Evidence map›Paper›PMID 33916656›Full record

ArticleCancers2021

Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors.

Martin Benej, Jinghai Wu, McKenzie Kreamer, Martin Kery, Sergio Corrales-Guerrero, Ioanna Papandreou, Terence M Williams, Zihai Li, Edward E Graves, Laura E Selmic and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 44% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

11 authors at 4 institutions in 1 country.

Martin BenejDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.ORCID 0000-0002-3116-445X
Jinghai WuDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.
McKenzie KreamerDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.
Martin KeryDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.
Sergio Corrales-GuerreroDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.ORCID 0000-0002-5107-3475
Ioanna PapandreouDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.
Terence M WilliamsDepartment of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Zihai LiPelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Edward E GravesDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Laura E SelmicDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0001-6695-6273
Nicholas C DenkoDepartment of Radiation Oncology, The Ohio State University Wexner Medical Center and OSU Comprehensive Cancer Center, Columbus, OH 43210, USA.
The Ohio State University Wexner Medical Center · USThe Ohio State University · USCity Of Hope National Medical Center · USStanford University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
TUMOR HYPOXIA--MOLECULAR STUDIES &CLINICAL EXPLOITATIONP01CA067166 · NCI · STANFORD UNIVERSITY · PI LE, QUYNH-THU XUAN · 1996 to 2017
$25.5M
Overcoming Hypoxic Resistance in Non-Small Cell Lung Cancer By Targeting Mitochondrial MetabolismR01CA262388 · NCI · OHIO STATE UNIVERSITY · PI DENKO, NICHOLAS C., LI, ZIHAI · 2021 to 2025
$3.6M
Overcoming hypoxic resistance to anti-cancer therapyR01CA255334 · NCI · OHIO STATE UNIVERSITY · PI DENKO, NICHOLAS C., LI, ZIHAI · 2021 to 2025
$2.9M
A phase 0 pilot study to determine if papaverine increases oxygenation in spontaneous canine soft tissue sarcomaR21CA226477 · NCI · OHIO STATE UNIVERSITY · PI DENKO, NICHOLAS C. · 2019 to 2021
$373k
Beaver County Foundation N/ANCI NIH HHS P01 CA67166NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA255334NCI NIH HHS R01 CA262388NCI NIH HHS R21 CA226477
6 · The paper itself

Abstract

backgroundHypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors.

methodsWe used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine.

resultsWe showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10-50 mm HgO

conclusionIn both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage.

Indexed as

hypoxiametabolismmitochondriapapaverineresistancetumor microenvironment

Identifiers

PMID33916656
PMCPMC8038388
OpenAlexW3146870043

What OpenQuestion holds

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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.