Search

Purpose: Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC. Methods: Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq). Results: We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1). Conclusion: We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance. [ABSTRACT FROM AUTHOR]

A novel strain of H3N8 influenza virus was isolated from domestic pigeons during the avian influenza virus (AIV) surveillance in wet markets in Anhui, China, during 2013. The virus was characterized by whole-genome sequencing with subsequent genetic comparison and phylogenetic analysis. Phylogenetic analysis revealed that the NA gene of AIV mapped to the North American lineage, and the remaining seven genes belong to a Eurasian lineage. These findings indicated that this H3N8 virus is a novel nature reassortant virus. Comparison of the hemagglutinin amino acid sequences indicated 9 substitutions. One substitution caused the loss of a potential glycosylation site, and six substitutions were not previously observed in avian H3 isolates. Q226 and T228 at the receptor binding sites suggested that Anhui-08 preferentially binds to a-2,3-linked sialic acid receptors, and the cleavage site sequence showed a low pathogenic feature. Animal experiments further confirmed that A/pigeon/Anhui/08/2013 (H3N8) is low or in pigeons. The results improve our understanding of these viruses as they evolve and also provide important information to aid ongoing risk assessment analyses because these zoonotic influenza viruses continue to circulate and adapt to new hosts. [ABSTRACT FROM AUTHOR]