共查询到18条相似文献,搜索用时 109 毫秒
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目的:探讨鼻咽癌及放疗后复发鼻咽癌组织中Ku70和DNA—PKcs的表达及其与鼻咽癌放射敏感性的关系。方法:符合入组条件的64例鼻咽癌活检标本,应用免疫组织化学技术检测Ku70和DNA—PKcs的表达,并分析两者之间的关系。结果:鼻咽非角化性癌中Ku70阳性率为83.87%,DNA—PKcs阳性率为74.19%;放疗后复发鼻咽癌中Ku70阳性率为84.85%,DNA—PKcs阳性率为81.82%。Ku70及DNA—PKcs的表达在鼻咽非角化性癌与放疗后复发鼻咽癌两组间比较,差异无显著性(P〉0.05)。在放疗后复发鼻咽癌中,Ku70与DNA—PKcs表达呈正相关(P〈0.001)。结论:Ku70和DNA—PKcs在放疗后复发鼻咽癌组织中的表达具有相关性,两者尚不能作为预测鼻咽痛放射敏感性的指标。 相似文献
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目的 研究鼻咽癌中CK、Tubulin-β及PCNA的表达,探讨其与鼻咽癌放疗后复发和转移的可能机制。方法裸鼠体内移植瘤实验观察鼻咽癌细胞F1、S1放射治疗前后的细胞形态、体内增殖和转移能力,采用免疫组织化学SP法检测裸鼠移植瘤组织、鼻咽癌及放疗后复发组织中CK、Tubulin-β及PCNA的表达。结果放射后F1、S1裸鼠移植瘤瘤体质量分别较未放射组的F1、S1裸鼠移植瘤瘤体质量低(P<005)。各组均无肺转移,放射治疗后S1裸鼠移植瘤淋巴结转移率高于F1组,但差异无统计学意义(P>005)。未放射组F1裸鼠移植瘤组织中PCNA表达高于未放射S1裸鼠移植瘤(P<0.05);放射治疗后S1裸鼠移植瘤中CK和PCNA表达均高于放射后的F1裸鼠移植瘤(P<0.05/0.01)。鼻咽癌放疗后复发组织中PCNA表达高于鼻咽癌组(P<0.05)。Spearman相关分析显示,鼻咽癌组织中CK与Tubulin-β、Tubulin-β与PCNA表达呈正相关关系,放疗后复发组织中CK与Tubulin-β和PCNA表达呈正相关(P<0.05)。鼻咽癌及放疗后复发组织中CK、Tubulin-β及PCNA的表达与患者年龄、性别、颈部淋巴结转移和临床分期无关。结论CK和Tubulin-β参与鼻咽癌放疗后复发的过程,并与细胞增殖关系密切,但不能独立作为鼻咽癌放疗后复发的预测指标。 相似文献
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目的:研究DNA-PKcs蛋白的表达与鼻咽癌各临床指标的相关性,探寻DNA-PKcs的表达与鼻咽癌放射敏感性的关系。方法:应用免疫组化法测定65例鼻咽低分化鳞癌DNA-PKcs蛋白的表达。结果:DNA-PKcs的表达在原发灶退缩情况、性别、患病年龄、原发灶大小、淋巴结转移等观察指标中其差异未见有统计学意义;II期 III期病例,与IVa期病例相比较,DNA-PKcs表达的差异有统计学意义(P=0.027);癌组织与癌旁正常组织DNA-PKcs的表达差异未见有统计学意义。结论:鼻咽癌组织中DNA-PKcs蛋白的表达与放疗后原发灶退缩情况无关,提示与鼻咽癌放射敏感性无确切相关性;该蛋白的表达与临床分期有一定关系;鼻咽癌癌组织与癌旁正常组织DNA-PKcs蛋白的表达具有一致性。 相似文献
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不同敏感性鼻咽癌细胞株中Ku蛋白表达情况比较 总被引:8,自引:2,他引:8
目的 比较作为DNA双链断裂修复蛋白DNA依赖性蛋白激酶 (DNA PK)的调节亚基70 Ku、80 Ku在不同放射敏感性鼻咽癌细胞株CNE1和CNE2中的表达情况。方法 成克隆实验测定鼻咽癌高分化鳞癌细胞CNE1和低分化鳞癌细胞CNE2不同剂量照射后的存活分数 ,用线性二次模型拟合剂量存活曲线并求出放射生物学参数α、β、SF2、MID以评价两株细胞的放射敏感性。Westernblot检测照射前和后不同时间及不同剂量CNE1、CNE2细胞中Ku的表达 ,检测蛋白条带的吸光度值做半定量分析。结果 CNE1在各个剂量点的存活分数均比CNE2高 ,MID也大于CNE2 (2 .35∶1.11) ,SF2也大于CNE1(0 .5 4∶0 .37)。Westernblot显示两株细胞中70 Ku、80 Ku均有表达 ,蛋白条带的吸光度值测定显示70 Ku在CNE1、CNE2细胞中分别为 2 0 .0 3± 7.5 6和 19.36± 6 .0 4 ,80 Ku分别为 2 5 .98± 12 .87和 2 3.74±9.2 4 (P值均 >0 .0 5 )。蛋白表达的定量和定性分析同样显示 4Gy照射后不同时间点及 0~ 16Gy照射后 12hKu的表达无统计学差异。结论 实验验证了CNE2比CNE1对放射更敏感 ;照射前后两个细胞均有70 Ku、80 Ku蛋白表达且无差异 ;CNE1、CNE2放射敏感性的差异与Ku蛋白表达量无明显关系。 相似文献
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放疗是鼻咽癌(NPC)首选治疗手段。众所周知,病理类型、临床分期、患者年龄、体质等是影响NPC预后的主要因素,但在日常的临床工作中也不难发现,前述情况基本相似的不同患者,其治疗效果却有较大差异,从而提示还有其他重要的影响预后的因素。随着基因组学研究进展,近年来一些学者从细胞水平对基因与恶性肿瘤放射敏感性的关系进行了初步探索,但NPC组织中基因表达与放射敏感性及放疗疗效的关系如何尚不清楚,因此,有必要进一步研究以指导临床放疗。 相似文献
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目的:探讨PET-CT和MRI在诊断鼻咽癌放疗后复发中的价值.方法:21例鼻咽癌放疗后患者均行PET-CT和MRI检查.依据病理组织活检和临床随访分别评价PET-CT和MRI对鼻咽癌放疗后复发检出的灵敏度、特异性、漏诊率、误诊率和准确度,并对两者的准确度比较.结果:PET-CT诊断鼻咽癌放疗后复发的灵敏度、特异性、漏诊率、误诊率和准确度分别为92.3%、100.00%、7.7%、0.00%和95.2%,MRI分别为100.00%、87.5%、0.00%、12.5%和95.2%,两者间准确度的差异没有统计学意义(P﹥0.05).结论:PET-CT和MRI在诊断鼻咽癌放疗后复发中均有较高的价值,两者间没有明显差别,两种诊断方法有各自的优缺点,应将两者结合起来,以提高诊断鼻咽癌放疗后复发的准确度. 相似文献
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背景与目的:DNA双链断裂(DNA double-strand break,DSB)是射线杀灭肿瘤细胞的主要机制,而同源重组(homologous recombination,HR)和非同源性末端连接(DNA nonhomologous end-joining,NHEJ)是DSB的两条重要修复途径.DNA-PK催化亚单位(catalytic subunit of DNA-dependent protein kinase,DNAPKcs)是NHEJ途径的主要修复蛋白之一,在DSB中发挥着重要作用.本研究旨在通过检测鼻咽癌组织中DNA-PKcs的表达情况,探讨其与鼻咽癌临床病理特征及预后的关系.方法:采用免疫组化SP法检测223例鼻咽癌患者组织中DNA.PKcs的表达,并结合患者的临床及预后资料进行分析.结果:223例鼻咽癌患者中,DNA.PKcs的过表达率为36.8%.卡方检验显示,DNA.PKcs表达强弱与患者的性别、年龄、病理分型及N分期的相关性均无统计学意义(P>0.05),与TNM分期、T分期、M分期均有关(P<0.05).单因素生存分析显示,DNA-PKes过表达患者5年总生存率低于低表达患者(54.6%vs.79.4%),差异有统计学意义(P<0.05).多因素Cox回归模型分析显示T、N、M分期及DNA-PKcs表达水平是影响鼻咽癌患者预后的独立因素(P<0.05).结论:DNA-PKcs在大部分鼻咽癌组织中均有表达,DNA-PKcs的表达水平与鼻咽癌患者预后相关,对患者的预后判断有一定的指导意义. 相似文献
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uPA在鼻咽癌组织中的表达及其意义 总被引:3,自引:0,他引:3
目的探讨尿激酶型纤溶酶原激活剂在鼻咽癌组织中的表达及其与鼻咽癌侵袭和转移的关系。方法应用RT—PCR和免疫组化方法检测55例鼻咽癌术后组织标本中uPA的表达,分析uPA表达与鼻咽癌临床病理特征的关系。结果鼻咽癌组织中都存在uPA基因的表达,并定位于细胞质和/或细胞膜中,uPA基因mRNA和蛋白质的检测均显示有淋巴结转移的癌组织uPA表达高于无淋巴结转移组,TNM分期Ⅲ~Ⅳa的癌组织高于Ⅰ~Ⅱ组,均有统计学意义。结论鼻咽癌组织中uPA基因及蛋白质表达与鼻咽癌的侵袭和转移密切相关。 相似文献
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Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma 总被引:4,自引:0,他引:4
Lee SW Cho KJ Park JH Kim SY Nam SY Lee BJ Kim SB Choi SH Kim JH Ahn SD Shin SS Choi EK Yu E 《International journal of radiation oncology, biology, physics》2005,62(5):S510-1457
PURPOSE: The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. METHODS AND MATERIALS: Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The overexpression of Ku70 or DNA-PKcs groups included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were performed to determine the prognostic factors that influenced locoregional control of NPC. RESULTS: The 5-year locoregional control rate was significantly higher in the low Ku70 group (Ku-) (85%) than in the high Ku70 group (Ku+) (42%) (p = 0.0042). However, there were no differences in the metastases-free survival rates between the 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. CONCLUSIONS: Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with nondisseminated NPC. 相似文献
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Ku70蛋白在鼻咽癌组织中的表达及临床意义 总被引:3,自引:0,他引:3
目的:探讨接受根治性放疗鼻咽癌(nasopharyngeal carcinoma,NPC)患者Ku70蛋白的表达与患者预后的关系。方法:符合入组条件的73例鼻咽癌放疗前活检标本,应用免疫组织化学技术检测Ku70的表达,并分析Ku70表达与NPC的分期,复发,转移,生存率之间的关系。结果:NPC原发灶中Ku70阳性表达率为98.7%。χ2分析Ku70蛋白高表达与T分期密切相关(P<0.01),与N分期和TNM分期无关。Cox分析显示Ku70蛋白与鼻咽癌的局控率、无进展生存率、总体生存率有关系,与无远处转移生存率无关。Ku70不或低表达者的局控率、无进展生存率、总体生存率均较高,反之则较低,各曲线之间差异具有统计学意义(P<0.05)。结论:Ku70的高表达能预测肿瘤复发,对判断鼻咽癌预后有重要的参考价值。 相似文献
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目的 探讨Ku70在鼻咽癌中的表达及其临床意义.方法 采用免疫组化SP法检测223例鼻咽癌石蜡标本中Ku70的表达情况,根据免疫反应强弱将其分为高表达和低表达两组(阴性表达归入低表达组),并结合临床资料分析Ku70表达高低与患者的临床病理特征及预后的关系.结果 Ku70在鼻咽癌组织中的高表达率为63.7%.单因素生存分析显示Ku70高表达组总生存率低于低表达组(x2=7.88,P=0.005),多因素分析显示性别、年龄、病理分型不是预后独立影响因素(x2=0.08、1.04、2.34,P=0.780、0.308、0.126),T、N、M分期是预后独立影响因素(x2=8.02、7.22、36.86,P=0.005、0.007、0.000),Ku70对鼻咽癌预后的独立影响接近临界值(x2=2.94,P=0.085).结论 初步研究发现Ku70对评价鼻咽痛的预后有参考价值,对患者预后的判断有一定的指导意义. 相似文献
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Pavón MA Parreño M León X Sancho FJ Céspedes MV Casanova I Lopez-Pousa A Mangues MA Quer M Barnadas A Mangues R 《International journal of cancer. Journal international du cancer》2008,123(5):1068-1079
5-Fluorouracil and cisplatin-based induction chemotherapy (IC) is commonly used to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The role of nonhomologous end joining (NHEJ) genes (Ku70, Ku80 and DNA-PKcs) in double-strand break (DSB) repair, genomic instability and apoptosis suggest a possible impact on tumor response to radiotherapy, 5-fluorouracil or cisplatin, as these agents are direct or indirect inductors of DSBs. We evaluated the relationship between Ku80, Ku70 or DNA PKcs mRNA expression in pretreatment tumor biopsies, and tumor response to IC or local recurrence, in 50 patients with HNSCC. Additionally, in an independent cohort of 75 patients with HNSCC, we evaluated the relationship between tumor Ku70 protein expression and the same clinical outcomes or patient survival. Tumors in the responder group had significantly higher mRNA levels for Ku70, Ku80 and DNA-PKcs than those in the nonresponder group. Ku70 mRNA was the marker most significantly associated with response to IC. Moreover, high tumor Ku70 mRNA expression was associated with significantly longer local recurrence-free survival (LRFS). Ku70 protein expression was also significantly related to response, and patients with higher percentage of tumor cells expressing Ku70 had longer LRFS. In addition, the percentage of Ku70 positive cells, tumor localization and node involvement were significantly associated with overall survival of patient. Therefore, Ku70 expression is a candidate predictive marker that could distinguish patients who are likely to benefit from chemoradiotherapy or radiotherapy after the induction chemotherapy treatment, suggesting a contribution of the NHEJ system in HNSCC clinical outcome. 相似文献
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Urano M Huang Y He F Minami A Ling CC Li GC 《International journal of radiation oncology, biology, physics》2008,71(2):533-541
PURPOSE: To evaluate the response of cells over-expressing dominant negative (DN) Ku70 to single and multiple small radiation doses. METHODS AND MATERIALS: Clones of fibroblasts over-expressing DNKu70, DNKu70-7, DNKu70-11, and parental Rat-1 cells were irradiated under oxic or hypoxic conditions with single or multiple doses. Cells were trypsinized 0 or 6 h after irradiation to determine surviving fraction (SF). RESULTS: Oxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.52 or 1.25 and 1.28 or 1.15 times more sensitive than oxic Rat-1 at SF of 0.5 and 0.1, respectively. Hypoxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.44 or 1.70 and 1.33 or 1.51 times more sensitive than hypoxic Rat-1 at SF of 0.5 and 0.1, respectively. To the multiple doses, oxic and hypoxic DNKu70-7 or -11 cells were 1.35 or 1.37 and 2.23 or 4.61 times more sensitive than oxic and hypoxic Rat-1, respectively, resulting in very small oxygen enhancement ratios. Namely, enhancement caused by DNKu70 under hypoxia after multiple doses was greater than that under oxic conditions and greater than that after single dose. CONCLUSIONS: Over-expression of DNKu70 enhances cells' response to radiation given as a single dose and as multiple small doses. The enhancement after multiple doses was stronger under hypoxic than under oxic conditions. These results encourage the use of DNKu70 fragment in a gene-radiotherapy. 相似文献
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DNA-PKcs表达与乳腺癌临床病理特征关系的研究 总被引:1,自引:0,他引:1
目的:研究DNA依赖蛋白激酶催化亚单位(DNA-PKcs)表达与浸润性乳腺癌临床病理特征的关系。方法:应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果:DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关(分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000);与ER表达呈正相关(rs=0.279,P=0.005);与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义(P>0.05)。结论:DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。 相似文献
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DNA-PKcs、Ku80及ATM备选宫颈癌放疗增敏靶点的体外研究 总被引:3,自引:0,他引:3
背景与目的:DNA双链断裂(DNA double strand break,DSB)是细胞受辐射后最致命的损伤,而DNA依赖蛋白激酶催化亚单位(DNA-dependent protein kinase catalytic subunit,DNA-PKcs)、Ku80和ATM(ataxia-telangiectasia mutated)为DSB的主要修复蛋白.宫颈癌是以放疗为主要治疗手段的肿瘤.但其肿瘤细胞对放射线的敏感性不同.本实验拟研究3种DSB修复蛋白的表达与宫颈癌细胞放射敏感性的关系.并探讨DSB修复蛋白成为宫颈癌放疗增敏靶点的可能性.方法:免疫组化法检测41例宫颈癌患者组织中DNA-PKcs、Ku80和ATM蛋白的表达情况;Western blot检测8株肿瘤细胞(包括4株宫颈癌细胞)中3种蛋白的表达,克隆形成实验检测SF2 (suivival fraction at 2 Gv)、α值,分析蛋白表达水平和SF2、α值的关系;利用靶向抑制DNA-PKcs的shRNA表达质粒和小分子抑制剂LY294002,分别抑制HeLa细胞DNA-PKcs蛋白表达和活性后,克隆形成实验和流式细胞仪检测HeLa细胞受6 MVX线照射后的SF2、α值和凋亡率变化.结果:在41例宫颈癌组织中,Ku80、DNA-PKcs和ATM的阳性率分别为70.73%、68.29%和19.51%:8株肿瘤细胞中Ku80、DNA.PKcs和ATM蛋白的相对表达量与各细胞SF2、α值各不相同,作Pearson线性相关分析后得出DNA-PKcs的表达水平与SF2之间有明显的正相关关系(r=0.72,P=0.04);靶向抑制DNA-PKcs的shRNA可以促进HeLa细胞的放射敏感性,其SF2值为0.37,显著低于对照HeLa细胞的0.53(P<0.05);单独接受50 μmol/L LY294002作用1 h HeIa细胞的凋亡率未见明显增加,但先经LY294002处理再照射6 Gy的HeLa细胞在48 h和72 h的凋亡率比单独照射6 Gy的HeLa细胞凋亡率显著增加(48 h点:t=3.25,P=0.03;72h点:t=3.01,P=0.04).结论:DNA-PKcs在宫颈癌组织中表达较高,且其表达水平可以预示肿瘤细胞的放射敏感性:抑制DNA-PKcs的表达或活性可以促进HeLa细胞的放射敏感性. 相似文献
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TFF1和HSP70在结肠癌中的表达及临床意义 总被引:2,自引:0,他引:2
目的 探讨TFF1和HSP70在结肠癌中表达及临床意义。方法 用免疫组化S-P法检测71例结肠癌术后组织和15例正常组织TFF1和HSP70表达。结果 结肠癌组织TFF1和HSP70表达率分别为57.7%和70.4%,高于正常组织(26.7%和40%;P=0.03;0.04)。TFF1表达与Dukes分期和分化程度有关(P=0.025;0.005)。HSP70表达与Dllkes分期和分化程度有关(P=0.032;0.031)。TFF1和HSP70均与性别、年龄、肿瘤浸润深度、生长方式、淋巴结转移和预后无关。TFF1和HSP70在结肠癌中表达呈正相关(r=0.306,P=0.1309)。结论 本实验首次研究TFF1与HSP70在结肠癌中的表达相关性,提示两者在肿瘤发生中可能存在相互作用。TFF1和HSP70在结肠癌高表达,可能参与肿瘤的发生发展过程。 相似文献