Exploring the Effects of Opioid-Related Drugs on the Clinical Outcome of Prostate Cancer Patients Via Integrated Bioinformatics Analysis

Molecular Biotechnology · 2025-01-20

Efficacy and safety of triplet regimen capecitabine, oxaliplatin, and irinotecan (XELOXIRI) as first-line chemotherapy for advanced pancreatic cancer

BMC Cancer · 2025-03-12 · 1 citations

BACKGROUND: The 5-fuorouracil, oxaliplatin and irinotecan (FOLFOXIRI) regimen is the standard first-line treatment for advanced pancreatic cancer (APC). Capecitabine, an oral prodrug of 5-fluorouracil, offers a more convenient and potentially safer alternative. We evaluated the efficacy and safety of the XELOXIRI regimen (capecitabine, oxaliplatin, irinotecan) in Chinese patients with APC. METHODS: This real-world study evaluated consecutive patients treated with the XELOXIRI regimen as first-line chemotherapy for APC at a national cancer center in China from August 2019 to June 2024. Treatment efficacy was assessed using the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), and safety was assessed using adverse events (AEs). RESULTS: Fifty-six patients were enrolled (median age, 60 years [range, 33-71]; 35 males, 21 females). Seventeen had locally advanced unresectable disease and 39 had metastatic disease. After a median follow-up of 19.8 months, the ORR was 33.9% (95% confidence interval [CI]: 21.8-47.8), disease control rate was 82.1% (95% CI: 69.6-91.1), and median response duration was 6.2 months (95% CI: 3.6-NA). Six patients with locally advanced disease and one with lung metastasis underwent R0 resection, with one achieving a pathological complete response. Median OS for the entire cohort was 16.2 months (95% CI: 10.6-23.2) and median PFS was 6.3 months (95% CI: 5.3-9.0). OS rates at 6, 12, and 18 months were 92.2%, 56.7%, and 35.6%, respectively; PFS rates were 53.9%, 20.2%, and 6.7%. For those who underwent R0 resection, median OS was not reached and median PFS was 12.3 months (95% CI: 11.9-NA).Treatment-related AEs (TRAEs)occurred in 94.6% of patients, with Grade 3 or higher TRAEs in 44.6%. No Grade 5 TRAEs or treatment-related deaths were observed. CONCLUSION: The XELOXIRI regimen demonstrated promising efficacy and manageable toxicity in the treatment of APC, providing a practical alternative to FOLFOXIRI, with similar outcomes and easier administration.

EZH2 crosstalk with RNA methylation promotes prostate cancer progression through modulation of m6A autoregulation pathway

Journal of Clinical Investigation · 2025-11-18 · 2 citations

N6-methyladenosine (m6A), the most predominant RNA modification in humans, participates in various fundamental and pathological bioprocesses. Dynamic manipulation of m6A deposition in the transcriptome is critical for cancer progression, though how this regulation is achieved remains understudied. Here, we report that, in prostate cancer (PCa), Polycomb group (PcG) protein Enhancer of Zeste Homolog 2 (EZH2) exerts an additional function in m6A regulation via its enzymatic activity. Mechanistically, EZH2 methylates and stabilizes FOXA1 proteins from degradation, which, in turn, facilitates the transcription of m6A reader YTHDF1. Through activating an m6A autoregulation pathway, YTHDF1 enhances the translation of METTL14 and WTAP, 2 critical components of the m6A methyltransferase complex (MTC), and thereby upregulates the global m6A level in PCa cells. We further demonstrate that inhibiting the catalytic activity of EZH2 suppresses the translation process globally through targeting the YTHDF1-m6A axis. By disrupting both the expression and interaction of key m6A MTC subunits, combinational treatment of EZH2 degrader MS8815 and m6A inhibitor STM2457 mitigates prostate tumor growth synergistically. Together, our study decodes a previously hidden interrelationship between EZH2 and mRNA modification, which may be leveraged to advance the EZH2-targeting curative strategies in cancer.

Protocol for mapping 2′-O-methylation using nanopore direct RNA-seq data with NanoNm

STAR Protocols · 2025-07-31 · 1 citations

2'-O-methylation (Nm) is pivotal in rRNA and the internal site of mRNA. Here, we present an integrated bioinformatics protocol for the identification of 2′-O-methylation using nanopore direct RNA sequencing (RNA-seq) data. We describe steps for software installation, data collection, and training the machine learning model. We then detail procedures for mapping 2′-O-methylation in both rRNA and mRNA in yeast and human cells. For complete details on the use and execution of this protocol, please refer to Li et al. 1 • Instructions for NanoNm software installation • Step-by-step guide for genome preparation and model training • Guidance for detecting 2′-O-methylation in rRNA from yeast, fly, and human samples • Procedures for 2′-O-methylation detection in human mRNA datasets Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. 2'-O-methylation (Nm) is pivotal in rRNA and the internal site of mRNA. Here, we present an integrated bioinformatics protocol for the identification of 2′-O-methylation using nanopore direct RNA sequencing (RNA-seq) data. We describe steps for software installation, data collection, and training the machine learning model. We then detail procedures for mapping 2′-O-methylation in both rRNA and mRNA in yeast and human cells.

Ketone drink enhances therapeutic efficacy in prostate cancer by targeting EZH2

Oncogenesis · 2025-07-12 · 1 citations

It is well established that EZH2, a lysine methyltransferase, is upregulated in most aggressive cancers, highlighting the importance of EZH2 in cancer progression. Recent research has shown that metabolic reprogramming is pivotal in various biological processes, including cancer. Despite this, evidence of EZH2's role in regulating cancer metabolism remains limited. Our study reveals a negative correlation between EZH2 and HMGCS2, a gene belonging to the HMG-CoA synthase, in prostate and breast cancers. Interestingly, HMGCS2 is inversely related to cancer progression and prognosis in these cancers. Furthermore, HMGCS2 is epigenetically repressed by EZH2 both in vitro and in vivo. Notably, restored EZH2 reduces the elevated HMGCS2 levels observed upon EZH2 depletion. Overexpression of HMGCS2 decreases tumorigenesis in both prostate and breast cancers. Additionally, β-hydroxybutyrate (BHB), a downstream metabolite of HMGCS2, impedes prostate cancer progression by targeting EZH2 via direct protein-compound interaction-mediated protein degradation. More importantly, the ketone drink of BHB administration dramatically reduces tumor size and weight in a therapy-resistant, castration-resistant prostate cancer patient-derived xenograft model. Combining a ketone drink with FDA-approved drugs enzalutamide and Tazemetostat further suppresses tumor progression. Overall, the EZH2-HMGCS2-BHB regulatory network plays a critical role in the progression of prostate cancer, and a ketone drink is a novel therapeutic tool for patients with aggressive prostate cancer.

Dynamic analysis of intrahepatic T cells reveals a unique group of restorative Cxcr3+ tissue-resident CD4 T cells in acute liver injury

Toxicology · 2025-01-17 · 3 citations

An EGFR Co-Amplified and De Novo Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-Driven Gene Programs

Research Square · 2025-06-24

ERRATUM: Roles of the HOXA10 gene during castrate-resistant prostate cancer progression

Endocrine Related Cancer · 2025-05-15

A multi-omics atlas of testicular development in Leiocassis longirostris: dynamic regulation of spermatogenesis

Comparative Biochemistry and Physiology Part D Genomics and Proteomics · 2025-12-03

Audiological characteristics following gene therapy in patients with autosomal recessive deafness 9

Med · 2025-05-22 · 7 citations

BACKGROUND: Gene therapy shows promising potential for patients with autosomal recessive deafness 9 (DFNB9), with ongoing clinical trials (ChiCTR2200063181). A deeper understanding of changes in audiological characteristics is crucial for optimizing the monitoring and evaluation of patients' recovery post-treatment. METHODS: Audiological data were collected from 10 DFNB9 patients who underwent gene therapy, including auditory brain stem response (ABR), auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and pure-tone audiometry (PTA) tests. FINDINGS: A clear ABR wave V was observed in all participants by 13 weeks. By 52 weeks, distinct ABR waves I and III were visible in some participants. The 1-kHz ABR wave V latency at 85 dB decreased significantly from 9.220 (range 9.015-9.810) ms at 4 weeks to 8.190 (range 7.780-8.530) ms at 52 weeks (p = 0.004), with a trend toward increased wave V amplitude (p = 0.055). Significant correlations were observed between PTA, ABR, and ASSR thresholds at 0.5-4 kHz. The DPOAE signal-to-noise ratio (SNR) at 26 weeks post-treatment showed no significant difference compared with pre-treatment SNR values, nor were there significant correlations between the pre-treatment SNR values and the post-treatment ABR thresholds. CONCLUSIONS: The study demonstrates that ABR and ASSR are reliable objective tools for assessing hearing recovery in DFNB9 patients after gene therapy. ABR reveals positive changes in the auditory pathway over time after gene therapy, enhancing our understanding of the impact of gene therapy on auditory pathway recovery. FUNDING: This work was funded by the National Natural Science Foundation of China.