Evidence map›Paper›PMID 38067241›Full record

ArticleCancers2023

Influence of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) on Glycolytic Metabolism of Canine Glioma: A Potential Improvement in Cancer Metabolism.

Hiroki Yamazaki, Seio Onoyama, Shunichi Gotani, Tatsuya Deguchi, Masahiro Tamura, Hiroshi Ohta, Hidetomo Iwano, Hidetaka Nishida, Peter J Dickinson, Hideo Akiyoshi

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
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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

10 authors at 4 institutions in 2 countries.

Hiroki YamazakiLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.
Seio OnoyamaLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.
Shunichi GotaniLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.
Tatsuya DeguchiLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.
Masahiro TamuraLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.ORCID 0000-0002-9721-304X
Hiroshi OhtaLaboratory of Veterinary Internal Medicine, Companion Animal Internal Medicine, Department of Companion Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.
Hidetomo IwanoLaboratory of Veterinary Biochemistry, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, 582-1 Bunkyodai-Midorimachi, Ebetsu 069-0836, Japan.ORCID 0000-0002-0838-1990
Hidetaka NishidaLaboratory of Small Animal Clinics, Veterinary Teaching Hospital, Graduate School of Veterinary Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara 52-5201, Japan.
Peter J DickinsonDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.ORCID 0000-0002-0037-2619
Hideo AkiyoshiLaboratory of Veterinary Surgery, Graduate School of Life and Environmental Sciences, Osaka Metropolitan University, 1-58 Rinku-Oraikita, Izumisano 598-8531, Japan.
Rakuno Gakuen University · JPAzabu University · JPOsaka Metropolitan University · JPUniversity of California, Davis · US

Funding

Kaken Pharmaceutical (Japan) 20K15682
6 · The paper itself

Abstract

The transcription factor hypoxia-inducible factor 1α (HIF-1α) drives metabolic reprogramming in gliomas (GLs) under hypoxic conditions, promoting glycolysis for tumor development. Evofosfamide (EVO) releases a DNA-alkylating agent within hypoxic regions, indicating that it may serve as a hypoxia-targeted therapy. The aim of this study was to investigate the glycolytic metabolism and antitumor effects of EVO in a canine GL model. Our clinical data showed that overall survival was significantly decreased in GL dog patients with higher HIF-1α expression compared to that of those with lower HIF-1α expression, and there was a positive correlation between HIF-1α and pyruvate dehydrogenase kinase 1 (PDK1) expression, suggesting that glycolytic activity under hypoxia conditions may contribute to poor outcomes in canine GL. Our glycolysis assay tests showed that the glycolytic ATP level was higher than the mitochondrial ATP level in three types of canine GL cell lines by activating the HIF-1 signal pathway under hypoxia conditions, resulting in an overall increase in total cellular ATP production. However, treatment with EVO inhibited the glycolytic ATP level in the GL cell lines under hypoxia conditions by targeting HIF-1α-positive cells, leading to decrease in total cellular ATP production. Our in vivo tests showed that EVO significantly reduced tumor development compared to controls and temozolomide in murine GL models. A metabolic analysis demonstrated that EVO effectively suppressed glycolytic metabolism by eliminating HIF-1α-positive cells, suggesting that it may restore metabolism in canine GLs. The evidence presented here supports the favorable preclinical evaluation of EVO as a potential improvement in cancer metabolism.

Indexed as

dogsevofosfamidegliomaglycolysisHIF-1α

Identifiers

PMID38067241
PMCPMC10705110
OpenAlexW4388898943

What Socratic 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 Socratic graph.