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Opportunities and Challenges of in vitro Synthetic Biosystem for Terpenoids Production
Yang Liyang,Gong Qiang,Lv Jifang,Zhou Bangyuan,Li Guilan,Guo JianQuan 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5
Terpenoids are a large variety of natural products with remarkable diverse biological functions, and have a wide range of applications in flavors, pharmaceuticals, biofuels, pigments, and so on. However, limited production of terpenoids from natural resources constrains their use of bulk commodity products. In vivo synthetic biosystem, harnessing living organisms to produce terpenoids, has been broadly used and in-depth reviewed for terpenoids production, which has inherent weaknesses, such as slow reaction rate, low product yield, toxic intermediates, and high separation cost. In vitro synthetic biosystem, harboring numerous enzymes and/or coenzymes assembled into an in vitro enzymatic bioreactions, can obviate part of problems associated with in vivo style. In this review, the general design of in vitro synthetic biosystem is presented with seven supporting examples: mevalonate, isoprene, limonene, pinene, farnesene, amorpha-4,11-diene and taxadiene. The efforts for the large-scale implementation of in vitro synthetic biosystem have been addressed to enzymes engineering, computational modeling and cofactors recycle. The review also discusses the challenges and solutions for the largescale implementation of in vitro synthetic biosystem around enzymes stability and cofactors recycle. This review may suggest in vitro synthetic biosystems become a realistic option for the production of diverse valuable terpenoids, even expand to other commodity chemicals.
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Ting Xu,Xicheng Wang,Ying Xin,Zhenghang Wang,Jifang Gong,Xiaotian Zhang,Yanyan Li,Congcong Ji,Yu Sun,Feilong Zhao,Depei Huang,Yuezong Bai,Jian Li,Lin Shen 대한암학회 2023 Cancer Research and Treatment Vol.55 No.2
Purpose The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.
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