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通过 iPS 细胞衍生感觉神经元分析探讨预测奥沙利铂诱导的慢性神经病变的人类长非编码 RNA 的血液生物标志物。

Exploration for Blood Biomarkers of Human Long Non-coding RNAs Predicting Oxaliplatin-Induced Chronic Neuropathy Through iPS Cell-Derived Sensory Neuron Analysis.

机构信息

Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.

出版信息

Mol Neurobiol. 2024 Sep;61(9):7168-7180. doi: 10.1007/s12035-024-04017-7. Epub 2024 Feb 19.


DOI:10.1007/s12035-024-04017-7
PMID:38374315
Abstract

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited. In this study, we explored extracellular long non-coding RNAs (lncRNAs) released from primary sensory neurons as biomarker candidates for oxaliplatin-induced peripheral neuropathy. Because many human-specific lncRNA genes exist, we induced peripheral sensory neurons from human induced pluripotent stem cells. Oxaliplatin treatment changed the levels of many lncRNAs in extracellular vesicles (EVs) released from cultured primary sensory neurons. Among them, the levels of release of lncRNAs that were considered to be selectively expressed in dorsal root ganglia were correlated with those of lncRNAs in plasma EV obtained from healthy individuals. Several lncRNAs in plasma EVs early after the initiation of treatment showed greater changes in patients who did not develop chronic neuropathy that persisted for more than 1 year than in those who did. Therefore, these extracellular lncRNAs in plasma EVs may represent predictive biomarkers for the development of chronic peripheral neuropathy induced by oxaliplatin.

摘要

奥沙利铂是一种基于铂的化疗药物,常引起急性和慢性周围感觉神经病,目前尚未确立有效的治疗方法。特别是慢性神经病在治疗完成后甚至可以持续多年,从而降低了患者的生活质量。为避免产生难治性的不良反应,人们期待在治疗早期就可以使用预测性生物标志物。在这项研究中,我们探索了从原代感觉神经元释放的细胞外长链非编码 RNA(lncRNA),作为奥沙利铂诱导的周围神经病的生物标志物候选物。因为存在许多人类特异性 lncRNA 基因,所以我们从人诱导多能干细胞诱导产生周围感觉神经元。奥沙利铂处理改变了培养的原代感觉神经元释放的细胞外囊泡(EV)中许多 lncRNA 的水平。其中,被认为在背根神经节中特异性表达的 lncRNA 的释放水平与从健康个体获得的血浆 EV 中的 lncRNA 水平相关。在治疗开始后早期,血浆 EV 中的几种 lncRNA 在未发展为持续 1 年以上的慢性神经病的患者中变化更大。因此,这些血浆 EV 中的细胞外 lncRNA 可能代表奥沙利铂诱导的慢性周围神经病发展的预测性生物标志物。

相似文献

[1]
Exploration for Blood Biomarkers of Human Long Non-coding RNAs Predicting Oxaliplatin-Induced Chronic Neuropathy Through iPS Cell-Derived Sensory Neuron Analysis.

Mol Neurobiol. 2024-9

[2]
Preventive action of benztropine on platinum-induced peripheral neuropathies and tumor growth.

Acta Neuropathol Commun. 2019-1-18

[3]
Oxaliplatin treatment impairs extension of sensory neuron neurites in vitro through miR-204 overexpression.

Neurotoxicology. 2018-7-18

[4]
Platinum-Based Drugs Cause Mitochondrial Dysfunction in Cultured Dorsal Root Ganglion Neurons.

Int J Mol Sci. 2020-11-16

[5]
Rosmarinic Acid Mitigates Mitochondrial Dysfunction and Spinal Glial Activation in Oxaliplatin-induced Peripheral Neuropathy.

Mol Neurobiol. 2018-2-9

[6]
Identification of drug transporters contributing to oxaliplatin-induced peripheral neuropathy.

J Neurochem. 2018-12-3

[7]
Role of the DNA base excision repair protein, APE1 in cisplatin, oxaliplatin, or carboplatin induced sensory neuropathy.

PLoS One. 2014-9-4

[8]
Early Stimulation of TREK Channel Transcription and Activity Induced by Oxaliplatin-Dependent Cytosolic Acidification.

Int J Mol Sci. 2020-9-28

[9]
Improvement of peripheral vascular impairment by a phosphodiesterase type 5 inhibitor tadalafil prevents oxaliplatin-induced peripheral neuropathy in mice.

J Pharmacol Sci. 2019-11-4

[10]
Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss.

Cancer Chemother Pharmacol. 2005-10

本文引用的文献

[1]
Bridging the Translational Gap in Chemotherapy-Induced Peripheral Neuropathy with iPSC-Based Modeling.

Cancers (Basel). 2022-8-15

[2]
Non-coding RNA-based regulation of inflammation.

Semin Immunol. 2022-1

[3]
Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer.

Int J Mol Sci. 2022-5-27

[4]
Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions.

Front Pain Res (Lausanne). 2022-3-14

[5]
MicroRNA sequence codes for small extracellular vesicle release and cellular retention.

Nature. 2022-1

[6]
iPSCs and DRGs: stepping stones to new pain therapies.

Trends Mol Med. 2022-2

[7]
Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity.

J Pers Med. 2021-7-16

[8]
Insights Into Exosomal Non-Coding RNAs Sorting Mechanism and Clinical Application.

Front Oncol. 2021-4-27

[9]
Oxaliplatin Neuropathy: Predictive Values of Skin Biopsy, QST and Nerve Conduction.

J Neuromuscul Dis. 2021

[10]
Blood molecular biomarkers for chemotherapy-induced peripheral neuropathy: From preclinical models to clinical practice.

Neurosci Lett. 2021-4-1

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