Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Cao, Wa,Li, Ai-Wu,Ren, Sheng-Xiang,Chen, Xiao-Xia,Li, Wei,Gao, Guang-Hui,He, Ya-Yi,Zhou, Cai-Cun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second-line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second-line chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.

Enhanced Carboxymethylcellulase Production by a Newly Isolated Marine Bacterium, Cellulophaga lytica LBH-14, Using Rice Bran

( Wa Gao ),( Eun Jung Lee ),( Sang Un Lee ),( Jian Hong Li ),( Chung Han Chung ),( Jin Woo Lee ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.10

The aim of this work was to establish the optimal conditions for production of carboxymethylcellulase (CMCase) by a newly isolated marine bacterium using response surface methodology (RSM). A microorganism producing CMCase, isolated from seawater, was identified as Cellulophaga lytica based 16S rDNA sequencing and the neighborjoining method. The optimal conditions of rice bran, ammonium chloride, and initial pH of the medium for cell growth were 100.0 g/l, 5.00 g/l, and 7.0, respectively, whereas those for production of CMCase were 79.9 g/l, 8.52 g/l, and 6.1. The optimal concentrations of K2HPO4, NaCl, MgSO4?7H2O, and (NH4)2SO4 for cell growth were 6.25, 0.62, 0.28, and 0.42 g/l, respectively, whereas those for production of CMCase were 3.72, 0.54, 0.70, and 0.34 g/l. The optimal temperature for cell growth and the CMCase production by C. lytica LBH-14 were 35℃ and 25℃, respectively. The maximal production of CMCase under optimized condition for 3 days was 110.8 U/ml, which was 5.3 times higher than that before optimization. In this study, rice bran and ammonium chloride were developed as carbon and nitrogen sources for the production of CMCase by C. lytica LBH-14. The time for production of CMCase by a newly isolated marine bacterium with submerged fermentations reduced to 3 days, which resulted in enhanced productivity of CMCase and a decrease in its production cost.

Enhanced Production of Cellobiase by Marine Bacterium Cellulophaga lytica LBH-14 from Rice Bran under Optimized Conditions Involved in Dissolved Oxygen

Wa Gao,정정한,Jianghong Li,이진우 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.1

The optimal conditions for production ofcellobiase by C. lytica LBH-14 at flask scale had beenpreviously reported. In this study, parameters involved indissolved oxygen in 7 and 100 L bioreactors were optimizedfor pilot-scale production of cellobiase. The optimalagitation speed and aeration rate for cell growth of C. lyticaLBH-14 were 400 rpm and 1.11 vvm in a 7 L bioreactor,whereas those for production of cellobiase were 330 rpmand 0.70 vvm. The analysis of variance (ANOVA) impliedthat significant factor for cell growth was the aeration rate,whereas those for production of cellobiase were theaeration rate as well as the agitation speed. The optimalinner pressures for cell growth and production of cellobiaseby C. lytica LBH-14 in a 100 L bioreactor were 0.00 and0.06 MPa, respectively. The maximal production of cellobiasein a 100 L bioreactor under optimized conditions using ricebran was 140.1 U/mL, which was 1.52 times higher thanthat in a flask scale.

Optimization of Mineral Salts in Medium for Enhanced Production of Pullulan by Aureobasidium pullulans HP-2001 Using an Orthogonal Array Method

Wa Gao,Yi-Joon Kim,정정한,Jianhong Li,이진우 한국생물공학회 2010 Biotechnology and Bioprocess Engineering Vol.15 No.5

Based on intuitive analyses and statistical calculations using data from orthogonal array experiments,the optimal concentrations of K2HPO4, NaCl, MgSO4·7H2O,and (NH4)2SO4 in cell growth medium of Aureobasidium pullulans HP-2001 were measured as 7.5, 1.0, 0.1, and 2.4g/L, respectively, whereas those for the production of pullulan were 2.5, 0.25, 0.8, and 0.3 g/L, respectively. The most important factor for cell growth and production of pullulan by A. pullulans HP-2001 was identified as K2HPO4. Optimal concentrations of glucose and yeast extract, along with the initial pH of the cell growth medium of A. pullulans HP-2001 containing optimized salt concentrations, were found to be 100.0, 10.0, and 6.0 g/L, respectively, whereas those for the production of pullulan were 100.0, 2.5, and 6.0 g/L, respectively. Conversion rates of pullulan from 10.0, 25.0, 50.0, 75.0, and 100.0 g/L of glucose in the presence of optimized salt concentrations were 26.0, 25.2,22.4, 17.9, and 14.1%, respectively, whereas those in the presence of previously reported salt concentrations were 26.6, 25.2, 19.9, 14.3, and 11.7%, respectively. Optimal salt concentrations for the production of pullulan by A. pullulans HP-2001 varied according to the concentrations of the carbon and nitrogen sources, especially at higher concentrations.

Enhanced Production of Cellobiase by a Marine Bacterium, Cellulophaga lytica LBH-14, in Pilot-Scaled Bioreactor Using Rice Bran

Wa Cao,김훙우,Jianhong Li,이진우 한국생명과학회 2013 생명과학회지 Vol.24 No.4

The aim of this work was to establish the optimal conditions for the production of cellobiase by a marine bacterium, Cellulophaga lytica LBH-14, using response-surface methodology (RSM). The optimal conditions of rice bran, ammonium chloride, and the initial pH of the medium for cell growth were 100.0 g/l, 5.00 g/l, and 7.0, respectively, whereas those for the production of cellobiase were 91.1 g/l, 9.02 g/l, and 6.6, respectively. The optimal concentrations of K2HPO4, NaCl, MgSO4∙7H2O, and (NH4)2SO4 for cell growth were 6.25, 0.62, 0.28, and 0.42 g/l, respectively, whereas those for the production of cellobiase were 4.46, 0.36, 0.27, and 0.73 g/l, respectively. The optimal temperatures for cell growth and for the production of cellobiase by C. lytica LBH-14 were 35 and 25℃, respectively. The maximal production of cellobiase in a 100 L bioreactor under optimized conditions in this study was 92.3 U/ml, which was 5.4 times higher than that before optimization. In this study, rice bran and ammonium chloride were developed as carbon and nitrogen sources for the production of cellobiase by C. lytica LBH-14. The time for the production of cellobiase by the marine bacterium with submerged fermentations was reduced from 7 to 3 days, which resulted in enhanced productivity of cellobiase and a decrease in its production cost. This study found that the optimal conditions for the production of cellobiase were different from those of CMCase by C. lytica LBH-14.

Pilot-scale Optimization of Parameters Related to Dissolved Oxygen for Mass Production of Pullulan by Aureobasidium pullulans HP-2001

Wa Gao(고와),Yi-Joon Kim(김이준),Chung-Han Chung(정정한),Jianhong Li(이잔홍),Jin-Woo Lee(이진우) 한국생명과학회 2010 생명과학회지 Vol.20 No.10

Aureobasidium pullulans HP-2001 균주를 사용하여 풀루란을 대량 생산을 위하여 7 l 및 100 l 생물배양기를 사용하여 용존산소와 관련된 조건을 최적화하였다. 풀루란의 생산에 최적인 탄소원과 질소원은 각각 50.0 g/l 포도당 및 2.5 g/l 효모추출물이었으며 플라스크 규모에서의 풀루란 변환율은 37%이었다. 풀루란 생산 균주의 생장에 최적인 배지의 초기 pH 및 배양온도는 7.5 및 30℃이었으나 풀루란의 생산에 최적인 배지의 초기 pH 및 배양 온도는 각각 6.0 및 25℃이었다. 7 l 생물배양기에서 Aureobasidium pullulans HP-2001 균주의 생육에 최적인 교반속도 및 통기량은 각각 600 rpm 및 2.0 vvm이었으나 풀루란 생산에 최적인 조건은 각각 500 rpm 및 1.0 vvm이었으며 최적 조건에서 풀루란의 생산농도는 18.13 g/l이었다. 100 l 생물배양기에서 풀루란 생산 균주의 생장에 최적인 내압은 0.0 ㎏f/㎠이었으나, 풀루란 생산에 최적인 내압은 0.4 ㎏f/㎠이었으며 최적 조건에서 풀루란의 생산 농도는 22.89 g/l이었다. 이는 내압이 없는 상태에 비하여 풀루란의 생산 농도가 1.38배 증가한 것이다. Parameters related to dissolved oxygen for the production of pullulan by Aureobasidium pullulans HP-2001 were optimized in 7 l and 100 l bioreactors. The optimal concentrations of glucose and yeast extract for the production of pullulan were 50.0 and 2.5 g/l, respectively, and its conversion rate from glucose was 37% at a flask scale. The optimal initial pH of the medium and temperature for cell growth were 7.5 and 30℃, whereas those for the production of pullulan were 6.0 and 25℃. The optimal agitation speed and aeration rate for cell growth were 600 rpm and 2.0 vvm in a 7 l bioreactor, whereas those for the production of pullulan were 500 rpm and 1.0 vvm. The production of pullulan with an optimized agitation speed of 500 rpm and aeration rate of 1.0 vvm was 18.13 g/l in a 7 l bioreactor. Maximal cell growth occurred without inner pressure, whereas the optimal inner pressure for the production of pullulan was 0.4 ㎏f/㎠ in a 100 l bioreactor. The production of pullulan under optimized conditions in this study was 22.89 g/l in a 100 l bioreactor, which was 1.38 times higher than that without inner pressure.

Enhanced Production of Cellobiase by a Marine Bacterium, Cellulophaga lytica LBH-14, in Pilot-Scaled Bioreactor Using Rice Bran

Wa Cao(고와),Hung-Woo Kim(김형우),Jianhong Li(이잔홍),Jin-Woo Lee(이진우) 한국생명과학회 2013 생명과학회지 Vol.23 No.4

본 연구의 목적은 통계학적 방법을 사용하여 해양미생물 Cellulophaga lytica LBH-14가 생산하는 cellobiase의 생산조건을 확립하는 것이었다. 이 균주의 생육에 최적인 미강, ammonium chloride 및 배지의 초기 pH는 100.0 g/l, 5.00 g/l 및 7.0이었으나, 이 균주가 생산하는 cellobiase의 생산에 최적인 조건은 각각 91.1 g/l, 9.02 g/l 및 6.6이었다. 이 균주의 생육에 최적인 K₂HPO₄, NaCl, MgSO₄?7H₂O 및 (NH₄)₂SO₄ 등과 같은 배지의 염농도는 각각 6.25, 0.62, 0.28 및 0.73 g/l이었으나, cellobiase 생산에 최적인 염들의 농도는 각각 4.46, 0.36, 0.27 및 0.73 g/l이었다. 또한, 균체의 생육 및 cellobiase의 생산에 최적인 온도는 각각 35 및 25℃이었다. 플라스크 규모에서 최적화한 조건으로 파이롯트 규모의 생물배양기에서 cellobiase를 생산한 결과, 이 균주가 생산하는 cellobiase의 생산성은 92.3 U/ml이었으며, 이는 최적화하기 전에 비하여 5.4배 향상된 것 이었다. 본 연구를 통하여 쌀 도정공정의 부산물인 미강 및 ammonium chloride를 cellobiase를 생산하는 기질로 개발하였으며 해양 미생물을 사용하여 cellobiase의 생산기간을 7일에서 3일로 단축시켰다. 또한, 본 연구를 통하여 C. lytica LBH-14가 생산하는 cellobiase의 최적 생산조건은 이 균주가 생산하는 CMCase의 최적 생산조건과 다르다는 사실을 확인하였다. The aim of this work was to establish the optimal conditions for the production of cellobiase by a marine bacterium, Cellulophaga lytica LBH-14, using response-surface methodology (RSM). The optimal conditions of rice bran, ammonium chloride, and the initial pH of the medium for cell growth were 100.0 g/l, 5.00 g/l, and 7.0, respectively, whereas those for the production of cellobiase were 91.1 g/l, 9.02 g/l, and 6.6, respectively. The optimal concentrations of K₂HPO₄, NaCl, MgSO₄·7H2O, and (NH₄)₂SO₄ for cell growth were 6.25, 0.62, 0.28, and 0.42 g/l, respectively, whereas those for the production of cellobiase were 4.46, 0.36, 0.27, and 0.73 g/l, respectively. The optimal temperatures for cell growth and for the production of cellobiase by C. lytica LBH-14 were 35 and 25℃, respectively. The maximal production of cellobiase in a 100 L bioreactor under optimized conditions in this study was 92.3 U/ml, which was 5.4 times higher than that before optimization. In this study, rice bran and ammonium chloride were developed as carbon and nitrogen sources for the production of cellobiase by C. lytica LBH-14. The time for the production of cellobiase by the marine bacterium with submerged fermentations was reduced from 7 to 3 days, which resulted in enhanced productivity of cellobiase and a decrease in its production cost. This study found that the optimal conditions for the production of cellobiase were different from those of CMCase by C. lytica LBH-14.

Effects of microRNA-135a on the epithelial–mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3β through the Wnt/β-catenin signaling pathway

Xia-Wa Mao,Jia-Quan Xiao,Zhong-Yi Li,Yi-Chun Zheng,Nan Zhang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial–mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative realtime PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups. miR-135a, β-catenin, cyclinD1 and vimentin expression increased, while GSK3β and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, β-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3β groups. These groups showed an opposite trend in GSK3β and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/β-catenin signaling pathway through the downregulation of GSK3β expression.

Enhanced production of carboxymethylcellulase by Cellulophaga lytica LBH-14 in pilot-scale bioreactor under optimized conditions involved in dissolved oxygen

이진우,Wa Cao,Sang-Un Lee,Jianhong Li 한국화학공학회 2013 Korean Journal of Chemical Engineering Vol.30 No.5

−The optimal conditions for the production of carboxymethylcellulase (CMCase) by Cellulophaga lytica LBH-14 at flask scale has been previously reported. In this study, we optimized the parameters involved in dissolved oxygen in 7 and 100 L bioreactors for pilot-scaled production of CMCase by C. lytica LBH-14. The optimal conditions of agitation speed and aeration rate for cell growth in 7 L bioreactors were 395 rpm and 0.98 vvm, whereas those for production of CMCase were 357 rpm and 0.55 vvm. The optimal inner pressures for cell growth and production of CMCase by C. lytica LBH-14 in 100 L bioreactors were 0.00 and 0.06MPa, respectively. The production of CMCase under an optimized inner pressure was 1.38 times higher than that without an inner pressure. The maximal production of CMCase by C. lytica under optimized conditions at pilot scale using rice bran and ammonium chloride was 153.6U/mL, which was 1.39 times higher than that at flask scale.

Development and characterization of a fully functional small anti-HER2 antibody

( Jie Gao ),( Bo Hua Le ),( Hui Mei Li ),( Xun Min Zhang ),( Da Peng Zhang ),( Lei Zhao ),( Chong Wang ),( Chen Fang ),( Wei Zhu Qian ),( Sheng Hou ),( Geng Kou ),( Hua Feng Wei ),( Shu Shi ),( Hao Wa 생화학분자생물학회 2009 BMB Reports Vol.42 No.10