Seven pradimicin-like polyketides were isolated from the dichloromethane extract of the marine sediment-derived Streptosporangium sp. CGMCC 4.7309, including five new hexaricins, D-H (1-5), and known hexaricins A (6) and C (7). Their structures were determined by HRESIMS, 1D and 2D NMR, and other spectroscopic analyses. The absolute configurations of compounds 1-5 were determined on the basis of circular dichroism and specific rotation data. All isolated compounds 1-7 were tested for their antioxidant capacities by DPPH scavenging, OH scavenging, andO̅ scavenging assays. Compounds 3 and 4 displayed stronger antioxidant activities than the positive control ( tert-butylhydroquinone). The relationship between structure and antioxidant activity is discussed. These compounds could be effective natural antioxidants with considerable pharmaceutical value.
Circulating tumor cells (CTCs) have important applications in clinical practice on early tumor diagnosis, prognostic prediction, and treatment evaluation. Platinum-based chemotherapy is a fundamental treatment for non-small cell lung cancer (NSCLC) patients who are not suitable for targeted drug therapies. However, most patients progressed after a period of treatment. Therefore, revealing the genetic information contributing to drug resistance and tumor metastasis in CTCs is valuable for treatment adjustment. In this study, we enrolled nine NSCLC patients with platinum-based chemotherapy resistance. For each patient, 10 CTCs were isolated when progression occurred to perform single cell–level whole-exome sequencing (WES). Meanwhile the patients’ paired primary-diagnosed formalin-fixed and paraffin-embedded samples and progressive biopsy specimens were also selected to perform WES. Comparisons of distinct mutation profiles between primary and progressive specimens as well as CTCs reflected different evolutionary mechanisms between CTC and lymph node metastasis, embodied in a higher proportion of mutations in CTCs shared with paired progressive lung tumor and hydrothorax specimens (4.4–33.3%) than with progressive lymphatic node samples (0.6–11.8%). Functional annotation showed that CTCs not only harbored cancer-driver gene mutations, including frequent mutations of EGFR and TP53 shared with primary and/or progressive tumors, but also particularly harbored cell cycle–regulated or stem cell–related gene mutations, including SHKBP1, NUMA1, ZNF143, MUC16, ORC1, PON1, PELP1, etc., most of which derived from primary tumor samples and played crucial roles in chemo-drug resistance and metastasis for NSCLCs. Thus, detection of genetic information in CTCs is a feasible strategy for studying drug resistance and discovering new drug targets when progressive tumor specimens were unavailable.
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