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Attention Score in Context
| Title |
Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis
|
|---|---|
| Published in |
Chinese Medical Journal, August 2023
|
| DOI | 10.1097/cm9.0000000000002816 |
| Pubmed ID | |
| Authors |
Fangming Liu, Yuting Wu, Baohui Zhang, Shuhui Yang, Kezhuo Shang, Jie Li, Pengju Zhang, Weiwei Deng, Linlin Chen, Liang Zheng, Xiaochen Gai, Hongbing Zhang |
| Abstract |
Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 (CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 (β-cateninΔ(ex3)/+), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus (HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| China | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 42. 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 01 November 2023.
All research outputs
#994,888
of 25,815,269 outputs
Outputs from Chinese Medical Journal
#71
of 2,665 outputs
Outputs of similar age
#17,957
of 359,215 outputs
Outputs of similar age from Chinese Medical Journal
#2
of 65 outputs
Altmetric has tracked 25,815,269 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,665 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has done particularly well, scoring higher than 97% 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 359,215 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.