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        Characterization of proteinase A excretion from Saccharomyces cerevisiae in high sugar stress conditions

        Liang Dong,Feng Li,Yongzhe Piao,Dong Sun,Rui Zhao,Cheng Li,Lina Cong,Changxin Zhao 한국응용생명화학회 2015 Applied Biological Chemistry (Appl Biol Chem) Vol.58 No.2

        High sugar concentration culturing was commonly used in modern fermentation industry. However, it leads to the reduction of the foam stability in beer brewing due to the excess secretion of proteinase A. To better understand the characterization of proteinase A excretion from Saccharomyces cerevisiae in high sugar stress conditions, the cultures were grown by using YNB medium with a high concentration of glucose. Pro-PrA isolated from the medium was purified by gel exclusion chromatography, and the PrA activity was detected using fluorescent substrate analysis. The relative molecular weight of the purified PrA and pro-PrA was estimated at 42 and 54 kDa, respectively, by SDS-PAGE. It indicated that the metabolic behavior of PrA in the high glucose culturing was quite different from the normal conditions, and glucose concentration may have a big influence on its secreted process. Further study showed that PrA was released at the logarithmic growth phase of the culturing, and the amount of PrA was 11 times higher compared with the normal culturing. PrA was considered to be activated by itself under acidic conditions. And it was also confirmed in this work that the step-wise pathway for the autoactivation known as a pseudo-PrA has a major contribution to the autoactivation process of PrA zymogen outside the cell.

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        Characterization of proteinase A excretion from Saccharomyces cerevisiae in high sugar stress conditions

        Dong, Liang,Li, Feng,Piao, Yongzhe,Sun, Dong,Zhao, Rui,Li, Cheng,Cong, Lina,Zhao, Changxin The Korean Society for Applied Biological Chemistr 2015 Applied Biological Chemistry (Appl Biol Chem) Vol.58 No.2

        High sugar concentration culturing was commonly used in modern fermentation industry. However, it leads to the reduction of the foam stability in beer brewing due to the excess secretion of proteinase A. To better understand the characterization of proteinase A excretion from Saccharomyces cerevisiae in high sugar stress conditions, the cultures were grown by using YNB medium with a high concentration of glucose. Pro-PrA isolated from the medium was purified by gel exclusion chromatography, and the PrA activity was detected using fluorescent substrate analysis. The relative molecular weight of the purified PrA and pro-PrA was estimated at 42 and 54 kDa, respectively, by SDS-PAGE. It indicated that the metabolic behavior of PrA in the high glucose culturing was quite different from the normal conditions, and glucose concentration may have a big influence on its secreted process. Further study showed that PrA was released at the logarithmic growth phase of the culturing, and the amount of PrA was 11 times higher compared with the normal culturing. PrA was considered to be activated by itself under acidic conditions. And it was also confirmed in this work that the step-wise pathway for the autoactivation known as a pseudo-PrA has a major contribution to the autoactivation process of PrA zymogen outside the cell.

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        Exploratory Analysis of Patients With Gastric/Gastroesophageal Junction Adenocarcinoma With or Without Liver Metastasis From the Phase 3 RAINBOW Study

        Kei Muro,Takatsugu Ogata,Yukiya Narita,Zev A. Wainberg,Eric Van Cutsem,Kensei Yamaguchi,Yongzhe Piao,Yumin Zhao,Patrick M. Peterson,Sameera R. Wijayawardana,Paolo Abada,Anindya Chatterjee 대한위암학회 2023 Journal of gastric cancer Vol.23 No.2

        Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM−) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM−: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM−: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan–Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM− subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM− (OS HR, 0.71 [LM+] vs. 0.88 [LM−]; PFS HR, 0.47 [LM+] vs. 0.76 [LM−]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

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