Reshaping the Diversity of Oxidized Polyquinane Sesquiterpenoids by Cytochrome P450s.

Polyquinane sesquiterpenoids (PQSTs) are complex compounds with two or three fused cabocyclopentane ring systems, and the biocatalysts for direct C-H bond oxidation on these scaffolds have rarely been discovered. In this study, we discovered two versatile fungal CYP450s capable of performing diverse oxidations on seven PQST scaffolds, resulting in the generation of 20 unique products. Our findings significantly expand the diversity of oxidized PQST scaffolds and provide important biocatalysts for the selective oxidation of inert carbons of terpenoids in future research.

Dynamic monitoring of serum specific tumor markers predicts the response to PD-1 blockade and prognosis of patients with malignant tumors.

BACKGROUND: Programmed cell death protein 1 (PD-1) blockade is a major advance in the treatment of malignancies, but there remain many problems in efficacy evaluation. The aim of this study was to determine whether dynamic monitoring of serum specific tumor markers (SSTMs) could predict the response to PD-1 blockade and prognosis in patients with malignancies. METHODS: The dynamic changes in SSTMs in 27 patients between January 1, 2018 and July 31, 2019 were analyzed retrospectively. The association between the SSTM response and the radiological response was evaluated using the χ2 test and Spearman's correlation analysis. Kaplan-Meier estimates and the log rank test were used to explore the correlation of SSTM dynamics with progression-free survival (PFS) and overall survival (OS). RESULTS: In this study, 85.3% of patients with malignant tumors had detectable SSTM. According to the changes of SSTM within the first 12 weeks of treatment, the patients were divided into a tumor marker increased group and a tumor marker decreased group. The change in SSTM was strongly associated with the change in target lesions (χ2=15.326, P≤0.001), and there was a positive correlation between them (Pearson Correlation r=0.727, P<0.0001). Patients with SSTM reduction had a significantly longer median OS (417 days) when compared with patients with SSTM elevation (median OS, 235 days; log rank χ2=6.323, P=0.012). The PFS in the SSTM reduction group (median PFS, not reached) was significantly longer than that in the elevation group (127 days; log rank χ2=8.843, P=0.003). In the study, one patient showed pseudoprogression and one showed a delayed response in the initial stage of PD-1 blockade. The diameter of the target lesions increased according to the Reaction Evaluation Criteria in Solid Tumor criteria, but the symptoms of discomfort were relieved significantly, and the SSTMs continued to decline dramatically. CONCLUSIONS: Dynamic monitoring of SSTMs can be used as a necessary supplement to imaging examination to evaluate the response to PD-1 blockade and predict the prognosis of patients with malignancies; it may also be helpful for clinical judgment of pseudoprogression and delayed response.