Evidence map›Paper›PMID 15690061›Full record

ArticleGene therapy2005

Hypoxia reduces adenoviral replication in cancer cells by downregulation of viral protein expression.

T Pipiya, H Sauthoff, Y Q Huang, B Chang, J Cheng, S Heitner, S Chen, W N Rom, J G Hay

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing 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

55 citing papers in PubMed.

  1. Oncolytic adenovirus in treating malignant ascites: A phase II trial and longitudinal single-cell study.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Observational
  10. Review
  11. Article
  12. Article
  13. Impact of Hypoxia over Human Viral Infections and Key Cellular Processes.International journal of molecular sciences · 2021
    Review
  14. Review
  15. Review
  16. Oxygen: viral friend or foe?Virology journal · 2020
    Review
  17. Oncolytic viruses for cancer immunotherapy.Journal of hematology & oncology · 2020
    Review
  18. Article
  19. Review
  20. Article
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

9 authors.

T PipiyaDivision of Pulmonary & Critical Care Medicine, New York University School of Medicine, New York, NY 10016, USA.
H Sauthoff
Y Q Huang
B Chang
J Cheng
S Heitner
S Chen
W N Rom
J G Hay

Funding

ZOPOLRESTAT IN SUBJECTS W/ PERIPHERAL SYMMETRICAL DIABETIC POLYNEUROPATHYM01RR000096 · NCRR · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NOVIK, YELENA · 1985 to 2008
$34.8M
Spread of Replicating Adenovirus in Pancreatic TumorsR01CA102053 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HAY, JOHN G. · 2003 to 2007
$1.8M
Strategies to Enhance Adenoviral Mediated Tumor KillingR01CA089086 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HAY, JOHN G. · 2001 to 2004
$1.2M
NCI NIH HHS R01CA102053NCI NIH HHS R01CA89086NCRR NIH HHS M01RR-00096
6 · The paper itself

Abstract

Successful cancer therapy using replicating viral vectors relies on the spread of virus from infected to uninfected cells. To date, there has been limited clinical success in the use of replicating adenoviruses. In animal models, established xenograft tumors are rarely eliminated despite the persistence of high viral titers within the tumor. Hypoxia is a prevalent characteristic of solid tumors, whereas adenovirus naturally infects tissues exposed to ambient oxygen concentrations. Here, we report that hypoxia (1% oxygen) reduces adenoviral replication in H1299 and A549 lung cancer cells, BxPC-3 pancreatic cancer cells, LNCaP prostate cancer cells and HCT116 colon cancer cells. However, hypoxia does not reduce cell viability or restrict S-phase entry. Importantly, the production of E1a and fiber proteins under hypoxic conditions was substantially decreased at 24 and 48 h compared to room air controls. In contrast, Northern analysis showed similar levels of E1a mRNA in room air and hypoxic conditions. In conclusion, a level of hypoxia similar to that found within solid tumors reduces the replication of adenoviral vectors by reduction of viral protein expression without a reduction in mRNA levels. To further improve oncolytic therapy using a replicating adenovirus, it is important to understand the mechanism through which hypoxia and the virus interact to control expression of viral and cellular proteins, and consequently to develop means to overcome decreased viral production in hypoxic conditions.

Indexed as

Genetic VectorsAdenoviridaeBlotting, NorthernCell HypoxiaDown-RegulationGenetic TherapyHumansHypoxia-Inducible Factor 1, alpha SubunitNeoplasmsRNA, MessengerRNA, ViralS PhaseTranscription FactorsTranscription, GeneticTumor Cells, CulturedViral ProteinsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRNA, MessengerRNA, ViralTranscription FactorsViral Proteins

Identifiers

PMID15690061

What OpenQuestion holds

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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.