Evidence map›Paper›PMID 27802108›Full record

ArticleRadiology2017

Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy.

John R Chevillet, Tatiana D Khokhlova, Maria D Giraldez, George R Schade, Frank Starr, Yak-Nam Wang, Emily N Gallichotte, Kai Wang, Joo Ha Hwang, Muneesh Tewari

Abstract read
In one paragraph

Article in Radiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
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

35 citing papers in PubMed.

  1. Focused ultrasound for brain metastases.Neuro-oncology advances · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound.Annual review of biomedical engineering · 2024
    Review
  13. Article
  14. Insights fromInternational journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2024
    Review
  15. Enhancement of Boiling Histotripsy by Steering the Focus Axially During the Pulse Delivery.IEEE transactions on ultrasonics, ferroelectrics, and frequency control · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. The histotripsy spectrum: differences and similarities in techniques and instrumentation.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

John R ChevilletFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Tatiana D KhokhlovaFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Maria D GiraldezFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
George R SchadeFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Frank StarrFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Yak-Nam WangFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Emily N GallichotteFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Kai WangFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Joo Ha HwangFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.
Muneesh TewariFrom the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Wash (J.R.C., E.N.G., M.D.G., M.T.); Institute for Systems Biology, Seattle, Wash (J.R.C., K.W.); Department of Medicine (T.D.K., J.H.H.), Department of Urology (G.R.S.), and Applied Physics Laboratory (F.S., Y.N.W.), University of Washington, Seattle, Wash; and Departments of Internal Medicine (M.D.G., M.T.) and Biomedical Engineering, Center for Computational Medicine and Bioinformatics, and the Biointerfaces Institute (M.T.), University of Michigan, 109 Zina Pitcher Pl, 1502 BSRB, SPC 2200, Ann Arbor, MI 48109.

Funding

Quantitative Systems BiologyP50GM076547 · NIGMS · INSTITUTE FOR SYSTEMS BIOLOGY · PI AITCHISON, JOHN D. · 2006 to 2016
$30.6M
Nonlinear Acoustics in Calibration/Metrology of High Intensity Focused UltrasoundR01EB007643 · NIBIB · UNIVERSITY OF WASHINGTON · PI KHOKHLOVA, VERA · 2008 to 2020
$6.9M
RNA as a Hormone: Systemic Signaling in Mammals via Circulating, Cell-Free SmallR01DK085714 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TEWARI, MUNEESH · 2009 to 2015
$4.0M
Blood-based biomarker amplification using high intensity focused ultrasound (HIFUK01EB015745 · NIBIB · UNIVERSITY OF WASHINGTON · PI KHOKHLOVA, TATIANA · 2012 to 2016
$722k
NIBIB NIH HHS K01 EB015745NIBIB NIH HHS R01 EB007643NIDDK NIH HHS R01 DK085714NIGMS NIH HHS P50 GM076547
6 · The paper itself

Abstract

Purpose To compare the abilities of three pulsed focused ultrasound regimes (that cause tissue liquefaction, permeabilization, or mild heating) to release tumor-derived microRNA into the circulation in vivo and to evaluate release dynamics. Materials and Methods All rat experiments were approved by the University of Washington Institutional Animal Care and Use Committee. Reverse-transcription quantitative polymerase chain reaction array profiling was used to identify candidate microRNA biomarkers in a rat solid tumor cell line. Rats subcutaneously grafted with these cells were randomly assigned among three pulsed focused ultrasound treatment groups: (a) local tissue liquefaction via boiling histotripsy, (b) tissue permeabilization via inertial cavitation, and (c) mild (<10°C) heating of tissue, as well as a sham-treated control group. Blood specimens were drawn immediately prior to treatment and serially over 24 hours afterward. Plasma microRNA was quantified with reverse-transcription quantitative polymerase chain reaction, and statistical significance was determined with one-way analysis of variance (Kruskal-Wallis and Friedman tests), followed by the Dunn multiple-comparisons test. Results After tissue liquefaction and cavitation treatments (but not mild heating), plasma quantities of candidate biomarkers increased significantly (P value range, <.0001 to .04) relative to sham-treated controls. A threefold to 32-fold increase occurred within 15 minutes after initiation of pulsed focused ultrasound tumor treatment, and these increases persisted for 3 hours. Histologic examination confirmed complete liquefaction of the targeted tumor area with boiling histotripsy, in addition to areas of petechial hemorrhage and tissue disruption by means of cavitation-based treatment. Conclusion Mechanical tumor tissue disruption with pulsed focused ultrasound-induced bubble activity significantly increases the plasma abundance of tumor-derived microRNA rapidly after treatment.

Indexed as

High-Intensity Focused Ultrasound AblationAnimalsBiomarkers, TumorBiopsyDisease Models, AnimalMaleMicroRNAsProstateProstatic NeoplasmsRatsBiomarkers, TumorMicroRNAs

Identifiers

PMID27802108
PMCPMC5375625

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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.