Evidence map›Paper›PMID 29649984›Full record

ArticleBMC cancer2018

BB-Cl-Amidine as a novel therapeutic for canine and feline mammary cancer via activation of the endoplasmic reticulum stress pathway.

Melissa M Ledet, Robyn Anderson, Rebecca Harman, Aaron Muth, Paul R Thompson, Scott A Coonrod, Gerlinde R Van de Walle

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Epigenetic Mechanisms in Canine Cancer.Frontiers in oncology · 2020
    Review
  13. Article
  14. 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

7 authors at 2 institutions in 1 country.

Melissa M LedetBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Robyn AndersonBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Rebecca HarmanBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Aaron MuthDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
Paul R ThompsonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
Scott A CoonrodBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Gerlinde R Van de WalleBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. grv23@cornell.edu.
Cornell University · USUniversity of Massachusetts Chan Medical School · US

Funding

Chemical probes to decipher PAD biologyR35GM118112 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Paul R Thompson · 2016 to 2026
$9.5M
Cornell Feline Health Center NAMorris Animal Foundation D14CA-063National Science Foundation DGE-1144153NIGMS NIH HHS R35 GM118112President's Councel of Cornell Women NA
6 · The paper itself

Abstract

backgroundMammary cancer is highly prevalent in dogs and cats and results in a poor prognosis due to critically lacking viable treatment options. Recent human and mouse studies have suggested that inhibiting peptidyl arginine deiminase enzymes (PAD) may be a novel breast cancer therapy. Based on the similarities between human breast cancer and mammary cancer in dogs and cats, we hypothesized that PAD inhibitors would also be an effective treatment for mammary cancer in these animals.

methodsCanine and feline mammary cancer cell lines were treated with BB-Cl-Amidine (BB-CLA) and evaluated for viability and tumorigenicity. Endoplasmic reticulum stress was tested by western blot, immunofluorescence, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Canine and feline mammary cancer xenograft models were created using NOD scid gamma (NSG) mice, and were treated with BB-CLA for two weeks.

resultsWe found that BB-CLA reduced viability and tumorigenicity of canine and feline mammary cancer cell lines in vitro. Additionally, we demonstrated that BB-CLA activates the endoplasmic reticulum stress pathway in these cells by downregulating 78 kDa Glucose-regulated Protein (GRP78), a potential target in breast cancer for molecular therapy, and upregulating the downstream target gene DNA Damage Inducible Transcript 3 (DDIT3). Finally, we established a mouse xenograft model of both canine and feline mammary cancer in which we preliminarily tested the effects of BB-CLA in vivo.

conclusionWe propose that our established mouse xenograft models will be useful for the study of mammary cancer in dogs and cats, and furthermore, that BB-CLA has potential as a novel therapeutic for mammary cancer in these species.

Indexed as

AmidinesAnimalsCatsDisease Models, AnimalDogsEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressEpithelial CellsFemaleGene ExpressionMammary Neoplasms, AnimalProtein-Arginine DeiminasesSignal TransductionXenograft Model Antitumor AssaysAmidinesEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanHspa5 protein, mouseProtein-Arginine DeiminasesBB-cl-AmidineEndoplasmic reticulum stressMammary cancerPeptidyl arginine deiminase

Identifiers

PMID29649984
PMCPMC5898062
OpenAlexW2806350715

What OpenQuestion 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 OpenQuestion graph.