Evidence map›Paper›PMID 29720580›Full record

ArticleMedical science monitor : international medical journal of experimental and clinical research2018

Targeting mTORC1/2 Complexes Inhibit Tumorigenesis and Enhance Sensitivity to 5-Flourouracil (5-FU) in Hepatocellular Carcinoma: A Preclinical Study of mTORC1/2-Targeted Therapy in Hepatocellular Carcinoma (HCC).

Yu Zhang, Qing-An Jia, Dhruba Kadel, Xiao-Fei Zhang, Quan-Bao Zhang

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Medical science monitor : international medical journal of experimental and clinical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 48 citations in OpenAlex.

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  9. Pharmacogenomics and personalized medicine · 2021
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  14. The nucleolus, an ally, and an enemy of cancer cells.Histochemistry and cell biology · 2018
    Review
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

5 authors at 3 institutions in 1 country.

Yu ZhangDepartment of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland).
Qing-An JiaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
Dhruba KadelDepartment of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland).
Xiao-Fei ZhangDepartment of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland).
Quan-Bao ZhangDepartment of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland).
Fudan University · CNHuashan Hospital · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND Although 5-Flourouracil(5-FU) is used as the first-choice treatment for advanced hepatocellular carcinoma (HCC), it is associated with acquired and intrinsic resistance. Hyperactivation of mTOR signaling has been linked to tumorigenesis and chemoresistance in HCC. The aim of this study was to evaluate and compare the antitumor effects of mTORC1 inhibitor everolimus and mTORC1/2 inhibitor AZD8055 and to examine the interaction between 5-FU and mTORC1/2 inhibitor in HCC. MATERIAL AND METHODS Using cultured HCC cells and mouse xenograft, the antitumor effects of everolimus and AZD8055 were analyzed as mono- and combination therapy with 5-Flourouracil. RESULTS TSC2-deficient HCC cell lines were more sensitive to everolimus and AZD8055. AZD8055, but not everolimus, potently prevented cells from transitioning from G1 phase to S phase in TSC2-high-expressing HCC cells. AZD8055 reduced phosphorylation of both mTORC1 and mTORC2 substrates. In contrast, everolimus reduced the phosphorylation of mTORC1 substrates, but increased the phosphorylation of AKT. Notably, AZD8055, but not everolimus, synergistically enhanced the efficacy of 5-FU via reversing 5-FU-induced upregulation of P-glycoprotein (P-gp). The synergistic antitumor effect of AZD8055 and 5-FU was also observed in a HCC xenograft mouse model. CONCLUSIONS TSC2 in HCC is a promising efficacy-predicting biomarker for the treatment of mTORC1/2 inhibitor. AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells. Moreover, the combination of mTORC1/2 inhibitor with 5-FU appears to be a promising option for HCC patients refractory to chemotherapy.

Indexed as

Molecular Targeted TherapyAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1CarcinogenesisCarcinoma, HepatocellularCell Cycle CheckpointsCell Line, TumorCell ProliferationDrug SynergismEverolimusFluorouracilG1 PhaseHumansLiver NeoplasmsMaleMechanistic Target of Rapamycin Complex 1(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanolATP Binding Cassette Transporter, Subfamily B, Member 1EverolimusFluorouracilMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesTSC2 protein, humanTsc2 protein, mouseTuberous Sclerosis Complex 2 ProteinTumor Suppressor Proteins

Identifiers

PMID29720580
PMCPMC5952809
OpenAlexW2799836092

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.