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中国神经肿瘤杂志 2013年第2期 112-112页

作者： Lasky JL 3rd Panosyan EH Plant A Davidson T Yong WH Prins RM Liau LM Moore TB Department of Pediatrics Division of Pediatric Hematology/ Oncology Harbor-UCLA Medical Center/LA Biomed David Geffen School of Medicine UCLA Torrance CA90502 USA

Immunotherapy has the potential to improve clinical outcomes with little toxicity for pediatric patients with brain *** conducted a pilot feasibility study of tumor lysate-pulsed dendritic cell(DC)vaccination in pediatric patients(1 to 18 years old)with newly diagnosed or recurrent high-grade glioma(HGG).A total of nine DC vaccine doses,each containing 1×10(6)cells per dose were administered to three out of the seven originally enrolled *** were limited to mild side-effects,except in one case

关键词： cell Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas high

曲古抑菌素A抑制人脑肿瘤细胞增殖及提高p21和p27蛋白表达

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癌症 2002年第10期21卷 1100-1105页

作者：王之敏胡锦周岱许志元 Lawrence C.Panasci 陈忠平苏州大学附属一院神经外科江苏苏州215006 上海市第六人民医院神经外科上海200233 Lady Davis Institute for Medical research Sir Mortimer B. Davis -Jewish General Hospital McGill University 3755 Cote Ste Catherine Montreal Quebec H3T 1E2 Canada 中山大学肿瘤防治中心神经外科广东广州510060

背景和目的:研究提示组蛋白乙酰化酶抑制剂曲古抑菌素A能诱导细胞凋亡。本研究拟探讨曲古抑菌素A对人脑肿瘤细胞的杀伤作用和机制。材料和方法:选用两种人脑肿瘤细胞株,一株为p53突变型的人胶质瘤细胞株T98G,另一株为p53野生型的人神经... 详细信息

背景和目的:研究提示组蛋白乙酰化酶抑制剂曲古抑菌素A能诱导细胞凋亡。本研究拟探讨曲古抑菌素A对人脑肿瘤细胞的杀伤作用和机制。材料和方法:选用两种人脑肿瘤细胞株,一株为p53突变型的人胶质瘤细胞株T98G,另一株为p53野生型的人神经母细胞瘤细胞株SKNSH;采用SRB细胞毒测定方法检测TSA作用后肿瘤细胞的增殖状态,用琼脂糖凝胶DNA电泳和流式细胞仪定性和定量分析肿瘤细胞凋亡情况,应用Western印迹分析TSA作用前后,肿瘤细胞中高度乙酰化的组蛋白H3、H4,内源性p53蛋白、乙酰化p53蛋白、以及细胞周期相关蛋白p21、p27的变化。结果:TSA在纳摩尔级浓度即能有效抑制肿瘤细胞增殖,并引起高度乙酰化的组蛋白分子H3和H4集聚;用320nM的TSA作用肿瘤细胞24小时,即发生显著的肿瘤细胞凋亡;TSA刺激肿瘤细胞48小时内,p21和p27蛋白表达显著增强,其中p21蛋白水平在4小时后时即明显升高,8小时达高峰;p27蛋白水平升高发生在8小时后,而内源性p53蛋白水平和乙酰化的p53蛋白水平未发生变化。结论:TSA在体外能有效抑制对传统化疗耐药的人脑肿瘤细胞生长,其抗肿瘤生长机理可能是通过上调p21和p27蛋白水平实现的,而不受内源性p53基因状态和蛋白改变的影响。

关键词：脑肿瘤组蛋白去乙酰化酶抑制剂 p21 p27 曲古抑菌素A 细胞增殖蛋白表达

Anti-PD-L1/TGF-BR fusion protein (SHR-1701) overcomes disrupted lymphocyte recovery-induced resistance to PD-1/PD-L1 inhibitors in lung cancer

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Cancer Communications 2022年第1期42卷 17-36页

作者： Bo Cheng Kaikai Ding Pengxiang Chen Jianxiong Ji Tao Luo Xiaofan Guo Wei Qiu Chunhong Ma Xue Meng Jian Wang Jinming Yu Yuan Liu Department of Radiation Oncology Shandong Cancer Hospital and InstituteCheeloo College of MedicineShandong UniversityJinanShandong 250012P.R.China Department of Radiation Oncology Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinanShandong 250012P.R.China Department of Neurosurgery Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinanShandong 250012P.R.China Department of Neurology Loma Linda University HealthLoma LindaCA 92354USA Shandong Key Laboratory of brain Functional Remodeling JinanShandong 250012P.R.China Department of Biomedicine University of BergenBergen 5009Norway Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of MedicineJinanShandong 250012P.R.China Department of Neurosurgery the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310000P.R.China

Background:Second-generation programmed cell death-protein 1/pro-grammed death-ligand 1(PD-1/PD-L1)inhibitors,such as bintrafusp alfa(M7824),SHR-1701,and YM101,have been developed to simultaneously block PD-1/PD-L1 and transforming growth factor-beta/transforming growth factor-beta receptor(TGF-P/TGF-βR).Consequently,it is necessary to identify predictive factors of lung cancer patients who are not only resistant to PD-1/PD-LI inhibitors but also sensitive to bifunctional *** purpose of this study was to search for such ***:Multivariable Cox regression was used to study the association between the clinical outcome of treatment with PD-1/PD-L1 inhibitors and lym-phocyte recovery after lymphopenia in lung cancer *** CMT167 lung cancer cells were engineered to express the firefly luciferase gene and implanted orthotopically in the lung of syngeneic *** imag-ing,flow cytometry,and immunohistochemistry were employed to detrmine response to immunotherapy and function of tumor-infiltrating immune ***:For lung cancer patients treated with anti-PD-1/PD-LI antibodies,poor lymphocyte recovery was associated with a shorter progression-free survival(PFS;Ptumors and peripheral immune organs of mice with poor lymphocyte recovery after ***,these mice failed to respond to anti-PD-1 antibodies but remained sensitive to the anti-PD-LI/TGF-βR fusion protein(SHR-1701).Consistently,SHR-1701 but not anti-PD-1 antibod-ies,markedly enhanced IFN-γproduction and Ki-67 expression in peripheral CD8+T cells from patients with impaired lymphocyte ***:Lung cancer patients with poor lymphocyte recovery and suffer-ing from persistent lymphopenia after previous chemotherapy are resistant to anti-PD-1/PD-L1 antibodies but might be sen

关键词： SHR impaired markedly

Protective effects of combination of Xuesaitong and aspirin on cerebral ischemia and reperfusion injury in rats

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Chinese Herbal Medicines 2018年第2期10卷 223-230页

作者： Na-na Zhao Shi-min Tang Xin-yue Li Yong-mei Wu Yu-ting Zhou Jin-feng Shen Song Fang Xiang-bao Meng Gui-bo Sun Xiao-bo Sun Institute of Medicinal Plant Development Peking Union Medical College and Chinese Academy of Medical SciencesZhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health ProductsKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal MedicineMinistry of EducationBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine(Natural Medicine)and Translational MedicineBeijing 100193China Heilongdiang University of Chinese Medicine Harbin 150040China Changchun University of Chinese Medicine Changchun 130117China North Minzu University Yinchuan 750021China China Resources Kunming Shenghuo Pharmaceutical Co. Ltd.Kunming 650217China

Objective：To investigate the protective effects of the combination of Xuesaitong（XST）and aspirin on cerebral ischemia and reperfusion injury（CIRI）in rats,and further explore the underlying ***：A total of 150 male Sprague-Dawley（SD）rats were randomly divided into five groups with 30rats in each group：sham group,middle cerebral artery occlusion/reperfusion（MCAO/R）model group,XST group,aspirin group,and XST＋aspirin *** were pretreated with XST,aspirin,or XST＋aspirin for7 *** hour after the last administration,a model of CIRI was induced by MCAO/*** deficits were assessed using Longa’s five-point *** edema was detected by the measurement of brain water *** volume of cerebral infarction was determined by 2,3,5-triphenyltetrazolium chloride（TTC）*** activities of superoxide dismutase（SOD）,catalase（CAT）,and glutathione peroxidase（GSH-Px）,as well as levels of malonaldehyde（MDA）were detected by commercial ***-linked immunosorbent assay（ELISA）was used to determine the levels of interleukin-1（）,interleukin-4（IL-4）,interleukin-6（IL-6）,interleukin-10（IL-10）,tumor necrosis factor-alphamonocyte chemotactic protein 1（MCP-1）,and kynurenine in serum,cerebral cortex,and hippocampus of MCAO/R *** protein expression of nuclear factor erythroid 2-related factor（Nrf2）,heme oxygenase-1（HO-1）,I-kappa B alpha（IκBα）,and nuclear factor kappa B（B）/p65 in the cortex were analyzed by western ***：Treatment of XST,aspirin,and XST＋aspirin significantly alleviated the neurological deficits,cerebral edema,and cerebral infarct volume induced by MCAO/*** of XST,aspirin,and XST＋aspirin also reduced MDA,,MCP-1,and kynurenine levels,and increased SOD,CAT,GSH-Px,IL-4,and IL-10 levels in serum,cerebral cortex,and hippocampus of MCAO/R ***,treatment of XST,aspirin,and XST＋aspirin decreased the expression of nuclearB/p65 and increased the expression of IκBα,nuclear Nrf2,and ***,the combinat

关键词： aspirin cerebral ischemia and reperfusion injury inflammation oxidative stress Xuesaitong(XST)

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904例同侧偏盲的临床与解剖相关性研究

世界核心医学期刊文摘（眼科学分册） 2006年第9期2卷 6-6页

作者： Kedar S. Lynn M.J. V.Biousse 桑延智 Neuro-ophthalmology Unit Emory Eye Center1365-B Clifton RoadNEAtlantaGA 30322United States Dr.

Objective:To describe the clinical characteristics and clinical-anatomic correlations of homonymous hemianopia(HH).Background:Homonymous hemianopia impairs visual function and frequently precludes *** knowledge of HH is based on relatively few cases with clinical-anatomic ***:The authors reviewed medical records of all patients with HH seen in their service between 1989 and *** characteristics,characteristics of visual field defects,causes of visual field defects,neuroradiologic definition of lesion location,and associated neurologic deficits were ***:A total of 904 HH were found in 852 patients.A total of 340 HH(37.6%)were complete and 564 HH(62.4%)were *** quadrantanopia(264 HH,29%)was the most common type of incomplete HH,followed by homonymous scotomatous defects(116 HH,13.5%),partial HH(114 HH,13%),and HH with macular sparing(66 HH,7%).A total of 407 HH(45.0%)were *** of HH included stroke(629 HH,69.6%),trauma(123,13.6%),tumor(102,11.3%),brain surgery(22,2.4%),demyelination(13,1.4%),other rare causes(13,1.4%),and unknown etiology(2,0.2%).The lesions were most commonly located in the occipital lobes(45%)and the optic radiations(32.2%).Every type of HH,except for unilateral loss of temporal crescent and homonymous sectoranopia,was found in all lesion locations along the retrochiasmal visual ***:Homonymous hemianopia is usually secondary to stroke,head trauma,and *** the characteristics of visual field defects can be helpful in lesion location,specific visual field defects do not always indicate specific brain locations.

关键词：临床特点相关性解剖学同侧偏盲神经损伤视野缺损少见病因

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作为癌前表现的脑部肿块患者的诊断评估

世界核心医学期刊文摘(神经病学分册) 2006年第1期 53-53页

作者： Mavrakis A.N. Halpern E.F. Barker II F.G. J.W. Henson 樊慧婷 StephenE. and Catherine Pappas center for Neuro-Oncology Massachusetts General Hospital 55 Fruit St. Boston MA 02114 United States Dr.

Background: Patients with a newly detected brain mass and no history of cancer often undergo extensive diagnostic testing in search of a systemic primary neoplasm prior to selection of a biopsy site, potentially leading to unnecessary expense and delay. We sought patterns in the evaluation of these patients to allow rapid selection of a biopsy site. Methods: We compared the diagnostic evaluation of 176 patients with newly detected brain masses who were ultimately determined to have a metastatic or primary lesion. Results: In 88 patients presenting with brain metastasis, lung cancer was markedly overrepresented as a primary tumor, occurring in 82%of patients. brain MRI and chest CT together identified the site for diagnostic biopsy in all except for two of the 176 patients. One-half of the patients with metastasis had brain biopsy as the primary diagnostic procedure, with 80%undergoing a craniotomy rather than needle biopsy. The initial management decision in the majority of metastasis patients was whether to perform a craniotomy for resection of tumor. Whereas patients with single and cerebellar lesions were most likely to undergo craniotomy, the extent of systemic disease did not affect the decision to recommend a neurosurgical procedure. The average time to biopsy for patients with metastatic and primary tumors was 4.7 days and 6.0 days. In this retrospective population, we estimated that evaluation with brain MRI and chest CT, followed by an early neurosurgical decision, could reduce the time to diagnosis by at least 10%. Conclusions: Chest CT and brain MRI, if used together as initial diagnostic studies, would have identified a biopsy site in 97%of patients with a newly detected brain mass.

关键词：诊断评估脑部肿块患者

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抗癌药紫杉醇的神经毒性和耳毒性

中华耳科学杂志 2011年第3期9卷 318-322页

作者：董杨施建蓉 Richard Salvi 丁大连 center for Hearing and Deafness State University of New York at BuffaloNY14214 上海中医药大学教学实验中心上海201203 上海交通大学第六人民医院耳鼻咽喉头颈外科上海市耳鼻咽喉科研究所上海200233 中南大学湘雅医院耳鼻咽喉头颈外科上海410007 日本东京大学 Tokyo 163-8001

紫杉醇（Paclitaxel，商品名Tax01）是从红豆杉科红豆杉属植物中提取得到的二萜类化合物，分子式为C47H51N014。1963年，美国化学家瓦尼和沃尔从一种生长在美国西部大森林中的太平洋杉的树皮和木材中分离到紫杉醇粗提物，在筛选实验中... 详细信息

紫杉醇（Paclitaxel，商品名Tax01）是从红豆杉科红豆杉属植物中提取得到的二萜类化合物，分子式为C47H51N014。1963年，美国化学家瓦尼和沃尔从一种生长在美国西部大森林中的太平洋杉的树皮和木材中分离到紫杉醇粗提物，在筛选实验中发现其具有很强的抗肿瘤活性。1971年分离出紫杉醇单体成分、确定其化学结构，并正式命名为紫杉醇。从1989到1990年在完成了紫杉醇的Ⅱ期和Ⅲ期临床试验后，

关键词：紫杉醇神经毒性耳毒性抗癌药二萜类化合物红豆杉属植物抗肿瘤活性红豆杉科

脑肿瘤的定量血氧水平依赖分析研究,T2*序列足够能评价氧合作用吗?

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国际医学放射学杂志 2012年第2期35卷 179-179页

作者： T.Christen B.Lemasson N.Pannetier R.Farion C.Remy G.Zaharchuk 卞读军 Inserm U836-GINquipe 5GrenobleFrance Department of Radiology Lucas Center for ImagingStanford University1201 Welch RdMC 5488StanfordCA 94305-5488

目的在脑肿瘤动物模型中,分析比较横向弛豫参数(T2)、宏观场多相性(△B0)以及血容量成分(BVf)对于血氧水平依赖(BOLD)MR成像测量血氧饱和度(SO2)的作用。材料与方法本项研究经过地方动物保护和利用组织批准。实验

关键词：肿瘤组织对侧大脑血氧饱和度氧合作用 BOLD T2 血氧

Role of nestin in glioma invasion

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World Journal of Translational Medicine 2015年第3期4卷 78-87页

作者： Alex Lin Luigi Marchionni Jeffrey Sosnowski David Berman Charles G Eberhart Eli E Bar Department of Pathology Johns Hopkins University School of Medicine Department of Oncology Johns Hopkins University School of Medicine Department of Orthopedic Surgery Johns Hopkins University School of Medicine Department of Ophthalmology Johns Hopkins University School of Medicine Department of Neurological Surgery School of Medicine Case Western Reserve University Case Comprehensive Cancer center Case Western Reserve University School of Medicine

AIM: To determine the role for the intermediate filament protein nestin in glioma invasion. METHODS: We examined the expression and function of nestin in gliomas(Grades Ⅱ-Ⅳ as defined by the World Health Organization). We determined nestin expression using Immunohistochemical methods. To elucidate nestin's biological function(s), we reduced m RNA levels by 61% and 87% in two glioblastomaderived neurosphere lines using short hairpin RNAs and determined the effect of reduced nestin expression on glioma cell proliferation and invasion using MTS and matrigel migration assays, respectively. We also utilized quantitative real time polymerase chain reaction assaysto determine the effect of reduced nestin expression on the expression of other markers associated with glioma stem cells and their differentiated progenies. RESULTS: We found a significant correlation between nestin immunoreactivity and astrocytoma tumor grade, with 36% of grade Ⅱ, 75% of grade Ⅲ, and 100% of grade Ⅳtumors expressing significant levels of the protein when assessed using immunohistochemistry. Reduction in nestin expression had no effect on cell growth in culture, but did retard the capacity of one line to migrate in-vitro on matrigel. Interestingly, in the line whose migration was not affected, m RNA levels of a second intermediate filament, synemin(also knowns as desmuslin), were elevated following introduction of sh RNA targeting nestin. As synemin was not induced in the line which required nestin for migration, it is a possibility that synemin may compensate for the loss of nestin in this process. CONCLUSION: Nestin expression is prominent in high-grade astrocytomas. Nestin is not required for cell growth but it may, however, be required for cell motility.

关键词： Nestin Stem cells Migration Glioma Neurosphere

第一代酪氨酸激酶抑制剂治疗中发生进展的非小细胞肺癌血浆表皮生长因子受体(EGFR)T790M突变提示了失败部位并预测了临床预后:一项前瞻性观察研究

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癌症 2018年第9期37卷 377-391页

作者： Shirong Zhang Lucheng Zhu Bing Xia Enguo Chen Qiong Zhao Xiaochen Zhang Xueqin Chen Xufeng Chen Shenglin Ma 转化医学中心杭州市第一人民医院南京医科大学浙江杭州310006 肿瘤科杭州市第一人民医院南京医科大学浙江杭州310006 杭州市肿瘤医院肿瘤科浙江杭州310000 浙江大学医学院附属邵逸夫医院呼吸科浙江杭州310020 浙江大学第一附属医院肿瘤科浙江杭州310006 Department of Cancer Genetics and Epigenetics City of Hope National Medical CenterDuarteCA 91010USA

背景与目的血浆循环肿瘤DNA(circulating tumor DNA,ctDNA)是检测表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M突变的理想方法。T790M突变是第一代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)耐药的主要机制。本研究旨在探讨ctDNA来源的T790M突变与非小细胞肺癌(non-small cell lung cancer,NSCLC)患者疾病失败部位及临床预后的关系。方法第一代TKI治疗发生进展的患者被分为局限胸内进展(chest limited,CF)、局限颅内进展(brain limited,BF)和其他部位进展(other,OF)组。采用扩增阻滞突变系统(amplification refractory mutation system,ARMS)和微滴式数字PCR(droplet digital PCR,ddPCR)对ctDNA中T790M突变进行了检测。采用Kaplan-Meier法分析了预后。结果 2种方法的总体一致性为78.3%。根据ARMS和ddPCR,OF组患者的T790M突变率明显高于BF组和CF组(P <0.001),OF组的T790M突变丰度也明显高于CF组和BF组(P <0.001)。AZD9291是T790M+患者最佳治疗选择,为EGFR-TKI治疗后进展的所有组中T790M+患者提供了最长的生存期;接受其他治疗的T790M-患者亚组的预后各不相同。结论本研究表明ctDNA中T790M突变与NSCLC患者EGFR-TKI治疗失败部位相关,失败部位和T790M突变状态对治疗选择和预后都有很大影响。

关键词：非小细胞肺癌表皮生长因子受体 T790M ctDNA 失败部位