Evidence map›Paper›PMID 34440874›Full record

ArticleCells2021

Intracellular Signaling Responses Induced by Radiation within an In Vitro Bone Metastasis Model after Pre-Treatment with an Estrone Analogue.

Jolene Helena, Anna Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne Mercier

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. 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 2 institutions in 1 country.

Jolene HelenaDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.ORCID 0000-0002-9657-9728
Anna JoubertDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.ORCID 0000-0002-6931-7554
Peace MabetaDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.ORCID 0000-0003-2218-7235
Magdalena CoetzeeDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Roy LakierDepartment of Radiation Oncology, Steve Biko Academic Hospital, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Anne MercierDepartment of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.ORCID 0000-0002-2030-9879
University of Pretoria · ZASteve Biko Hospital · ZA

Funding

Cancer Association of South Africa AOV741Cancer Association of South Africa AOW228Struwig-Germeshuysen Trust AON074The National Research Foundation NRF 105992, 90523, 85818The School of Medicine Research Committee of the University of Pretoria (RESCOM) AOR984
6 · The paper itself

Abstract

2-Ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16) is an in silico-designed estradiol analogue which has improved the parent compound's efficacy in anti-cancer studies. In this proof-of-concept study, the potential radiosensitizing effects of ESE-16 were investigated in an in vitro deconstructed bone metastasis model. Prostate (DU 145) and breast (MDA-MB-231) tumor cells, osteoblastic (MC3T3-E1) and osteoclastic (RAW 264.7) bone cells and human umbilical vein endothelial cells (HUVECs) were representative components of such a lesion. Cells were exposed to a low-dose ESE-16 for 24 hours prior to radiation at non-lethal doses to determine early signaling and molecular responses of this combination treatment. Tartrate-resistant acid phosphatase activity and actin ring formation were investigated in osteoclasts, while cell cycle progression, reactive oxygen species generation and angiogenic protein expression were investigated in HUVECs. Increased cytotoxicity was evident in tumor and endothelial cells while bone cells appeared to be spared. Increased mitotic indices were calculated, and evidence of increased deoxyribonucleic acid damage with retarded repair, together with reduced metastatic signaling was observed in tumor cells. RAW 264.7 macrophages retained their ability to differentiate into osteoclasts. Anti-angiogenic effects were observed in HUVECs, and expression of hypoxia-inducible factor 1-α was decreased. Through preferentially inducing tumor cell death and potentially inhibiting neovascularization whilst preserving bone physiology, this low-dose combination regimen warrants further investigation for its promising therapeutic application in bone metastases management, with the additional potential of limited treatment side effects.

Indexed as

ApoptosisBone Morphogenetic Protein 7Bone NeoplasmsCell CycleCell Line, TumorCell SurvivalDNA DamageEstrenesHumansHuman Umbilical Vein Endothelial CellsHypoxia-Inducible Factor 1, alpha SubunitMatrix Metalloproteinase 9OsteoclastsRadiation-Sensitizing AgentsSignal TransductionSulfonamides2-ethyl-3-O-sulfamoylestra-1,3,5(10)16-tetraeneBMP7 protein, humanBone Morphogenetic Protein 7EstrenesHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMatrix Metalloproteinase 9MMP9 protein, humanRadiation-Sensitizing AgentsSulfonamidesSuperoxidesangiogenesisapoptosisbone metastasiscancerESE-16osteoblastsosteoclastsradiosensitization

Identifiers

PMID34440874
PMCPMC8394480
OpenAlexW3194206624

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.