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| 1 | 脑胶质瘤诊疗指南(2022版)显示文摘脑胶质瘤是指起源于脑神经胶质细胞的肿瘤,是最常见的原发性颅内肿瘤,2021年第五版世界卫生组织(WHO)中枢神经系统肿瘤分类(以下简称新版分类)将脑胶质瘤分为1~4级,1、2级为低级别脑胶质瘤(low-grade glioma,LGG),3、4级为高级别脑胶质瘤(high-grade glioma,HGG)[1]。本指南主要涉及星形细胞、少突胶质细胞和室管膜细胞来源的成人LGG、HGG的诊治[2,3]。 | 国家卫生健康委员会医政医管局 中国抗癌协会脑胶质瘤专业委员会 中国医师协会脑胶质瘤专业委员会 江涛 张伟 樊星 刘幸 刘彦伟 陈宝师 柴睿超 王政 李冠璋 王引言 蒋传路 康春生 康德智 李维平 李文斌 刘云会 马文斌 毛庆 毛颖 牟永告 邱晓光 万经海 王伟民 杨学军 尤永平 于如同 余新光 | 2022 | 中华神经外科杂志2022，38，8： | 55 |
| 2 | Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma显示文摘The blood–brain barrier(BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme(GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel(PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles(NPs). Here we characterize PTX-loaded human serum albumin(HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P(SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content(7.89%) and entrapment efficiency(85.7%) with a spherical structure(about 150 nm) and zeta potential of -12.0 mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells(BCECs) and U87 cells was greatly improved.The low IC_(50), prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment. | Chunhui Ruan Lisha Liu Yifei Lu Yu Zhang Xi He Xinli Chen Yujie Zhang Qinjun Chen Qin Guo Tao Sun Chen Jiang | 2018 | Acta Pharmaceutica Sinica B2018，8，1： | 19 |
| 3 | IDO1 in cancer: a Gemini of immune checkpoints显示文摘Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。 | Lijie Zhai Erik Ladomersky Alicia Lenzen Brenda Nguyen Ricky Patel Kristen L Lauing Meijing Wu Derek A Wainwright | 2018 | Cellular & Molecular Immunology2018，15，5： | 17 |
| 4 | Circular RNAs and human glioma显示文摘As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved. | Jinglei Liu Kun Zhao Nunu Huang Nu Zhang | 2019 | Cancer Biology & Medicine2019，16，1： | 16 |
| 5 | nsights into molecular therapy of glioma: current .-hallenges and next generation blueprint显示文摘Glioma 说明人的大脑肿瘤的多数。与占优势的治疗政体,病人有差的幸存率。尽管有在主流的 glioma 治疗的当前的开发,为 glioma 的痊愈看起来从活动范围。glioma 和获得的电阻的渗透性的性质 substancially 限制治疗学的选择。glioma 和 proteogenomic 描述的复杂 pathobiology 的更好的说明可能最后为更复杂、有效的联合政体的设计打开新奇大街。这能被个别地定制进步 neuroimaging 技术完成,终止有 激活prodrug 基因的 DNA 合成, silencing gliomagenesis 基因(基因治疗),指向的 miRNA oncogenic 活动( miRNA-mRNA 相互作用),有干细胞治疗的联合 Hedgehog-Gli/Akt 禁止者,作为抗原采用肿瘤 lysates 由细胞毒素的 T 淋巴细胞(树枝状的房间种痘)为肿瘤特定的癌症干细胞的有效弄空采购原料,妄想的反的采纳转移因此,现在的评论捕获与分子的机制象外科,放射和化疗的限制一样在 glial tumorigenesis 包含了联系的最近的趋势。在这篇文章,我们极其也讨论下一代为 glioma 的成功的治疗的分子的治疗学的策略和他们的机制。 | Y RAJESH Ipsita PAL Payel BANIK Sandipan CHAKRABORTY Sachin A BORKAR Goutam DEY Ahona MUKHERJEE Mahitosh MANDAL | 2017 | Acta Pharmacologica Sinica2017，38，5： | 16 |
| 6 | Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy显示文摘Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy. | Caifang Gao Jianming Liang Ying Zhu Chengli Ling Zhekang Cheng Ruixiang Li Jing Qin Weigen Lu Jianxin Wang | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 12 |
| 7 | Brain stem cells as the cell of origin in glioma显示文摘Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery. | Aram S Modrek N Sumru Bayin Dimitris G Placantonakis | 2014 | World Journal of Stem Cells2014，6，1： | 12 |
| 8 | 嗜铬细胞瘤和副神经节瘤的诊断与临床管理显示文摘嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)临床少见但不罕见。因其临床表现多样且严重程度不一,常容易漏诊误诊;同时,PPGL的治疗过程常因缺乏循证医学依据指导,临床医生的决策严重依赖经验,故而经验缺乏的临床机构常常在诊疗上困难重重,并且难以实现正确而充分的术前准备。为了规范PPGL的诊疗过程以及帮助基层医疗机构更好地识别、诊断、治疗PPGL,本中心参考近年来国内外最新相关指南、荟萃分析并结合国内研究完成该文。 | 胡嘉禄 崔兆强 葛均波 | 2020 | 中华高血压杂志2020，28，2： | 12 |
| 9 | Topical delivery of nerve growth factor for treatment of ocular and brain disorders显示文摘Neurotrophins are a family of proteins that support neuronal proliferation, survival, and differentiation in the central and peripheral nervous systems, and are regulators of neuronal plasticity. Nerve growth factor is one of the best-described neurotrophins and has advanced to clinical trials for treatment of ocular and brain diseases due to its trophic and regenerative properties. Prior trials over the past few decades have produced conflicting results, which have principally been ascribed to adverse effects of systemic nerve growth factor administration, together with poor penetrance of the blood-brain barrier that impairs drug delivery. Contrastingly, recent studies have revealed that topical ocular and intranasal nerve growth factor administration are safe and effective, suggesting that topical nerve growth factor delivery is a potential alternative to both systemic and invasive intracerebral delivery. The therapeutic effects of local nerve growth factor delivery have been extensively investigated for different ophthalmic diseases, including neurotrophic keratitis, glaucoma, retinitis pigmentosa, and dry eye disease. Further, promising pharmacologic effects were reported in an optic glioma model, which indicated that topically administered nerve growth factor diffused far beyond where it was topically applied. These findings support the therapeutic potential of delivering topical nerve growth factor preparations intranasally for acquired and degenerative brain disorders. Preliminary clinical findings in both traumatic and non-traumatic acquired brain injuries are encouraging, especially in pediatric patients, and clinical trials are ongoing. The present review will focus on the therapeutic effects of both ocular and intranasal nerve growth factor delivery for diseases of the brain and eye. | Gemma Eftimiadi Marzia Soligo Luigi Manni Daniela Di Giuda Maria Lucia Calcagni Antonio Chiaretti | 2021 | Neural Regeneration Research2021，16，9： | 11 |
| 10 | 胶质瘤干细胞——胶质瘤治疗新靶点显示文摘胶质瘤是中枢神经系统发病率最高的恶性肿瘤。胶质瘤干细胞(glioma stem cells,GSC)的研究突破对其治疗有重要意义。GSC可能来源胶质细胞失分化或神经干细胞(neural stem cell,NSC)肿瘤性转化,有独特的生物学特性,GSC细胞内的信号通路异常与之形成有关。GSC内原癌功能miRNA高表达.抑癌功能miRNA低表达。GSC存在于血管性、缺氧性、免疫性三种微环境中并与其相互作用。未来,结合靶向GSC及其微环境可改善治疗效果,但提高选择性很关键。 | 李霁虹 刘啸白 刘丽波 | 2015 | 解剖科学进展2015，21，1： | 11 |
| 11 | The oncometabolite 2-hydroxyglutarate inhibits microglial activation via the AMPK/mTOR/NF-kB pathway显示文摘Microglia,the brain-resident macrophage,is known as the innate immune cell type in the central nervous system.Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development.Mutations of isocitrate dehydrogenases 1 and 2(IDH1/2)frequently occur in gliomas,which leads to accumulation of oncometabolic product 2-hydroxyglutarate(2HG).Moreover,IDH1/2 mutations were found to correlate with better prognosis in glioma patients.In thepresent study,we investigated the effects of the 2HG on microglial inflammatory activation.We showed that the conditioned media(CM)from GL261 glioma cells stimulated the activation of BV-2 microglia cells,evidenced by markedly increased expression of interleukin-6(IL-6),IL-1β,tumor necrosis factor-a(TNF-α),CCL2(C-C motif chemokine ligand 2)and CXCL10(C-X-C motif chemokine 10).CM-induced expression of proinflammatory genes was signifcantly suppressed by pretreatment with a synthetic cell-permeable 2HG(1 mM)or a nuclear factor-kB(NF-KB)inhibitor BAY11-7082(10μM).In lipopolysaccharide(LPS)-or TNF-a-stimulated BV-2 microglia cells and primary microglia,pretreatment with 2HG(0.25-1 mM)dose-dependently suppressed the expression of proinflammatory genes.We further demonstrated that 2HG significantly suppressed LPS-induced phosphorylation of IkB kinase a/β(IKKa/B),lkBa and p65,IkB degradation,and nuclear translocation of p65 subunit of NF-KB,as well as NF-KB transcriptional activity.Similarly,ectopic expression of mutant isocitrate dehydrogenase 1(IDH1)(R132H)significantly decreased TNF-a-induced activation of NF-KB signaling pathway,Finally,we revealed that activation of adenosine 5'-monophosphate-activated protein kinase(AMPK)and subsequent inhibition of mammalian target of rapamycin(mTOR)signaling contributed to theinhibitory effect of 2HG on NF-KB signaling pathway in BV-2 cells.Taken together,these results,for the frst time,show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF KB signaling pathway and provide evidence that oncometabolite 2HG may regulate glioma development via modulating microglial activation in tumor microenvironment. | Chao-jun Han Ji-yue Zheng Lin Sun Hui-cui Yang Zhong-qiang Cao Xiao-hu Zhang Long-tai Zheng Xue-chu Zhen | 2019 | Acta Pharmacologica Sinica2019，40，10： | 11 |
| 12 | ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron显示文摘Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H_(2)O_(2) via Fenton reaction,in which the role of activating transcription factor 3(ATF3)remains elusive.Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica,which has shown potent antitumor activity against various tumors,including glioma.In this study,we showed that brucine inhibited glioma cell growth in vitro and in vivo,which was paralleled by nuclear translocation of ATF3,lipid peroxidation,and increases of iron and H_(2)O_(2).Furthermore,brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine(500μM)or improved by ferric ammonium citrate(500μM).Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1(50μM)or liproxstatin-1(30μM)rescued brucine-induced glioma cell death.Moreover,knockdown of ATF3 prevented brucine-induced accumulation of iron and H_(2)O_(2) and glioma cell death.We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress.ATF3 promoted brucine-induced H_(2)O_(2) accumulation via upregulating NOX4 and SOD1 to generate H_(2)O_(2) on one hand,and downregulating catalase and xCT to prevent H_(2)O_(2) degradation on the other hand.H_(2)O_(2) then contributed to brucine-triggered iron increase and transferrin receptor upregulation,as well as lipid peroxidation.This was further verified by treating glioma cells with exogenous H_(2)O_(2) alone.Moreover,H_(2)O_(2) reversely exacerbated brucine-induced ER stress.Taken together,ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H_(2)O_(2) and iron. | Shan Lu Xuan-zhong Wang Chuan He Lei Wang Shi-peng Liang Chong-cheng Wang Chen Li Tian-fei Luo Chun-sheng Feng Zhen-chuan Wang Guang-fan Chi Peng-fei Ge | 2021 | Acta Pharmacologica Sinica2021，42，10： | 10 |
| 13 | Intratumor heterogeneity,microenvironment,and mechanisms of drug resistance in glioma recurrence and evolution显示文摘Glioma is the most common lethal tumor of the human brain.The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months.The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas.Unlike primary glioblastoma that usually develop de novo in the elderly,secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis.Based on various evolutional trajectories brought on by clonal and subclonal alterations,the evolution patterns of glioma vary according to different theories.Some important features distinguish the normal brain from other tissues,e.g.,the composition of the microenvironment around the tumor cells,the presence of the blood-brain barrier,and others.The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer.Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment.However,the detailed reasons for the progression and recurrence of glioma remain controversial.In this review,we introduce the different mechanisms involved in glioma progression,including tumor heterogeneity,the tumor microenvironment and drug resistance,and their pre-clinical implements in clinical trials.This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma. | Zhaoshi Bao Yongzhi Wang Qiangwei Wang Shengyu Fang Xia Shan Jiguang Wang Tao Jiang | 2021 | Frontiers of Medicine2021，15，4： | 10 |
| 14 | Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy显示文摘Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system(CNS) damage which endangers the patients' lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier(BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix(ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors. | Xiao Zhao Rujing Chen Mei Liu Jianfang Feng Jun Chen Kaili Hu | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 9 |
| 15 | 转移性嗜铬细胞瘤和副神经节瘤的治疗现状及进展显示文摘嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)是一种罕见的神经内分泌肿瘤,具有恶性潜能。目前尚无批准用于该病全身治疗的方案。本文对转移性嗜铬细胞瘤和副神经节瘤(metastatic pheochromocytoma and paraganglioma,mPPG)的手术、核素治疗、化疗、靶向药物治疗和免疫治疗等治疗方案的现状及进展作一综述,以期为mPPG全身治疗的临床研究提供理论依据。 | 翟雪佳 于顺利 樊青霞 宋丽杰 | 2019 | 中华泌尿外科杂志2019，40，12： | 9 |
| 16 | Effects of nursing care in fast-track surgery on postoperative pain, psychological state, and patient satisfaction with nursing for glioma显示文摘BACKGROUND The brain is the most complex organ in the human body.Treatment for a glioma always involves a multi-disciplinary team.Nursing care in fast-track surgery or enhanced recovery after surgery is such kind of work implemented by an interdisciplinary team to provide services to patients to improve their outcomes.AIM To explore the effects of nursing care in fast-track surgery on postoperative pain,psychological state,and patient satisfaction with nursing for glioma.METHODS From June 2018 to June 2020,138 patients who underwent operation for glioma at Cancer Hospital Affiliated to Chongqing University were selected.They were categorized into groups according to different nursing care that they received.Of them,69 patients receiving nursing care in fast-track surgery were included in an experimental group,and 69 patients receiving conventional postoperative nursing were included in a control group.Visual analogue scale was used to evaluate postoperative pain in the two groups immediately after the operation and at 3 d after the operation.Self-rating anxiety scale(SAS)and self-rating depression scale(SDS)were used to evaluate the psychological status of patients immediately after operation and on the 3rd postoperative day.A self-made satisfaction scale for patient satisfaction with nursing was used to evaluate and compare patient satisfaction with nursing between the two groups.RESULTS Time to excretion,time to out-of-bed activities,and length of hospital stay were significantly shorter in the observation group than in the control group(P<0.05).There was no significant difference in duration of operative time or intraoperative bleeding between the two groups(P>0.05).There was no significant difference in postoperative pain score between the two groups(P>0.05).The pain score was significantly lower in the observation group than in the control group at 3 d after the operation(P<0.05).There was no significant difference in postoperative SAS or SDS score between the two groups(P>0.05).SAS and SDS scores were significantly lower in the observation group than in the control group at 3 d after operation(P<0.05).The rate of patient satisfaction with nursing was 94.2%in the observation group,which was significantly higher than that(81.2%)of the control group(P<0.05).CONCLUSION Nursing care in fast-track surgery can relieve postoperative pain,anxiety,and depression,and improve patient satisfaction with nursing in patients with glioma,which is worthy of clinical application. | Yan-Hong Deng Yi-Mei Yang Jian Ruan Lin Mu Shi-Qiang Wang | 2021 | World Journal of Clinical Cases2021，9，20： | 8 |
| 17 | Prognostic implications of epidermal growth factor receptor variant Ⅲ expression and nuclear translocation in Chinese human gliomas显示文摘Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma. | Kaiyuan Yang Xiaohui Ren Liyuan Tao Peipei Wang Haihui Jiang Li Shen Yiming Zhao Yong Cui Mingxiao Li Song Lin | 2019 | Chinese Journal of Cancer Research2019，31，1： | 8 |
| 18 | YB-1, a new biomarker of glioma progression, is associated with the prognosis of glioma patients显示文摘(YB-1 ) Y 盒子蛋白质 1 是在各种各样的癌症表示的多功能的细胞的蛋白质,并且是在癌症治疗的一个潜在的目标。尽管有证据出现,那 YB-1 在人的癌症起一个作用,在 glioma 的 YB-1 表示的临床的意义没被建立。在现在的学习,我们在 glioma 肿瘤调查了 YB-1 水平并且分析了在 YB-1 水平和恶意的 glioma 的等级之间的关系,与提供为在临床、基本的研究背景的 gliomas 的诊断和治疗的新想法的目的。108 个病人的一个总数,与等级的 gliomas 包括 14, 31, 30,和 33 分别地,我, II, III,和 IV 在这研究被包括。YB-1 的 mRNA 和蛋白质层次被发现在等级 IV 和降低等级的肿瘤之间显著地不同。在脑髓的液体的 YB-1 层次比在等级在等级 III 和 IV glioma 病人是显著地更高的我和 II 病人。染色的 Immunofluorescence 被用来在细胞质和原子核检测 YB-1 的层次,并且结果显示细胞内部的分发显著地与 glioma 的病理学的等级被联系。YB-1 的高水平与弄短的幸存被联系,建议 YB-1 起在人的 glioma 的前进的一个作用。 | Jin Zheng Jiangwei Zhang Guangyue Li Huilin Gong | 2016 | Acta Biochimica et Biophysica Sinica2016，48，4： | 8 |
| 19 | Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma显示文摘Glioblastoma(GBM)is an incurable and highly heterogeneous brain tumor,originating from human neural stem/progenitor cells(hNSCs/hNPCs)years ahead of diagnosis.Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels,the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling.Here,we established two highly penetrant hNSC-derived malignant glioma models,which resemble the histopathology and transcriptional heterogeneity of human GBM.Integrating time-series analyses of whole-exome sequencing,bulk and single-cell RNA-seq,we reconstructed gliomagenic trajectories,and identified a persistent NSC-like population at all stages of tumorigenesis.Through trajectory analyses and lineage tracing,we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells,which sequentially generate malignant heterogeneity and induce tumor phenotype transitions.We further uncovered stage-specific oncogenic cascades,and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor.Importantly,the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations,during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis.Together,our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs,and provide a blueprint for potential early-stage treatment/diagnosis for GBM. | Xiaofei Wang Ran Zhou Yanzhen Xiong Lingling Zhou Xiang Yan Manli Wang Fan Li Chuanxing Xie Yiming Zhang Zongyao Huang Chaoqiong Ding Kaidou Shi Weida Li Yu Liu Zhongwei Cao Zhen-Ning Zhang Shengtao Zhou Chong Chen Yan Zhang Lu Chen Yuan Wang | 2021 | Cell Research2021，31，6： | 8 |
| 20 | MicroRNA-184 promotes proliferation ability of glioma cells by regulating FOXO3显示文摘Objective:To investigate the effect of microRNA(miR-184)on regulating the genesis.development and prolifration of glioma cells.Methods:Lipidosome was used to transfect miR-184 mimic and inhibitor to glioma cell ling,and the cell proliferation ability changes were determined by MTT and plate cloning experiment after the transfection.WB test was used to measure the levels of cyclinD1,p27 and FOXO3.Meanwhile.QPCR was used to detect miR-184expression in glioma cell line.glioma tissues and adjacent tissues.Luciferase experiment was used to test 3'UTR gene targeting regulation of miR-184 and FOXO3.Results:QPCR results showed a significaat lower miR-184 expression level in glioma cell line and glioma tissues than that in juxtacancerous tissue.MTT and plate cloning experiments have shown that after overexpressing of miR-184,the cell proliferation capacity of glioma U87 and T98G was signifieantly increased,which was significantly inhibited after the inhibition of miN-184.WB results showed a lower expression level of p27 in U87 and T98G cells,and a higher expression level of cyclind1after over-expressing of miR-184 wss observed.However.a lower expression level of eyelinD1and a higher expression level of p27 after the inhibition of miR-184.The luciferase activity was inhibited after the over-expressing of miR-184.Conclusions:MiR-184 can affect the proliferation abilities of glioma cells and regulate the cell cycle related protein.It plays an important role in the occurrence and development of gliomas. | Qing-Ke Cui Wei-Dong Liu Jian-Xin Zhu Yun-Hua Wang Zhi-Gang Wang | 2014 | Asian Pacific Journal of Tropical Medicine2014，7，10： | 7 |
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