COX-2和MMP-9在食管鳞癌组织中的表达及其与血管生成的关系

目的: 观察食管鳞癌组织、癌旁正常黏膜中环氧化酶-2(COX-2)及基质金属蛋白酶-9(MMP-9)的表达及其与微血管密度(MVD)的关系, 探讨COX-2和MMP-9对食管鳞癌血管生成的作用与意义.方法: 应用SP法对90例食管鳞癌组织和34例癌旁正常黏膜的COX-2、MMP-9及CD34进行免疫组织化学染色, 检测癌组织、癌旁正常食管黏膜组织的COX-2与MMP-9表达及MVD, 并分析COX-2、MMP-9的表达与MVD之间, 以及他们与食管鳞癌临床病理特征之间的关系.结果: 食管鳞癌组织中COX-2、MMP-9的阳性表达率和MVD分别为84.8%、82.2%和29.70±3.82, 显著高于癌旁正常黏膜的20.6%、14.7%和15.1±2.38. COX-2的表达与肿瘤的TNM分期、分化程度和淋巴结转移密切相关( P<0.01). MMP-9、MVD的表达与肿瘤的TNM分期和淋巴结转移密切相关( P<0.01);COX-2表达与MVD呈显著正相关( r = 0.607,P<0.01); COX-2与MMP-9的表达正相关( r =0.740, P<0.01); MMP-9的表达与MVD值之间呈正相关( r = 0.718, P<0.01).结论: COX-2与MMP-9异常表达在食管鳞癌的血管生成中起重要作用, COX-2、MMP-9及其诱导的血管生成与食管鳞癌的侵袭和转移密切相关.     

胃腺癌组织中COX-2和VEGF-C的表达及意义

采用免疫组化和RT—PCR技术,检测64份胃腺癌组织中环氧化酶-2（COX-2）和血管内皮细胞生长因子-C（VEGF-C）的表达。结果显示癌组织中COX-2和VEGF—C的表达均高于相应癌旁正常组织,二者的表达有明显相关性,且与癌细胞授润深度、淋巴结转移密切相关。认为COX-2和VEGF—C高表达在胃腺癌浸润和转移中发挥重要作用。     

PDTC对人肺腺癌A549细胞COX-2、VEGF表达的影响及意义

核因子-κB(NF—κB)广泛存在于真核细胞,是一多功能的核转录因子,被激活后参与调控多种细胞因子、黏附因子及酶的表达,在炎症、肿瘤等疾病的发生、发展中起重要作用。研究证实环氧化酶-2(COX-2)和血管内皮生长因子(VEGF)在多种恶性肿瘤中表达增高,与肿瘤血管生成、侵袭转移密切相关。有研究发现,NF-κB可能参与COX-2及VEGF表达的调控。     

COX-2与卵巢癌的相关性研究进展

环氧化酶（COX）是前列腺素H2合成的限速酶,在花生四稀酸转变成前列腺素（PGS）的过程中发挥着重要作用,包括COX-1和COX-2两种同工酶。研究发现。COX-2与绝大多数恶性肿瘤的发生发展有关。现将其与卵巢癌的相关性研究进展情况综述如下。     

COX-2、VEGF在子宫内膜癌中的表达及意义

目的 探讨环氧化酶-2（COX-2）和血管内皮生长因子（VEGF）在子宫内膜癌发生发展中的作用。方法 采用免疫组化SP法检测41例子宫内膜癌和15例正常子宫内膜组织中COX-2、VEGF的表达。结果 子宫内膜癌组织中COX-2、VEGF的阳性表达率明显高于正常子宫内膜组织（P均〈0．05,）;低分化和肌层浸润〉1／2者的子宫内膜癌组织中COX-2表达明显高于中、高分化和肌层浸润≤1／2（P〈0．05）者;COX-2表达阳性的子宫内膜癌,其VEGF阳性率明显高于COX-2表达阴性者（P〈0．05）。结论 COX-2在子宫内膜癌组织中呈高表达,并可上调VEGF的表达,二者可能与子宫内膜癌的发生发展有关。     

喉癌组织中COX-2、VEGF、MVD的表达及意义

采用免疫组化法检测50例喉癌组织中诱导型环氧合酶（COX-2）、血管内皮生长因子（VEGF）的表达，用CD34。标记新生血管内皮细胞，观察微血管密度（MVD）。喉癌组织中COX-2、VEGF的阳性表达率分别为62％和68％，MVD为（51．62±16．64）条／200倍视野。COX-2和VEGF的表达与喉癌病理学分级及临床分期有关。表明喉癌组织中COX-2呈高表达，COX-2与肿瘤新生血管形成有关，检测癌组织中COX-2、VEGF有助于喉癌的绢织学分级和预后判断。     

老年宫颈鳞癌组织中COX-2和MMP-9的表达变化及意义

目的探讨环氧化酶(COX)-2和基质金属蛋白酶(MMP)-9的表达在老年宫颈鳞癌中,发生发展中的作用评价。方法应用免疫组化SP法检测60例宫颈鳞癌(观察组)、60例正常宫颈组织(对照组)中COX-2和MMP-9的表达水平,并分析COX-2和MMP-9的表达与临床病理特征的关系。结果观察组COX-2和MMP-9表达的阳性率明显高于对照组(P0.01);观察组中COX-2和MMP-9的阳性率与淋巴结转移、肿瘤最大直径及Ki67的表达密切相关。结论 COX-2和MMP-9的高表达在宫颈癌的发生、发展中均起作用,联合检测可能与子宫颈鳞癌的预后密切相关。     

COX-2与P—gp在乳腺癌组织中的表达及其临床意义

目的探讨环氧化酶-2（COX-Z）与P糖蛋白（P—gp）在乳腺癌组织中的表达及临床意义。方法应用免疫组织化学染色法检测60例乳腺癌组织和10例正常乳腺组织中COX-2与P．gP蛋白的表达情况。结果60例乳腺癌组织中COX-2表达阳性率为56．7％（34／60）,P-gP表达阳性率为38．3％（23／60）;COX．2和P-gP均与淋巴结转移有关（P〈0．05）,乳腺癌组织中COX-2与P—gP表达呈正相关（r：0．413,P〈0．01）,10例正常乳腺组织中无COX-2与P-gP蛋白的表达。结论COX-2可能对多药耐药基因编码产物P-gp表达增高有影响,从而介导了乳腺癌多药耐药的产生。     

COX-2及VEGF在育龄妇女子宫内膜息肉中的表达

目的通过检测环氧化酶-2(COX-2)及血管内皮生长因子(VEGF)在子宫内膜息肉(EP)组织与正常子宫内膜中随月经周期的不同表达,探讨其在EP发生发展中的作用及其引起不孕的机制。方法采用免疫组化法检测40例EP患者息肉组织、周围内膜组织(增殖期10例、分泌期30例、分泌中期20例)及40例正常对照组(增殖期10例、分泌期30例、分泌中期20例)子宫内膜中COX-2及VEGF蛋白的表达。结果 COX-2和VEGF的表达主要位于子宫内膜的腺体。正常内膜COX-2和VEGF分泌期表达均高于增殖期,息肉组织中COX-2和VEGF的表达明显高于周围内膜组织,分泌中期息肉组织子宫内膜COX-2和VEGF显著低于正常对照组子宫内膜的表达。结论息肉组织中COX-2及VEGF的高表达提示其与EP的发病密切相关,而COX-2及VEGF在息肉周围内膜中的低表达可能影响EP患者的胚胎着床。     

IL-10、COX-2在幽门螺杆菌相关性胃炎组织中的表达及相关性研究

目的了解IL-10、COX-2在幽门螺杆菌（H.pylori）相关性胃炎组织中的表达及相关性,为免疫治疗H.pylori相关性胃炎及预防胃癌发生提供临床和实验依据。方法收集因上腹部不适等症状于我院行胃镜检查诊断为胃炎者110例,取胃窦部黏膜活检标本3块,分别行快速尿素酶试验、Warthin-Starry嗜银染色、HE染色。根据H.pylori科研诊断标准,110例标本中符合实验研究的共74例,其中H.pylori阳性59例,H.pylori阴性15例。免疫组化方法检测74例标本中IL-10、COX-2蛋白的表达情况。结果IL-10、COX-2在H.pylori（＋）胃炎中的阳性表达率分别为49.15%、59.32%,与H.pylori（-）组的13.33%、20.00%相比,两种因子的阳性表达率均显著增加（P〈0.05）。H.pylori（＋）组,IL-10、COX-2在慢性活动性胃炎中的阳性表达率分别为32.26%、74.19%,在非活动性胃炎的阳性表达率分别为67.86%、42.86%。IL-10在慢性活动性胃炎的阳性表达率低于非活动性胃炎（P〈0.02）;COX-2在慢性活动性胃炎的阳性表达率高于非活动性胃炎（P〈0.03）。H.pylori（＋）组,IL-10、COX-2在慢性浅表性胃炎中的阳性表达率分别为64.00%、44.00%,慢性萎缩性胃炎分别为38.10%、61.90%,肠化生及异型增生分别为38.46%、84.62%。IL-10在3组之间差异无显著性（P〉0.05）;COX-2的表达呈递增趋势,在肠化及异型增生组表达显著增高,与浅表性胃炎相比,差异显著（P〈0.05）,其余各组两两相比无显著性差异（P〉0.05）;H.pylori（＋）组,IL-10与COX-2的表达呈显著负相关,相关系数r=-0.566（P〈0.001）。结论 IL-10、COX-2两种因子的产生与H.pylori感染相关;COX-2与胃癌的发生有关,是胃癌发生的早期事件,IL-10可能抑制了COX-2的过度表达及活性,在H.pylori相关胃炎及胃癌癌前病变中发挥保护作用。     

Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer

BACKGROUND AND AIM: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer. METHODS: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis). RESULTS: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19-9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density. CONCLUSIONS: Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer.     

Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors

BACKGROUND AND AIM: Recent advances in colonoscopic techniques have led to the increased detection of, and interest in, superficial type colorectal tumors, and a new category, the 'laterally spreading tumor (LST)', has been proposed. However, the characteristics of the genetic alterations in these LSTs have not yet been fully determined. We therefore classified LSTs as LST-granular (LST-G) or LST-non-granular (LST-NG), according to their macroscopic appearance, and examined the genetic alterations in these two tumor groups compared with those in protruded type tumors. METHODS: We obtained a total of 62 colorectal tumors, including 26 protruded type, 17 LST-G and 19 LST-NG, from specimens resected surgically or endoscopically. We examined K-ras codon 12 mutations by using the polymerase chain reaction-restriction fragment length polymorphism method and by fluorescence direct sequencing. We also performed immunohistochemistry to analyze cyclooxygenase (COX)-2 and gastrin abnormalities. RESULTS: The incidence of K-ras mutation was 50.0% in protruded type tumors, 76.5% in LST-G, and 26.3% in LST-NG. The frequencies of COX-2 overexpression were 73.1, 88.2, and 31.6%, respectively, and those of gastrin overexpression were 61.5, 82.4, and 26.3%, respectively. Therefore, LST-G is similar to protruded type tumors in that the incidence of K-ras mutation and the frequencies of COX-2 and gastrin overexpression are high. LST-NG differs from both of these tumor types in that the values of these three indicators are all low. CONCLUSIONS: These results show that LST-G and LST-NG have different genetic alterations.     

环氧化酶2在大肠癌中的表达及其与大肠癌生物学特性的关系

[目的]通过观察环氧化酶2（Cyclooxygenase-2,COX-2）在大肠腺瘤、大肠癌中的表达及其与大肠癌生物学特性的关系,初步探讨其在大肠癌发生、发展过程中的作用机制。[方法]应用免疫组织化学染色法对78例大肠癌组织、21例大肠腺瘤组织和13例正常大肠黏膜组织进行免疫组化染色;应用它检验分析COX-2的表达情况及其与大肠癌临床病理特征的关系。[结果]大肠癌组织中COX-2阳性表达率为78．21％,明显高于大肠腺瘤的52．38％和正常大肠黏膜组织的7．69％（P〈0．05）;COX-2表达与大肠癌的Duke＇s分期、分化程度、淋巴结转移有相关性（P〈0．05）,而与大肠癌患者的性别、组织学类型无关（P〉0．05）。[结论]COX-2在大肠癌组织中表达率明显高于大肠腺瘤,而正常大肠黏膜中表达率极低或不表达;COX-2表达与大肠癌生物学特性有明显相关性。     

Quantifying the expression of tumor marker genes in lung squamous cell cancer with RNA sequencing

Background

We measured the expression of some commonly used tumor markers with RNA sequencing (RNA-Seq) to identify any that might be useful for the evaluation of squamous cell lung cancer and identify possible correlations between these tumor markers and any clinical characteristics.

Methods

RNA-Seq was performed on five pairs of squamous-cell lung cancer and normal tissues and another 39 squamous-cell lung cancer tissues obtained by our department between September and December, 2012. The expression of 13 commonly used tumor markers was determined.

Results

All of the patients in our study were male. The expressions of CA125, CYFRA21-1, NSE and SCC increased in tumor samples and there were statistically significant differences between squamous cell lung cancer and normal tissues (P=0.008, P<0.001, P<0.001, P=0.001). The expression of β2M and CA15-3 was reduced in squamous cell carcinoma relative to normal tissues and there was no significant difference in the expression of other tumor markers, including AFP, AFU, CT, FER and HE4.

Conclusions

CA125, CYFRA21-1, NSE and SCC may be appropriate tumor markers for squamous cell lung cancer.     

IL-21R、MMP-2在非小细胞肺癌中的表达及相关性研究

目的检测白介素-21受体(interleukin-21R,IL-21R)、基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)在非小细胞肺癌(Non-small-cell lung cancer,NSCLC)癌组织中的表达,并探讨IL-21R、MMP-2的表达在NSCLC发生、发展及浸润转移的影响。方法采用免疫组化法检测50例NSCLC组织及20例正常肺组织对照组中IL-21R、MMP-2的表达,分析其阳性表达率与NSCLC患者临床病理特征的关系,并探讨其相关性。结果 NSCLC癌组织中IL-21R、MMP-2的阳性表达率均显著高于正常肺组织,且两者表达呈负相关(P0.05);IL-21R和MMP-2的表达与淋巴结转移、临床分期及组织分化程度相关。结论 NSCLC中MMP-2的表达与其浸润转移正相关,其表达增加表示NSCLC有较高恶性生物学行为;IL-21R的表达与NSCLC浸润转移的呈负相关,且IL-21R、MMP-2在NSCLC发生及浸润过程中具有相关性。     

肺癌中瘦素受体的表达及其在血管生成中的作用

目的研究瘦素受体（OB-R）、血管内皮生长因子（VEGF）和微血管密度（MVD）在肺癌组织中的表达,探讨瘦素受体在肺癌血管生成中的作用和机制。方法免疫组化法检测40例肺癌组织和正常对照组织中OB-R、MVD、VEGF的表达。结果肺癌及正常肺组织瘦素受体的阳性表达率分别为67．50％、37．50％,两组比较差异有统计学意义（P〈0．05）。瘦素受体的表达与性别年龄,肿物大小,病理类型无关（P〉0．05）,而与MVD,淋巴转移有关（P〈0．05）,肺癌组织中OB—R阳性组的MVD较阴性组高。VEGF阳性组的MVD明显高于阴性组。OB—R与VEGF表达部位一致,呈正相关（P〈0．05）。结论肺癌组织中OB-R表达增多对肺癌血管成生成促进作用,并且该作用可能与VEGF的上调有关。     

Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer

Non-steroidal anti-inflammatory drugs (NSAIDs), both cyclooxygenase-2 (COX-2) selective and nonselective inhibitors, are amongst the most popular medications worldwide. Whilst their anti-inflammatory effect is well known, recent studies have demonstrated an unexpected effect in both the prevention and treatment of several types of cancer. The anticancerous effect of NSAIDs is believed to be mainly due to the inhibition of COX-2, which is overexpressed in many types of cancer and may play a major role in tumourigenesis. In this review, we will describe the possible mechanisms for NSAIDs anticancer effect and summarize the major clinical studies in cancer prevention and treatment. We will also discuss the effect of the recent reports of adverse cardiovascular effects on anticancer research of the selective COX-2 inhibitors.     

环氧合酶-2抑制剂对大鼠急性肺损伤的作用

目的探讨急性肺损伤（ALI）肺组织环氧合酶－2（COX-2）mRNA表达的变化以及选择性COX－2抑制剂Meloxicam的干预作用。方法脂多糖（LPS）诱发大鼠ALI模型,采用逆转录-聚合酶链反应,检测其肺组织COX-2mRNA表达并观察其前列腺素（PGs）、动脉血氧分压（PaO2）及病理变化。结果静息状态的大鼠肺组织表达少量的COX-2mRNA,在ALI大鼠肺组织COX-2mRNA大量表达,Meloxicam可减轻肺组织病理损伤、降低PGs产量,使PaO2下降程度减轻。结论COX-2是ALI时PGs升高的主要同工酶,Meloxicam可抑制COX-2活性,对ALI具有一定的防治作用。     

尼美舒利对人胃癌SGC-7901细胞PGE2合成及COX-2、VEGF表达的影响

目的观察尼美舒利对人胃癌SGC-7901细胞前列腺素E2（PGE2）合成及环氧合酶（COX）-2、血管内皮生长因子（VEGF）表达的影响，探讨其抑制胃癌血管生成的机制。方法对人胃癌SGC-7901细胞进行培养．免疫组织化学、放射免疫法检测不同浓度尼美舒利作用后细胞COX-2、PGE2、VEGF的表达。结果与阴性对照组相比。尼美舒利100、200μmol／L作用48h后SGC-7901细胞的COX-2、VEGF表达明显降低（P〈0．05），COX-2与VEGF的表达呈正相关（r=0．8080，P〈0．05）；随着尼美舒利浓度的升高，PGE2分泌逐渐降低。结论抑制COX-2的活性与表达、减少PGE。的合成及由此引起的VEGF表达降低，在抑制胃癌血管生长中可能具有一定作用。     

去氢骆驼蓬碱通过下调COX-2表达抑制胃癌细胞迁移和侵袭

目的探讨去氢骆驼蓬碱对人胃癌MKN-45细胞环氧化酶-2(cyclooxygenase-2,COX-2)表达、迁移和侵袭的影响。方法 MKN-45细胞接种于含10%胎牛血清的RPMI-1640培养液中,常规培养24h后加去氢骆驼蓬碱(2、4、8、16、32μg/ml),同时设置对照组不加药物,空白组只加培养液不含细胞,分别培养24h、48h、72h,MTT法检测细胞增殖率;western blot法检测COX-2表达;划痕损伤愈合实验及Transwell小室基质侵袭实验检测胃癌细胞体外迁移和侵袭。结果去氢骆驼蓬碱剂量依赖性抑制MKN-45细胞COX-2表达(P0.01);与对照组相比,去氢骆驼蓬碱组MKN-45细胞迁移和侵袭能力明显下降(P0.01)。结论去氢骆驼蓬碱可能通过下调COX-2表达抑制胃癌细胞迁移和侵袭。