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Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

ABSTRACT: Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

PROVIDER: PRJNA514863 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8437180.fastq.gz	Fastqsanger.gz
	SRR8437190.fastq.gz	Fastqsanger.gz
	SRR8437200.fastq.gz	Fastqsanger.gz
	SRR8437181.fastq.gz	Fastqsanger.gz
	SRR8437191.fastq.gz	Fastqsanger.gz

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Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.

2019-06-01 | GSE125002 | GEO

Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine, cisplatin and oxaliplatin

Project description:Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine, cisplatin and oxaliplatin

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Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine

2019-06-01 | GSE125001 | GEO

Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney_Tumor]

Project description:Cisplatin is a potent chemotherapeutic drug, widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, such as nephrotoxicity and chemotherapy-induced peripheral neuropathy. Therefore, there is an urgent medical need to identify novel strategies that would limit cisplatin-induced toxicity. In the present study, we provide evidence that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) significantly protects from cisplatin-induced nephrotoxicity and neuropathic pain in experimental models of acute and sub-chronic cisplatin intoxication. Importantly, we also demonstrate that the anti-tumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and even potentiated at the molecular level. Altogether, the present results support the use of istradefylline as a new valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.

2022-09-12 | GSE179246 | GEO

Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney]

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αO-conotoxin GeXIVA[1,2] reduced neuropathic pain and changed gene expression in chronic oxaliplatin-induced neuropathy mice model

Project description:Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR) specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models, however the related mechanisms remains unclear. Here we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA-sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks have no effect on mice normal pain threshold or locomotor activity and anxiety-like behavior as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA-sequencing results identified 209 differentially expressed genes (DEGs) in CIPN model, simultaneously injection of GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin induced CIPN management.

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Activation of S1P2 is protective against cisplatin-induced peripheral neuropathy

Project description:To elucidate the molecular mechanisms underlying the neuroprotective role of S1P2, we conduct RNASeq on dorsal root ganglions (DRGs) collected from a cisplatin-induced peripheral neuropathy (CIPN) rat model.

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Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine

Project description:Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine

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Lidocaine for Oxaliplatin-induced Neuropathy

Project description:Oxaliplatin-induced neuropathy is a major dose-limiting side effect in patients with colorectal cancer treated with the FOLFOX chemotherapy regimen. Hypersensitivity to cold is the sensory hallmark of oxaliplatin-induced neuropathy, and it can predict the development of long-term neuropathy. In this study, the investigators aim to determine whether intravenous lidocaine can prevent oxaliplatin-induced cold hypersensitivity.

| 2252152 | ecrin-mdr-crc

Activation of S1P2 is protective against cisplatin-induced peripheral neuropathy

Project description:Activation of S1P2 is protective against cisplatin-induced peripheral neuropathy

| PRJNA987890 | ENA