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X Demographics
Mendeley readers
Attention Score in Context
| Title |
A Small β-Carboline Derivative “B-9-3” Modulates TGF-β Signaling Pathway Causing Tumor Regression in Vivo
|
|---|---|
| Published in |
Frontiers in Pharmacology, July 2018
|
| DOI | 10.3389/fphar.2018.00788 |
| Pubmed ID | |
| Authors |
Hui Zhong, Abdelkader Daoud, Jichun Han, Xiaohong An, Caili Qiao, Lanlan Duan, Yichuan Wang, Zhenfeng Chen, Jia Zhou, Jing Shang |
| Abstract |
Targeting tumor microenvironment (TME) is crucial in order to overcome the anti-cancer therapy resistance. In this study, we report the antitumor activity of a newly synthesized β-carboline derivative "B-9-3." Here, this small molecule showed a promising antitumor activity in vivo along with an enhanced immune response as reflected by a reduction of regulatory T cells and increased CD4+/CD8+ T cells. Further, B-9-3 decreased the number of myofibroblasts not only in the tumor but also in the lung suggesting an anti-metastatic action. The reduction of myofibroblasts was associated with lower expression of epithelial-to-mesenchymal transition markers and a decrease of phosphorylated SMAD2/3 complex indicating the implication of TGF-β signaling pathway in B-9-3's effect. The blockade of myofibroblasts induction by B-9-3 was also verified in vitro in human fibroblasts treated with TGF-β. To elucidate the mechanism of B-9-3's action on TGF-β pathway, first, we investigated the molecular interaction between B-9-3 and TGF-β receptors using docking method. Data showed a weak interaction of B-9-3 with the ATP-binding pocket of TGFβRI but a strong one with a ternary complex formed of extracellular domains of TGFβRI, TGFβRII, and TGF-β. In addition, the role of TGFβRI and TGFβRII in B-9-3's activity was explored in vitro. B-9-3 did not decrease any of the two receptors' protein level and only reduced phosphorylated SMAD2/3 suggesting that its effect was more probably due to its interaction with the ternary complex rather than decreasing the expression of TGF-β receptors or interfering with their ATP-binding domains. B-9-3 is a small active molecule which acts on the TGF-β signaling pathway and improves the TME to inhibit the proliferation and the metastasis of the tumor with the potential for clinical application. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 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 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 5 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Postgraduate | 1 | 20% |
| Student > Doctoral Student | 1 | 20% |
| Student > Master | 1 | 20% |
| Unknown | 2 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 1 | 20% |
| Nursing and Health Professions | 1 | 20% |
| Chemistry | 1 | 20% |
| Medicine and Dentistry | 1 | 20% |
| Unknown | 1 | 20% |
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 04 August 2018.
All research outputs
#20,529,173
of 23,098,660 outputs
Outputs from Frontiers in Pharmacology
#10,328
of 16,458 outputs
Outputs of similar age
#287,671
of 329,151 outputs
Outputs of similar age from Frontiers in Pharmacology
#275
of 407 outputs
Altmetric has tracked 23,098,660 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 16,458 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,151 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 407 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.