCarcinoma, HepatocellularEndothelial PAS Domain-Containing Protein 1High-Intensity Focused Ultrasound AblationHumansHypoxia-Inducible Factor 1, alpha SubunitLiver NeoplasmsMiceMice, NudeNeoplasm TransplantationNeovascularization, PathologicReceptor, EphA2Transplantation, HeterologousTreatment FailureBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitReceptor, EphA2Vascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID24551189
PMCPMC3923841

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Registered trials

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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.