Evidence map›Paper›PMID 31942393›Full record

ArticlePlastic and reconstructive surgery. Global open2019

Discovery of Novel Small Molecules that Block Myofibroblast Formation: Implications for Capsular Contracture Treatment.

Rachel H Park, Stephen J Pollock, Richard P Phipps, Howard N Langstein, Collynn F Woeller

Open access · goldAbstract read
In one paragraph

Article in Plastic and reconstructive surgery. Global open, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

5 authors at 2 institutions in 1 country.

Rachel H ParkUniversity of Rochester School of Medicine and Dentistry, Rochester, N.Y.
Stephen J PollockDepartment of Environmental Medicine, University of Rochester Medical Center, Rochester, N.Y.
Richard P PhippsDepartment of Environmental Medicine, University of Rochester Medical Center, Rochester, N.Y.
Howard N LangsteinDivision of Plastic and Reconstructive Surgery, University of Rochester Medical Center, Rochester, N.Y.
Collynn F WoellerDepartment of Ophthalmology, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.
University of Rochester Medical Center · USUniversity of Rochester · US

Funding

Dysregulation of common metabolic and transcriptional pathways in heart and lung fibrosisR01HL133761 · NHLBI · UNIVERSITY OF ROCHESTER · PI SMALL, ERIC M, WOELLER, COLLYNN FREMONT · 2016 to 2019
$2.1M
NHLBI NIH HHS R01 HL133761
6 · The paper itself

Abstract

Capsular contracture is a devastating complication that occurs in patients undergoing implant-based breast reconstruction. Ionizing radiation drives and exacerbates capsular contracture in part by activating cytokines, including transforming growth factor-beta (TGF-β). TGF-β promotes myofibroblast differentiation and proliferation, leading to excessive contractile scar formation. Therefore, targeting the TGF-β pathway may attenuate capsular contracture.

methodsA 20,000 small molecule library was screened for anti-TGF-β activity. Structurally diverse anti-TGF-β agents were identified and then tested on primary human capsular fibroblasts. Fibroblasts were irradiated or not, and then treated with both TGF-β and candidate molecules. Resulting cells were then analyzed for myofibroblast activity using myofibroblast markers including alpha-smooth muscle actin, collagen I, Thy1, and periostin, using Western Blot, quantitative real-time polymerase chain reaction, and immunofluorescence.

resultsHuman capsular fibroblasts treated with TGF-β showed a significant increase in alpha-smooth muscle actin, collagen I, and periostin levels (protein and/or mRNA). Interestingly, fibroblasts treated with latent TGF-β and 10 Gy radiation also showed significantly increased levels of myofibroblast markers. Cells that were treated with the novel small molecules showed a significant reduction in myofibroblast activation, even in the presence of radiation.

conclusionsSeveral novel small molecules with anti-TGF-β activity can effectively prevent human capsular fibroblast to myofibroblast differentiation in vitro, even in the presence of radiation. These results highlight novel therapeutic options that may be utilized in the future to prevent radiation-induced capsular contracture.

Identifiers

PMID31942393
PMCPMC6908376
OpenAlexW2978132500

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.