共查询到20条相似文献,搜索用时 15 毫秒
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Patrick Kwok-Shing Ng Jun Li Kang Jin Jeong Shan Shao Hu Chen Yiu Huen Tsang Sohini Sengupta Zixing Wang Venkata Hemanjani Bhavana Richard Tran Stephanie Soewito Darlan Conterno Minussi Daniela Moreno Kathleen Kong Turgut Dogruluk Hengyu Lu Jianjiong Gao Collin Tokheim Gordon B. Mills 《Cancer cell》2018,33(3):450-462.e10
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脑胶质瘤p53基因突变与临床病理的关系 总被引:2,自引:0,他引:2
[目的]探讨p53突变在脑胶质瘤发生发展中的作用及其与临床病理特征的关系.[方法]利用聚合酶链反应-单链构象多态性分析(PCR-SSCP)及LSAB免疫组化法对已确诊的48例脑胶质瘤进行p53基因突变以及蛋白表达的检测.[结果]48例胶质瘤中p53蛋白阳性表达率41.7%(20/48).在高级别(Ⅲ、Ⅳ级)中p53表达率明显高于低级别(Ⅱ级)的肿瘤,分别是63.2%、27.6%(P<0.05).PCR-SSCP检测发现17例(35.4%)呈现p53基因突变,均位于5~8外显子,突变例数依次为7(41.2%)、1(5.9%)、4(23.5%)、5(29.4%).两种方法检测的符合率为89.6%(43/48).p53基因的突变与患者性别、年龄、肿瘤部位及大小无关.[结论]胶质瘤中p53突变多在第5~8外显子,p53基因突变在胶质瘤的发生进展中起重要作用. 相似文献
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C.I.V. FRANKLIN 《Journal of Medical Imaging and Radiation Oncology》1991,35(3):253-256
Two hundred and seventy eight patients with histo-logically proven grade 3 or grade 4 astrocytomas were referred to the Queensland Radium Institute for consideration of radiotherapy between January 1980 and December 1987. The role of radiation in the management of these tumours was examined with respect to the effects of field size, dose and age. It was found that field size did not have a significant effect on survival; in particular whole brain irradiation for patients with grade 4 tumours was not a significant advantage. The doses used at the Queensland Radium Institute produce similar survivals to those used in other centres. The effect of age was significant. For grade 3 tumours there was a survival advantage to those under 50 years receiving radiation, but not to those above that age. For grade 4 tumours, the survival advantage was for those under 60 years, but those over 60 years did seem to get some benefit although the difference did not reach significance. It is suggested that, as the tumour is generally incurable, these patients may be better served by a short simple palliative course of radiation. 相似文献
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目的 :研究人脑胶质瘤中PTEN蛋白表达和PTEN基因突变情况。方法 :应用免疫组化技术和聚合酶链反应 -单链构象多态性分析 (PCR SSCP)技术 ,检测 10 2例人脑胶质瘤中PTEN蛋白表达及PTEN基因突变。结果 :PTEN阳性染色主要定位于细胞质中。 10 2例中PTEN蛋白表达 5 5 / 10 2(5 3 9% ) ,高分化组 (Ⅰ级和Ⅱ级 ) 32 / 39(82 1% )与低分化组 (Ⅲ级和Ⅳ级 ) 2 3/ 6 3(36 5 % )之间差异有极显著意义 ,P <0 0 1;4 2例胶质母细胞瘤中共有 11例发生PTEN基因突变 ,突变率为 2 6 % (11/ 4 2 ) ;6 0例其他胶质瘤中仅 1例发生突变 ,胶质母细胞瘤突变率显著高于其他胶质瘤 ,χ2 =11 6 2 ,P <0 0 1。结论 :PTEN基因突变或缺失在人脑胶质瘤的发生发展中起重要作用 ,与肿瘤恶性分化程度密切相关 相似文献
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Phase II Studies of RMP-7 and Carboplatin in the Treatment of Recurrent High Grade Glioma 总被引:3,自引:0,他引:3
Gregor A Lind M Newman H Grant R Hadley DM Barton T Osborn C 《Journal of neuro-oncology》1999,44(2):137-145
The selective bradykinin analogue, RMP-7, transiently increases the permeability of the blood brain barrier and the delivery of hydrophilic agents into brain tumours. In 87 recurrent glioma patients (WHO Grade III/IV, median age 46, Karnofsky 70%) clinical and Magnetic Resonance Imaging (MRI) responses to i.v. cycles (q 28 days) of RMP-7 (300 ng/kg given as a 10 min infusion) and carboplatin (AUC 4-9) were assessed. 45 of these patients were chemotherapy naive (CN-RMP) and 42 had received one prior course of chemotherapy (CP-RMP). Neurological impairment, performance status and steroid use were measured prior to dosing at each cycle and tumour volume by 3-D MRI at the end of cycles 2, 4, 6, 9 and 12. Clinical evaluation of response demonstrated that 61% of CN-RMP patients were either stable or improved whilst this was 39% for CP-RMP patients, of which 37% and 8% improved respectively. Radiological evaluation showed 79% of CN-RMP patients were either stable, partial or complete responses and 24% for CP-RMP patients, of which 32% and 5% were CR or PR respectively.The median duration of response was 30.3 weeks in CN-RMP patients and 19.6 weeks in the CP-RMP group. Lack of response was associated with substantial baseline tumour volume. Drug toxicity was as previously reported for carboplatin. 11 patients had treatment-associated transient focal seizures. These results indicate that RMP-7 and carboplatin have significant activity in recurrent malignant glioma following radiotherapy. 相似文献
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Loss or Somatic Mutations of hMSH2 Occur in Hereditary Nonpolyposis Colorectal Cancers with hMSH2 Germline Mutations 总被引:4,自引:0,他引:4
Shi-Long Lu Yoshimitsu Akiyama Hiromi Nagasaki Tadashi Nomizu Eiichi Ikeda Shozo Baba Kyosuke Ushio Takeo Iwama Kazuo Maruyama Yasuhito Yuasa 《Cancer science》1996,87(3):279-287
Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2 . To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2 -related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function. 相似文献
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Shigeko Umeki Seishi Kyoizumi Yoichiro Kusunoki Nori Nakamura Masao Sasaki Takesaburo Mori Yuichi Ishikawa John B. Cologne Mitoshi Mitoshi 《Cancer science》1991,82(12):1349-1353
Exposure to ionizing radiation has long been well-recognized as a risk factor for cancer development. Since ionizing radiation can induce mutations, an accurate way of measuring somatic mutation frequencies could be a useful tool for evaluating cancer risks. In the present study, we have examined in vivo somatic mutation frequencies at the erythrocyte glycophorin A (GPA) and T-cell receptor (TCR) loci in 18 Thorotrast patients who have been continuously irradiated with alpha-particles emitted from the internal deposition of thorium dioxide and who thus have increased risks of certain malignant tumors. When compared with controls, the results showed a significantly higher frequency of mutants at the lymphocyte TCR loci but not at the erythrocyte GPA loci in the Thorotrast patients. The discrepancy between the results of the two assays is discussed. 相似文献
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目的 探讨EGFL7基因在人脑胶质瘤组织中的表达及其意义。方法 收集36例新鲜胶质瘤标本,其中包括21例低度恶性(Ⅰ~Ⅱ级)及15例高度恶性者 (Ⅲ~Ⅳ级),用RT-PCR检测其EGFL7 mRNA的表达。另收集45例胶质瘤石蜡标本,其中包括24例低度恶性(Ⅰ~Ⅱ级)及21例高度恶性者(Ⅲ~Ⅳ级),用免疫组织化学检测EGFL7蛋白的表达情况。并分析EGFL7蛋白表达与胶质瘤病理分级的关系。结果EGFL7 mRNA及其蛋白在人脑胶质瘤中存在表达,EGFL7蛋白表达主要定位于肿瘤细胞及血管内皮细胞的胞质。其表达与肿瘤的恶性程度有明显的相关性(t=4.399,P<0.01);EGFL7在正常脑组织中没有表达。结论人脑胶质瘤中肿瘤细胞及其血管内皮细胞EGFL7均呈增高表达并且与其肿瘤恶性程度具有明显相关性,提示EGFL7在胶质瘤的发生发展中发挥重要作用。 相似文献
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目的探讨术后放疗对高级别胶质瘤的临床疗效。方法对40例术后病理检查证实为高级别胶质瘤患者,术后2~4周内行放射治疗,均行MRI/CT定位,随机分为2组实施放疗。一组以术前MRI与术后CT(MRI术前/CT术后)融合为参照勾画靶区;另一组以术后MRI与术后CT(MRI术后/CT术后)融合为参照勾画靶区。随访复发时间和部位,评价两组疗效。结果 MRI术前/CT术后组平均复发时间及生存时间较MRI术后/CT术后组长,有统计学意义,MRI术后/CT术后组边缘复发及野外复发例数明显多于MRI术前/CT术后组。结论以MRI术前/CT术后融合为参照勾画靶区更精准,可明显提高高级别胶质瘤患者的生存率。 相似文献
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Bamford S Dawson E Forbes S Clements J Pettett R Dogan A Flanagan A Teague J Futreal PA Stratton MR Wooster R 《British journal of cancer》2004,91(2):355-358
The discovery of mutations in cancer genes has advanced our understanding of cancer. These results are dispersed across the scientific literature and with the availability of the human genome sequence will continue to accrue. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information related to human cancer. To populate this resource, data has currently been extracted from reports in the scientific literature for somatic mutations in four genes, BRAF, HRAS, KRAS2 and NRAS. At present, the database holds information on 66 634 samples and reports a total of 10 647 mutations. Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website. 相似文献
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背景与目的:近几年来,少枝胶质细胞瘤,特别是有染色体1p/19q的联合缺失者被证实对烷化剂化疗敏感,成为预后良好的标志物。本实验旨在研究低级别胶质瘤中1p/19q的联合缺失率和与标本中1p/19q的缺失百分比相关的分子病理特征。方法:搜集北京天坛医院低级别胶质瘤标本25例,应用免疫荧光原位杂交(fluorescence in situ hybridization,FISH)的方法对1p36和19q13的缺失程度进行定量分析,统计其在低级别胶质瘤中的联合缺失率,并应用Spearman秩相关分析方法分析标本中1p36、19q13缺失百分比与P170、MGMT、MMP-9、PTEN、EGFR、P53、VEGF、Ki-67、TOPO-Ⅱ、GST-π的分子病理结果的关系。结果:在25例低级别胶质瘤标本中,星形细胞瘤10例,少枝胶质细胞瘤3例,少枝星形细胞瘤12例。在星形细胞瘤、少枝胶质瘤和少枝星形细胞瘤中,1p/19q联合缺失率分别为40%、67%和50%。1p36、19q13的缺失程度与MGMT表达呈负相关,(P分别为0.042和0.015),1p36的缺失程度与GST-π表达呈负相关(P=0.024)。结论:在低级别胶质瘤中,1p/19q的联合缺失率与国外报道相似,MGMT、GST-π的低表达可能与1p、19q的缺失有关。 相似文献
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Outcome of Second Line Treatment of Recurrent High- Grade Glioma by re-Irradiation or Bevacizumab-based Chemotherapy: A Cross Sectional Study
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Kazem AnvariMehri ShahabadiJames S WelshSeyed Alireza JavadiniaElham Zarei 《Asian Pacific journal of cancer prevention》2023,24(5):1507-1511
Introduction: Currently, there is no standard of treatment for the management of the recurrent high-grade glioma. Re-resection, re-irradiation, and chemotherapy are among main treatment options without any proven efficacy. Aim: To compare the outcome of second line treatment of recurrent high-grade glioma by re-irradiation or bevacizumab-based chemotherapy. Methods: Retrospectively, patients with the recurrent high-grade glioma treated by re-irradiation (ReRT group) (34 patients) or bevacizumab-based chemotherapy (Bev group) (40 patients) as the first-file after the first recurrence were compared in term of first-line progression free survival (PFS), second-line PFS, and overall survival (OS). Results: Both groups were similar in term of gender (p=0.859), age (=0.071), type of first-line treatment (p=0.227), and performance status (p=0.150). With a median follow-up of 31 months (m), mortality rate was 41.2% and 70% in the ReRT and Bev groups, respectively. In the Bev and ReRT groups, median OS was 27 m (95% confidence interval (CI) 20-33.9 m) vs. 132 m (95% CI 52.9-211 m) (p<0.0001), median first-line PFS was 11 m (95% CI 7.14-28.7 m) vs. 37 m (95% CI 8.42-65.75 m) (p<0.0001), and median second-line PFS was 7 m (95% CI 3.9-10 m) vs. 9 m (95% CI 5.5-12.4 m) (p=0.564), respectively. Conclusion: The PFS is similar after the second line treatment of recurrent primary central nervous system malignancies either by re-irradiation or bevacizumab-based chemotherapy. 相似文献
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Paunu N Syrjäkoski K Sankila R Simola KO Helén P Niemelä M Matikainen M Isola J Haapasalo H 《Journal of neuro-oncology》2001,55(3):159-165
The high incidence of gliomas in Li-Fraumeni families and the high frequency of somatic p53 mutations in sporadic glial tumors have raised the possibility that germline p53 mutations could play an important role in familial aggregation of gliomas. In the present study, 18 families with two or more gliomas were screened for germline p53 mutation. The families were identified through questionnaires sent to 369 consecutive glioma patients operated at Tampere University Hospital during 1983-1994. In these families, a family history of cancer was verified through the Finnish Cancer Registry. Interestingly, the questionnaires reveled only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fufilled the criteria for classic Li-Fraumeni syndrome. Immunostaining analysis of p53 protein accumulation suggested that alterations of the p53 gene are as common in familial as in sporadic gliomas. Sequencing analysis of exons 4-10 of the p53 gene revealed no germline mutations in any of the 18 families. Thus, although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial glioma patients suggests that the p53 gene is not a common susceptibility gene in case of familial gliomas. The p53 tumor suppressor gene seems to have a similar role in the tumorigenesis of most familial and sporadic gliomas. 相似文献
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目的探讨蒿甲醚(Artemether)对SD大鼠原位脑胶质瘤的抑瘤作用。方法采用四甲基偶氮唑蓝(MTT)法测定不同浓度蒿甲醚对大鼠C6脑胶质瘤细胞株的生长抑制作用,计算半数抑制浓度(IC50)。立体定位仪对48只(雌、雄各半)SD大鼠建立脑胶质瘤原位模型,随机分为6组:对照组;模型组,蒿甲醚33.3 mg/(kg·d)、50.0 mg/(kg·d)、66.6 mg/(kg·d);联合用药组,蒿甲醚50.0 mg/(kg·d)+ 硫酸亚铁1.5 mg/(kg·d);阳性药对照组。采用灌胃给药法连续给予各组SD大鼠用药10天,对照组给予0.9%氯化钠溶液。肿瘤体积按a2bπ∕6(a为肿瘤的短径,b为肿瘤的长径)计算。全脑标本用4%多聚甲醛固定。肿瘤组织做病理观察。结果蒿甲醚抑制大鼠C6脑胶质瘤细胞增殖,其抑制作用呈剂量和时间依赖性;模型组和联合用药组对SD大鼠原位脑胶质瘤的抑瘤率分别为:54.5%、61.0%、64.5%和69.8%;模型组组间比较,蒿甲醚66.6 mg/(kg·d)用药组的抑瘤率明显高于蒿甲醚33.3 mg/(kg·d)用药组;各实验组间比较,联合用药组的抑瘤率显著高于模型组33.3 mg/(kg·d)。结论口服蒿甲醚对SD大鼠脑部原位接种C6脑胶质瘤有明显的抑瘤作用。 相似文献
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《Asian Pacific journal of cancer prevention》2014,15(6):2847-2850
Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germlinemutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An associationbetween mutations in germline cells and aging has been demonstrated. This suggests a higher incidence ofchildhood cancer including retinoblastoma among children of older parents. Materials and Methods: In thepresent study we aimed to determine the association of paternal and maternal age with an increased risk ofretinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who wereborn during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studyingthe mean age of parents and in order to know whether parental age of patients is different from parental age ofcontrol group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs)and 95% confidence intervals (CIs) were calculated. Results: The results of statistical analysis including thestudy of mean parental age by the use of (t-test) compare averages test showed a significant difference betweenparental ages of patients and controls. Logistic regression showed that coefficients were significant for maternalbut not paternal age. Conclusions: Our findings indicate that advanced maternal age can increase the risk ofretinoblastoma in offspring, but the paternal age has no significant effect. 相似文献
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Bauman GS MacDonald W Moore E Ramsey DA Fisher BJ Amberger VR Del Maestro RM 《Journal of neuro-oncology》1999,44(3):223-231
We sought to characterize the effects of radiation alone and in combination with BCNU and dexamethasone on malignant glioma invasion. A model of malignant glioma invasion into a gel matrix of collagen type I was used to characterize response to radiation treatment for four malignant glioma cell lines (C6, U251, U373, A172) and nine primary human glioblastoma explants. A radiation dose dependent inhibition of invasion was noted for the C6 astrocytoma cell line but not the other cell lines or explants. Addition of BCNU and dexamethasone to radiation produced additional inhibition of invasion among the cell lines and explants but could not suppress invasion entirely. 相似文献
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目的:探讨连接蛋白43(CX43)基因表达在胶质瘤中的临床意义、预后价值及其在肿瘤免疫微环境中的作用。方法:基于癌症基因组图谱(TCGA)数据库胶质瘤病人的mRNA数据及相关临床信息,利用R语言统计分析CX43基因在592例具有不同病理特征的胶质瘤患者间的表达差异。采用Kaplan-Meier生存分析法评价其预后价值,基因集富集分析(GSEA)探究CX43在胶质瘤中的潜在作用机制,用CIBERSORTx分析CX43 mRNA与胶质瘤免疫细胞浸润的关系。最后利用34例术后石蜡标本进行免疫组化验证分析。结果:与对照组比较,CX43 mRNA在异柠檬酸脱氢酶野生型、染色体1p/19q无共缺失的样本中表达水平显著升高(P<0.01)。CX43高表达的胶质瘤患者预后较差(P<0.01)。GSEA结果提示CX43 mRNA高表达组在9个特征基因集中富集。CIBERSORTx免疫浸润分析提示CX43 mRNA高表达组中单核细胞、巨噬细胞M2表型、活化树突状细胞显著升高(P<0.05)。免疫组化结果提示CX43蛋白高表达与1p/19q无共缺失相关,并伴CD163阳性的M2样巨噬细胞增多。结论:CX43高表达与胶质瘤1p/19q无共缺失病理分型相关,为胶质瘤不良预后因子,且可能具有诱导巨噬细胞向M2表型极化的作用。 相似文献
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目的探讨蒿甲醚(Artemether)抗SD大鼠原位脑胶质瘤血管生成作用。方法采用四甲基偶氮唑蓝(MTT)法测定不同浓度蒿甲醚对大鼠C6脑胶质瘤细胞株的生长抑制作用,计算半数抑制浓度(IC50)。采用立体定位仪在SD大鼠大脑皮质层接种C6脑胶质瘤细胞(1×106/μl)40只,雌、雄各半;随机分为5组,每组8只。在接种第3天后,各组采用灌胃给药法连续给药10天。于接种后的第20天解剖大鼠,经活体左心室灌注4%多聚甲醛,固定肿瘤的全脑标本。在大鼠脑部接种穿刺点做冠状切口,按垂直和水平方向测量肿瘤大小。肿瘤体积=a2bπ∕6(a为肿瘤的短径,b为肿瘤的长径)。全脑标本用4%多聚甲醛固定,肿瘤组织做病理观察,免疫组化方法检测移植瘤组织微血管密度。结果各实验组血管计数分别为Ⅰ组(39±4),Ⅱ组(29±6),Ⅲ组(12±8),Ⅳ组(10±5),生理盐水组为(52±7)。各实验组血管计数均明显少于生理盐水对照组,差异有统计学意义(分别P<0.05, P<0.01)。各实验组SD大鼠原位脑胶质瘤体积较对照组显著减小。结论在一定剂量范围内,蒿甲醚具有明显抑制SD大鼠原位脑胶质瘤血管生成作用;蒿甲醚抑制原位脑胶质瘤生长和转移的机制之一是透过血脑屏障抑制脑胶质瘤血管生成。 相似文献