Evidence map›Paper›PMID 26935219›Full record

ArticleBMC cancer2016

The anti-fibrotic agent pirfenidone synergizes with cisplatin in killing tumor cells and cancer-associated fibroblasts.

Melanie Mediavilla-Varela, Kingsley Boateng, David Noyes, Scott J Antonia

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 115 citations in OpenAlex.

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18 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Melanie Mediavilla-VarelaDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
Kingsley BoatengDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
David NoyesDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
Scott J AntoniaDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. scott.antonia@moffitt.org.
Moffitt Cancer Center · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
NCI NIH HHS P30 CA076292NCI NIH HHS P30-CA76292
6 · The paper itself

Abstract

backgroundAnti-fibrotic drugs such as pirfenidone have been developed for the treatment of idiopathic pulmonary fibrosis. Because activated fibroblasts in inflammatory conditions have similar characteristics as cancer-associated fibroblasts (CAFs) and CAFs contribute actively to the malignant phenotype, we believe that anti-fibrotic drugs have the potential to be repurposed as anti-cancer drugs.

methodsThe effects of pirfenidone alone and in combination with cisplatin on human patient-derived CAF cell lines and non-small cell lung cancer (NSCLC) cell lines were examined. The impact on cell death in vitro as well as tumor growth in a mouse model was determined. Annexin V/PI staining and Western blot analysis were used to characterize cell death. Synergy was assessed with the combination index method using Calcusyn software.

resultsPirfenidone alone induced apoptotic cell death in lung CAFs at a high concentration (1.5 mg/mL). However, co-culture in vitro experiments and co-implantation in vivo experiments showed that the combination of low doses of cisplatin (10 μM) and low doses of pirfenidone (0.5 mg/mL), in both CAFs and tumors, lead to increased cell death and decreased tumor progression, respectively. Furthermore, the combination of cisplatin and pirfenidone in NSCLC cells (A549 and H157 cells) leads to increased apoptosis and synergistic cell death.

conclusionsOur studies reveal for the first time that the combination of cisplatin and pirfenidone is active in preclinical models of NSCLC and therefore may be a new therapeutic approach in this disease.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCisplatinCoculture TechniquesDisease Models, AnimalDrug SynergismFibroblastsHumansNeoplasmsPyridonesTransforming Growth Factor betaXenograft Model Antitumor AssaysAntineoplastic AgentsCisplatinpirfenidonePyridonesTransforming Growth Factor beta

Identifiers

PMID26935219
PMCPMC4776434
OpenAlexW2291267698

What OpenQuestion holds

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LicenceCC BY
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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.