Evidence map›Paper›PMID 29985394›Full record

ArticleNature communications2018

Heterogeneity in tumor chromatin-doxorubicin binding revealed by in vivo fluorescence lifetime imaging confocal endomicroscopy.

Hugh Sparks, Hiroshi Kondo, Steven Hooper, Ian Munro, Gordon Kennedy, Christopher Dunsby, Paul French, Erik Sahai

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.3field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  14. Multiphoton intravital microscopy of rodents.Nature reviews. Methods primers · 2022
    Article
  15. Article
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  17. Article
  18. Contribution of advanced fluorescence nano microscopy towards revealing mitotic chromosome structure.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021
    Review
  19. Review
  20. Single-Cell Intravital Microscopy of Trastuzumab Quantifies Heterogeneous in vivo Kinetics.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2020
    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

8 authors at 2 institutions in 1 country.

Hugh SparksTumor Cell Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0001-9900-6610
Hiroshi KondoTumor Cell Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Steven HooperTumor Cell Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Ian MunroPhotonics Group, Physics Department, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Gordon KennedyPhotonics Group, Physics Department, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Christopher DunsbyPhotonics Group, Physics Department, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. christopher.dunsby@imperial.ac.uk.
Paul FrenchPhotonics Group, Physics Department, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. paul.french@imperial.ac.uk.
Erik SahaiTumor Cell Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK. erik.sahai@crick.ac.uk.ORCID http://orcid.org/0000-0002-3932-5086
Imperial College London · GBThe Francis Crick Institute · GB

Funding

Cancer Research UK FC001144Wellcome Trust FC001144
6 · The paper itself

Abstract

We present an approach to quantify drug-target engagement using in vivo fluorescence endomicroscopy, validated with in vitro measurements. Doxorubicin binding to chromatin changes the fluorescence lifetime of histone-GFP fusions that we measure in vivo at single-cell resolution using a confocal laparo/endomicroscope. We measure both intra- and inter-tumor heterogeneity in doxorubicin chromatin engagement in a model of peritoneal metastasis of ovarian cancer, revealing striking variation in the efficacy of doxorubicin-chromatin binding depending on intra-peritoneal or intravenous delivery. Further, we observe significant variations in doxorubicin-chromatin binding between different metastases in the same mouse and between different regions of the same metastasis. The quantitative nature of fluorescence lifetime imaging enables direct comparison of drug-target engagement for different drug delivery routes and between in vitro and in vivo experiments. This uncovers different rates of cell killing for the same level of doxorubicin binding in vitro and in vivo.

Indexed as

AnimalsAntibiotics, AntineoplasticCell Line, TumorChromatinDoxorubicinDrug Delivery SystemsFluorescenceHumansMice, NudeMicroscopy, ConfocalNeoplasmsXenograft Model Antitumor AssaysAntibiotics, AntineoplasticChromatinDoxorubicin

Identifiers

PMID29985394
PMCPMC6037736
OpenAlexW2810921156

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.