Evidence map›Paper›PMID 26993595›Full record

ArticleOncotarget2016

Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth.

Zsuzsanna Nemeth, Eva Csizmadia, Lisa Vikstrom, Mailin Li, Kavita Bisht, Alborz Feizi, Sherrie Otterbein, Brian Zuckerbraun, Daniel B Costa, Pier Paolo Pandolfi and 4 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
  3. The role of gasotransmitters in Parkinson's disease: Interplay of nitric oxide, carbon monoxide, and hydrogen sulfide.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  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

14 authors at 5 institutions in 4 countries.

Zsuzsanna NemethDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Eva CsizmadiaDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Lisa VikstromDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mailin LiDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Kavita BishtDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Alborz FeiziDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sherrie OtterbeinDepartment of Surgery, Section of Trauma and Acute Care Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Brian ZuckerbraunDepartment of Surgery, Section of Trauma and Acute Care Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Daniel B CostaCancer Center Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Pier Paolo PandolfiCancer Center Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Janos FillingerDepartment of Pathology, National Koranyi Institute of TB and Pulmonology, Budapest, Hungary.
Balazs DömeDepartment of Tumor Biology, National Koranyi Institute of TB and Pulmonology, Budapest, Hungary.
Leo E OtterbeinDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Barbara WegielDepartment of Surgery, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Beth Israel Deaconess Medical Center · USOrszágos Korányi Tbc és Pulmonológiai Intézet · HUUniversity of Pittsburgh Medical Center · USComprehensive Cancer Center Vienna · ATNational Heart Foundation of Australia · AU

Funding

Role of biliverdin reductase during sterile inflammation in the liver.R01DK104714 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEGIEL, BARBARA · 2016 to 2020
$2.0M
Heme degradation pathway and immunomodulation in prostate cancer.R21CA169904 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEGIEL, BARBARA · 2013 to 2014
$411k
NCI NIH HHS R21 CA169904NIDDK NIH HHS R01 DK104714
6 · The paper itself

Abstract

We hypothesized that tumor-associated macrophages (TAMs) are controlled by the diffusible gas carbon monoxide (CO). We demonstrate that induction of apoptosis in lung tumors treated with low doses of CO is associated with increased CD86 expression and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (Erk) 1/2 pathway in tumor microenvironment. Presence of CD86-positive cells was required for the anti-tumoral effects of CO in established A549 xenografts. We show that the effects of CO on tumor stroma and reprogramming of macrophages towards the anti-tumoral phenotype is mediated by reactive oxygen species (ROS)-dependent activation of MAPK/Erk1/2-c-myc pathway as well as Notch 1-dependent negative feedback on the metabolic enzyme heme oxygenase-1 (HO-1). We find a similar negative correlation between HO-1 and active MAPK-Erk1/2 levels in human lung cancer specimens.In summary, we describe novel non-cell autonomous mechanisms by which the diffusible gas CO dictates changes in the tumor microenvironment through the modulation of macrophages.

Indexed as

AnimalsApoptosisB7-2 AntigenBiomarkers, TumorCarbon MonoxideCell ProliferationCells, CulturedHeme Oxygenase-1HumansLung NeoplasmsMacrophagesMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3p38 Mitogen-Activated Protein KinasesB7-2 AntigenBiomarkers, TumorCarbon MonoxideCD86 protein, humanHeme Oxygenase-1HMOX1 protein, humanMAPK1 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3p38 Mitogen-Activated Protein KinasesReactive Oxygen Speciescarbon monoxideimmunotherapymacrophagestumor microenvironment

Identifiers

PMID26993595
PMCPMC5029674
OpenAlexW2342169450

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.