The 2-series eicosanoids are structurally related lipid-soluble hormones synthesized by cyclooxygenase enzymes from arachidonic acid. These compounds have well-established roles in the inflammatory response and the co...The 2-series eicosanoids are structurally related lipid-soluble hormones synthesized by cyclooxygenase enzymes from arachidonic acid. These compounds have well-established roles in the inflammatory response and the coagulation cascade. More recently, the eicosanoids have garnered attention for their potential roles in cancers of the lung, colon, breast, and brain. In this paper, we review the contributions of the different cyclooxygenase metabolites (i.e. prostaglandins, prostacyclins and thromboxanes) to cancer development, progression and recurrence, with special attention paid to their relevance to glioma biology. Our review suggests that 2-series eicosanoids merit further study as possible targets for therapy in patients with glioma.展开更多
目的探讨亲环蛋白B(cyclophilin B,PPIB)在脑胶质瘤中的表达与临床病理特征、患者生存期的关系,以及与肿瘤相关巨噬细胞浸润的相关性。方法基于癌症基因组数据集(The Cancer Genome Atlas,TCGA)数据库资料,比对正常、低级别和高级别脑...目的探讨亲环蛋白B(cyclophilin B,PPIB)在脑胶质瘤中的表达与临床病理特征、患者生存期的关系,以及与肿瘤相关巨噬细胞浸润的相关性。方法基于癌症基因组数据集(The Cancer Genome Atlas,TCGA)数据库资料,比对正常、低级别和高级别脑胶质瘤中PPIB的表达情况,采用免疫组织化学染色方法检测脑胶质瘤病理组织中PPIB的表达;基于TCGA数据库临床病例资料,分析脑胶质瘤PPIB表达与临床病理特征的关系;采用Kaplan-Meier法评估PPIB表达差异对脑胶质瘤患者生存期的影响;免疫荧光法分析脑胶质瘤病理组织中PPIB表达及其与肿瘤相关巨噬细胞浸润的相关性。结果高级别脑胶质瘤中PPIB的表达明显高于正常组织及低级别脑胶质瘤;PPIB与胶质瘤级别、IDH野生型、1p/19q非共缺失等显著相关(P<0.001);PPIB高表达患者的总生存期、无进展间隔期均低于PPIB低表达患者;除高级别脑胶质瘤病理组织中PPIB表达升高外,PPIB高表达区域伴随大量肿瘤相关巨噬细胞浸润。结论相较于低级别胶质瘤,高级别胶质瘤PPIB表达水平更高,且PPIB表达区域存在明显肿瘤相关巨噬细胞浸润。提示PPIB可能作为脑胶质瘤患者独立预后因素,为患者预后判断提供参考。展开更多
目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene...目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。展开更多
Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have tr...Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.展开更多
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 ma...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.展开更多
Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII ex...Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinico-pathologic findings, survival data, and expres-sion of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the en-dothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.展开更多
Molecular biomarkers are commonly used for the management of several types of malignant tumours in routine clinical practice. However, this is not the case for malignant gliomas. Cytokines and Angiogenesis factors are...Molecular biomarkers are commonly used for the management of several types of malignant tumours in routine clinical practice. However, this is not the case for malignant gliomas. Cytokines and Angiogenesis factors are potential candidates due to their intrinsic role in tumourigenesis. Pre- and post-operative serum from 36 malignant glioma patients and 36 controls was analysed using the Bio-Plex Pro Angiogenesis and Cytokines Assay (Bio-Rad, USA). Amongst the molecules tested, the serum concentration of follistatin was significantly higher in patients than in controls. Moreover, the serum concentration of follistatin of the patients postoperatively was significantly reduced compared to that preoperatively. Factors such as age and gender did not affect the concentrations of follistatin measured in the serum of patients pre- and post-operatively as well as healthy controls. This is the first report of follistatin as potential biomarker for the detection of malignant gliomas.展开更多
合成磁共振成像(synthetic magnetic resonance imaging, Sy MRI)是一种新兴的磁共振定量弛豫技术,可以量化组织的弛豫时间和质子密度,仅通过一次扫描就能同时获得多种定量弛豫图,直接用于组织定量分析,为临床提供更多有价值的诊断信息...合成磁共振成像(synthetic magnetic resonance imaging, Sy MRI)是一种新兴的磁共振定量弛豫技术,可以量化组织的弛豫时间和质子密度,仅通过一次扫描就能同时获得多种定量弛豫图,直接用于组织定量分析,为临床提供更多有价值的诊断信息。Sy MRI最先应用于颅脑疾病诊断以及脑实质发育情况检测等。随着Sy MRI技术发展及恶性肿瘤发病率不断升高,Sy MRI技术亦逐渐被应用到临床常见恶性肿瘤的影像诊断中。本文对Sy MRI技术的基本原理及其在乳腺癌、恶性胶质瘤、前列腺癌、直肠癌、膀胱癌、子宫内膜癌、宫颈癌等常见恶性肿瘤中的研究进展进行综述,以期为恶性肿瘤的鉴别诊断及分型、诊疗规划和预后评估等提供依据及参考。展开更多
BACKGROUND： Glioma is the most common intracranial tumor and has a poor patient prognosis. The presence of brain tumor stem cells was gradually being understood and recognized, which might be beneficial for the treat...BACKGROUND： Glioma is the most common intracranial tumor and has a poor patient prognosis. The presence of brain tumor stem cells was gradually being understood and recognized, which might be beneficial for the treatment of glioma. OBJECTIVE： To use bibliometric indexes to track study focuses on glioma stem cell, and to investigate the relationships among geographic origin, impact factors, and highly cited articles indexed in Web of Science. METHODS： A list of citation classics for glioma stem cells was generated by searching the database of Web of Science-Expanded using the terms ＂glioma stem cell＂ or ＂glioma, stem cell＇＂ or ＂brain tumor stem cell＂. The top 63 cited research articles which were cited more than 100 times were retrieved by reading the abstract or full text if needed. Each eligible article was reviewed for basic information on subject categories, country of origin, journals, authors, and source of journals. Inclusive criteria： （1） articles in the field of glioma stem cells which was cited more than 100 times; （2） fundamental research on humans or animals, clinical trials and case reports; （3） research article; （4） year of publication： 1899-2012; and （5） citation database： Science Citation Index-Expanded. Exclusive criteria： （1） articles needing to be manually searched or accessed only by telephone; （2） unpublished articles; and （3） reviews, conference proceedings, as well as corrected papers. RESULTS： Of 2 040 articles published, the 63 top-cited articles were published between 1992 and 2010. The number of citations ranged from 100 to 1 754, with a mean of 280 citations per article. These citation classics came from nineteen countries, of which 46 articles came from the United States. Duke University and University of California, San Francisco led the list of classics with seven papers each. The 63 top-cited articles were published in 28 journals, predominantly Cancer Research and Cancer Cell, followed by Cell Stem Cell and Nature. CONCLUSION： Our bibliometric analysis provides a historical perspective on the progress of glioma stem cell research. Articles originating from outstanding institutions of the United States and published in high-impact journals are most likely to be cited.展开更多
BACKGROUND： Overwhelming evidence suggests that tumor bulks are comprised of differentiated tumor cells and cancer stem cells （CSCs）. The stem cell-like side-population （SP） cells account for a minor fraction of ...BACKGROUND： Overwhelming evidence suggests that tumor bulks are comprised of differentiated tumor cells and cancer stem cells （CSCs）. The stem cell-like side-population （SP） cells account for a minor fraction of the total tumor cells, yet are apparently the cells capable of tumor initiation, growth, maintenance, and recurrence. OBJECTIVE： To identify potential stem cell-like cancer cells in a U87 human brain glioma cell line on the basis of dye efflux, clone formation, and multi-drug resistance capacity. DESIGN, TIME AND SETTING： The cellular and molecular biology experiment was performed at the Laboratory of Shanghai Institute of Hematology and Laboratory of Shanghai Institute of Endocrinology in Ruijin Hospital; in vivo contrast observational animal trial was performed at Experimental Animal Center, School of Medicine, Shanghai Jiao Tong University from June 2007 to May 2008. MATERIALS： The U87 cell line was provided by the Shanghai Institute of Cancer Research, Chinese Academy of Science; DMEM/F12 （1 ： 1） and fetal bovine serum were purchased from Gibco Invitrogen, USA; human recombinant basic fibroblast growth factors were purchased from BD Bioscience, USA; Hoechst 33342, Verapamil, and methyl thiazolyl tetrazolium were purchased from Sigma, USA; phycoerythrin-labeled anti-human-CD133 was purchased from Milteny Biotec, Germany; SYBR PrimeScriptTM RT-PCR kit was purchased from TaKaRa Biotechnology, Dalian, China. METHODS： Monolayer cultured cells were harvested by 0.25% Trypsin-EDTA and suspended at a 1 ×10^6/mL dilution in PBS containing 2% FBS, and were stained with Hoechst 33342 dye, either alone or in combination with Verapamil. Following fluorescence-activated cell sorting, SP and non-SP subsets were cultivated with serum-containing （DMEM plus 10% fetal bovine serum） or serum-free culture medium [DMEM/F12 （1： 1） ＋ 1× B27 supplement ＋ 10 ng/mL basic fibroblast growth factors ＋ 1× L-glutamine] to determine growth characteristics in vitro. Finally, single free U87 cells and subsets （SP or non-SP cells） were subcutaneously injected into the backs of 5-week-old nude mice for in vivo tumorigenicity. MAIN OUTCOME MEASURES： Cell morphology and clonogenicity were observed under inverted microscope; SP phenotype and fluorescent antibody labeling were analyzed by MoFIoTM flow cytometry; ABC transporter mRNA expression was evaluated by semi-quantitative real-time RT-PCR; efflux capacity for anti-neoplastic drugs from the U87 cell line and subsets was measured with the MTT assay, then detected by enzyme-linked immunosorbent assay at a wavelength of 490 nm; in vivo tumorigenicity in immunodeficient nude mice was evaluated by diameter size. RESULTS： During in vitro passages, human U87 cells maintained a stable SP fraction profile and exhibited the ability to form neurosphere-like clones. SP cell proliferation decreased compared with non-treated U87 cells. CD133 expression was reduced in the SP and non-SP cells. Freshly sorted SP fractions expressed higher levels of ABC drug transporter genes, and exhibited increased potential for cytotoxic drug resistance. The in vivo malignancy of U87 cells was largely dependent on non-SP cells in nude mice, and tumors that formed from the non-SP fraction developed faster and larger compared with tumors from the SP fraction. CONCLUSION： The SP cell component was a key factor that influenced mRNA expression and cytotoxic drug resistance. In particular, cancer stem cells or tumor-initiating cells were not exclusively enriched in the SP subset of the U87 cell line, and non-SP cells were even more tumorigenic.展开更多
文摘The 2-series eicosanoids are structurally related lipid-soluble hormones synthesized by cyclooxygenase enzymes from arachidonic acid. These compounds have well-established roles in the inflammatory response and the coagulation cascade. More recently, the eicosanoids have garnered attention for their potential roles in cancers of the lung, colon, breast, and brain. In this paper, we review the contributions of the different cyclooxygenase metabolites (i.e. prostaglandins, prostacyclins and thromboxanes) to cancer development, progression and recurrence, with special attention paid to their relevance to glioma biology. Our review suggests that 2-series eicosanoids merit further study as possible targets for therapy in patients with glioma.
文摘目的探讨亲环蛋白B(cyclophilin B,PPIB)在脑胶质瘤中的表达与临床病理特征、患者生存期的关系,以及与肿瘤相关巨噬细胞浸润的相关性。方法基于癌症基因组数据集(The Cancer Genome Atlas,TCGA)数据库资料,比对正常、低级别和高级别脑胶质瘤中PPIB的表达情况,采用免疫组织化学染色方法检测脑胶质瘤病理组织中PPIB的表达;基于TCGA数据库临床病例资料,分析脑胶质瘤PPIB表达与临床病理特征的关系;采用Kaplan-Meier法评估PPIB表达差异对脑胶质瘤患者生存期的影响;免疫荧光法分析脑胶质瘤病理组织中PPIB表达及其与肿瘤相关巨噬细胞浸润的相关性。结果高级别脑胶质瘤中PPIB的表达明显高于正常组织及低级别脑胶质瘤;PPIB与胶质瘤级别、IDH野生型、1p/19q非共缺失等显著相关(P<0.001);PPIB高表达患者的总生存期、无进展间隔期均低于PPIB低表达患者;除高级别脑胶质瘤病理组织中PPIB表达升高外,PPIB高表达区域伴随大量肿瘤相关巨噬细胞浸润。结论相较于低级别胶质瘤,高级别胶质瘤PPIB表达水平更高,且PPIB表达区域存在明显肿瘤相关巨噬细胞浸润。提示PPIB可能作为脑胶质瘤患者独立预后因素,为患者预后判断提供参考。
文摘目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。
文摘Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.
基金Supported by The Medical Scientist Training Program at NYU School of Medicine to Modrek ASNYSTEM Institutional training grant#CO26880 to Bayin NS+1 种基金NIH/NINDS(1 R21 NS087241-01)the NYU Cancer Institute Developmental Projects Program and the NYU Clinical and Translational Science Institute(NYU CTSA grant#UL1TR000038 from the National Center for the Advancement of Translational Science NCATS,NIH)to Placantonakis DG
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.
文摘Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinico-pathologic findings, survival data, and expres-sion of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the en-dothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.
文摘Molecular biomarkers are commonly used for the management of several types of malignant tumours in routine clinical practice. However, this is not the case for malignant gliomas. Cytokines and Angiogenesis factors are potential candidates due to their intrinsic role in tumourigenesis. Pre- and post-operative serum from 36 malignant glioma patients and 36 controls was analysed using the Bio-Plex Pro Angiogenesis and Cytokines Assay (Bio-Rad, USA). Amongst the molecules tested, the serum concentration of follistatin was significantly higher in patients than in controls. Moreover, the serum concentration of follistatin of the patients postoperatively was significantly reduced compared to that preoperatively. Factors such as age and gender did not affect the concentrations of follistatin measured in the serum of patients pre- and post-operatively as well as healthy controls. This is the first report of follistatin as potential biomarker for the detection of malignant gliomas.
文摘合成磁共振成像(synthetic magnetic resonance imaging, Sy MRI)是一种新兴的磁共振定量弛豫技术,可以量化组织的弛豫时间和质子密度,仅通过一次扫描就能同时获得多种定量弛豫图,直接用于组织定量分析,为临床提供更多有价值的诊断信息。Sy MRI最先应用于颅脑疾病诊断以及脑实质发育情况检测等。随着Sy MRI技术发展及恶性肿瘤发病率不断升高,Sy MRI技术亦逐渐被应用到临床常见恶性肿瘤的影像诊断中。本文对Sy MRI技术的基本原理及其在乳腺癌、恶性胶质瘤、前列腺癌、直肠癌、膀胱癌、子宫内膜癌、宫颈癌等常见恶性肿瘤中的研究进展进行综述,以期为恶性肿瘤的鉴别诊断及分型、诊疗规划和预后评估等提供依据及参考。
文摘BACKGROUND： Glioma is the most common intracranial tumor and has a poor patient prognosis. The presence of brain tumor stem cells was gradually being understood and recognized, which might be beneficial for the treatment of glioma. OBJECTIVE： To use bibliometric indexes to track study focuses on glioma stem cell, and to investigate the relationships among geographic origin, impact factors, and highly cited articles indexed in Web of Science. METHODS： A list of citation classics for glioma stem cells was generated by searching the database of Web of Science-Expanded using the terms ＂glioma stem cell＂ or ＂glioma, stem cell＇＂ or ＂brain tumor stem cell＂. The top 63 cited research articles which were cited more than 100 times were retrieved by reading the abstract or full text if needed. Each eligible article was reviewed for basic information on subject categories, country of origin, journals, authors, and source of journals. Inclusive criteria： （1） articles in the field of glioma stem cells which was cited more than 100 times; （2） fundamental research on humans or animals, clinical trials and case reports; （3） research article; （4） year of publication： 1899-2012; and （5） citation database： Science Citation Index-Expanded. Exclusive criteria： （1） articles needing to be manually searched or accessed only by telephone; （2） unpublished articles; and （3） reviews, conference proceedings, as well as corrected papers. RESULTS： Of 2 040 articles published, the 63 top-cited articles were published between 1992 and 2010. The number of citations ranged from 100 to 1 754, with a mean of 280 citations per article. These citation classics came from nineteen countries, of which 46 articles came from the United States. Duke University and University of California, San Francisco led the list of classics with seven papers each. The 63 top-cited articles were published in 28 journals, predominantly Cancer Research and Cancer Cell, followed by Cell Stem Cell and Nature. CONCLUSION： Our bibliometric analysis provides a historical perspective on the progress of glioma stem cell research. Articles originating from outstanding institutions of the United States and published in high-impact journals are most likely to be cited.
基金the Natural Science Foundation of Shanghai,No. 08ZR 1413800
文摘BACKGROUND： Overwhelming evidence suggests that tumor bulks are comprised of differentiated tumor cells and cancer stem cells （CSCs）. The stem cell-like side-population （SP） cells account for a minor fraction of the total tumor cells, yet are apparently the cells capable of tumor initiation, growth, maintenance, and recurrence. OBJECTIVE： To identify potential stem cell-like cancer cells in a U87 human brain glioma cell line on the basis of dye efflux, clone formation, and multi-drug resistance capacity. DESIGN, TIME AND SETTING： The cellular and molecular biology experiment was performed at the Laboratory of Shanghai Institute of Hematology and Laboratory of Shanghai Institute of Endocrinology in Ruijin Hospital; in vivo contrast observational animal trial was performed at Experimental Animal Center, School of Medicine, Shanghai Jiao Tong University from June 2007 to May 2008. MATERIALS： The U87 cell line was provided by the Shanghai Institute of Cancer Research, Chinese Academy of Science; DMEM/F12 （1 ： 1） and fetal bovine serum were purchased from Gibco Invitrogen, USA; human recombinant basic fibroblast growth factors were purchased from BD Bioscience, USA; Hoechst 33342, Verapamil, and methyl thiazolyl tetrazolium were purchased from Sigma, USA; phycoerythrin-labeled anti-human-CD133 was purchased from Milteny Biotec, Germany; SYBR PrimeScriptTM RT-PCR kit was purchased from TaKaRa Biotechnology, Dalian, China. METHODS： Monolayer cultured cells were harvested by 0.25% Trypsin-EDTA and suspended at a 1 ×10^6/mL dilution in PBS containing 2% FBS, and were stained with Hoechst 33342 dye, either alone or in combination with Verapamil. Following fluorescence-activated cell sorting, SP and non-SP subsets were cultivated with serum-containing （DMEM plus 10% fetal bovine serum） or serum-free culture medium [DMEM/F12 （1： 1） ＋ 1× B27 supplement ＋ 10 ng/mL basic fibroblast growth factors ＋ 1× L-glutamine] to determine growth characteristics in vitro. Finally, single free U87 cells and subsets （SP or non-SP cells） were subcutaneously injected into the backs of 5-week-old nude mice for in vivo tumorigenicity. MAIN OUTCOME MEASURES： Cell morphology and clonogenicity were observed under inverted microscope; SP phenotype and fluorescent antibody labeling were analyzed by MoFIoTM flow cytometry; ABC transporter mRNA expression was evaluated by semi-quantitative real-time RT-PCR; efflux capacity for anti-neoplastic drugs from the U87 cell line and subsets was measured with the MTT assay, then detected by enzyme-linked immunosorbent assay at a wavelength of 490 nm; in vivo tumorigenicity in immunodeficient nude mice was evaluated by diameter size. RESULTS： During in vitro passages, human U87 cells maintained a stable SP fraction profile and exhibited the ability to form neurosphere-like clones. SP cell proliferation decreased compared with non-treated U87 cells. CD133 expression was reduced in the SP and non-SP cells. Freshly sorted SP fractions expressed higher levels of ABC drug transporter genes, and exhibited increased potential for cytotoxic drug resistance. The in vivo malignancy of U87 cells was largely dependent on non-SP cells in nude mice, and tumors that formed from the non-SP fraction developed faster and larger compared with tumors from the SP fraction. CONCLUSION： The SP cell component was a key factor that influenced mRNA expression and cytotoxic drug resistance. In particular, cancer stem cells or tumor-initiating cells were not exclusively enriched in the SP subset of the U87 cell line, and non-SP cells were even more tumorigenic.
