Yang Zhang

Plasmonic Fiber Optic Sensing Platform for Point-of-Care Pharmacokinetic Monitoring of Platinum Chemotherapeutics: Toward Ultratrace Multi-omics Precision Chemotherapy Management

Precision chemotherapy management requires efficient and ultrasensitive dynamic monitoring of drug pharmacokinetics alongside real-time tracking of critical biomarker responses, yet existing clinical diagnostic systems neither achieve real-time integration of these critical parameters nor provide point-of-care testing (POCT) capabilities within a unified analytical framework. Here, we develop a plasmonic fiber-optic sensing platform based on tilted fiber Bragg grating surface plasmon resonance (TFBG-SPR) for point-of-care pharmacokinetic monitoring of platinum chemotherapeutics. By utilizing programmable DNA-based biosensors, our system achieves femtomolar-level detection limits for platinum drugs in minimal sample volumes (10 μL, 100-fold dilution). The platform's modular design enables rapid adaptation to diverse molecular targets with ultratrace multichannel spectral detection, providing inherent capability for parallelized multiomics monitoring by simultaneously addressing chemotherapeutics, DNA, RNA, and protein targets. In a longitudinal clinical cohort study via our proposed sensing platform, we observed an inverse correlation between platinum drug concentrations and miRNA-21 expression levels in colorectal cancer patients undergoing dose-adjusted chemotherapy, while ovarian cancer patients exhibited dynamic miRNA-21 responses to platinum drug concentration variations. These findings highlight the potential utility of miRNA-21 as a candidate biomarker for further investigation into drug efficacy and tumor progression mechanisms. By integrating ultratrace drug monitoring with targeted multiomics profiling on a unified platform─a critical prerequisite for data standardization in future artificial intelligence-driven analysis, our platform bridges the gap between clinical pharmacokinetics and molecular biomarker analysis, offering a fundamental POCT tool for precision chemotherapy optimization and personalized cancer management.

The vasculogenic mimicry, CD146 + and CD105 + microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (

Multiregion whole-genome sequencing depicts intratumour heterogeneity and punctuated evolution in ovarian clear cell carcinoma

BackgroundOvarian clear cell carcinoma (OCCC) arises from endometriosis and represents a difficult-to-treat gynaecological malignancy, in part, because its spatial intratumour heterogeneity and temporal evolutionary trajectories have not been explicitly defined.MethodsWe performed whole-genome sequencing on six pathologically confirmed patients with OCCC. An R package named KataegisPortal was developed to identify and annotate loci of localised hypermutations. Immunohistochemical staining was conducted on a tissue microarray containing 143 OCCC specimens.ResultsMultiregion analysis demonstrated considerable degrees of subclonal diversification, ascribable to dynamic mutagenic processes, as well as macroevolutionary events including the acquisition of aneuploidy and chromoplexy. KataegisPortal unveiled APOBEC-mediated kataegis in the early phases of OCCC pathogenesis. We further showed evidence that APOBEC3A and APOBEC3B were frequently expressed in OCCC and possibly regulated by the MAPK pathway. Notably, APOBEC3B-expressing OCCC displayed favourable prognosis and appreciable immunogenicity manifested by marked cytotoxic T-cell infiltration.ConclusionsThese results point to an appealing model of punctuated tumour evolution underlying OCCC neoplastic transformation and progression, which may pose formidable challenges of early detection and intervention, and indicate the intratumour heterogeneity of cancer-driving alterations, yielding important implications for molecular diagnosis and targeted treatment of this lethal disease.

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance

Cervical cancer (CC) is among the most prevalent cancers among female populations with high recurrence rates all over the world. Cisplatin (DDP) is the first-line treatment for multiple cancers, including CC. The main problem associated with its clinical application is drug resistance. This study is aimed at investigating the function and downstream regulation mechanism of forkhead-box A1 (FOXA1) in CC, which was verified as an oncogene in several cancers. Using GEO database and bioinformatics analysis, we identified FOXA1 as a possible oncogene in CC. Silencing of FOXA1 inhibited CC cell growth, invasion, and chemoresistance. Afterwards, the downstream gene of FOXA1 was predicted using a bioinformatics website and validated using ChIP and dual-luciferase assays. SIX4, a possible target of FOXA1, promoted CC cell malignant aggressiveness and chemoresistance. In addition, overexpression of SIX4 promoted phosphorylation of PI3K and AKT proteins and activated the PI3K/AKT signaling pathway. Further overexpression of SIX4 reversed the repressive effects of FOXA1 knockdown on CC cell growth, invasion, and chemoresistance in DDP-resistant cells. FOXA1-induced SIX4 facilitates CC progression and chemoresistance, highlighting a strong potential for FOXA1 to serve as a promising therapeutic target in CC.