Evidence map›Paper›PMID 26696368›Full record

ArticleNeoplasia (New York, N.Y.)2015

In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment.

Amy T Shah, Kirsten E Diggins, Alex J Walsh, Jonathan M Irish, Melissa C Skala

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
14.9field-weighted citation impact, top 1% 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

62 citing papers in PubMed, 106 citations in OpenAlex.

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2 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

5 authors at 2 institutions in 1 country.

Amy T ShahDepartment of Biomedical Engineering, Vanderbilt University, Station B, Box 1631, Nashville, TN, 37235, USA.
Kirsten E DigginsDepartment of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.
Alex J WalshDepartment of Biomedical Engineering, Vanderbilt University, Station B, Box 1631, Nashville, TN, 37235, USA.
Jonathan M IrishDepartment of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Melissa C SkalaDepartment of Biomedical Engineering, Vanderbilt University, Station B, Box 1631, Nashville, TN, 37235, USA; Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: m.skala@vanderbilt.edu.
Vanderbilt University · USVanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Training in Cellular and Molecular Imaging of CancerR25CA136440 · NCI · VANDERBILT UNIVERSITY · PI GORE, JOHN C · 2009 to 2013
$2.1M
Cellular-level Optical Metabolic Imaging to Predict Drug Response in CancerR01CA185747 · NCI · VANDERBILT UNIVERSITY · PI SKALA, MELISSA CAROLINE · 2014 to 2019
$1.6M
Targeting the B Cell Receptor Signaling Network in LymphomaR00CA143231 · NCI · VANDERBILT UNIVERSITY · PI IRISH, JONATHAN MICHAEL · 2012 to 2014
$715k
NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NCI NIH HHS R00 CA143231NCI NIH HHS R00 CA143231-03NCI NIH HHS R01 CA185747NCI NIH HHS R25 CA136440NCI NIH HHS R25 CA136440-04
6 · The paper itself

Abstract

Subpopulations of cells that escape anti-cancer treatment can cause relapse in cancer patients. Therefore, measurements of cellular-level tumor heterogeneity could enable improved anti-cancer treatment regimens. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. The optical redox ratio (fluorescence intensity of NAD(P)H divided by FAD) reflects global cellular metabolism. The fluorescence lifetime (amount of time a fluorophore is in the excited state) is sensitive to microenvironment, particularly protein-binding. High-resolution imaging of the optical redox ratio and fluorescence lifetimes of NAD(P)H and FAD (optical metabolic imaging) enables single-cell analyses. In this study, mice with FaDu tumors were treated with the antibody therapy cetuximab or the chemotherapy cisplatin and imaged in vivo two days after treatment. Results indicate that fluorescence lifetimes of NAD(P)H and FAD are sensitive to early response (two days post-treatment, P<.05), compared with decreases in tumor size (nine days post-treatment, P<.05). Frequency histogram analysis of individual optical metabolic imaging parameters identifies subpopulations of cells, and a new heterogeneity index enables quantitative comparisons of cellular heterogeneity across treatment groups for individual variables. Additionally, a dimensionality reduction technique (viSNE) enables holistic visualization of multivariate optical measures of cellular heterogeneity. These analyses indicate increased heterogeneity in the cetuximab and cisplatin treatment groups compared with the control group. Overall, the combination of optical metabolic imaging and cellular-level analyses provide novel, quantitative insights into tumor heterogeneity.

Indexed as

Antineoplastic AgentsCell Line, TumorCell ProliferationCetuximabCisplatinFlavin-Adenine DinucleotideHumansMicroscopy, Fluorescence, MultiphotonNADPNeoplasmsOxidation-ReductionSingle-Cell AnalysisTime FactorsTumor BurdenXenograft Model Antitumor AssaysAntineoplastic AgentsCetuximabCisplatinFlavin-Adenine DinucleotideNADP

Identifiers

PMID26696368
PMCPMC4688562
OpenAlexW2192927701

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.