环氧合酶-2在胃癌与癌前病变和其他胃黏膜组织中表达的研究

目的:研究胃癌与癌前病变和其他胃黏膜组织中环氧合酶-2(COX-2)的表达情况,探讨COX-2蛋白作为肿瘤分子标记物对胃癌和癌前病变进行辅助诊断的意义.方法:收集胃镜活检的正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、胃黏膜肠化生、胃黏膜不典型性增生和胃癌组织,用免疫组织化学染色法检测COX-2蛋白在各种组织中的阳性表达情况.以正常胃黏膜组织和正常兔血清作阴性对照.结果:COX-2蛋白在胃癌前病变和和胃癌组织中的表达阳性率为48%-84%.胃癌和胃黏膜不典型性增生标本中COX-2蛋白表达阳性率显著高于正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎和胃黏膜肠上皮化生标本(P<0.05).而胃癌组织COX-2蛋白表达的阳性率与胃黏膜不典型性增生组之间无显著性差异(P>0.05).此外,慢性萎缩性胃炎和胃黏膜肠化生标本与正常胃黏膜和慢性浅表性胃炎标本之间COX-2蛋白表达阳性率亦有显著性差异(P<0.05);所有病变组的COX-2蛋白表达阳性率均比正常胃黏膜组显著性地升高 (P<0.05).结论:胃癌与癌前病变组织中COX-2蛋白的表达显著升高,COX-2蛋白可作为肿瘤标记物对胃癌和胃癌前病变进行辅助诊断.     

血清与组织中MG7抗原表达对胃癌前病变风险预测的临床意义

背景与目的:多年来,许多科研人员致力于探索诊断胃癌及癌前疾病的生物学标志物.本研究通过对不同类型胃黏膜活检组织胃癌相关抗原(MG7-Ag)的表达和血清MG7-Ag含量的检测,探讨两者的相关性及对胃癌前病变风险预报的临床应用价值.方法:125例胃黏膜活检组织及其血清标本(正常胃黏膜12例,浅表性胃炎21例,胃黏膜糜烂溃疡24例,萎缩性胃炎15例,异型增生22例,胃癌31例),采用SP免疫组织化学二步法染色检测胃黏膜标本中MG7-Ag的表达情况;采用酶联免疫吸附实验检测血清MG7-Ag的含量.结果:①MG7-Ag在12例正常胃黏膜中无表达,在31例胃癌中表达率为93.55%,由浅表性胃炎(14.29%)或胃糜烂溃疡(33.33%)进展至萎缩性胃炎(86.67%)或异型增生(81.82%)再进展至胃癌(93.55%),MG7-Ag表达率依次逐渐上升,差异有显著性(P<0.05).②血清MG7-Ag含量从浅表性胃炎(3.0±0.6)、胃黏膜糜烂溃疡(2.8±2.0)、萎缩性胃炎(3.8±1.2)/异型增生(3.9±1.7)到胃癌组(7.0±4.6)有升高趋势,并且各组间比较差异均有非常显著性(P<0.01).胃癌患者血清MG7-Ag含量明显高于其他胃病患者,差异有显著性(P<0.05).③从浅表性胃炎到胃黏膜糜烂溃疡进展至萎缩性胃炎/异型增生再进展至胃癌,随着其病变组织MG7-Ag原位表达的上升,其血清MG7-Ag浓度有上升趋势,并且各组间比较差异均有非常显著性(P<0.01).两者具有良好的相关性(rs=0.346,P=0.001).结论:①MG7-Ag在胃疾病的动态表达提示胃黏膜细胞恶性程度与MG7-Ag的表达呈正相关,血清MG7-Ag与组织MG7-Ag表达有良好的相关性.②临床有望将MG7-Ag作为胃癌前病变随访,进行癌变风险预测以及早期诊断胃癌的预警标志物.③以血清标本代替组织标本检测UMG7-Ag具有取材方便,患者依从性好等优点,便于临床推广应用.     

胃癌及癌前病变细胞凋亡与Caspase-9,Bax表达的关系

目的:探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用.方法:应用免疫组化S-P法检测 Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法(TUNEL法)检测相应胃组织细胞凋亡.结果:Caspase-9蛋白在非癌胃黏膜组(慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生)阳性表达率分别为 100.00%、86.67%、50.00%、42.85%,呈逐渐下降趋势.慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异(P＜0.05),肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异(P＞0.05).Bax蛋白在48例非癌胃组织中的阳性表达率分别为:慢性浅表性胃炎100.00%、慢性萎缩性胃炎80.00%、肠上皮化生56.25%、不典型增生57.14%,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异(P＜0.05).慢性浅表性胃炎、慢性萎缩性胃炎 、肠上皮化生、不典型增生、胃癌组织中,AI值( 细胞凋亡指数)分别为(14.72±2.68)%、(10.02±2.34)%、(7.55±2.80)%、(6.09±2.35)%、(3.26±1.23)%,呈逐渐下降趋势,有显著性差异(P＜0.05).结论:Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生.     

RASSF1A在胃癌中的甲基化检测及表达

目的:探讨RASSF1A基因在胃癌及癌前病变组织中的表达及与启动子区甲基化的关系.方法: RT-PCR方法检测40例胃癌、20例中-重度慢性萎缩性胃炎伴肠上皮化生和不典型增生组织及20例癌旁正常组织RASSF1A mRNA表达,甲基化特异性PCR方法检测RASSF1A启动子区CpG岛甲基化状态;Western blot方法检测RASSF1A蛋白表达.结果: RASSF1AmRNA和蛋白表达水平在胃腺癌组织中明显低于中-重度慢性萎缩性胃炎伴肠上皮化生和不典型增生组及癌旁正常组织;RASSF1A在胃癌组织、中-重度慢性萎缩性胃炎伴肠上皮化生和不典型增生组织和正常组织中的甲基化频率分别为80%、25%和5%, 差异有显著性 (P<0.01);在胃癌组织中,RASSF1A mRNA阳性表达组甲基化明显低于表达缺失组.结论: 胃癌组织RASSF1A mRNA和蛋白表达缺失或低下与其启动子甲基化程度增高有关,启动子甲基化参与了胃癌的发生发展.     

胃癌及癌前病变细胞凋亡与Caspase-9，Bax表达的关系

目的：探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用。方法：应用免疫组化S—P法检测Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法（TUNEL法）检测相应胃组织细胞凋亡。结果：Caspase-9蛋白在非癌胃黏膜组（慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生）阳性表达率分别为100．00％、86．67％、50．00％、42．85％,呈逐渐下降趋势。慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异（P〈0．05）,肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异（P〉0．05）。Bax蛋白在48例非癌胃组织中的阳性表达率分别为：慢性浅表性胃炎100．00％、慢性萎缩性胃炎80．00％、肠上皮化生56．25％、不典型增生57．14％,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异（P〈0．05）。慢性浅表性胃炎、慢性萎缩性胃炎、肠匕皮化生、不典型增生、胃癌组织中,AI值（细胞凋亡指数）分别为（14．72±2．68）％、（10．02±2．34）％、（7．55±2．80）％、（6．09±2．35）％、（3．26±1．23）％,呈逐渐下降趋势,有显著性差异（P〈0．05）。结论：Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生。     

胃癌及癌前病变组织中TGFα和cyclin E的表达及两者关联性分析

背景与目的:研究发现,转化生长因子α(transforminggrowthfactoralpha,TGFα)或细胞周期素E(cyclinE)表达增高与肿瘤的发生、发展关系密切。但在胃癌前病变中的表达报道较少;两者表达的关联性分析未见报道。本研究旨在检测TGFα和cyclinE在慢性浅表性胃炎、胃癌前病变和胃癌组织中的表达情况,分析两者表达的关联性。方法:用免疫组织化学方法,检测TGFα和cyclinE在上述组织中的表达,分析两者表达在不同病理组织中的差异,以及两者表达的关联性。结果:在慢性浅表性胃炎、肠上皮化生、不典型增生及胃癌组织中,TGFα表达的阳性率分别为15.1%、53.6%、51.7%和61.7%,cyclinE分别为7.5%、28.6%、37.9%和42.6%,两者在肠上皮化生、不典型增生和胃癌的表达均高于在慢性浅表性胃炎的表达(均P<0.05)。在中-高分化腺癌和低分化腺癌,TGFα表达的阳性率分别为41.7%和81.0%,cyclinE分别为16.7%和57.1%,两者在低分化腺癌的表达均高于在中-高分化腺癌的表达(均P<0.05)。在胃慢性炎症组织(含癌前病变)以及在胃癌组织,TGFα和cyclinE的表达均存在显著的关联(分别为P<0.001和P=0.005)。结论:在慢性浅表性胃炎、癌前病变和胃癌组织中,TGFα和cyclinE的表达随病变严重程度以及胃癌恶性程度的增高而增高;且两者表达存在显著的关联     

血管内皮生长因子在胃癌和癌前病变组织中的表达及其临床意义

目的 :探讨血管内皮生长因子 (全文简称VEGF)在胃癌及癌前病变组织中的表达及临床价值。方法 :采用免疫组化S -P法检测胃癌手术标本 5 2例 ,慢性萎缩性胃炎伴肠上皮化生 14例、不典型增生 18例、胃腺瘤 12例组织中的VEGF蛋白表达和胃癌标本的微血管计数 (MVD)。结果 :慢性萎缩性胃炎伴肠化生患者VEGF表达为 35 71% ,不典型增生为 38 89% ,胃腺瘤为 4 1 6 7% ,三者之间无显著性差异 (P <0 0 5 )。胃癌的表达为 6 3 4 6 % ,与癌前病变组相比有显著性差异(P <0 0 5 )。VEGF表达阳性的肿瘤组织其MVD明显高于阴性者 (P <0 0 5 )。VEGF的高表达与胃癌的浸润深度、淋巴结转移有明显相关性 (P <0 0 5 ) ,与癌组织中不同分化程度无关 (P >0 0 5 )。结论 :VEGF在癌前病变中可出现不同程度的表达 ,但在胃癌中有高水平表达 ,与肿瘤的恶性进程和预后有关     

胃癌和胃癌前病变中NHE1蛋白的表达及其意义

目的探讨NHE1蛋白在胃癌和胃癌前病变中的表达及意义。方法对收集的65例各类胃病标本的NHE1蛋白表达进行检测,高倍镜视野下阳性细胞数占视野10%以下视为阴性,10%以上视为阳性。结果在65例标本中,NHE1蛋白阳性表达率在正常胃黏膜中0%(0/10);异型增生20.00%(1/5);肠上皮化生23.08%(3/13);慢性萎缩性胃炎16.67%(2/12);胃癌80.00%(20/25)。胃癌与正常胃黏膜和各型胃癌前病变相比,差异具有统计学意义(P<0.01)。结论 NHE1在慢性萎缩性胃炎、肠上皮化生、异型增生中的表达不断上调,在胃癌组织中NHE1蛋白超表达;NHE1可能是肿瘤治疗的一个有效的靶点。     

MG7和PGC在胃癌及癌前疾病中的表达及意义

[目的]探讨胃癌相关抗原（MG7）和胃蛋白酶原C（PGC）在不同胃疾病中的动态表达,并对其在胃癌前疾病及胃癌诊断中的价值评价。[方法]采用免疫组织化学染色检测125例胃黏膜标本中MG7和PGC的表达情况。[结果]①MG7-Ag在12例正常胃黏膜中无表达,在31例胃癌中表达率为93．55％,由浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,MG7-Ag表达率依次逐渐上升（P〈0．05）。PGC—Ag在12例正常胃黏膜中全部阳性表达（100％）,在31例胃癌中表达率显著下降（6．45％）,从浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,PGC—Ag表达率依次逐渐下降（P〈0．05）。②单独应用MG7和PGC诊断试验的灵敏度高;将MG7和PGC联合进行串联试验,提高了诊断胃癌的特异度和准确度。[结论]①MG7抗原和PGC抗原两个指标与胃疾病的发生发展有良好的相关性。②MG7抗原和PGC抗原联合检测可以提高特异度,可以用于胃癌的诊断和癌前疾病的筛查。     

胃癌组织COX-2、bcl-2和ki-67的表达及其临床意义

目的　探讨环氧合酶 - 2 (COX- 2 )、bcl- 2和 ki- 6 7基因蛋白在胃癌及不典型增生中的表达及意义。方法　采用免疫组化染色 (S- P方法 )检测上述基因蛋白。结果　浅表性胃炎、萎缩性胃炎、肠上皮化生、不典型增生、早期胃癌及进行期胃癌的 COX- 2基因蛋白表达率分别为 2 1.7%、2 5 .9%、2 2 .7%、6 5 .4 %、6 3.6 %及 5 6 .1% ,且胃癌及不典型增生的表达率显著高于前 3者 (P<0 .0 1) ;bcl- 2基因蛋白表达率分别为 2 1.7%、33.3%、5 9.1%、76 .9%、72 .8%及 6 0 .9% ,以胃癌及不典型增生最高 ;ki- 6 7基因蛋白表达率分别为 2 6 .1%、5 5 .6 %、5 4 .5 %、6 1.5 %、72 .7%及 80 .5 % ,胃癌及不典型增生的 ki- 6 7表达率显著高于浅表性胃炎 (P<0 .0 5 ) ,提示它在整个胃癌演变序列中不断增强。结论　 COX- 2和 bcl- 2基因蛋白过表达在胃癌演变序列中 ,以不典型增生及胃癌组织最高 ;ki- 6 7蛋白表达率在整个胃癌演变序列中不断增强 ,尤其不典型增生及胃癌表达率显著增高。以上从基因表达水平提示不典型增生可能与胃癌的发生密切相关     

c-fos proto-oncogene expression in human NK/LGL cells: expression is not constitutive and is associated with functional activation

Unlike mature myeloid and monocytic cells and cell lines committed to terminal myelomonocytic differentiation, highly purified preparations of human natural killer cells/large granular lymphocytes (NK/LGL) did not spontaneously express the c-fos proto-oncogene. Transient expression of c-fos in NK/LGL was associated with functional activation with IL-2, IFN-gamma, LPS and PMA, which increased their cytotoxic activity, lymphokine secretion and in vitro chemotaxis. These results, together with the finding that T-cell receptor genes are in germ-line configuration in the vast majority of peripheral blood NK/LGL, are compatible with the hypothesis that these cells represent a separate hematopoietic lineage.     

CDH22 expression is reduced in metastatic melanoma

Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein implicated in cell-cell adhesion and cancer metastasis. The expression of CDH22 has been shown to be increased in colorectal cancers. However, the role of CDH22 in melanomagenesis is not known. To investigate the role of CDH22 in melanoma progression, we examined the expression of CDH22 in melanocytic lesions at different stages and analysed the correlation between CDH22 expression and clinicopathlogic parameters and patient survival. Using tissue microarray and immunohisto-chemistry, we evaluated CDH22 staining in 76 dysplastic nevi, 247 primary melanomas, and 143 metastatic melanomas. We found that metastatic melanomas had a significantly higher percentage of negative CDH22 staining than dysplastic nevi (P = 0.012) and primary melanomas (P = 0.038). CDH22 expression was also reduced in thick (≥2 mm) and ulcerative melanomas (P = 0.003 and 0.022, respectively). Melanomas of AJCC stage II, III, and IV had a higher percentage of negative CDH22 staining than AJCC stage I melanomas (P = 0.004, P < 0.0001, and P = 0.009, respectively). Melanomas with negative CDH22 expression had significantly poorer disease-specific 5-year survival than those with positive CDH22 staining. Additionally, CDH22 expression depended on AJCC stage to predict patient survival. These data indicate that reduced CDH22 expression is associated with melanoma metastasis and poor patient prognosis.     

DMBT1 expression is down-regulated in breast cancer

Background  

We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle.     

Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia

A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin‐induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser‐capture microdissection. We also investigated the effects of Insig2‐targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC‐1 and MIA PaCa‐2 pancreatic cancer cell lines showed >2‐fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O₂) than under normoxic conditions (21% O₂). Cell proliferation was significantly decreased in SUIT‐2 cells and cell invasion was significantly decreased in SUIT‐2, Capan‐2, and CFPAC‐1 cells after transfection of the Insig2‐targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P < 0.001) and pancreatic intraepithelial neoplasia cells (P = 0.082). In analyses of IDC cells, the levels of Insig2 mRNA expression were significantly higher in late‐stage patients than in early‐stage patients. The present data suggest that Insig2 is associated with the malignant potential of pancreatic cancer under hypoxic conditions. (Cancer Sci 2011; 102: 1137–1143)     

CIP2A expression is increased in prostate cancer

Background

The CIP2A protein is a recently characterized oncoprotein which inhibits protein phosphatase 2A activity. Expression of CIP2A has been detected in several carcinomas, but its expression and significance in prostate cancer has not been examined so far.

Methods

Expression of the CIP2A protein was studied using immunohistochemistry in prostate cancer (n = 59) and in benign prostatic hyperplasia (n = 20) specimens. The CIP2A staining scores were compared with several clinicopathological parameters.

Results

Expression of CIP2A was increased in prostate cancer epithelium as compared with the benign hyperplastic epithelium (p < 0.001). The expression of CIP2A was associated with high Gleason scores (p < 0.001) and among patients treated with radical prostatectomy, CIP2A expression was associated with pre-treatment risk stratification (p = 0.011) and pathological T-class (p = 0.031). No statistically significant association was detected between CIP2A expression and prostate specific antigen concentrations.

Conclusions

Expression of the CIP2A protein is increased in prostate cancer specimens and its expression is associated with poorly differentiated and high-risk tumors.