Enhanced N-acetyl-D-neuraminic production from glycerol and N-acetyl-D-glucosamine by metabolically engineered Escherichia coli with a two-stage pH-shift control strategy.

Typical N-acetyl-D-neuraminic acid (Neu5Ac) production uses N-acetyl-D-glucosamine (GlcNAc) and excess pyruvate as substrates in the enzymatic or whole-cell biocatalysis process. In a previous study, a Neu5Ac-producing biocatalytic process via engineered Escherichia coli SA-05/pDTrc-AB/pCDF-pck-ppsA was constructed without exogenous pyruvate. In this study, glycerol was found to be a good energy source compared with glucose for the catalytic system with resting cells, and Neu5Ac production increased to 13.97 ± 0.27 g L-1. In addition, a two-stage pH shift strategy was carried out, and the Neu5Ac yield was improved to 14.61 ± 0.31 g L-1. The GlcNAc concentration for Neu5Ac production was optimized. Finally, an integrated strategy was developed for Neu5Ac production, and the Neu5Ac yield reached as high as 18.17 ± 0.27 g L-1. These results provide a new biocatalysis technology for Neu5Ac production without exogenous pyruvate.

Combinational Treatment of Doxorubicin With Neoadjuvant Docetaxel for Different Subtypes of Patients With Breast Cancer.

AIM: The aim of this study is to characterize the effect of chemotherapy drug doxorubicin with neoadjuvant drug docetaxel for different molecular subtypes. METHODS: A total of 83 patients with late-stage breast cancer were chosen to undergo treatment and compared to these patients to the combinational treatment to identify the molecular characteristics that can predict the responses. RESULTS: Total response rate is 81.9% (68/83 patients). Among them, 7 patients show pathological complete response of 8.4%, 12 patients show clinical complete response of 14.5%, 49 patients show partial response of 59%, and 15 patients show stable disease of 18.1%. The comparison among different subtypes of breast cancer, including luminal A, luminal B, basal-like, and ERBB2+ subtypes, did not show statistical significant differences to the treatment of combinational treatment for the complete response rate, including pathological complete response and clinical complete response. Comparing with luminal A and luminal B subtypes, the ERBB2+ and basal-like subtypes have better complete response and response rate rates. The disease-free survival rate and overall survival rate at 29 months after treatment did not show statistical significant differences among different subtypes of patients with breast cancer. CONCLUSION: The molecular subtypes of breast cancer can predict responses to the combinational treatment of doxorubicin with docetaxel, and ERBB2+ and basal-like subtypes have better response rate and complete response rate. There is correlation of estrogen receptor and KI-67 level changes with response rate as well, where KI-67 high patients are more sensitive to the treatment.