Evidence map›Paper›PMID 25947947›Full record

ArticleBMC cancer2015

Reducing tumor growth and angiogenesis using a triple therapy measured with Contrast-enhanced ultrasound (CEUS).

Philipp Marius Paprottka, Svenja Roßpunt, Michael Ingrisch, Clemens C Cyran, Konstantin Nikolaou, Maximilian F Reiser, Brigitte Mack, Olivier Gires, Dirk A Clevert, Pamela Zengel

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

10 authors at 1 institution in 1 country.

Philipp Marius PaprottkaInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. philipp.paprottka@med.uni-muenchen.de.
Svenja RoßpuntInstitute for Ear, Nose and Throat Medicine, Ludwig Maximilian University Hospital, Munich, Germany. svenja-rosspunt@web.de.
Michael IngrischInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. michael.ingrisch@med.lmu.de.
Clemens C CyranInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. clemens.cyran@med.lmu.de.
Konstantin NikolaouInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. konstantin.nikolaou@uni-tuebingen.de.
Maximilian F ReiserInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. maximilian.reiser@med.lmu.de.
Brigitte MackInstitute for Ear, Nose and Throat Medicine, Ludwig Maximilian University Hospital, Munich, Germany. brigitte.mack@med.lmu.de.
Olivier GiresInstitute for Ear, Nose and Throat Medicine, Ludwig Maximilian University Hospital, Munich, Germany. olivier.gires@med.lmu.de.
Dirk A ClevertInstitute for Clinical Radiology, Ludwig Maximilian University Hospital, Munich, Germany. dirk.clevert@med.lmu.de.
Pamela ZengelInstitute for Ear, Nose and Throat Medicine, Ludwig Maximilian University Hospital, Munich, Germany. pamela.zengel@med.lmu.de.
Ludwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo evaluate the in vivo response by detecting the anti-angiogenic and invasion-inhibiting effects of a triple-combination-therapy in an experimental-small-animal-squamous-cell-carcinoma-model using the "flash-replenishment" (FR) method to assess tissue hemodynamics via contrast-enhanced-ultrasound (CEUS).

methodsHuman hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 22-female-athymic-nude-rats. After seven days of subcutaneous tumor growth, FR-measurements were performed on each rat. Treatment-group and control-group were treated every day for a period of one week, with the treatment-group receiving solvents containing a triple therapy of Upamostat®, Celecoxib® and Ilomastat® and the control-group solvents only. On day seven, follow-up measurements were performed using the same measurement protocol to assess the effects of the triple therapy. VueBox® was used to quantify the kinetic parameters and additional immunohistochemistry analyses were performed for comparison with and validation of the CEUS results against established methods (Proliferation/Ki-67, vascularization/CD31, apoptosis/caspase3).

resultsCompared to the control-group, the treatment-group that received the triple-therapy resulted in a reduction of tumor growth by 48.6% in size. Likewise, the immunohistochemistry results showed significant decreases in tumor proliferation and vascularization in the treatment-group in comparison to the control-group of 26%(p ≤ 0.05) and 32.2%(p ≤ 0.05) respectively. Correspondingly, between the baseline and follow-up measurements, the therapy-group was associated with a significant(p ≤ 0.01) decrease in the relative-Blood-Volume(rBV) in both the whole tumor(wt) and hypervascular tumor(ht) areas (p ≤ 0.01), while the control-group was associated with a significant (p ≤ 0.01) increase of the rBV in the wt area and a non-significant increase (p ≤ 0.16) in the ht area. The mean-transit-time (mTT) of the wt and the ht areas showed a significant increase (p ≤ 0.01) in the follow-up measurements in the therapy group.

conclusionThe triple-therapy is feasible and effective in reducing both tumor growth and vascularization. In particular, compared with the placebo-group, the triple-therapy-group resulted in a reduction in tumor growth of 48.6% in size when assessed by CEUS and a significant reduction in the number of vessels in the tumor of 32% as assessed by immunohistochemistry. As the immunohistochemistry supports the CEUS findings, CEUS using the "flash replenishment"(FR) method appears to provide a useful assessment of the anti-angiogenic and invasion-inhibiting effects of a triple combination therapy.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsCelecoxibCell Line, TumorCell ProliferationFemaleHumansHydroxamic AcidsHypopharyngeal NeoplasmsIndolesNeovascularization, PathologicOximesPiperazinesRatsSulfonamidesTreatment OutcomeCelecoxibHydroxamic AcidsilomastatIndolesOximesPiperazinesSulfonamidesupamostat

Identifiers

PMID25947947
PMCPMC4435644
OpenAlexW1948348338

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.