| 1 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 2 | Suppression of starch synthase I(SSI) by RNA interference alters starch biosynthesis and amylopectin chain distribution in rice plants subjected to high temperature显示文摘Based on known cDNAs of rice starch synthase isoforms,we constructed dsRNA interference vectors for starch synthase I(SSI)to produce transgenic plants containing starch with a moderately high amylose content.We investigated the effect of SSI suppression on grain quality traits,starch biosynthesis,and amylopectin chain distribution in rice plants exposed to two different temperature regimes.The activities and transcripts of BEs,DBEs,and other SS isoforms were further investigated to clarify the effect of SSI suppression on these key enzymes and their specific isoforms under different temperature treatments.Suppression of SSI by RNAi altered grain starch component and amylopectin chain distribution,but it exerted only a slight effect on total starch content(%)and accumulation amount(mg kernel?1)and on starch granule morphology and particle size distribution.Under normal temperature(NT),insignificant differences in kernel weight,chalky kernel proportion,chalky degree,and starch granule morphology between SSI-RNAi line and its wild type(WT)were observed.However,amylose content(AC)level and granule-bound starch synthase(GBSS)activity in rice endosperms were markedly increased by SSI-RNAi suppression.The chalky kernel proportion and chalky degree of SSIRNAi lines were significantly higher than those of WT under high temperature(HT)exposure at filling stage.Inhibition of SSI by RNAi affected amylopectin chain distribution and raised starch gelatinization temperature(GT)in two ways:directly from the SSI deficiency itself and indirectly by reducing BEIIb amounts in an SSI-deficient background.The deficiency of SSI expression led to an alteration in the susceptibility of grain chalkiness occurrence and starch gelatinization temperature to HT exposure,owing to a pleiotropic effect of SSI deficiency on the expression of other genes associated with starch biosynthesis. | Qian Zhao Xiaoxia Du Zhanyu Han Yu Ye Gang Pan Muhammad-Asad-Ullah Asad Qifa Zhou Fangmin Cheng | 2019 | The Crop Journal2019，7，5： | 2 |
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