Mass Spectrometric-Based Proteomics for Biomarker Discovery in Osteosarcoma: Current Status and Future Direction

Due to a lack of novel therapies and biomarkers, the clinical outcomes of osteosarcoma patients have not significantly improved for decades. The advancement of mass spectrometry (MS), peptide quantification, and downstream pathway analysis enables the investigation of protein profiles across a wide range of input materials, from cell culture to long-term archived clinical specimens. This can provide insight into osteosarcoma biology and identify candidate biomarkers for diagnosis, prognosis, and stratification of chemotherapy response. In this review, we provide an overview of proteomics studies of osteosarcoma, indicate potential biomarkers that might be promising therapeutic targets, and discuss the challenges and opportunities of mass spectrometric-based proteomics in future osteosarcoma research

Gut Microbiota-Mediated Pharmacokinetic Drug–Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans

Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed together in certain groups of patients, including solid organ transplant recipients. However, little is known about the pharmacokinetic drug–drug interactions (DDIs) between these two medications. Therefore, the present study aimed to determine the effects of TMP-SMX on MPA pharmacokinetics in humans and to find out the relationship between MPA pharmacokinetics and gut microbiota alteration. This study enrolled 16 healthy volunteers to take a single oral dose of 1000 mg mycophenolate mofetil (MMF), a prodrug of MPA, administered without and with concurrent use of TMP-SMX (320/1600 mg/day) for five days. The pharmacokinetic parameters of MPA and its glucuronide (MPAG) were measured using high-performance liquid chromatography. The composition of gut microbiota in stool samples was profiled using a 16S rRNA metagenomic sequencing technique during pre- and post-TMP-SMX treatment. Relative abundance, bacterial co-occurrence networks, and correlations between bacterial abundance and pharmacokinetic parameters were investigated. The results showed a significant decrease in systemic MPA exposure when TMP-SMX was coadministered with MMF. Analysis of the gut microbiome revealed altered relative abundance of two enriched genera, namely the genus Bacteroides and Faecalibacterium, following TMP-SMX treatment. The relative abundance of the genera Bacteroides, [Eubacterium] coprostanoligenes group, [Eubacterium] eligens group, and Ruminococcus appeared to be significantly correlated with systemic MPA exposure. Coadministration of TMP-SMX with MMF resulted in a reduction in systemic MPA exposure. The pharmacokinetic DDIs between these two drugs were attributed to the effect of TMP-SMX, a broad-spectrum antibiotic, on gut microbiota-mediated MPA metabolism