Evidence map›Paper›PMID 29623758›Full record

ArticleCell cycle (Georgetown, Tex.)2018

Targeting altered cancer methionine metabolism with recombinant methioninase (rMETase) overcomes partial gemcitabine-resistance and regresses a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer.

Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Thinzar M Lwin, Takashi Higuchi, Tasuku Kiyuna, Masuyo Miyake and 4 more

Open access · bronzeAbstract read
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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.4field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Metabolic targeting of malignant tumors: a need for systemic approach.Journal of cancer research and clinical oncology · 2023
    Review
  7. Review
  8. Targeting the methionine addiction of cancer.American journal of cancer research · 2022
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. 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 3 institutions in 2 countries.

Kei Kawaguchia AntiCancer, Inc. , San Diego , CA.
Kentaro Miyakea AntiCancer, Inc. , San Diego , CA.
Qinghong Hana AntiCancer, Inc. , San Diego , CA.
Shukuan Lia AntiCancer, Inc. , San Diego , CA.
Yuying Tana AntiCancer, Inc. , San Diego , CA.
Kentaro Igarashia AntiCancer, Inc. , San Diego , CA.
Thinzar M Lwina AntiCancer, Inc. , San Diego , CA.
Takashi Higuchia AntiCancer, Inc. , San Diego , CA.
Tasuku Kiyunaa AntiCancer, Inc. , San Diego , CA.
Masuyo Miyakea AntiCancer, Inc. , San Diego , CA.
Hiromichi Oshiroa AntiCancer, Inc. , San Diego , CA.
Michael Bouvetb Department of Surgery , University of California , San Diego , CA.
Michiaki Unnoc Department of Surgery, Graduate School of Medicine , Tohoku University , Sendai , Japan.
Robert M Hoffmana AntiCancer, Inc. , San Diego , CA.
AntiCancer (United States) · USUniversity of California, San Diego · USTohoku University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic cancer is a recalcitrant disease. Gemcitabine (GEM) is the most widely-used first-line therapy for pancreatic cancer, but most patients eventually fail. Transformative therapy is necessary to significantly improve the outcome of pancreatic cancer patients. Tumors have an elevated requirement for methionine and are susceptible to methionine restriction. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer to determine the efficacy of recombinant methioninase (rMETase) to effect methionine restriction and thereby overcome GEM-resistance. A pancreatic cancer obtained from a patient was grown orthotopically in the pancreatic tail of nude mice to establish the PDOX model. Five weeks after implantation, 40 pancreatic cancer PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n = 10); GEM (100 mg/kg, i.p., once a week for 5 weeks, n = 10); rMETase (100 units, i.p., 14 consecutive days, n = 10); GEM+rMETase (GEM: 100 mg/kg, i.p., once a week for 5 weeks, rMETase: 100 units, i.p., 14 consecutive days, n = 10). Although GEM partially inhibited PDOX tumor growth, combination therapy (GEM+rMETase) was significantly more effective than mono therapy (GEM: p = 0.0025, rMETase: p = 0.0010). The present study is the first demonstrating the efficacy of rMETase combination therapy in a pancreatic cancer PDOX model to overcome first-line therapy resistance in this recalcitrant disease.

Indexed as

AnimalsAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsCarbon-Sulfur LyasesDeoxycytidineDrug Administration ScheduleDrug Resistance, NeoplasmGemcitabineGene ExpressionHumansInjections, IntraperitonealMaleMethionineMiceMice, NudeMolecular Targeted TherapyAntimetabolites, AntineoplasticCarbon-Sulfur LyasesDeoxycytidineGemcitabineL-methionine gamma-lyaseMethionineRecombinant Proteinsgemcitabinemethionine dependencenude miceorthotopicpancreatic cancerpatient-derived orthotopic xenograft (PDOX)precision therapyRecombinant methioninase

Identifiers

PMID29623758
PMCPMC6056209
OpenAlexW2795762460

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.