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1.
p53、ras p21、c-erbB-2和nm23在肺癌组织中的表达   总被引:6,自引:0,他引:6  
目的:探讨癌基因与肺癌临床病理特征及预后的关系。方法:应用免疫组化SP法对58 例肺癌行p53、rasp21、cerbB2和nm23 的检测。结果:癌组织中阳性反应检出率分别为46-6% 、24-1 % 、50-0 % 和53-4 % ,腺癌和差分化癌ras p21 、cerbB2表达高于鳞癌和分化好的癌( P< 0-05) ,术后长期生存患者rasp21 、cerbB2 表达低于短期死亡患者(P< 0-05 ,P< 0-01),吸烟患者ras p21 表达高于不吸烟患者(P< 0-05) ,淋巴结癌转移阴性组nm23 表达高于淋巴结癌转移阳性组( P< 0-01),p53 与ras p21、cerbB2 阳性表达具有协同性( P< 0-05) 。结论:肺癌发生发展和转移与rasp21 、cerbB2 的激活和p53 、nm23 的失活密切相关,部分基因的改变存在协同性,ras p21 基因的激活与吸烟有关,ras p21、cerbB2 的检测对判断肺癌预后有价值。  相似文献   

2.
nm23—H1,c—erbB—2基因表达与结直肠癌转移的?…   总被引:2,自引:0,他引:2  
目的:探讨nm23-H1,c-erbB-2基因表达与结直肠癌转移的关系,方法:采用免疫组化SABC法,检测了85例结直肠癌中nm23-H1,c-erbB-2基因的蛋白产物,结果:DukesD期结直场癌中nm23-H1基因表达显著低于DukesA,B,C各期(P〈0.01),c-erbB-2基因表达则显著高于Dukes,A,B,C各期(P〈0.01),两基因在DukesA,B,C各期间的阳性表达差异  相似文献   

3.
目的:分析广西地区肝癌中c-myc、N-ras癌基因的表达与乙型肝炎病毒(HBV)感染的关系及其在肝癌发生中的作用。方法:应用原位cDNA-RNA杂交方法和免疫组化方法检测31例广西地区肝癌和相应癌旁组织中的c-mycmRNA、N-rasmRNA和HBsAg、HBxAg。结果:肝癌及癌旁均有较高的c-myc,N-ras癌基因的表达。检出率都在85%以上,其在不同分化程度肝癌中的表达差异无显著性意义:HBsAg和HBxAg的检出率分别为87.09%和79.31%。癌基因的表达与HBsAg,HBxAg的检出呈平行的状态。结论:c-myc、N-ras在广西地区肝癌的形成和保持恶性表型中有协同作用。HBxAg可能有激活c-myc、N-ras癌基因的作用  相似文献   

4.
目的:探讨nm23-H1、c-erbB-2基因表达与结直肠癌转移的关系。方法:采用免疫组化SABC法,检测了85例结直肠癌中nm23-H1、c-erbB-2基因的蛋白产物。结果:DukesD期结直肠癌中nm23-H1基因表达显著低于DukesA、B、C各期(P<0.01),c-erbB-2基因表达则显著高于DukesA、B、C各期(P<0.01),两基因在DukesA、B、C各期间的阳性表达差异无显著性(P>0.05)。结论:nm23-H1与结直肠癌的肝转移呈负相关,c-erbB-2呈正相关,但两基因与淋巴结转移均无显著相关;两基因在蛋白水平上存在负相关性  相似文献   

5.
目的:分析了广西地区地癌中c-myc、N-ras癌基因的表达与乙型肝病毒(HBV)感染的关系及其在肝癌发生中的作用。方法:应用原位cDNA-RNA杂交方法和免疫组化方法检测31例广西地区肝癌和相应癌旁组织中c-myc mRNA、N-rasmRNA和HBsAg、HBxAg。结果:肝癌及癌旁均有较高的c-myc,N-ras癌基因的表达。检出率都在85%以上,其在不同发化程度肝癌中的表达差异无显著性意义  相似文献   

6.
nm23-H1、p53、PCNA表达与大肠癌浸润转移的关系   总被引:14,自引:1,他引:14  
目的:研究大肠癌中nm23-H1、p53、PCNA的表达与浸润转移的关系。方法:应用LSAB免疫组织化学方法检测74例大肠癌中nm23-H1、p53、PCNA和Ⅳ型原的表达。结果:大肠癌中nm23-H1、p53和PCNA的阳性率分别为71.6%、52.7%和81.1%。大肠癌中nm23-H1低表达与淋巴结转移有关(P<0.025),nm23-H1的表达在Ⅳ型胶原表达不同的肠癌中无明显差异(P>0.05);p53和PCNA过表达与浸润程度和淋巴结转移有关(P<0.05),p53和PCNA的表达在Ⅳ型胶原表达不同的肠癌中有非常显著的差异(P<0.005);大肠癌中p53过表达与nm23-H1低表达有关(P<0.01)。结论:实验结果揭示p53基因突变对于nm23-H1基因的失活有一定影响,其作用机制有待深入研究。nm23-H1低表达可能仅在大肠癌转移过程中发挥作用,p53过表达可在大肠癌浸润转移过程及细胞增殖中起重要作用。  相似文献   

7.
食管癌中Cath-D、nm23-H1蛋白的表达及其临床病理意义   总被引:1,自引:0,他引:1  
目的:探讨组织蛋白酶D(Cath-D)、肿瘤转移抑制基因表达蛋白(nm23-H1)的表达与食管癌临床病理特点及预后的关系。方法:应用免疫组织化学S-P法,以兔抗Cath-D、鼠抗nm23-H1抗体标记60例食管癌和5例正常的食管粘膜。观察不同分化程度和组织类型食管癌的表达情况,并比较其阳性率。结果:癌组织Cath-D阳性36例(60.0%),nm23-H1阳性35例(58.3%)。Cath-D的表达与癌组织分化程度、浸润深度、淋巴结转移和预后均无关(P>0.05);而nm23-H1蛋白的表达则与癌组织分化程度及淋巴结转移有关(P<0.05,P<0.01),与癌组织浸润深度和预后无关(P>0.05)。结论:nm23-H1可作为一种食管癌淋巴结转移的重要生物学标记物,但Cath-D、nm23-H1与预后的关系仍需进一步研究。  相似文献   

8.
目的观察血小板衍生性生长因子(PDGF)对体外培养的人肾小球系膜细胞(MsC)生长、基质合成和分泌以及c┐myc癌基因表达的影响。方法体外培养的MsC培养液中掺入5┐溴脱氧尿嘧啶(BrdU),采用BrdU单克隆抗体免疫组化法检测MsC的增殖情况;应用[3H]脯氨酸掺入酶消化法测定MsC细胞内、外胶原蛋白总量;采用Northern印迹法检测纤维连接蛋白(FN)、Ⅳ型胶原、核癌基因c┐mycmRNA表达结果。结果(1)BrdU掺入法的阳性细胞标记指数在对照组为19.5%,PDGF组为34.5%(P<0.01);(2)MsC经PDGF作用后,细胞内、外胶原蛋白量分别为2.69±0.60%和3.87±0.65%,较正常对照组1.25±0.50%和1.61±0.51%明显增加(P<0.01);(3))Northern印迹法显示PDGF组细胞的FN、Ⅳ型胶原及c┐mycmRNA的表达明显高于正常组。结论PDGF不仅可刺激肾小球MsC的增殖和胶原蛋白合成,而且可从基因转录水平增加FN、Ⅳ型胶原及c┐myc癌基因的表达。由此推断PDGF在肾小球疾病的发生、发展中可能起着重要作用  相似文献   

9.
乳腺癌c-erbB-2、nm23基因扩增及产物表达   总被引:4,自引:0,他引:4  
目的:探讨乳腺癌癌基因和抑癌基因表达与预后的关系。方法:应用组织原位杂交及免疫组化技术对25例新鲜乳腺癌标本的c-erbB-2、nm23基因扩增及产物表达进行了检测。结果:c-erbB-2、mRNA杂交信号主要位于癌细胞胞浆中,杂交颗粒的多少不均,阳性细胞呈异质性分布,c-erbB-2蛋白在该组表达率为40%(10/25),c-erbB-2蛋白阳性颗粒分布于癌细胞膜上,随着肿瘤恶性程度的增加,c-erbB-2基因扩增及蛋白表达都增加(P<0.05)。nm23基因扩增及产物表达却随肿瘤恶性程度的增加而减少(P<0.05),nm23mRNA杂交颗粒位于胞浆中,蛋白的表达可见于胞浆中,少数见核中阳性,该组nm23蛋白表达率为44%(11/25)。结论:c-erbB-2、nm23基因扩增及产物表达呈负相关关系(P<0.05),且与乳腺癌临床病理特征密切相关  相似文献   

10.
骨肉瘤N—ras,c—myc基因异常及其蛋白产物的表达   总被引:1,自引:0,他引:1  
目的:探讨癌基因N-ras,c-myc及其蛋白表达与骨肉瘤的关系,方法:Southernblot和免疫组织化学(LSAB法)同步检查9例人骨肉瘤N-ras,c-myc癌基因和其p21rasc-myc蛋白产物表达,结果:N-ras基因1例有为失改变,检出率11%(1/9),c-myc基因有3例为扩增改变,检出率33%(3/9),p21ras,c-myc基因蛋白表达阳性率分别为78%(7例),89%(  相似文献   

11.
nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma   总被引:18,自引:0,他引:18  
BACKGROUND: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene.AIMS: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression. MATERIALS/METHODS: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real time" RT-PCR. RESULTS: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours. CONCLUSIONS: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis.  相似文献   

12.
The nm23 gene is now generally accepted as one of the suppressor genes for metastasis in many types of human cancer. To investigate the role of the nm23 gene in gastric cancer, we examined the expression of nm23-H1 mRNA, mutations, and loss of heterozygosity (LOH) of the nm23-H1 gene in gastric cancers. The expression of nm23-H1 mRNA was examined by Northern blot analysis in eight paired sets of specimens. The expression was higher in primary cancer specimens and metastatic lymph nodes than their corresponding normal gastric mucosa in all eight sets of specimens examined, while it was similar between primary cancer specimens and metastatic lymph nodes. The mutations of the nm23-H1 gene were examined in an additional 11 sets of specimens, including eight sets of analysed by Northern blotting, by polymerase chain reaction single-strand conformation polymorphism analysis, no mutation being found in any of the 11 sets of specimens tested. LOH of the nm23-H1 gene was also examined in additional 12 sets of specimens, among which seven (58%) specimens were informative for LOH. LOH was identified in one (14%) out of these seven informative sets. These results suggest that nm23 may not be the metastasis suppressor gene and the alteration of this gene not play an important role in the process of metastasis of gastric cancer.  相似文献   

13.
乳腺癌组织中uPA、uPAR及nm23-H1的表达   总被引:15,自引:0,他引:15  
目的 观察乳腺癌组织中uPA、uPAR、nm2 3 H1的表达并探讨与腋窝淋巴结转移的关系。方法 用免疫组化EnVi sion两步法检测 6 9例乳腺癌组织中uPA、uPAR和nm2 3 H1表达的分布情况 ,观察其与肿瘤的分化程度以及与腋窝淋巴结转移的关系。结果  (1)uPA阳性表达定位于癌细胞胞质 ;uPAR和nm2 3 H1阳性表达定位于癌细胞胞膜及胞质 ,多数癌旁乳腺上皮细胞呈nm2 3 H1阳性表达 ;高分化乳腺癌 (Ⅰ级 )uPA和uPAR表达阳性率 (30 0 %和 2 5 0 %)低于中低分化乳腺癌 (Ⅱ、Ⅲ级 ) (分别为 6 8 1%、72 7%和 70 0 %、74 1%) (P <0 0 5 ) ;nm2 3 H1表达阳性率在乳腺癌组织不同分化程度间差异无显著性 (P >0 0 5 ) ;(2 )腋窝淋巴结有转移者uPA和uPAR的表达阳性率 (73 2 %和 75 6 %)高于无淋巴结转移者 (35 7%和35 7%) (P <0 0 5 ) ;有腋窝淋巴结转移者nm2 3 H1的表达阳性率 (2 4 4 %)显著低于无淋巴结转移者 (5 0 0 %) (P <0 0 5 ) ;uPA、uPAR和nm2 3 H1的表达与淋巴结转移的个数均无关 ;(3)uPA阳性表达的癌组织其nm2 3 H1表达阳性率 (15 0 %)低于uPA阴性表达的癌组织 (6 2 1%) (P <0 0 5 )。结论 uPA和uPAR的高表达与乳腺癌腋窝淋巴结转移密切相关 ;uPA、uPAR和nm2 3 H1可以作为乳腺癌侵袭与淋巴结转移的  相似文献   

14.
Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies.  相似文献   

15.
目的 探讨黏附分子CD44、上皮性钙黏附蛋白(E-cad )和转移抑制基因nm23-H1与甲状腺滤泡源性癌分化、浸润转移的关系。方法 采用免疫组织化学SP法和EnVision法检测42例滤泡癌和54例乳头状癌中CD44、E-cad和nm23-h1的表达。结果 CD44主要表达于癌细胞及浸润淋巴细胞膜,低分化滤泡癌和有转移乳头状癌CD44表达分别高于高分化滤泡癌和无转移乳头状癌,E-cad阳性物质和nm23-H1阳性率高于滤泡癌,转移癌的阳性率和表达强度低于原发灶。甲状腺滤泡原性癌CD44检测阳性率高于E-cad和nm23-H1。在滤泡癌中E-cad与nm23-H1的表达之间呈正相关关系,而在乳头状癌中呈正相关趋势。CD44与E-cad的表达、CD44与nm23-H1的表达之间在滤泡癌和乳头状癌均呈负相关趋势。结论 综合检测CD44、E-cad和nm23对甲状腺滤泡源性癌的诊断、预后评估具有一定参考价值。  相似文献   

16.
The nm 23 gene product, which possesses nucleoside diphosphate kinase activity, is a possible mediator of cancer cell invasion and metastasis. It has been divided into two distinct gene products, nm23-H1 and nm23-H2. We have developed a method for detecting nm 23-H1 and nm 23-H2 RNA using the polymerase chain reaction, based on the amplification of complementary DNA copies of nm 23-H1 and nm 23-H2 RNA. Using this method, the nm 23-H1 and nm 23-H2 messenger (m)RNA levels in 35 thyroid papillary carcinomas, 11 metastatic lymph nodes from patients with thyroid papillary carcinomas, five thyroid follicular adenomas, and three normal thyroid tissue samples were studied. Both nm 23-H1 and nm 23-H2 mRNA were expressed ubiquitously in normal and malignant thyroid tissues. However, in metastatic lymph nodes no (3 of 11) or weak expression (8 of 11) of nm 23-H1 mRNA was observed, the extent of which was inversely proportional to the degree of cancer cell occupancy, whereas nm 23-H2 mRNA was expressed and the levels were similar to those in other tissue tested. These results show that nm 23-H1 only may play a role in cancer cell invasion and metastasis although the exact mechanisms involved have yet to be elucidated.  相似文献   

17.
18.
应用免疫组化检测88例肝细胞癌(HCC)中nm23-H1蛋白的表达。癌旁肝组织强阳性表达,51例肝癌组织阳性表达(58%)。阳性产物主要定位于肿瘤细胞胞浆。nm23-H1蛋白表达与HCC肿瘤体积,组织分型及Edmondson分级无关,而与肝内或肝外转移显著负相关。结果表明nm23-H1在抑制HCC肝内或肝外转移中起着重要作用,有可能成为评价HCC病人预后的一项新指标。  相似文献   

19.
Prognostic implication of nm23-H1 expression in colorectal carcinomas   总被引:12,自引:0,他引:12  
Dursun A  Akyürek N  Günel N  Yamaç D 《Pathology》2002,34(5):427-432
AIMS: Expression of nm23 has been identified as a potential metastatic suppressor. In this study, nm23-H1 expression, clinicopathological parameters and influences on clinical outcomes were investigated in colorectal carcinoma patients. METHODS: Immunostaining was performed on 185 colorectal carcinomas using a polyclonal anti-nm23-H1 antibody. RESULTS: The nm23-H1 immunoreactivity was weak in 31 (17%), moderate in 48 (26%) and strong in 106 (57%) cases. The well differentiated adenocarcinomas showed significantly strong staining for nm23-H1 compared with the moderately and poorly differentiated adenocarcinomas (chi2 test, P<0.001). Advanced tumour stages were associated with reduced nm23-H1 expression (P<0.001). There was an inverse correlation with angiolymphatic invasion, nodal metastasis and liver metastasis (univariate logistic regression analysis, P<0.001). In univariate analysis, patients with reduced expression of nm23-H1 had significantly shorter overall and disease-free survival than the strong expression group (log-rank test for trend, P=0.002 and P=0.003, respectively). CONCLUSIONS: Our results indicated that reduced nm23-H1 expression showed poor prognosis in colorectal carcinomas. As a result, nm23-H1 expression might be a useful marker to predict outcome while planning treatment.  相似文献   

20.
nm23-H1 is a candidate gene for the suppression of cancer metastasis. Several studies on human breast, hepatocellular, gastric, ovarian, and colon carcinomas and melanomas have shown that reduced nm23-H1 expression was closely related to metastatic progression with poor prognosis. However, the biochemical mechanism by which nm23-H1 suppresses the metastasis has yet to be elucidated. In this study, we analyzed the correlation between nm23 expression, cell motility, and the invasive abilities of six different oral squamous cell carcinoma cell lines (HSC2, HSC3, HSC4, KB, OSC19, and OSC20). Reduced mRNA/protein expression of the nm23-H1 was observed in three cell lines (HSC2, HSC3, and HSC4). These cell lines exhibited increased cell motility and an invasive character on organotypic raft culture. On the other hand, the cell lines (KB, OSC19, and OSC20) that showed a higher expression of nm23-H1 exhibited a threefold to fivefold reduced motility and also reflected fewer invasions compared to the former three cell lines. Because the HSC3 cells demonstrated the lowest nm23-H1 expression with the highest cell motility and invasive character, we established nm23-H1-transfected HSC3 cell lines to investigate whether exogenous nm23-H1 protein could inhibit cell migration and invasive activity. These transfectants showed a significant reduction in cell motility with exogenous nm23-H1 in a dose-dependent manner, and exhibited a noninvasive character. An immunofluorescence study demonstrated a distinct stress-fiber distribution at peripheral region of these transfectants. However, no significant difference of matrix metalloproteinase (MMP)-2 and MMP-9 expression was observed between mock transfectant and nm23-H1-transfected cells. These findings suggest that nm23-H1 inhibits the invasive activity of oral squamous cell carcinoma by suppression of cell motility without altering the MMP-2 and MMP-9 status.  相似文献   

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