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Mendeley readers
Attention Score in Context
| Title |
Hedgehog inhibitor sonidegib potentiates 177Lu-octreotate therapy of GOT1 human small intestine neuroendocrine tumors in nude mice
|
|---|---|
| Published in |
BMC Cancer, August 2017
|
| DOI | 10.1186/s12885-017-3524-x |
| Pubmed ID | |
| Authors |
Johan Spetz, Britta Langen, Nils Rudqvist, Toshima Z. Parris, Khalil Helou, Ola Nilsson, Eva Forssell-Aronsson |
| Abstract |
(177)Lu-octreotate can be used to treat somatostatin receptor expressing neuroendocrine tumors. It is highly effective in animal models, but clinical studies have so far only demonstrated low cure rates. Hedgehog inhibitors have shown therapeutic effect as monotherapy in neuroendocrine tumor model systems and might be one option to enhance the efficacy of (177)Lu-octreotate therapy. The aim of this study was to determine the therapeutic effect of combination therapy using (177)Lu-octreotate and the Hedgehog signaling pathway inhibitor sonidegib. GOT1-bearing BALB/c nude mice were treated with either sonidegib (80 mg/kg twice a week via oral gavage), a single injection of 30 MBq (177)Lu-octreotate i.v., or a combination of both. Untreated animals served as controls. Tumor size was measured twice-weekly using calipers. The animals were killed 41 d after injection followed by excision of the tumors. Total RNA was extracted from each tumor sample and then subjected to gene expression analysis. Gene expression patterns were compared with those of untreated controls using Nexus Expression 3.0, IPA and Gene Ontology terms. Western blot was carried out on total protein extracted from the tumor samples to analyze activation-states of the Hh and PI3K/AKT/mTOR pathways. Sonidegib monotherapy resulted in inhibition of tumor growth, while a significant reduction in mean tumor volume was observed after (177)Lu-octreotate monotherapy and combination therapy. Time to progression was prolonged in the combination therapy group compared with (177)Lu-octreotate monotherapy. Gene expression analysis revealed a more pronounced response following combination therapy compared with both monotherapies, regarding the number of regulated genes and biological processes. Several cancer-related signaling pathways (i.e. Wnt/β-catenin, PI3K/AKT/mTOR, G-protein coupled receptor, and Notch) were affected by the combination therapy, but not by either monotherapy. Protein expression analysis revealed an activation of the Hh- and PI3K/AKT/mTOR pathways in tumors exposed to (177)Lu-octreotate monotherapy and combination therapy. A comparative analysis of the different treatment groups showed that combination therapy using sonidegib and (177)Lu-octreotate could be beneficial to patients with neuroendocrine tumors. Gene expression analysis revealed a functional interaction between sonidegib and (177)Lu-octreotate, i.e. several cancer-related signaling pathways were modulated that were not affected by either monotherapy. Protein expression analysis indicated a possible PI3K/AKT/mTOR-dependent activation of the Hh pathway, independent of SMO. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 21 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 19% |
| Student > Bachelor | 3 | 14% |
| Other | 1 | 5% |
| Professor | 1 | 5% |
| Lecturer | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 9 | 43% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 19% |
| Medicine and Dentistry | 4 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
| Mathematics | 1 | 5% |
| Physics and Astronomy | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 8 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 August 2017.
All research outputs
#20,442,790
of 22,997,544 outputs
Outputs from BMC Cancer
#6,528
of 8,356 outputs
Outputs of similar age
#277,323
of 317,853 outputs
Outputs of similar age from BMC Cancer
#119
of 137 outputs
Altmetric has tracked 22,997,544 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,356 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 137 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.