Evidence map›Paper›PMID 30536712›Full record

ArticleInternational journal of cancer2019

Modeling and multiscale characterization of the quantitative imaging based fibrosis index reveals pathophysiological, transcriptome and proteomic correlates of lung fibrosis induced by fractionated irradiation.

Cheng Zhou, Mahmoud R Moustafa, Liji Cao, Mark Kriegsmann, Martin Winter, Christian Schwager, Bleddyn Jones, Shijun Wang, Tobias Bäuerle, Ping-Kun Zhou and 4 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

8 citing papers in PubMed, 16 citations in OpenAlex.

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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 8 institutions in 4 countries.

Cheng ZhouTranslational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mahmoud R MoustafaTranslational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Liji CaoDivision of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mark KriegsmannInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Martin WinterDivision of Molecular and Translational Radiation Oncology, Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation research in Oncology (NCRO), Heidelberg, Germany.
Christian SchwagerTranslational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bleddyn JonesGray Laboratory, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
Shijun WangDepartment of Pediatric Nephrology, Gastroenterology & Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Tobias BäuerleInstitute of Radiology, University Hospital Erlangen, Erlangen, Germany.
Ping-Kun ZhouBeijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
Martina SchnölzerDivision of Molecular and Translational Radiation Oncology, Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation research in Oncology (NCRO), Heidelberg, Germany.
Wilko WeichertInstitute of Pathology, Technical University of Munich (TUM), Munich, Germany.
Juergen DebusTranslational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Amir AbdollahiTranslational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-8016-5897
German Cancer Research Center · DEBeijing Radiation Center · CNHeidelberg University · DEMedizinische Hochschule Hannover · DESuez Canal University · EGTechnical University of Munich · DEUniversitätsklinikum Erlangen · DEUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pulmonary fibrosis represents a leading cause of morbidity and mortality worldwide. Therapy induced lung fibrosis constitutes a pivotal dose-limiting side effect of radiotherapy and other anticancer agents. We aimed to develop objective criteria for assessment of fibrosis and discover pathophysiological and molecular correlates of lung fibrosis as a function of fractionated whole thoracic irradiation. Dose-response series of fractionated irradiation was utilized to develop a non-invasive and quantitative measure for the degree of fibrosis - the fibrosis index (FI). The correlation of FI with histopathology, blood-gas, transcriptome and proteome responses of the lung tissue was analyzed. Macrophages infiltration and polarization was assessed by immunohistochemistry. Fibrosis development followed a slow kinetic with maximum lung fibrosis levels detected at 24-week post radiation insult. FI favorably correlated with radiation dose and surrogates of lung fibrosis i.e., enhanced pro-inflammatory response, tissue remodeling and extracellular matrix deposition. The loss of lung architecture correlated with decreased epithelial marker, loss of microvascular integrity with decreased endothelial and elevated mesenchymal markers. Lung fibrosis was further attributed to a switch of the inflammatory state toward a macrophage/T-helper cell type 2-like (M2/Th2) polarized phenotype. Together, the multiscale characterization of FI in radiation-induced lung fibrosis (RILF) model identified pathophysiological, transcriptional and proteomic correlates of fibrosis. Pathological immune response and endothelial/epithelial to mesenchymal transition were discovered as critical events governing lung tissue remodeling. FI will be instrumental for deciphering the molecular mechanisms governing lung fibrosis and discovery of novel targets for treatment of this devastating disease with an unmet medical need.

Indexed as

AlgorithmsAnimalsBlood Gas AnalysisDose Fractionation, RadiationFemaleLongitudinal StudiesMiceMice, Inbred C57BLPositron Emission Tomography Computed TomographyProteomicsPulmonary FibrosisRadiation Injuries, ExperimentalTh2 CellsTranscriptomeEMT/EndoMTfractionated radiotherapyM2 macrophagespulmonary fibrosisradiation-induced lung fibrosisTh2-like response

Identifiers

PMID30536712
PMCPMC6590477
OpenAlexW2905180866

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.