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Feiwei Zhang,Dairong Qiao,Hui Xu,Chong Liao,Shilin Li,Yi Cao 한국미생물학회 2009 The journal of microbiology Vol.47 No.3
Xylose reductase (XR) is a key enzyme in xylose metabolism because it catalyzes the reduction of xylose to xylitol. In order to study the characteristics of XR from Candida tropicalis SCTCC 300249, its XR gene (xyl1) was cloned and expressed in Escherichia coli BL21 (DE3). The fusion protein was purified effectively by Ni2+-chelating chromatography, and the kinetics of the recombinant XR was investigated. The Km values of the C. tropicalis XR for NADPH and NADH were 45.5 µM and 161.9 µM, respectively, which demonstrated that this XR had dual coenzyme specificity. Moreover, this XR showed the highest catalytic efficiency (kcat=1.44×104 min-1) for xylose among the characterized aldose reductases. Batch fermentation was performed with Saccharomyces serivisiae W303-1A:pYES2XR, and resulted in 7.63 g/L cell mass, 93.67 g/L xylitol, and 2.34 g/L·h xylitol productivity. This XR coupled with its dual coenzyme specificity, high activity, and catalytic efficiency proved its utility in in vitro xylitol production.
Mok, Tony S.K.,Wu, Yi-Long,Yu, Chong-Jen,Zhou, Caicun,Chen, Yuh-Min,Zhang, Li,Ignacio, Jorge,Liao, Meilin,Srimuninnimit, Vichien,Boyer, Michael J.,Chua-Tan, Marina,Sriuranpong, Virote,Sudoyo, Aru W.,J American Society of Clinical Oncology 2009 Journal of clinical oncology Vol.27 No.30
<B>Purpose</B><P>This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC).</P><B>Patients and Methods</B><P>Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m<SUP>2</SUP>days 1 and 8) and either cisplatin (75 mg/m<SUP>2</SUP>day 1) or carboplatin (5 × area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety.</P><B>Results</B><P>The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC) -erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease.</P><B>Conclusion</B><P>Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.</P>