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INTRODUCTION Colorectal cancer is the most common cancer ofthe Western world and accounts for approx.Elevenpercent of all cancer deaths in the United States.Aswith other malignancies,colorectal adenocarcinomais thought to develop through the accumulation ofgenetic alterations that inhibit cell growth.Two of theoncogenes that have been implicated in this processare bcl-2and p53,the products of which are involvedin apoptosis,cell proliferation and tumor develop-ment(Garewal et al.,1996).S… 相似文献
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采用S-P免疫组织化学的方法,配对检测了37例大肠癌组织及同一病人的正常粘膜上皮中p53蛋白的表达情况。结果表明,p53蛋白表达阳性19例,阴性18例,阳性率为51.4％,而配对的大肠正常粘膜检测结果均呈p53阴性;p53蛋白表达与病人性别、年龄、Dukes分期等因素无明显相关性,而与淋巴结转移、浸润深度和不同分化程度等存在明显相关性。提示p53蛋白的检测可以作为大肠癌病人病情诊断和预后分析的辅助手段。 相似文献
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采用免疫组化技术和PCR-SSCP技术对高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜及大肠腺瘤型息肉的P21、P53蛋白表达和K-ras基因、p53基因突变进行了检测,检测结果高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜和大肠腺瘤型息肉六组P21蛋白表达阳性率分别为57.5％、62.5％、75％、13.3％、6.7％、50％,p53蛋白表达阳性率分别为30％、37.5％、50％、4.4％、22％、33.3％,K-ras基因突变率分别为32.5％、37.5％、62.5％、2.2％、0％、16.7％,p53基因突变率分别为22.5％、25％、37.5％、0％、0％、0％.结果表明大肠腺癌P21、P53蛋白表达比大肠腺瘤增多,但增加不显著(P>0.05), 二组均比癌旁粘膜和正常粘膜P21、P53蛋白表达阳性率高(P<0.01);大肠腺癌K-ras基因和p53基因突变率比大肠腺瘤、癌旁粘膜和正常粘膜组显著增加(P<0.01);高、中、低分化大肠癌各组中,随恶性程度增加,P21、P53蛋白表达增加,K-ras基因和p53基因突变率增加,但均不显著(P>0.05).说明K-ras基因、p53基因突变及其蛋白表达产物P21、P53在细胞癌变、癌细胞恶性表型维持中起重要作用。 相似文献
4.
目的 :探讨p5 3蛋白在食管癌组织发生中表达的意义。方法 :应用免疫组织化学技术检测 72例食管鳞状上皮癌 ,19例增生鳞状上皮及 17例正常食道鳞状上皮中 p5 3蛋白的表达。结果 :p5 3在食管癌组织中的阳性率为 4 7.95 % (35 / 72 ) ,在增生鳞状上皮中的阳性率为 36 .84 % (7/ 19) ,在正常食道鳞状上皮中的阳性率为 5 .88% (1/ 17) ,正常组与增生组和癌变组比较均有显著性差异 (P <0 .0 5 )。p5 3蛋白与癌的分化程度、淋巴结有无转移和浸润深度等指标均无明显关系。结论 :p5 3蛋白与食管癌的发生、发展有关。 相似文献
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Objective
Many investigations have studied the associations between matrix metalloproteinase-9 (MMP-9) C1562T polymorphisms and coronary artery disease (CAD). However, the conclusions of these studies were inconsistent. Therefore, this study was aimed at clarifying the association between MMP-9 C1562T polymorphisms and CAD in a large-scale meta-analysis.Methods
The PubMed and Embase databases were retrieved to collect all publications on the association between MMP-9 C1562T polymorphisms and CAD. Then the odd ratios (ORs) and 95% confidence intervals (95% CIs) for C1562T TT+TC versus CC genotype between CAD and the control groups were evaluated. Subgroup analysis was also performed according to different races. The meta-analysis was performed by Stata 10.0.Results
Sixteen case-control studies were included in our meta-analysis, involving 11 032 CAD patients and 4628 non-CAD controls. Compared with C allele carriers, East Asian T allele carriers TT+TC had a significantly higher risk of CAD (OR=1.43; 95% CI: 1.03–1.99; P=0.031); however, there were no significant associations in Western populations (OR=1.06; 95% CI: 0.96–1.18; P=0.240) or West Asians (OR=1.13; 95% CI: 0.75–1.70; P=0.565). When further analyzing the association between C1562T polymorphisms and myocardial infarction (MI, the most serious type of CAD), the risk of TT+TC genotype versus CC genotype for MI was significantly higher for the overall (OR=1.21; 95% CI: 1.04–1.40; P=0.012) and for East Asians (OR=1.58; 95% CI: 1.26–1.97; P=0.000) but not in Western populations (OR=1.12; 95% CI: 0.99–1.26; P=0.078).Conclusions
Our meta-analysis suggested an obvious ethnic difference in the association between MMP-9 C1562T polymorphisms and CAD. MMP-9 C1562T polymorphism was significantly related to CAD in East Asians. However, no significant associations were observed in either West Asians or Western populations. 相似文献6.
INTRODUCTIONCoronaryarterydisease (CAD)continuestobethemajorcauseofmorbidityandmortalityinourcountry .TheactivityofbloodcoagulationfactorshasbeenshowntobeanimportantriskindicatorforCAD .However,circulatinglevelsofcoagulationfactorsmaynotaccuratelyreflectt… 相似文献
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Di JZ Han XD Gu WY Wang Y Zheng Q Zhang P Wu HM Zhu ZZ 《Journal of Zhejiang University. Science. B》2011,12(10):805-811
Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum, bladder, breast, head and
neck, and testicular germ cells. The aim of this study was to examine whether global hypomethylation in blood leukocyte DNA
is associated with the risk of hepatocellular carcinoma (HCC). A total of 315 HCC cases and 356 age-, sex- and HBsAg status-matched
controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing long interspersed element-1 (LINE-1)
repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing. We observed that the median methylation level
in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower than that in controls (79.5% 5mC) (P=0.004, Wilcoxon rank-sum test). The odds ratios (ORs) of HCC for individuals in the third, second, and first (lowest) quartiles
of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7–1.8), 1.4 (95% CI 0.8–2.2), and 2.6 (95% CI 1.7–4.1) (P for trend <0.001), respectively, compared to individuals in the fourth (highest) quartile. A 1.9-fold (95% CI 1.4–2.6) increased
risk of HCC was observed among individuals with LINE-1 methylation below the median compared to individuals with higher (>median)
LINE-1 methylation. Our results demonstrate for the first time that individuals with global hypomethylation measured in LINE-1
repeats in blood leukocyte DNA have an increased risk for HCC. Our data provide the evidence that global hypomethylation detected
in the easily obtainable DNA source of blood leukocytes may help identify individuals at risk of HCC. 相似文献
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目的:探讨P_(53)、Bcl-2基因蛋白在大肠癌中的表达及临床病理联系。方法:对88例大肠癌手术切除标本进行石蜡切片SP法免疫组织化学染色。结果:P_(53)、Bcl-2基因在大肠癌组织中表达率分别为55.68％(49/88)、63.63％(56/88),癌旁移行区粘膜上皮及腺体P_(53)、Bcl-2阳性表达率分别为3.12％(2/64)、31.25％(20/64),二者均有显著性差异(P<0.01)。P_(53)与大肠癌浸润深度有关(P<0.05),而与组织学类型、分化程度、有无淋巴结转移关系不显著(P>0.05)。Bcl-2的表达率在无淋巴结转移大肠原发癌中高于有淋巴结转移的大肠原发癌(P<0.01)。而在淋巴结转移癌组织中Bcl-2表达率高于原发癌组织Bcl-2表达率,差异有显著性(P<0.05)。结论:P_(53)、Bcl-2在大肠癌组织中均有高表达,可能与细胞恶变有密切关系,P_(53)与大肠癌浸润进展有关,与其它生物学行为关系不大;Bcl-2在大肠癌无淋巴结转移前有高表达,在淋巴结转移癌中的表达高于原发癌,提示Bcl-2的表达参与大肠癌转移的形成。 相似文献
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Objective: To determine whether polymorphisms in the genes for coagulation factor. II, V, VII could predispose an individual
to increase risk for coronary artery disease (CAD) and/or myocardial infarction (MI) in Chinese. Methods: We screened coagulation
factor II(G20210A), V(G1691A), VII (R353Q and HVR4) genotype in 374 patients undergoing coronary angiography by polymerase
chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results: The R353Q and HVR4 gemotype of the
factor VII distribution was in accordance with Hardy-Weinberg equilibrium. The frequencies of FVII genotype or allele did
not show statistically significant differences between CAD group and controls or between male and female. The frequencies
of the Q allele and (RQ+QQ) genotype were significantly higher among the CAD patients without myocardial infarction (MI) history
than among those with MI history (P<0.05). However, HVR4 polymorphism was not significantly different within groups. We only find one normal control of factorII
(G20210A) mutation. No coagulation factor V(G1691A) mutation was found in the CAD patients and controls. Conclusion: The factor
II(G20210A), V(G1691A) mutation is absent and may not be a major genetic factor for CAD and/or MI; the Q allele of the R353
Q polymorphism of the factor VII gene may be a protective genetic factor against myocardial infarction in Chinese.
Project (No. 021103166) supported by a grant from the Key Project of Science and Technology Commission of Zhejiang Province,
China 相似文献
10.
He Liu Xia Jiang Ming-wu Zhang Yi-feng Pan Yun-xian Yu Shan-chun Zhang Xin-yuan Ma Qi-long Li Kun Chen 《Journal of Zhejiang University. Science. B》2013,14(1):47-57
The initiators caspase-9(CASP9) and caspase-10(CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis.This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer(CRC) susceptibility in a population-based study.A two-stage designed population-based case-control study was carried out,including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls.A total of eight tag selected single nucleotide polymorphisms(SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information(NCBI) datasets and genotyped by restriction fragment length polymorphism(RFLP) assay.Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk.In the first stage,from eight tag SNPs,three polymorphisms rs4646077(odds ratio(OR) AA+AG:0.654,95% confidence interval(CI):0.406-1.055;P=0.082),rs4233532(OR CC:1.667,95% CI:0.967-2.876;OR CT:1.435,95% CI:0.998-2.063;P=0.077),and rs2881930(OR CC:0.263,95% CI:0.095-0.728,P=0.036) showed possible association with CRC risk.However,none of the three SNPs,rs4646077(OR AA+AG:1.233,95% CI:0.903-1.683),rs4233532(OR CC:0.892,95% CI:0.640-1.243;OR CT:1.134,95% CI:0.897-1.433),and rs2881930(OR CC:1.096,95% CI:0.620-1.938;OR CT:1.009,95% CI:0.801-1.271),remained significant with CRC risk in the validation set,even after stratification for different tumor locations(colon or rectum).In addition,never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set(OR:1.755,95% CI:1.319-2.334).Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration.In addition,tea drinking was a protective factor for CRC. 相似文献
11.
研究血管内皮生长因子(VEGF)936*T/C基因多态性与胃癌之间的关系,了解该基因多态性对胃癌生成及发展的影响。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测胃癌患者和健康者外周血的VEGF936*T/C基因型。结果,胃癌患者外周血中VEGF936*T/C基因型或等位基因与健康者相比无差异(精确概率法计算基因型P=0.226;卡方检验等位基因x2=2.934,P=0.087)。Ⅲ、Ⅳ期病理分期患者C/C基因型和C等位基因比例(66.7%和82.0%)明显大于Ⅰ、Ⅱ期(12.9%和1.2%),两者差异有统计学意义(基因型:x2=14.215,P=0.000;等位基因:x2=28.430,P=0.000)。结果表明,VEGF936*C/C基因多态性与胃癌的生成无关,而与胃癌的进展相关。 相似文献
12.
Jian Chen Qing-wei Zhao Gen-ming Shi Lin-run Wang 《Journal of Zhejiang University. Science. B》2012,13(11):875-883
Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger’s test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger’s test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, 95% CI 0.266–0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392–0.941, P=0.026; GA+AA vs. GG model: OR=1.259, 95% CI 0.931–1.701, P=0.135; GG+GA vs. AA model: OR=0.455, 95% CI 0.313–0.663, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients. 相似文献
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目的:为了探讨细胞凋亡促进基因bax在尿路上皮癌中染色的表达及意义以及与p53蛋白表达的相互关系。方法:对65例尿路上皮癌石蜡标本进行免疫组化。结果:bax蛋白阳性率为50.77％,且与肿瘤病理分级有关,其阳性细胞主要分布于高分化癌及浅表性癌。分级间比较有显著性差异(P<0.05)。分期间比较差异无显著性。p53蛋白阳性率为46.15％,与bax相反,在低分化及浸润性癌组织阳性率明显高于高分化及浅表性癌(P<0.05)。结论:作为细胞凋亡促进基因bax丢失与p53基因突变一样与尿路上皮癌的发生发展有关。检测bax与D53基因蛋白可进一步了解尿路上皮癌生物学信息,也为临床提供更有价值的预后判断指标。 相似文献
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WU Xiao-mo§ FU Jing-geng§ GE Wang-zhong ZHU Jiang-yan WANG Jun-yong ZHANG Wei QIAN Wei HUO Ke-ke 《Journal of Zhejiang University. Science. B》2007,8(2):81-87
INTRODUCTION Hepatocellular carcinoma (HCC) is the sixth most common cancer in new cases per year (626 000) and the third most common cancer resulting in death (598 000) (Parkin et al., 2005). China is the country most seriously suffering from HCC, accounting for 55% of total cases and deaths worldwide per year. The clinical behavior of HCC is heterogeneous and difficult to predict, and in patients undergoing resec-tion, recurrence rates can be as high as 50% in two years and life ex… 相似文献
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目的:探讨P53、C-myc蛋白在睾丸肿瘤中的表达及其临床价值.方法:应用免疫组化技术法检测47例睾丸肿瘤P53、C-myc蛋白阳性表达水平.结果:发现P53、C-myc蛋白表达阳性率分别为44.7%(21/47)和51.1%(24/47),其阳性率与肿瘤临床分期呈显著正相关(P<0.05),P53蛋白阳性表达与C-myc蛋白阳性表达呈高度正相关(P<0.05).结论:联合检测P53、C-myc蛋白有助于判断睾丸肿瘤的恶性程度及患者的预后. 相似文献
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目的:探讨ER与P53蛋白在胃癌中表达的相关性。方法:对119例胃癌标本进行石蜡切片和S-P免疫组织化学染色。结果:ER与P53在胃癌中的表达率分别为66.39％(79/119)和68.07％(81/119),ER与P53蛋白表达呈正相关(rs=0.513)。结论:ER与P53蛋白在胃癌的发生、发展过程中具有互相促进和互相调节的作用。 相似文献
18.
Dao-fa TIAN Ying-chun HE Fang-guo LU Fa-qing TANG 《Journal of Zhejiang University. Science. B》2009,10(3)
Objective: To investigate the enhancive effect ofN, N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC). Methods: TgN(p53mt-LMPI)/HT transgenic mice and the same strain of C57BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, I.e., TgN(p53mt-LMPI)/I-IT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls.At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression ofTRAF2, c-Jun, and pl 6 by immunohistochemistry. Results: Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) recep-tor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01). Conclusion: TgN(p53mt-LMP1)/HT mice hold inherited con-stitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p 16. 相似文献
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目的探讨ER、PR、P53、bcl-2在大肠良恶性病变中的表达相关性.方法利用ER、PR、P53及bcl-2特异性抗体对75例大肠良恶性肿瘤进行SABC免疫组织化学染色.结果四种抗体联合表达率在47例大肠恶性肿瘤、28例良性增生性疾病和41例癌旁移行区粘膜分别为26.83%、10.7%和0.10例大肠息肉P53和bcl-2均无表达,41例癌旁移行区未见P53表达.ER、PR联合表达率在大肠癌(42.55%)明显高于癌旁(17.07%),P53和bcl-2联合表达率在癌、良性增生和癌旁分别为48.94%、17.80%和0,三者间差异显著.而四种抗体表达与患者性别、年龄无关.结论ER、PR、P53和bcl-2表达与大肠肿瘤发生有关.P53基因突变是人类大肠癌发生的最常见的遗传学改变之一,bcl-2是大肠癌发生的早期分子水平标志;激素及其受体改变促进肿瘤的发生并且雌、孕激素受体水平与肿瘤的病理分化程度有关. 相似文献