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Biomedical subjects

Xiaomei Zhang

Publications and source records attributed to Xiaomei Zhang.

2 recordsLinked to original sources

Molecular diagnostic tests for isoniazid-resistant tuberculosis: a scoping review.

The paucity of diagnostic tests for isoniazid-resistant tuberculosis is concerning, given its status as the most common form of drug-resistant tuberculosis and a gateway to multidrug-resistant diseases. Molecular drug-susceptibility testing has improved access to timely diagnosis of rifampicin-resistant tuberculosis, but testing for isoniazid-resistant tuberculosis still remains rare. In this Review, we assessed the characteristics of molecular drug-susceptibility testing for detection of isoniazid-resistant tuberculosis, referencing the WHO target product profiles. 9243 citations were screened to select 238 studies published between 2000 and 2024. The diagnostics options have expanded rapidly since 2020, with 27 nucleic acid amplification tests, eight line probe assays, five DNA microarrays, two targeted next-generation sequencing platforms, and two whole-genome sequencing platforms. Most of the evaluated molecular drug-susceptibility tests met diagnostic performance targets but were often complex and costly. Although a few low-complexity nucleic acid amplification tests met key target product profile criteria, additional field validation and greater efforts are needed to ensure optimal feasibility and affordability for low-resource settings.

Isoniazid

An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy.

UNLABELLED: Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in A Robust TNBC Evaluation fraMework to Improve Survival clinical trial (ARTEMIS, NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing to the lungs. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlighted dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations revealed a complex network of adaptations associated with chemoresistance. Overall, this PDX biobank provides a valuable tool for tackling the most pressing issues facing the clinical management of TNBC. SIGNIFICANCE: The development of a patient-derived xenograft biobank that comprehensively captures the genomic and transcriptional diversity of triple-negative breast cancer promises to be a robust resource to investigate and overcome chemoresistance and metastasis.

Animals