CD15抗原和bcl-2基因蛋白在甲状腺癌中的表达及相关性研究

目的 研究甲状腺癌组织中ＣＤ１５抗原和ｂｃｌ－２基因蛋白的表达与肿瘤发生和转移的关系,并探讨ＣＤ１５与ｂｃｌ－２基因蛋白表达的关系。方法 应用微波－ＬＳＡＢ免疫组织化学法检测５０例甲状腺癌、４５例甲状腺腺瘤和２０例癌旁正常甲状腺组织中ＣＤ１５和ｂｃｌ－２基因蛋白表达。结果 在甲状腺癌组织中ＣＤ１５和ｂｃｌ－２基因蛋白表达阳性率分别为６８．０％和４６．０％,均显著高于甲状腺腺瘤和癌旁正常甲状腺组织（     

OVER-EXPRESSION OF METALLOTHIONEIN AND DRUG-RESISTANCE IN BLADDER CANCER

Metallothionein (MT) in tumor cells has been implicated as one of the factors involved in mechanisms of resistance to anti-cancer drugs, including cis-diaminedichroloplatinum (CDDP) and adriamycin (ADM). The relationship between the expression of MT and chemotherapy with anti-cancer drugs was studied in CDDP- and ADM-resistant human bladder cancer cell lines and tissue samples from clinical cases. In drug-resistant cell lines (T-24/ADM, CI-7/CDDP) established in our laboratory, MT expression was studied by immunohistochemistry using the avidin-biotin peroxidase complex (ABC) method and radioimmunoassay (RIA), using anti-MT antibody. In addition, other potentfal mechanisms of drug resistance, such as P-glycoprotein expression were examined and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione-S-transferase (GST) determined in these cell lines. The results of these investigations demonstrate that the expression of MT in resistant cell lines increased 2.1- and 2.5-fold when compared with parent cell lines (CI-7, T-24). GSH, GSSG and GST levels were unchanged and P-glycoprotein was not over-expressed. A total of 120 tissue samples from 35 clinical cases of bladder cancer, before and after chemotherapy, were stained for MT which was detected in 10 of the 35 cases before chemotherapy. The incidence of MT expression was significantly higher (p less than 0.05) in cases with lower pathological tumor grades. By analyzing the MT staining after chemotherapy in the cases whose MT staining was negative before chemotherapy, it was found that cases receiving continuous administration (intravesical chemotherapy or peroral chemotherapy) showed a higher incidence (9/13) of positive staining for MT, than patients receiving intermittent administration (intravenous chemotherapy) (1/8), (p less than 0.05). These results demonstrate that: 1) a correlation exists between MT expression and tumor differentiation and 2) repetitive and continuous administration of anti-cancer drugs results in increased MT expression in bladder cancer cells. MT expression may therefore be one of the mechanisms by which urothelial tumors acquire resistance to anti-cancer drugs.     

凋亡相关基因bcl-2和bax在胆管癌组织中表达的意义

目的　探讨细胞凋亡抑制基因ｂｃｌ－ ２ 和凋亡促进基因ｂａｘ 在胆管癌组织中的表达。方法　应用免疫组化方法对２０ 例胆管癌（ＣＨＣ）和７例先天性胆总管囊肿（ＣＣＣ）组织中ｂｃｌ－ ２和ｂａｘ 蛋白进行检测。结果　２０例ＣＨＣ中有１例ｂｃｌ－ ２ 蛋白表达阳性（５％ ）,７例ＣＣＣ中ｂｃｌ－ ２均表达阴性。２０例ＣＨＣ中有１１ 例ｂａｘ 蛋白表达阳性（５５％ ）,７例ＣＣＣ中仅１ 例表达阳性（１４．２９％ ）,两组间差异有显著意义（Ｐ＜ ０．０１）。结论　ｂｃｌ－ ２ 和ｂａｘ 蛋白的改变在胆管癌发生发展过程中不起重要作用。     

乳腺癌基质金属蛋白酶的表达及其意义

目的 研究基质金属蛋白酶（ＭＭＰｓ）与乳腺癌的关系。方法 采用文献回顾的方法对基质金属蛋白酶在乳腺癌中的表达及其意义加以综述。结果 正常状态下，人体内基质金属蛋白酶与其组织抑制剂保持一种平衡状态，而在体外及体内的多项研究中发现，在乳腺癌中多种基质金属蛋白酶有增强的表达。结论 乳腺癌的生长，浸润及转移与基质金属蛋白酶的表达及其抑制剂的关系密切。基质金属蛋白酶可能为一个新的有价值的乳腺癌预后指标，基质     

肝细胞肝癌中5-LOX的表达及其与bcl-2和bax表达的关系

目的研究肝细胞癌（HCC）中5-脂氧合酶（5-LOX）的表达与bcl-2和bax表达的关系及其可能机制。方法检测48例HCC癌组织及其癌旁组织,应用RT-PCR和免疫组织化学S-P法检测5-LOX、bcl-2和bax的表达情况。结果在癌、癌旁组织中5-LOX、bcl-2和bax基因mRNA表达分别是30/48、33/48、24/48和12/48、9/48、36/48,与癌旁组织比较,差异有显著性（P〈0.05）。HCC中5-LOX蛋白阳性率为56.3%,与bcl-2蛋白的表达呈显著正相关（r=0.447,P〈0.01）,但与bax蛋白表达呈显著负相关（r=-0.567,P〈0.01）。结论5-LOX与肝细胞肝癌的发生、发展关系密切;其机制可能是通过上调bcl-2及同时下调bax等凋亡相关调节因子表达水平有关。     

瘢痕Bcl-2基因与细胞增殖和凋亡的关系

目的:探讨增生性瘢痕成纤维细胞Bcl-2基因表达水平与细胞增殖活性及凋亡程度的关系。方法:用原位杂交、免疫组化染色ABC法,对79例增生性瘢痕组织分别检测Bcl-2mRNA、Bcl-2蛋白和增殖细胞核抗原的表达,并用TUNEL法作原位细胞凋亡检测。结果:75例（94.9％）表达Bcl-2mRNA,70例（88.6％）表达Bcl-2蛋白,两者表达水平呈正相关（rs=0.989,P<0.01）;随成纤维细胞Bcl-2蛋白表达水平升高其增殖活性相应增加,而凋亡相应减少,Bcl-2蛋白+++组与++组（P<0.05）及前两组分别与-组和+组间（P<0.01）两项指标差异均有显著性。结论:增生性瘢痕中成纤维细胞Bcl-2基因高表达可抑制其凋亡,可能由此引起的细胞凋亡减少与其他基因异常所致的细胞过度增殖共同导致瘢痕的形成。     

大肠癌bcl-2基因表达和重排的研究

应用ＡＢＣ免疫组化及半巢式ＰＣＲ法分别对６４例大肠癌中ｂｃｌ－２的蛋白表达及重排进行了检测。结果：ｂｃｌ－２基因异常表达与重排在肠肠癌早期即已出现,随着病程演变,发生率显著增加;ｂｃｌ－２基因的重排在有淋巴结转移者亦明显多于无淋巴结转移者。两法联合应用相比较,以重排列能反映大肠癌分子特性。本提示：ｂｃｌ－２基因参与大肠癌发生发展过程的调节,并在大肠癌细胞的增殖、进展及转移中起重要作用;研究大肠癌ｂ     

胆囊病变时bcl-2和p16蛋白产物的表达和意义

以２５例胆囊粘膜异型增生和４０例胆囊腺癌标本用免疫组化方法观察ｂｃｌ－２和ｐ１６蛋白的表达,并与正常胆囊粘膜比较。结果;在正常胆囊粘膜中均未ｂｃｌ－２和ｐ１６表达,而胆囊粘膜上皮导型增生及胆囊腺癌组织中,两者的表达阳性率较正常组织明显增高,且ｂｃｌ－２和ｐ１６蛋白的阳笥率随着异型增生程度的增高而增加;ｐ１６的表达还与胆囊腺癌之浸润程度及淋巴结转移有关。     

VEGF-C和VEGF-D在胰腺癌中表达及其意义

目的 探讨VEGF-C和VEGF-D在胰腺癌中表达及其与胰腺癌临床病理学特征之间的关系.方法 运用免疫组织化学(SP法)检测30例胰腺癌、癌旁组织、正常胰腺组织中VEGF-C、VEGF-D蛋白表达,且比较VEGF-C、VEGF-D蛋白表达与临床病理等因素之间的相关性.结果 VEGF-C、VEGF-D蛋白在胰腺癌中表达分别为70%(21/30)、73%(22/30)且在胰腺癌、癌旁组织、正常组织表达呈下降趋势.VEGF-C、VEGF-D表达与淋巴转移、临床病理分期呈正相关性(P＜0.05),与胰腺癌组织学分化呈负相关(P＜0.001).结论 VEGF-C、VEGF-D与胰腺癌发生、发展密切相关,与胰腺癌的临床分期、组织分化、以及淋巴转移密切相关,VEGF-C、VEGF-D有望成为胰腺癌抗淋巴道转移的治疗的靶蛋白.     

乳腺癌中bcl-2蛋白表达的意义

为探讨抑凋亡基因ｂｃｌ－２蛋白表达在乳腺癌中的意义,应用免疫组织化学的方法,对１２５例浸润性乳腺癌患者的石蜡包埋组织切片中ｂｃｌ－２,雌激素受体,孕激素受体及ｐ＾５３基因的表达产物进行检测。结果：ｂｃｌ－２蛋白在浸润性导管癌中的表达为６３．３％,而在浸润性小叶癌中为８８．９％,二者间菜显著性间谍;在浸润性导管癌中,ｂｃｌ－２蛋白的表达与原发癌大小及肿瘤分级呈负相关,与ＥＲ,ＰＲ的表达呈正相关,与ｐ     

THE MOLECULAR CHARACTERISTICS OF BLADDER CANCER IN YOUNG PATIENTS

Purpose

The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods.

Materials and Methods

We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohitochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y.

Results

Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical abberations (mosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer.

Conclusions

These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.     

IMMUNE REACTIONS IN PATIENTS WITH BLADDER AND PROSTATIC CANCER1

Although there are many reports of cellular immune reactions in bladder and prostatic carcinoma patients, few have demonstrated the presence of humoral reactivity. The use of microtechniques, especially the enzyme-linked immunosorbent assay (ELISA), has made sequential studies possible on patients with early or small tumours. Using this assay, the presence of serum antibodies has been demonstrated in both bladder and prostate patients, the specificities of these reactions being checked against a battery of different tumours and normal tissues. In many of the patients, with low or transient antibody levels, the presence of circulating immune complexes was shown by the Raji cell assay and analysed by double counter-current immunoelectrophoresis (DCIE). The content of these complexes appeared to be either antibody and tumour antigen or antibody and antiimmunoglobulin. In a small series of cryosurgically treated prostatic carcinoma patients, the course of these antibodies was monitored over several weeks, and the fluctuations in antibody levels were related to the presence of these different types of complexes.     

肝癌及癌旁组织中p16的表达及其临床意义

目的 探讨抑癌基因p16在肝癌及癌旁中的表达及意义。方法 应用免疫组化方法对50例肝细胞癌（HCC）及癌旁肝硬化组织（44例）手术切除石蜡包埋标本进行p16基因蛋白表达的测定，结合临床病理指标（Child分级、肿瘤大小、Edmondson分级、转移及生存期）进行分析。结果 p16基因在HCC中的阳性表达48％（24／50），癌旁91％（40／44）。p16基因表达与HCC的分化程度密切相关（p=0.014），在分化Ⅰ-Ⅱ级中P16阳性率59％（19／32）明显高于Ⅲ-Ⅳ级的27.8%（5／18）。结论 p16基因在HCC的发生及分化中起重要的调控作用，且P16的失活可能发生在HCC的早期。     

胆囊癌组织中p21、p53及bcl-2癌基因蛋白的表达及意义

为探讨胆囊良恶性病变组织中ｐ２１,ｐ５３及ｂｃｌ－２癌基因蛋白的表达及其与胆囊癌预后的关系,以及在胆囊良恶性病变的鉴别诊断中的作用,采用免疫组织化学ＡＢＣ法,分别测定了４０例胆囊癌及８例胆囊腺瘤型息肉组织中ｐ２１,ｐ５３及ｂｃｌ－２癌基因蛋白的表达情况。结果;胆囊癌组织中ｐ２１,ｐ５３及ｂｃｌ－２癌基因蛋白表达阳性率分别为５２．５％,５２．５％和７０．０％,在胆囊腺瘤型息肉中３者分别为０％,０％和