Evidence map›Paper›PMID 39700124›Full record

ArticlePloS one2024

Plasma and serum concentrations of VEGF-A121, but not of VEGF-A165, increase post-bevacizumab administration.

Masashi Okawa, Munekazu Yamakuchi, Aryal Bibek, Kazunori Takenouchi, Drew N Maywar, Shingo Yamada, Keiichi Inoue, Kazuhiko Higurashi, Junichi Nakazawa, Masahiro Kawahira and 12 more

Abstract read
In one paragraph

Article in PloS one, 2024. 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
–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

3 citing papers in PubMed.

  1. Quantification of vitreous VEGF-A121 and VEGF-A165 using an isoform-specific ELISA in proliferative diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Article
  2. Article
  3. 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

22 authors.

Masashi OkawaDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Munekazu YamakuchiDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.ORCID 0000-0003-2181-7194
Aryal BibekDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Kazunori TakenouchiDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.ORCID 0000-0003-1946-457X
Drew N MaywarElectrical and Computer Engineering Technology, Rochester Institute of Technology, Rochester, New York, United States of America.ORCID 0000-0002-2674-0520
Shingo YamadaShino-Test Corporation, Sagamihara, Japan.
Keiichi InoueShino-Test Corporation, Sagamihara, Japan.
Kazuhiko HigurashiShino-Test Corporation, Sagamihara, Japan.
Junichi NakazawaDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, Japan.
Masahiro KawahiraDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, Japan.
Tomoko KodamaDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, Japan.
Kiyonori TanoueKagoshima University Hospital Clinical Laboratory, Kagoshima, Japan.
Yoko OyamaDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Sadayuki HigashiDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Chieko FujisakiDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Hirohito HashinokuchiKagoshima University Hospital Clinical Laboratory, Kagoshima, Japan.
Akito TabaruDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Hideaki KandaDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Shuji TachiokaDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Yutaka ImotoDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Teruto HashiguchiDepartment of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Yoshiharu SogaDepartment of Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.ORCID 0000-0001-6718-6960

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVEGF-A concentrations were measured in the blood of bevacizumab-treated cancer patients in previous studies, but a consensus has not formed that would develop VEGF-A into a clinical biomarker. Recently, methods to strictly distinguish between the VEGF-A isoforms have been developed but have not yet been applied to cancer patients undergoing bevacizumab treatment.

methodsAn ELISA that strictly distinguishes between VEGF-A121 and VEGF-A165-the major isoforms of VEGF-A-and a commercially available ELISA for VEGF-A are used to determine the concentration of VEGF-A121, VEGF-A165, and VEGF-A in the blood of 12 patients with advanced colorectal cancer receiving bevacizumab therapy.

resultsThe serum and plasma concentrations of VEGF-A121 increased substantially post-bevacizumab administration; the median increase in serum was 860.8 pg/mL, 95% confidence interval (CI) [468.5, 1128.9], p = 0.0024, and in plasma was 808.6 pg/mL, 95% CI [748.7, 874.0], p = 0.00049. In stark contrast, VEGF-A165 after bevacizumab administration decreased in serum by a medium change of -73.8 pg/mL, 95% CI [-149.4, -10.2], p = 0.0034, with 83.3% of the post-bevacizumab concentrations falling below the high-accuracy threshold of 38 pg/mL; in plasma, all pre and post VEGF-A165 concentrations fell below this threshold. Concentrations of VEGF-A121 and VEGF-A165 in platelets did not change to a statistically significant degree. Adding recombinant VEGF-A121 (and -A165) or bevacizumab to plasma in patients post-bevacizumab administration increased or decreased, respectively, VEGF-A121 and VEGF-A165 levels. The increase in VEGF-A121 in plasma and serum after bevacizumab administration may be due to the dissociation of the complex of tumor-derived VEGF-A121 and bevacizumab when it moves from the stroma into the blood.

conclusionsThe VEGF-A121 isoform has been uniquely demonstrated as a clear marker of bevacizumab therapy in both plasma and serum, motivating further research on pursuing these isoforms as biomarkers in cancer care.

Indexed as

BevacizumabColorectal NeoplasmsVascular Endothelial Growth Factor AAdultAgedAngiogenesis InhibitorsBiomarkers, TumorEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMiddle AgedProtein IsoformsAngiogenesis InhibitorsBevacizumabBiomarkers, TumorProtein IsoformsVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID39700124
PMCPMC11658504

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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.