乳腺癌白介素8基因表达及其临床意义

目的探讨乳腺癌组织中白介素8(interleukin-8,IL-8)基因表达及其临床意义.方法建立实时定量RT-PCR方法,检测122例乳腺肿瘤及其邻近正常乳腺组织中的IL-8 mRNA及内参GAPDH的表达水平,以IL-8 N=(IL-8拷贝数/GAPDH拷贝数)来计算IL-8表达水平,并计算同一患者肿瘤组织与正常组织中IL-8 N比值,定义为T/N比值,分析IL-8基因表达(T/N)与临床病理参数的关系.结果102例乳腺癌组织中IL-8 N明显高于其周围邻近的正常乳腺组织(P＜0.01),而8例乳腺良性肿瘤组织与其相应的正常乳腺组织中IL-8 N水平无统计学差异(P=0.37).乳腺癌组织中IL-8 N及T/N比值明显高于乳腺良性肿瘤,且T/N比值与淋巴结转移呈正相关,而与绝经状态、雌激素受体(ER)及孕激素受体(PR)状态呈负相关.结论乳腺癌组织高表达IL-8,实时定量RT-PCR技术检测乳腺癌组织中IL-8表达水平可作为评价乳腺癌进展及判断预后的指标.     

肺癌中SPARC和TGFβ1的表达及意义

目的 探讨肺癌组织中SPARC和TGFβ1的表达及相互关系。方法 采用原位杂交法检测SPARC mRNA和TGFβ1 mRNA在71例肺癌和30例癌旁正常组织中的表达。结果 （1）SPARC mRNA在肺癌中的阳性表达高于癌旁正常肺组织（P<0.05）,在癌组织中主要表达于间质纤维细胞中,其在肺癌组织中的表达与肺癌的临床分期及淋巴结转移有关（P均<0.05）。（2）TGFβ1 mRNA在肺癌中的阳性表达高于癌旁正常肺组织（P<0.05）,其在肺癌组织中的表达与肿瘤大小、临床分期及淋巴结转移有关（P均<0.05）。（3）SPARC mRNA和TGFβ1 mRNA在肺癌中的表达呈负相关性（r=-0.356,P=0.002）。结论 肺癌组织中SPARC的高表达可以抑制肺癌的进展,而TGFβ1的高表达可促进肺癌的进展,并参与肺癌的转移过程。此二者在肺癌的发生、发展中可能起着重要的作用。     

Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance

BACKGROUND: To investigate the relationship between the expression of glucose-regulated protein94 (GRP94) and GRP78 at the level of mRNA and protein in vivo and in human lung cancer. METHODS: RT-PCR, real-time PCR, immunohistochemistry and/or Western blot were used in 54 cases of lung cancer and corresponding normal lung tissue. RESULTS: The expression pattern of GRP94 and GRP78 was similar. There was a significant overexpression of GRP94 and GRP78 at both mRNA and protein levels in cancer tissues as compared to normal tissues. The relative levels of GRP94 and GRP78 mRNA evaluated by RT-PCR in cancer and normal lung tissue were: GRP94: 3.48+/-2.06 versus 2.01+/-1.83; GRP78: 3.64+/-1.87 versus 2.21+/-1.54; by real-time PCR were: GRP94: 2.89+/-0.64 versus 1.12+/-0.54; GRP78: 2.56+/-0.82 versus 0.96+/-0.42. The relative level of GRP94 and GRP78 protein by Western blot in cancer and normal lung tissue were: GRP94: 3.46+/-1.72 versus 1.81+/-0.92; GRP78: 4.84+/-2.55 versus 1.91+/-1.15, indicating an approximate 2-fold and a 3-fold increase in GRP94 and GRP78 protein in cancer tissue as compared with normal tissue. Immunohistochemistry result for GRP94 and GRP78 in cancer and normal tissue was similar, that is: a stronger stain was observed in cancer tissue (main intensity of staining ++ to +++) compared to normal tissue (main intensity of staining + to ++). All the difference for GRP94 and GRP78 between the two tissues were significant (p<0.05). Furthermore, the overexpression of GRP94 and GRP78 in the cancer tissue correlated with grade of differentiation and stage of tumors. There was stronger expression in poorly differentiated tumors than in well-moderately differentiated tumors (p<0.05). There was also stronger expression in stage III than in stages I and II tumors (p<0.05). No statistically significant differences were found among various pathologic types of tumors. Correlation analysis showed that there is a positive correlation between GRP94 and GRP78. CONCLUSION: The expression pattern of GRP94 and GRP78 was similar in human lung cancer. They both were related with the differentiation and progression of the cancer. The expression at mRNA and protein level may be valuable in evaluating the grade of differentiation and clinical stage of human lung cancer.     

白细胞介素-18mRNA在非小细胞肺癌中的表达及其临床意义

目的:检测IL-18mRNA在非小细胞肺癌及癌组织中的表达,探讨其对非小细胞肺癌发生和发展过程的影响。方法:为非小细胞肺癌患者35例,男24例,女11例,年龄42-76岁,平均56岁,其中鳞癌17例(48.57%),腺癌13例(37.14%),腺鳞癌5例(14.29%)。对照组均来自距离肿瘤边缘2-4cm的正常肺组织。肿瘤直径≥4cm者6例(17.14%);肿瘤直径<4cm者29例(82.86%)。用RT-PCR法检测35例肺癌肿瘤组织细胞内和癌旁正常组织中的IL-18mRNA水平的表达。结果:在35例非小细胞肺癌中IL-18mRNA阳性表达率为100%,与癌旁正常组织比较,肺癌IL-18阳性表达率明显增高,差异有统计学意义(P<0.05)。结论:IL-18mRNA在NSCLC发展过程中发挥重要作用,其表达与患者年龄、性别和肿瘤组织类型无明显相关性,而与病理学分级、肿瘤T分期和有无淋巴结转移相关。     

胰腺癌生长抑素受体报告基因表达与其靶向显像的相关性研究

目的探讨荷胰腺癌裸鼠模型肿瘤组织生长抑素受体(SSTR)报告基因的mRNA表达水平与99mTc-sandostatin显像对肿瘤的靶向诊断价值及二者的相关性。方法建立荷胰腺癌动物模型,对18只荷胰腺癌裸鼠模型行99mTc-sandostatin显像,勾画感兴趣区,计算瘤体与对侧正常组织的放射性比值(T/NT),用RT-PCR方法检测肿瘤组织SSTR1、SSTR2、SSTR5 mRNA的表达水平,对各SSTR亚型表达水平与T/NT比值进行相关性分析。结果13只荷胰腺癌裸鼠肿瘤清晰显影,瘤组织有较高的局灶性放射性浓聚;6 h T/NT比值达2.53±0.84。5只荷胰腺癌裸鼠显像弱阳性或阴性,6 hT/NT比值为1.04±0.06。肿瘤组织有SSTR1、SSTR2、SSTR5 mRNA表达,SSTR1、SSTR2的表达水平与肿瘤显像阳性裸鼠T/NT比值呈正相关,r分别为0.597(P<0.05)和0.807(P<0.01)。结论荷胰腺癌裸鼠肿瘤组织有SSTR表达,SSTR2尤为显著9。9mTc-sandostatin受体显像对荷胰腺癌动物模型有很好的靶向诊断价值;肿瘤99mTc-sandostatin摄取程度同SSTR1、SSTR2表达水平正相关。     

蛋白激酶ARIα亚单位与肺癌临床病理特征的相关性研究

目的　探讨蛋白激酶A(PKA)RIαmRNA表达与肺癌临床病理特征的相关性。方法　采用逆转录 聚合酶链反应 (RT PCR)的方法 ,检测 5 4例肺癌患者癌组织及相应远端正常组织中PKARIαmRNA的表达水平。结果　 (1)PKARIαmRNA在肺癌组织中的表达 (6 6 .7% )明显高于相应远端正常组织 (2 0 .4 % ,P <0 .0 1)。 (2 )PKARIαmRNA表达与肺癌TNM分期明显相关 (P <0 .0 1) ,临床分期级别越高 ,PKARIαmRNA表达越高。 (3)淋巴结转移阳性者的PKARIαmRNA表达水平 ,明显高于淋巴结转移阴性者 (P <0 .0 1)。 (4 )PKARIαmRNA表达与肿瘤组织学类型、分化及肿瘤大小无相关性(P >0 .0 5 )。结论　PKARIαmRNA在肺癌组织中过表达 ,提示PKARIαmRNA在肺癌的发生、发展、转移和预后中起重要作用     

Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung.

Matrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2 and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal lung epithelial cells to gain an insight into the function of these MMPs in squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2 and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue from the same patients by immunohistology and gelatin zymography. The majority of tumor cells were positive for MMP-1 (mean +/- SD: 67.3 +/- 26.7%) and MMP-9 (64.7 +/- 22.8%), whereas a significantly lower percentage of normal bronchoepithelial cells (47.3 +/- 25.4 and 40.3 +/- 24.2%, respectively; p < 0.01) and fibroblasts located in the tumor-surrounding tissue (39.7 +/- 14.3 and 38.1 +/- 24.1%, respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any immunoreactivity for MMP-2 (4.4 +/- 6.7%), whereas a higher percentage of fibroblasts tested positive for this enzyme (8.6 +/- 13.1%; p < 0.01). Using gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and further activation in the tumor tissue may be involved in the high invasive and metastatic potential of squamous cell carcinomas of the lung. Comparing the results from immunohistology and zymography can give indications for distribution and activity of proteinases, especially certain MMPs such as MMP-2.     

环氧化酶-2在肺癌组织中的表达及其临床意义

目的　探讨环氧化酶 2 (COX 2 )在肺癌组织中的表达及其临床意义。方法　以 β actin基因为参照 ,采用逆转录聚合酶链反应 (RT PCR)技术 ,检测 41例肺癌组织及相应的癌旁组织、5例远离肿瘤的正常肺组织中COX 2mRNA的表达 ;同时用免疫组化S P法检测COX 2蛋白的表达。结果　COX 2mRNA在肺癌组织中的表达率 ( 63 .4% )显著增高 ;相应的癌旁组织表达率也明显增高 ,而在正常肺组织中不表达。癌组织与癌旁组织、正常肺组织的COX 2mRNA表达率相互比较 ,均有显著性差异 (P <0 .0 5 )。免疫组织化学检测显示 ,5 8.5 % ( 2 4/ 41)的肺癌组织COX 2蛋白呈阳性表达。COX 2蛋白的表达与肺癌的临床分期、淋巴结转移、肿瘤大小无关 (P >0 .0 5 )。结论　肺癌组织COX 2mRNA和COX 2蛋白表达率在大多数肺癌组织中明显增高 ,在癌旁病变中也相应增高 ,COX 2的激活发生在肺癌形成的较早时期 ,在肺癌发生发展中具有重要作用