Evidence map›Paper›PMID 26592553›Full record

ArticleScientific reports2015

MLN4924 Synergistically Enhances Cisplatin-induced Cytotoxicity via JNK and Bcl-xL Pathways in Human Urothelial Carcinoma.

I-Lin Ho, Kuan-Lin Kuo, Shing-Hwa- Liu, Hong-Chiang Chang, Ju-Ton Hsieh, June-Tai Wu, Chih-Kang Chiang, Wei-Chou Lin, Yu-Chieh Tsai, Chien-Tso Chou and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

29 citing papers in PubMed, 45 citations in OpenAlex.

  1. Regulation of the water channel aquaporin-2 by cullin E3 ubiquitin ligases.American journal of physiology. Renal physiology · 2024
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  2. Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024
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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

14 authors at 3 institutions in 1 country.

I-Lin HoDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Kuan-Lin KuoDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Shing-Hwa- LiuGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hong-Chiang ChangDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Ju-Ton HsiehDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
June-Tai WuGraduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chih-Kang ChiangGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Wei-Chou LinDepartment of Pathology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Yu-Chieh TsaiDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Chien-Tso ChouDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Chen-Hsun HsuDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Yeong-Shiau PuDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
Chung-Sheng ShiGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Kuo-How HuangDepartment of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.
National Taiwan University Hospital · TWNational Taiwan University · TWChang Gung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma. However, the response rate is only 40-65%. This study investigated the anti-tumor effect and underlying mechanisms of the combination of cisplatin and the NEDD8-activating enzyme inhibitor MLN4924 in human bladder urothelial carcinoma. The combination of cisplatin and MLN4924 exerted synergistic cytotoxicity on two high-grade bladder urothelial carcinoma cell lines, NTUB1 and T24 (combination index <1). MLN4924 also potentiated the cisplatin-induced apoptosis and activation of caspase-3 and -7, phospho-histone H2A.X and PARP. c-Jun N-terminal kinase (JNK) activation and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) were also observed during cisplatin and MLN4924 treatment. Inhibition of JNK activation partially restored cell viability and Bcl-xL expression. Bcl-xL overexpression also rescued cell viability. MLN4924 significantly potentiated cisplatin-induced tumor suppression in urothelial carcinoma xenograft mice. In summary, MLN4924 synergistically enhanced the anti-tumor effect of cisplatin via an increase in DNA damage, JNK activation and down-regulation of Bcl-xL in urothelial carcinoma cells. These findings provide a new therapeutic strategy for the treatment of bladder cancer.

Indexed as

AnimalsAntineoplastic AgentsApoptosisbcl-X ProteinCarcinoma, Transitional CellCaspase 3Caspase 7Cell Line, TumorCisplatinCyclopentanesDrug CombinationsDrug SynergismGene Expression Regulation, NeoplasticHistonesHumansMAP Kinase Kinase 4Antineoplastic AgentsBCL2L1 protein, humanbcl-X ProteinCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7CisplatinCyclopentanesDrug CombinationsH2AX protein, humanHistonesMAP Kinase Kinase 4NEDD8 ProteinNEDD8 protein, humanpevonedistatPoly(ADP-ribose) PolymerasesPyrimidinesUbiquitins

Identifiers

PMID26592553
PMCPMC4655337
OpenAlexW2172572878

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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.