Evidence map›Paper›PMID 31907371›Full record

ArticleCell death & disease2020

Novel HDAC inhibitor Chidamide synergizes with Rituximab to inhibit diffuse large B-cell lymphoma tumour growth by upregulating CD20.

Xu-Wen Guan, Hua-Qing Wang, Wei-Wei Ban, Zhi Chang, Hai-Zhu Chen, Li Jia, Feng-Ting Liu

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

Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

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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

7 authors at 4 institutions in 2 countries.

Xu-Wen GuanDepartment of Hematology and Oncology, Tianjin Union Medical Center, 300191, Tianjin, China.
Hua-Qing WangDepartment of Hematology and Oncology, Tianjin Union Medical Center, 300191, Tianjin, China.
Wei-Wei BanTianjin Medical University, Tianjin, China.
Zhi ChangDepartment of Hematology and Oncology, Tianjin Union Medical Center, 300191, Tianjin, China.
Hai-Zhu ChenDepartment of Hematology and Oncology, Tianjin Union Medical Center, 300191, Tianjin, China.
Li JiaCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-6076-8455
Feng-Ting LiuDepartment of Hematology and Oncology, Tianjin Union Medical Center, 300191, Tianjin, China. liufengtingtj@outlook.com.
Tianjin People's Hospital · CNQueen Mary University of London · GBTianjin Medical University Cancer Institute and Hospital · CNUnion Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Loss of CD20 is a major obstacle for the retreatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL) with Rituximab-associated regimens. Histone deacetylation causes gene silencing and inhibits CD20 expression. Chidamide is a novel inhibitor for histone deacetylases (HDACs). We hypothesize that Chidamide could overcome Rituximab-mediated down-regulation of CD20 and facilitate Rituximab-induced killing. In this study, we determine the mechanism of synergy of Chidamide with Rituximab in DLBCL using in vitro and in vivo models. We found that the levels of CD20 protein surface expression on five DLBCL cell lines were significantly and positively correlated with the sensitivities of cells to Rituximab. Treatment with Rituximab significantly reduced CD20 surface expression at the protein levels. RNA sequencing showed that Chidamide significantly increased expression of more than 2000 transcriptomes in DLBCL cells, around 1000 transcriptomes belong to the cell membrane and cell periphery pathways, including MS4A1. Chidamide significantly increased CD20 surface expression in DLBCL cell lines. Combination with Chidamide significantly synergized Rituximab-induced cell death in vitro and significantly inhibited tumour growth in DLBCL-bearing xenograft mice. A patient with relapsed/refractory DLBCL achieved a complete response after three cycles combined treatment with Chidamide and Rituximab. In conclusion, our data demonstrate for the first time that inhibition of HDACs by Chidamide significantly enhanced Rituximab-induced tumour growth inhibition in vitro and in vivo. We propose that CD20 surface expression should be used clinically to evaluate treatment response in patients with DLBCL. Chidamide is a promising sensitizer for the retreatment of DLBCL with Rituximab.

Indexed as

Up-RegulationAminopyridinesAnimalsAntigens, CD20ApoptosisBenzamidesCell LineageCell Line, TumorCell ProliferationDown-RegulationDrug SynergismGene Expression Regulation, NeoplasticGene OntologyHematopoiesisHistone Deacetylase InhibitorsHumansAminopyridinesAntigens, CD20BenzamidesHistone Deacetylase InhibitorsN-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamideRituximabRNA, Messenger

Identifiers

PMID31907371
PMCPMC6944697
OpenAlexW2998650473

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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.