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A facile and sensitive method of quantifying glutaminase binding to its ninhibitor CB-839 in tissues

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Journal of Genetics and Genomics 2020年第7期47卷 389-395页

作者： Yicheng Chen Yiqing Zhao David L.Bajor zhenghe wang J.Eva Selfridge Department of Genetics and Genome Sciences Case Western Reserve University10900 Euclid AvenueClevelandOH44106USA Department of Medicine Case Western Reserve University10900 Euclid AvenueClevelandOH.44106USA Case Comprehensive Cancer Center Case Western Reserve University10900 Euclid AvenueClevelandOH44106USA Seidman Cancer Center University Hospitals Cleveland Medical CenterWOO Euclid AvenueClevelandOH44106USA

Many cancer types reprogram their metabolism to become addicted to *** of the critical enzymes in the utilization of glutamine in these cells is ***-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine *** its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical ***,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft ***,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical *** assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.

关键词： Glutaminase Method Cancer

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

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Genes & Diseases 2023年第4期10卷 1702-1713页

作者： Yamu Li Zhonghua Liu Yiqing Zhao Jie Yang Tsan Sam Xiao Ronald A.Conlon zhenghe wang Department of Genetics and Genome Sciences Case Western Reserve UniversityClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA Department of Physiology and Biophysics Case Western Reserve UniversityClevelandOH 44106USA Department of Integrative Structural and Computational Biology The Scripps Research Institute10550 North Torrey Pines RdTRY-21La JollaCA 92037USA.

How PD-L1 expression is regulated in cancer is poorly ***,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four members of the EGF receptor family,all with protein tyrosine kinase ***3 is a pseudokinase with a high binding affin-ity to *** showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell *** ERBB3 ATP-binding mutant cells dramatically reduce IFN-g-induced PD-L1 ***,ERBB3 regulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling *** is the transcription factor that regulates PD-L1 gene expression in CRC *** of a tumor-derived ERBB3 mutation located in the ki-nase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy,suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune check-point therapy.

关键词： Colon cancer ERBB3 Immunotherapy PD-L1 Pseudokinase

Mutations in TP53, ZNF750, and RB1 typify ocular sebaceous carcinoma

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Journal of Genetics and Genomics 2019年第6期46卷 315-318页

作者： Yongyang Bao J. Eva Selfridge Janet wang Yiqing Zhao Junqi Cui Kishore Guda zhenghe wang Yanbo Zhu Department of Pathology The Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 China Seidman Cancer Center University Hospitals Cleveland Medical Center Cleveland OH 44106 USA Case Comprehensive Cancer Center Cleveland OH 44106 USA Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH 44106 USA

Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;Yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).

关键词： Sebaceous carcinoma (SC) RB1 TP53 ZNF750

Research highlights from ACACR members

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Genes & Diseases 2018年第4期5卷 301-301页

作者： zhenghe John wang Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineGI Cancer Genetics ProgramCase Comprehensive Cancer Center10900 Euclid AvenueClevelandOH 44106-7285USA Association of Chinese Americans in Cancer Research(ACACR)BaltimoreMDUSA

*** He at The University of Chicago and his collaborator at the ShanghaiTech University found that N6-methyladenosine(m6A)facilitates hippocampus-dependent learning and memory through YTHDF1,a m6A binding protein that... 详细信息

关键词： Chicago stimulus synthesis

Targeting glutamine metabolism in PIK3CA mutant colorectal cancers

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Genes & Diseases 2016年第4期3卷 241-243页

作者： Xiujing Feng Yujun Hao zhenghe wang Department of Genetics and Genome Sciences and Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA

We recently reported that PIK3CA mutant colorectal cancers(CRCs)are addicted to glutamine through up-regulation of glutamate pyruvate transaminase 2(GPT2).A GPT2 inhibitor suppresses in vivo growth of PIK3CA mutant,but not wild-type,*** study indicates that targeting glutamine may be an effective approach to treat CRCs with PIK3CA mutations.

关键词： PIK3CA metabolism colorectal

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沉积盆地中的两种沉积响应模式

地球学报 2008年第1期29卷 103-108页

作者：王正和中国地质大学能源学院北京100083

当沉积盆地系统中某种沉积影响因素发生变化时,其中的沉积充填过程与样式也会表现出相应规律的变化。这可称之为沉积对盆地变化的响应或沉积响应。从逻辑思辨及实际资料出发,根据沉积盆地可能的发育演化特征,提出了两类理论上的盆地沉... 详细信息

当沉积盆地系统中某种沉积影响因素发生变化时,其中的沉积充填过程与样式也会表现出相应规律的变化。这可称之为沉积对盆地变化的响应或沉积响应。从逻辑思辨及实际资料出发,根据沉积盆地可能的发育演化特征,提出了两类理论上的盆地沉积响应模式,即镜像沉积模式和拉锯式沉积模式。对于这两类模式的理解将有助于从整体上更好的认识盆地中地层的系统充填过程,也有助于油气勘探中油气藏分布规律的预测。

关键词：盆地沉积响应层序

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基于智能手机的惯性导航轨迹生成算法

工矿自动化 2015年第5期41卷 87-90页

作者：王郑合昆明理工大学信息工程与自动化学院云南昆明650500

针对传统的手机惯性导航技术存在无法精确计步和计算步长的问题,提出了一种基于智能手机的惯性导航轨迹生成算法。该算法根据智能手机上三轴加速度传感器捕捉的人走路时产生的三轴加速度,利用基于Mealy状态机的计步算法计算人所走过的步... 详细信息

针对传统的手机惯性导航技术存在无法精确计步和计算步长的问题,提出了一种基于智能手机的惯性导航轨迹生成算法。该算法根据智能手机上三轴加速度传感器捕捉的人走路时产生的三轴加速度,利用基于Mealy状态机的计步算法计算人所走过的步数,并获得每一步的起止时间戳;根据三轴陀螺仪所获取的数据及每一步的起止时间戳,结合指南针读数,计算人走过的每一步所发生的方向变化;根据不同步长的人行走时所产生的不同加速度,基于最小二乘法估计人的步长;根据路径起点的坐标,结合步长及方向变化,计算人走过的每一步相对于路径起点的坐标,得到人的运动轨迹。仿真结果表明该算法能够达到较高的惯性导航精度。

关键词：惯性导航导航轨迹智能手机三轴陀螺仪

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准南上二叠统芦草沟组非常规油气储层特征

岩性油气藏 2017年第5期29卷 28-35页

作者：王正和余谦中国地质调查局成都地质调查中心成都610081

为了深化准噶尔盆地南缘阜康—乌鲁木齐段非常规油气资源的认识,通过野外地质调查、岩心观察、薄片鉴定、样品分析测试等对上二叠统芦草沟组非常规储层特征进行了详细研究。结果表明:构成非常规油气储层的岩石类型有3种,分别为以粉砂岩... 详细信息

为了深化准噶尔盆地南缘阜康—乌鲁木齐段非常规油气资源的认识,通过野外地质调查、岩心观察、薄片鉴定、样品分析测试等对上二叠统芦草沟组非常规储层特征进行了详细研究。结果表明:构成非常规油气储层的岩石类型有3种,分别为以粉砂岩为主的细粒沉积岩、以黏土岩为主的细粒沉积岩及碳酸盐岩;芦草沟组上段、中段和下段炭质细粒沉积岩密度分别为2.3~2.8 g/cm^3,2.3~2.4 g/cm^3和2.4~2.5 g/cm^3。炭质细粒沉积岩密度与TOC含量具有较好的负相关性,孔隙度以0~2%为主,渗透率以0~0.1 mD为主,比表面积以0.1~0.5 m^2/g及1.0~2.0 m^2/g为主。芦草沟组非常规油气储集空间类型由纳米—微米级微孔和2期构造缝隙构成。

关键词：细粒沉积岩储层芦草沟组非常规油气准噶尔盆地南缘

中国2014年7～14岁学生血红蛋白水平及贫血状况分析

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中华流行病学杂志 2017年第5期38卷 588-591页

作者：杨招庚王政和马军北京大学公共卫生学院儿童青少年卫生研究所 100191

目的了解我国7～14岁学生血红蛋白水平及贫血流行状况。方法基于2014年全国学生体质与健康调研数据库，抽取检测了血红蛋白的7、9、12和14岁共71130名学生作为研究对象，采用2011年WHO贫血诊断标准，了解研究对象血红蛋白水平和贫血患... 详细信息

目的了解我国7～14岁学生血红蛋白水平及贫血流行状况。方法基于2014年全国学生体质与健康调研数据库，抽取检测了血红蛋白的7、9、12和14岁共71130名学生作为研究对象，采用2011年WHO贫血诊断标准，了解研究对象血红蛋白水平和贫血患病率，分析我国7—14岁学生贫血流行现状。结果2014年我国7、9、12和14岁学生血红蛋白水平分别为（129．25±11．37）g／L、（131．04±11．08）g／L、（135．02±12．12）g／L和（138．47±13．97）g／L，贫血检出率分别为9．0％、6．5％、8．6％和7．7％，其中男生为（135．49±13．33）g／L，女生为（131．38±11．67）g／L。总体贫血患病率为7．9％，其中女生（9．7％）显著高于男生（6．2％）（P〈0．01）；乡村学生（8．8％）显著高于城市（7．1％）（P〈0．001）。消瘦、正常、超重和肥胖学生的血红蛋白水平分别为（133．19±12．56）g／L、（133．28±12．76）g／L、（134．24±12．73）g／L和（133．79±12．16）g／L；贫血率分别为8．8％、8．3％、6．7％和5．9％，四组间差异有统计学意义（P〈0．001）。结论我国7—14岁学生贫血检出率仍较高，且在不同性别、城乡、年龄以及营养状况人群中存在差异。

关键词：血红蛋白贫血学生营养状况