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A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, May 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (51st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

Mentioned by

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1 patent

Citations

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44 Dimensions

Readers on

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31 Mendeley
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Title
A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma
Published in
Journal of Experimental & Clinical Cancer Research, May 2018
DOI 10.1186/s13046-018-0765-8
Pubmed ID
Authors

Hanjie Yi, Xianglei Yan, Qiuyun Luo, Luping Yuan, Baoxia Li, Wentao Pan, Lin Zhang, Haibo Chen, Jing Wang, Yubin Zhang, Yifan Zhai, Miao-Zhen Qiu, Da-Jun Yang

Abstract

Gastric cancer is the leading cause of cancer related death worldwide. Radiation alone or combined with chemotherapy plays important role in locally advanced and metastatic gastric adenocarcinoma. MDM2-p53 interaction and downstream signaling affect cellular response to DNA damage which leads to cell cycle arrest and apoptosis. Therefore, restoring p53 function by inhibiting its interaction with MDM2 is a promising therapeutic strategy for cancer. APG-115 is a novel small molecule inhibitor which blocks the interaction of MDM2 and p53. In this study, we investigated that the radiosensitivity of APG-115 in gastric adenocarcinoma in vitro and in vivo. The role of APG-115 in six gastric cancer cells viability in vitro was determined by CCK-8 assay. The expression level of MDM2, p21, PUMA and BAX in AGS and MKN45 cell lines was measured via real-time PCR (RT-PCR). The function of treatment groups on cell cycle and cell apoptosis were detected through Flow Cytometry assay. Clonogenic assays were used to measure the radiosensitivity of APG-115 in p53 wild type gastric cancer cell lines. Western blot was conducted to detect the protein expressions of mdm2-p53 signal pathway. Xenograft models in nude mice were established to explore the radiosensitivity role of APG-115 in gastric cancer cells in vivo. We found that radiosensitization by APG-115 occurred in p53 wild-type gastric cancer cells. Increasing apoptosis and cell cycle arrest was observed after administration of APG-115 and radiation. Radiosensitivity of APG-115 was mainly dependent on MDM2-p53 signal pathway. In vivo, APG-115 combined with radiation decreased xenograft tumor growth much more significantly than either single treatment. Moreover, the number of proliferating cells (Ki-67) significantly decreased in combination group compared with single treatment group. In summary, we found that combination of MDM2-p53 inhibitor (APG-115) and radiotherapy can enhance antitumor effect both in vitro and in vivo. This is the first report on radiosensitivity of APG-115 which shed light on clinical trial of the combination therapy of radiation with APG-115 in gastric adenocarcinoma.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Other 4 13%
Researcher 4 13%
Student > Ph. D. Student 4 13%
Student > Doctoral Student 3 10%
Student > Master 2 6%
Other 5 16%
Unknown 9 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 23%
Medicine and Dentistry 5 16%
Agricultural and Biological Sciences 2 6%
Chemistry 2 6%
Immunology and Microbiology 1 3%
Other 1 3%
Unknown 13 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 12 May 2022.
All research outputs
#8,538,940
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#574
of 2,382 outputs
Outputs of similar age
#137,215
of 338,899 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#11
of 33 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,382 research outputs from this source. They receive a mean Attention Score of 4.8. This one has gotten more attention than average, scoring higher than 68% of its peers.
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 338,899 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.