Evidence map›Paper›PMID 29187018›Full record

ArticleCell cycle (Georgetown, Tex.)2018

Targeting methionine with oral recombinant methioninase (o-rMETase) arrests a patient-derived orthotopic xenograft (PDOX) model of BRAF-V600E mutant melanoma: implications for chronic clinical cancer therapy and prevention.

Kei Kawaguchi, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Bartosz Chmielowski, Scott D Nelson and 8 more

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

Article in Cell cycle (Georgetown, Tex.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

26 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
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  3. Review
  4. Review
  5. Review
  6. Article
  7. Bioactive peptides for anticancer therapies.Biomaterials translational · 2023
    Review
  8. Review
  9. Targeting the methionine addiction of cancer.American journal of cancer research · 2022
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Recombinant-methioninase-producingCancer diagnosis & prognosis
    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

18 authors at 5 institutions in 2 countries.

Kei Kawaguchia AntiCancer , Inc. , San Diego , CA , USA.
Qinghong Hana AntiCancer , Inc. , San Diego , CA , USA.
Shukuan Lia AntiCancer , Inc. , San Diego , CA , USA.
Yuying Tana AntiCancer , Inc. , San Diego , CA , USA.
Kentaro Igarashia AntiCancer , Inc. , San Diego , CA , USA.
Tasuku Kiyunaa AntiCancer , Inc. , San Diego , CA , USA.
Kentaro Miyakea AntiCancer , Inc. , San Diego , CA , USA.
Masuyo Miyakea AntiCancer , Inc. , San Diego , CA , USA.
Bartosz Chmielowskid Div. of Hematology-Oncology , University of California , Los Angeles , CA , USA.ORCID 0000-0002-2374-3320
Scott D Nelsone Dept. of Pathology , University of California , Los Angeles , CA , USA.
Tara A Russellf Div. of Surgical Oncology , University of California , Los Angeles , CA , USA.ORCID 0000-0002-3912-3601
Sarah M Drye Dept. of Pathology , University of California , Los Angeles , CA , USA.
Yunfeng Lie Dept. of Pathology , University of California , Los Angeles , CA , USA.
Arun S Singhd Div. of Hematology-Oncology , University of California , Los Angeles , CA , USA.
Mark A Eckardtg Department of Surgery, Yale School of Medicine , New Haven , CT , USA.ORCID 0000-0002-9528-8419
Michiaki Unnoc Dept. of Surgery, Graduate School of Medicine , Tohoku University , Sendai , Japan.
Fritz C Eilberf Div. of Surgical Oncology , University of California , Los Angeles , CA , USA.ORCID 0000-0003-3336-9333
Robert M Hoffmana AntiCancer , Inc. , San Diego , CA , USA.
University of California, Los Angeles · USUniversity of California San Diego · USAntiCancer (United States) · USTohoku University · JPYale University · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

The elevated methionine (MET) use by cancer cells is termed MET dependence and may be the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo. We previously reported that rMETase, administrated by intra-peritoneal injection (ip-rMETase), could inhibit tumor growth in a patient-derived orthotopic xenograft (PDOX) model of a BRAF-V600E mutant melanoma. In the present study, we compared ip-rMETase and oral rMETase (o-rMETase) for efficacy on the melanoma PDOX. Melanoma PDOX nude mice were randomized into four groups of 5 mice each: untreated control; ip-rMETase (100 units, i.p., 14 consecutive days); o-rMETase (100 units, p.o., 14 consecutive days); o-rMETase+ip-rMETase (100 units, p.o.+100 units, i.p., 14 consecutive days). All treatments inhibited tumor growth on day 14 after treatment initiation, compared to untreated control (ip-rMETase, p<0.0001; o-rMETase, p<0.0001; o-rMETase+ip-rMETase, p<0.0001). o-rMETase was significantly more effective than ip-rMETase (p = 0.0086). o-rMETase+ip-rMETase was significantly more effective than either mono-therapy: ip-rMETase, p = 0.0005; or o-rMETase, p = 0.0367. The present study is the first demonstrating that o-rMETase is effective as an anticancer agent. The results of the present study indicate the potential of clinical development of o-rMETase as an agent for chronic cancer therapy and for cancer prevention and possibly for life extension since dietary MET reduction extends life span in many animal models.

Indexed as

Xenograft Model Antitumor AssaysAdministration, OralAgedAnimalsCarbon-Sulfur LyasesFemaleHumansMelanomaMice, NudeMutationProto-Oncogene Proteins B-rafRecombinant ProteinsCarbon-Sulfur LyasesL-methionine gamma-lyaseProto-Oncogene Proteins B-rafRecombinant Proteinsmelanomamethionine dependencenude miceoral administrationorthotopicPDOXpyridoxal-L-phosphateRecombinant methioninase

Identifiers

PMID29187018
PMCPMC5914727
OpenAlexW2772407589

What OpenQuestion holds

Textmetadata
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.