Evidence map›Paper›PMID 39004737›Full record

ArticleMolecular cancer2024

Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the "Smart" exosome nanoparticle therapy.

Xin Wu, Chunmei Ban, Woding Deng, Xuewei Bao, Ning Tang, Yupeng Wu, Zhixuan Deng, Jianbin Xiong, Qiangqiang Zhao

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In one paragraph

Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

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3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

9 authors.

Xin WuDepartment of Spine Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Chunmei BanDepartment of Hematology, Liuzhou People's Hospital affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
Woding DengXiangya School of Medicine, Central South University, Changsha, China.
Xuewei BaoDepartment of Hematology, The Qinghai Provincial People's Hospital, Xining, Qinghai, China.
Ning TangDepartment of Orthopedics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yupeng WuDepartment of Spine Surgery, First Affiliated Hospital of University of South China, Hengyang, Hengyang, Hunan, China.
Zhixuan DengInstitute of Cell Biology, Hengyang Medical School, University of South China, Hengyang, Hengyang, Hunan, China.
Jianbin XiongDepartment of Orthopaedics, Liuzhou Municipal Liutie Central Hospital, Liuzhou, Guangxi, China.
Qiangqiang ZhaoDepartment of Hematology, Liuzhou People's Hospital affiliated to Guangxi Medical University, Liuzhou, Guangxi, China. zgxyws@163.com.

Funding

National Natural Science Foundation of China 82260365
6 · The paper itself

Abstract

backgroundDiffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4's resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL.

methodsWe utilized a DLBCL-resistant cell line with high PDK4 expression (SU-DHL-2/R). We infected it with short hairpin RNA (shRNA) lentivirus for RNA sequencing, aiming to identify significantly downregulated mRNA in resistant cells. Techniques including immunofluorescence, immunohistochemistry, and Western blotting were employed to determine PDK4's localization and expression in resistant cells and its regulatory role in phosphorylation of Histone deacetylase 8 (HDAC8). Furthermore, we engineered advanced exosome nanoparticle complexes, aCD20@Exo

resultsWe found that PDK4 initiates HDAC8 activation by phosphorylating the Ser-39 site, suppressing CD20 protein expression through deacetylation. The aCD20@Exo

conclusionsThis study demonstrates that PDK4 contributes to rituximab resistance in DLBCL by modulating CD20 expression via HDAC8 phosphorylation. The designed exosome nanoparticles effectively overcome this resistance by targeting the PDK4/HDAC8/CD20 pathway, representing a promising approach for drug delivery and treating patients with Rituximab-resistant DLBCL.

Indexed as

Drug Resistance, NeoplasmExosomesLymphoma, Large B-Cell, DiffuseNanoparticlesRituximabAnimalsApoptosisCell Line, TumorGene Expression Regulation, NeoplasticHumansMicePyruvate Dehydrogenase Acetyl-Transferring KinaseXenograft Model Antitumor AssaysPDK4 protein, humanPyruvate Dehydrogenase Acetyl-Transferring KinaseRituximabAdvanced exosome nanoparticlesDiffuse large B-cell lymphomaImmunotherapyPDK4Rituximab resistanceTargeted therapy

Identifiers

PMID39004737
PMCPMC11247735

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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.