Evidence map›Paper›PMID 39119834›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Methuosis Inducer SGI-1027 Cooperates with Everolimus to Promote Apoptosis and Pyroptosis by Triggering Lysosomal Membrane Permeability in Renal Cancer.

Yu Luo, Bing Guan, Xiaoqi Deng, Peide Bai, Haichao Huang, Chaohao Miao, Anran Sun, Zhipeng Li, Dianqiang Yang, Xuegang Wang and 5 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

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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

15 authors.

Yu LuoThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Bing GuanThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Xiaoqi DengDepartment of Nephrology, Zigong Fourth People's Hospital, Zigong, Sichuan, 643000, P. R. China.
Peide BaiThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Haichao HuangThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Chaohao MiaoThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Anran SunThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Zhipeng LiThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Dianqiang YangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
Xuegang WangThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Zhiqiang ShaoXiamen University Laboratory Animal Center, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
Yulong WuDepartment of Urology, The Fifth Hospital of Xiamen, Xiamen, Fujian, 361101, P. R. China.
Jinchun XingThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Bin ChenThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.
Tao WangThe Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, P. R. China.ORCID 0000-0001-6402-5571

Funding

Fujian Provincial Department of Science and Technology 2020J05304Fujian Provincial Department of Science and Technology 2022J011353National Natural Science Foundation of China 82170776National Natural Science Foundation of China 82370763National Natural Science Foundation of China 82370764Xiamen Municipal Bureau of Science and Technology 3502Z20209013
6 · The paper itself

Abstract

The mTOR inhibitor everolimus has been approved as a sequential or second-line therapy for renal cell carcinoma (RCC). However, the development of drug resistance limits its clinical applications. This study aims to address the challenge of everolimus resistance and provide new insights into the treatment of advanced RCC. Here, the cytotoxicity of the DNA methyltransferase 1 (DNMT1) inhibitor SGI-1027 in inducing cell vacuolation and methuosis is discovered and demonstrated for the first time. Additionally, SGI-1027 exerts synergistic effects with everolimus, as their combination suppresses the growth, migration, and invasion of renal cancer cells. Mechanistically, apoptosis and GSDME-dependent pyroptosis triggered by lysosomal membrane permeability (LMP) are observed. The upregulation of GSDME expression and increased lysosomal activity in renal cancer cells provide a therapeutic window for the combination of these two drugs to treat renal cancer. The combination treatment exhibits effective anti-tumor activity and is well tolerated in a subcutaneous tumor model. Overall, this study validates and reveals the specific cytotoxicity property of SGI-1027 and its potent synergistic effect with everolimus, offering new insights into advanced RCC therapy and everolimus-resistance overcoming.

Indexed as

ApoptosisCarcinoma, Renal CellEverolimusKidney NeoplasmsLysosomesPyroptosisAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalHumansImidazolesMiceNaphthoquinonesAntineoplastic AgentsEverolimusImidazolesNaphthoquinonessepantroniumeverolimuslysosomemethuosispyroptosisrenal cell carcinomaSGI‐1027

Identifiers

PMID39119834
PMCPMC11481186

What OpenQuestion holds

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Registered trials

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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.