Evidence map›Paper›PMID 24736631›Full record

ArticlePloS one2014

Dll4-notch signalling blockade synergizes combined ultrasound-stimulated microbubble and radiation therapy in human colon cancer xenografts.

Ahmed El Kaffas, Joris Nofiele, Anoja Giles, Song Cho, Stanley K Liu, Gregory J Czarnota

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
  2. Review
  3. Overview of Therapeutic Ultrasound Applications and Safety Considerations: 2024 Update.Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Application of Ultrasound Combined with Microbubbles for Cancer Therapy.International journal of molecular sciences · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

6 authors at 3 institutions in 1 country.

Ahmed El KaffasDepartment of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Joris NofieleDepartments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Anoja GilesDepartment of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Song ChoDepartment of Oncology Research, MedImmune, Maryland, United States of America.
Stanley K LiuDepartment of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Gregory J CzarnotaDepartment of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Sunnybrook Health Science Centre · CAHealth Sciences Centre · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumour vasculature acts as an essential lifeline for tumour progression and facilitates metastatic spread. Novel vascular targeting strategies aiming to sustain vascular shutdown could potentially induce substantial damage, resulting in a significant tumour growth delay. We investigated the combination of two novel complementary vascular targeting agents with radiation therapy in a strategy aiming to sustain vascular disruption. Experiments were carried out with delta-like ligand 4 (Dll4) blockade (angiogenesis deregulator) treatment administered in combination with a radiation-based vascular destruction treatment in a highly aggressive well-perfused colon cancer tumour line implanted in female athymic nude mice. Tumours were treated with permutations of radiation, ultrasound-stimulated microbubbles (USMB) and Dll4 monoclonal antibody (mAb). Tumour vascular response was assessed with three-dimensional power Doppler ultrasound to measure active flow and immunohistochemistry. Tumour response was assessed with histochemical assays and longitudinal measurements of tumour volume. Our results suggest a significant tumour response in animals treated with USMB combined with radiation, and Dll4 mAb, leading to a synergistic tumour growth delay of up to 24 days. This is likely linked to rapid cell death within the tumour and a sustained tumour vascular shutdown. We conclude that the triple combination treatments cause a vascular shutdown followed by a sustained inhibition of angiogenesis and tumour cell death, leading to a rapid tumour vascular-based 'collapse' and a significant tumour growth delay.

Indexed as

MicrobubblesSignal TransductionAnimalsCell DeathCell Line, TumorColonic NeoplasmsDisease Models, AnimalHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMicePlatelet Endothelial Cell Adhesion Molecule-1Receptors, NotchTumor BurdenUltrasonography, Doppler, ColorXenograft Model Antitumor Assaysdelta proteinIntracellular Signaling Peptides and ProteinsMembrane ProteinsPlatelet Endothelial Cell Adhesion Molecule-1Receptors, Notch

Identifiers

PMID24736631
PMCPMC3988033
OpenAlexW2076898121

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.