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Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn–AhR–AQP4 signaling pathway

Signal Transduction and Targeted Therapy 2020年第1期5卷 2348-2360页

作者： Lisha Du Zikang Xing bangbao tao Tianqi Li Dan Yang Weirui Li Yuanting Zheng Chunxiang Kuang Qing Yang State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversitySonghu Road 2005Shanghai 200438China Department of Neurosurgery Xinhua HospitalShanghai Jiaotong UniversitySchool of MedicineKongjiang Road 1665Shanghai 200092China Department of Chemistry Tongji UniversitySiping Road 1239Shanghai 200092China Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityHandan Road 220Shanghai 200433China

Indoleamine 2,3-dioxygenase 1(IDO1),indoleamine 2,3-dioxygenase 2(IDO2),and tryptophan 2,3-dioxygenase(TDO)initiate the first step of the kynurenine pathway(KP),leading to the transformation of L-tryptophan(Trp)into L-kynurenine(Kyn)and other downstream *** is known as an endogenous ligand of the aryl hydrocarbon receptor(AhR).Activation of AhR through TDO-derived Kyn is a novel mechanism to support tumor growth in ***,the role of IDO1 and IDO2 in this mechanism is still ***,by using clinical samples,we found that the expression and activity of IDO1 and/or TDO(IDO1/TDO)rather than IDO2 were positively correlated with the pathologic grades of *** expression of IDO1/TDO rather than IDO2 was positively correlated with the Ki67 index and overall *** expression of IDO1/TDO was positively correlated with the expression of aquaporin 4(AQP4),implying the potential involvement of IDO1/TDO in glioma cell ***,we found that IDO1/TDO accounted for the release of Kyn,which activated AhR to promote cell motility via the Kyn–AhR–AQP4 signaling pathway in U87MG glioma ***103,an IDO1/TDO dual inhibitor,could block the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway and exert anti-glioma effects in GL261 orthotopic glioma ***,our results showed that the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway is a new mechanism underlying the malignancy of gliomas,and suggest that both IDO1 and TDO might be valuable therapeutic targets for gliomas.

关键词： IDO1 AQP4 glioma

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FTO interacts with FOXO3a to enhance its transcriptional activity and inhibits aggression in gliomas

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1321-1323页

作者： bangbao tao Xuehua Huang Juanhong Shi Jun Liu Shu Li Chunyan Xu Jun Zhong Liang Wan Baohui Feng Bin Li Department of Neurosurgery Xinhua HospitalSchool of MedicineShanghai Jiaotong University1665 Kongjiang Road200092 ShanghaiChina Department of Pain Xinhua HospitalSchool of MedicineShanghai Jiaotong University1665 Kongjiang Road200092 ShanghaiChina Department of Pathology Tongji HospitalSchool of MedicineSchool of MedicineShanghai Tongji University389 Xincun Road200062 ShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Wannan Medical College10 Kangfu Road241001 WuhuAnhuiChina Department of Pathophysiology Wannan Medical College22 Wenchang Road241002 WuhuAnhuiChina

Dear Editor,Gliomas represent the most common primary brain tumors in adults and few targeted therapies are ***,it’s imperative to explore novel target genes in *** mass and obesity-associated(FTO)gene encodes an alphaketoglutarate-dependent dioxygenase,which demethylates N6-methyladenosine on single-strand RNA.1 FTO is highly expressed in the brain but its potential contribution to gliomas is ***3a belongs to the forkhead family of transcription factors and it mediates important cellular processes like apoptosis and proliferation by regulating its target gene expression.2 Interestingly,genetic variants of FOXO33 and FTO4 are associated with longevity in human,suggesting that FTO and FOXO3a might share convergent effects in biological ***,we investigated the involvement of potential FTO–FOXO3a interaction in gliomas.

关键词： FOXO3a glioma expression

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MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment

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Cellular & Molecular Immunology 2016年第5期13卷 658-668页

作者： Hua He Maojin Yao Wenhao Zhang bangbao tao Feili Liu Shu Li Yan Dong Chenran Zhang Yicheng Meng Yuxin Li Guohan Hu Chun Luo Hui Zong Yicheng Lu Department of Neurosurgery Changzheng Hospital Second Affiliated Hospital of Second Military Medical University 415 Fengyang Road Shanghai 200003 P.R.China Department of Microbiology Immunology and Cancer Biology School of Medicine University of Virginia USA Department of Hematology Xinhua Hospital School of Medicine Shanghai Jiaotong University Shanghai China Department of Neurosurgery Xinhua Hospital School of Medicine Shanghai Jiaetong University Shanghai China Department of Pathophysiology Wannan Medical College 22 Wenchang Road Wuhu 241002 China

Although temozolomide （TMZ） is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to identity prognostic markers for outcome prediction and to develop chemo-sensitizing agents. Here, the gene expression profiles of TMZ-resistant and TMZ-sensitive samples were compared by microarray analysis, and mitogen-activated protein kinase kinase 2 （MEK2） was upregulated specifically in resistant glioma cells but not in sensitive tumor cells or non-tumor tissues. Moreover, a comprehensive analysis of patient data revealed that the increased level of MEK2 expression correlated well with the advancement of glioma grade and worse prognosis in response to TMZ treatment. Furthermore, reducing the level of MEK2 in U251 glioma cell lines or xenografted glioma models through shRNA-mediated gene knockdown inhibited cell proliferation and enhanced the sensitivity of cells toward TMZ treatment. Further analysis of tumor samples from glioma patients by real-time PCR indicated that an increased MEK2 expression level was closely associated with the activation of many drug resistance genes. Finally, these resistance genes were downregulated after MEK2 was silenced in vitro, suggesting that the mechanism of MEK2-induced chemo-resistance could be mediated by the transcriptional activation of these resistance genes. Collectively, our data indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ.

关键词： glioma MEK2 temozolomide

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Correction:Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn-AhR-AQP4 signaling pathway

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3796-3797页

作者： Lisha Du Zikang Xing bangbao tao Tianqi Li Dan Yang Weirui Li Yuanting Zheng Chunxiang Kuang Qing Yang State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Songhu Road 2005 Shanghai 200438 China Institute of Science and Technology for Brain-Inspired Intelligence Fudan University Handan Road 220 Shanghai 200433 China Department of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine Kongjiang Road 1665 Shanghai 200092 China Department of Chemistry Tongji University Siping Road 1239 Shanghai 200092 China

In the process of collating the raw data,the authors noticed the inadvertent mistakes in Fig.4h&6g that need to be *** correct data are provided as *** key findings of the article are not affected by the *** apologize for the inadvertent *** authors mistakenly placed the wrong representative image showing the invasion ability of U87MG cells in the IFN-γ+1-MT *** correct version of Fig.4h is shown above.

关键词： mistake correction invasion

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Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Knockdown of CDK6 enhances glioma sensitivity to chemotherap...

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2011中华医学会神经外科学学术会议

作者： Bing Li Hua He bangbao tao Xiaojie Lu guohan Hu luo Chun Yicheng lu 第二军医大学长征医院无锡市第二人民医院

Chemotherapy is widely used for the treatment of glioma. Clinical observations showed that brain neoplasm tissues are resistance to chemotherapy, making glioma very difficult to be completely removed or controlled. Ho... 详细信息

关键词： CDK6 chemotherapy glioma drug resistance MDR

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Manifestation, management, and outcome of 23 patients with giant cell glioblastoma multiforme in China

Manifestation, management, and outcome of 23 patients with g...

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2011中华医学会神经外科学学术会议

作者： bangbao tao1 Hua he1 Yicheng Lu1 1.Shanghai Neurosurgerical institute

Giant cell glioblastoma (GCG) is a variant of glioblastoma multiforme that has a distinct clinicopathology. In this retrospective study, 23 cases of GCG diagnosed between January 2006 and November 2009 in the Chinese ... 详细信息

关键词： Giant cell glioblastoma Radiation Chemotherapy

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人Plecstrin同源域家族A成员1表达与胶质瘤恶性表型相关性研究

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中国神经精神疾病杂志 2021年第3期47卷 149-154页

作者：刘俊陈铭陶帮宝张卿云皖南医学院第二附属医院神经外科芜湖241000 上海交通大学医学院附属新华医院神经外科马鞍山市中心医院神经外科

目的研究人Plecstrin同源域家族A成员1(Pleckstrin homology like domain family A member 1,PHLDA1)与胶质瘤恶性表型关系。方法收集马鞍山市中心医院神经外科和上海新华医院神经外科2015年1月至2020年4月65例原发脑胶质瘤的速冻标本... 详细信息

目的研究人Plecstrin同源域家族A成员1(Pleckstrin homology like domain family A member 1,PHLDA1)与胶质瘤恶性表型关系。方法收集马鞍山市中心医院神经外科和上海新华医院神经外科2015年1月至2020年4月65例原发脑胶质瘤的速冻标本。从接受尸检的非胶质瘤患者中收集了5份脑组织样本作为对照。利用免疫组化方法检测样品中的PHLDA1表达。采用免疫荧光、流式细胞术、集落形成法、体外细胞迁移侵袭法对成人胶质瘤U87细胞系和U251细胞系进行胶质瘤表型分析。结果免疫组化结果显示,随着胶质瘤WHO分级的增加,PHLDA1染色强度增加(x^(2)趋势=24.145,P<0.01)。3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐比色法(MTT试验)结果显示,与空白对照组和阴性干扰组相比,当SiRNA干扰敲低PHLDA1后,U87和U251培养48 h后的增殖率显著降低(P<0.05)。流式细胞仪检测显示,PHLDA1干扰后,U87和U251细胞凋亡率高于对照组(P<0.01),G0-G1期细胞比例低于对照组(P<0.05)而S期比例高于对照组(P<0.01)。transwell试验显示,PHLDA1干扰组的U87和U251迁移率明显低于对照组(P<0.01)。结论PHLDA1在胶质瘤中过表达。功能分析显示PHLDA1在胶质瘤的迁移和侵袭中起重要作用。PHLDA1可能成为胶质瘤新的潜在治疗靶点。

关键词：人Plecstrin同源域家族A成员1 脑胶质瘤细胞增值迁移细胞表型

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Expression and pathologic correlation analysis of CD151 in human gliomas

Expression and pathologic correlation analysis of CD151 in h...

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2011中华医学会神经外科学学术会议

作者： bangbao tao1 Hua He1 Yan Dong1 Yicheng Lu1 1.Shanghai Neurosurgerical institute

Objective To investigate the expression level of CD151 in different grade gliomas and the relationship between theexpression of CD151 and survival time of patients with gliomas. Methods There were 6, 21 and 42 cases i... 详细信息

关键词： glioma CD151 immunohistochemistry polymerase chain reaction

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激素在垂体生长激素腺瘤预后判断中的意义

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中华神经外科疾病研究杂志 2007年第4期6卷 377-378页

作者：顾昌伟陶帮宝孙青芳上海交通大学医学院附属瑞金医院神经外科上海200025

垂体生长激素腺瘤是一种相对罕见的疾病,生长激素(growth hormone,GH)高分泌发生在青春期骨骺闭合前表现为巨人症,成年后主要是肢端肥大症,约占垂体腺瘤的20%,总发病率在15.7～75.8/百万.肢端肥大症是个缓慢进展的疾病,临床上主要表现... 详细信息

垂体生长激素腺瘤是一种相对罕见的疾病,生长激素(growth hormone,GH)高分泌发生在青春期骨骺闭合前表现为巨人症,成年后主要是肢端肥大症,约占垂体腺瘤的20%,总发病率在15.7～75.8/百万.肢端肥大症是个缓慢进展的疾病,临床上主要表现为疲劳感、关节疼痛、头痛、感觉异常及过量出汗.

关键词：垂体生长激素腺瘤肢端肥大症生长激素口服糖耐量试验胰岛素样生长因子.1 治愈缓解

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Effect of lamellarization on the microstructure and mechanical properties of marine 10Ni5CrMoV steel

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 402-413页

作者： tao Zou Yanwu Dong Zhouhua Jiang Shuyang Du Yushuo Li School of Metallurgy Northeastern UniversityShenyang 110819China Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819China Key Laboratory for Ecological Metallurgy of Multimetallic Ores(Ministry of Education) Northeastern UniversityShenyang 110819China

Multistage heat treatment involving quenching(Q),lamellarizing(L),and tempering(T)is applied to marine 10Ni5CrMoV *** microstructure and mechanical properties were studied by multiscale characterizations,and the kinetics of reverse austenite transformation,strain hardening behavior,and toughening mechanism were further *** lamellarized specimens possess low yield strength but high toughness,especially cryogenic *** leads to the development of film-like reversed austenite at the martensite block and lath boundaries,refining the martensite structure and lowering the equivalent grain *** analysis of austenite reversion based on the JMAK model shows that the isothermal transformation is dominated by the growth of reversed austenite,and the maximum transformation of reversed austenite is reached at the peak temperature(750℃).The strain hardening behavior based on the modified Crussard-Jaoul analysis indicates that the reversed austenite obtained from lamellarization reduces the proportion of martensite,significantly hindering crack propagation via martensitic transformation during the *** a consequence,the QLT specimens exhibit high machinability and low yield *** with the QT specimen,the ductile-brittle transition temperature of the QLT specimens decreases from-116 to-130℃due to the low equivalent grain size and reversed austenite,which increases the cleavage force required for crack propagation and absorbs the energy of external load,*** work provides an idea to improve the cryogenic toughness of marine 10Ni5CrMoV steel and lays a theoretical foundation for its industrial application and comprehensive performance improvement.

关键词： 10Ni5CrMoV steel lamellarizing reversed austenite cryogenic toughness ductile-brittle transition temperature

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