尿激酶型纤溶酶原uPA和P27蛋白在乳腺癌中的表达及其意义

目的　探讨正常乳腺组织、良性病变乳腺组织、乳腺癌中uPA和P2 7蛋白的表达水平及其意义。方法　应用免疫组织化学方法对 8例正常乳腺组织、2 4例良性病变乳腺组织及 66例乳腺癌中uPA、P2 7蛋白的表达进行测定。结果　uPA和P2 7蛋白在 66例乳腺癌中的高表达率分别为 5 7.6%、5 3 .0 % ,uPA在乳腺癌中的表达水平明显高于正常和良性病变乳腺组织 (P <0 .0 5 ) ;而P2 7蛋白在乳腺癌的表达水平明显低于正常和良性病变乳腺组织 (P <0 .0 5 )。uPA和P2 7蛋白在乳腺癌中的表达有显著相关性 ,它们与乳腺癌的病理学特征显著相关。结论　P2 7蛋白和uPA的表达水平可能与乳腺癌的发生、发展和预后有关 ,而且对于指导乳腺癌的治疗有一定的临床意义。     

ERK1/2和cyclinD1蛋白在卵巢上皮性肿瘤组织中的表达及其意义

 目的　探讨卵巢上皮性肿瘤组织中细胞外信号调节激酶 (ERK1/ 2 )及细胞周期素D1(cyclinD1)的表达及意义。方法　应用免疫组织化学技术 ,检测 49例卵巢上皮性癌组织 ,2 6例良性卵巢上皮性肿瘤组织及 10例正常卵巢组织中ERK1/ 2和cyclinD1蛋白表达。 结果　ERK1/ 2和cyclinD1在卵巢上皮性癌组织中的表达阳性率显著高于正常卵巢组织和良性卵巢上皮性肿瘤组织 (P <0 .0 1)。Ⅲ～Ⅳ期卵巢癌组织中的ERK1/ 2和cyclinD1蛋白表达水平高于Ⅰ～Ⅱ期卵巢癌 (P <0 .0 5)。ERK1/ 2和cyclinD1蛋白表达阳性率呈明显的正相关 (P <0 .0 5)。结论　ERK 1/ 2和cyclinD1在卵巢上皮性癌发生、发展中起重要作用 ,ERK通过诱导cyclinD1蛋白过表达使卵巢上皮性癌细胞增殖和演进     

DNA修复基因hrad51在乳腺良、恶性病变中的表达及其生物学意义

目的　初步探讨 DNA修复基因 hrad5 1在乳腺组织病变和乳腺癌发生中的生物学意义。方法　应用S- P免疫组化法 ,分别检测了 hrad5 1蛋白在乳腺纤维腺瘤、乳腺导管上皮不典型增生、乳腺癌癌旁正常组织及乳腺癌中的表达情况。结果　 (1) hrad5 1蛋白在乳腺纤维腺瘤、导管上皮不典型增生、乳腺癌癌旁正常组织及乳腺癌中的表达率分别为 4 .0 %、13.6 %和 10 .0 %和 39.2 % ;(2 )乳腺癌中 hrad5 1蛋白的高表达与肿瘤组织分级之间 (P=0 .0 0 0 )、TNM分期之间 (P=0 .0 2 6 )呈正相关 ,与 ER的阳性表达之间 (P=0 .0 35 )呈负相关。结论　 (1) hrad5 1蛋白在不同病变乳腺组织中呈现不同表达 ,在乳腺癌组织中存在高度表达 ;(2 )检测 hrad5 1蛋白的表达情况可望成为评价乳腺癌患者预后的一个新指标     

p21~(WAF1/CIP1)在乳腺癌中的表达及意义

目的　探讨p2 1WAF1/CIP1蛋白在乳腺癌中表达的临床意义。方法　运用免疫组化SP法半定量检测p2 1蛋白在癌旁正常乳腺组织、乳腺癌组织中的表达。结果　p2 1蛋白表达位于细胞核 ,呈棕黄色。在 2 0例癌旁正常乳腺组织中 ,无p2 1蛋白表达。在 69例乳腺癌组织中有 3 0例p2 1蛋白阳性表达。在乳腺癌组织中 ,随组织学分级升高 ,p2 1阳性率下降 (P <0 0 5 ) ,随临床分期升高 ,p2 1阳性率下降 (P <0 0 5 )。有淋巴结转移组p2 1阳性率低于无淋巴结转移组 (P <0 0 5 )。p2 1蛋白阳性表达者术后 5年无瘤生存率高于p2 1蛋白阴性者术后 5年无瘤生存率 (P <0 0 5 )。结论　p2 1蛋白可用来评估乳腺癌细胞分化情况及转移潜能 ,可判断乳腺癌患者预后。     

环氧化酶-2在乳腺浸润癌中的表达及临床意义

 目的　研究环氧化酶 2 (COX 2 )在乳腺浸润癌中的表达情况及其与乳腺癌临床病理特征的关系。方法　应用免疫组织化学 (SP法 )检测 83例乳腺浸润癌 (其中有周围组织浸润 6 2例 ,伴腋淋巴结转移 4 7例 )和 35例癌旁组织中COX 2的表达。结果　COX 2在乳腺浸润癌中的阳性表达率为 73.5 %(6 1/ 83) ,显著高于癌旁组织 (P <0 .0 0 1) ;乳腺浸润癌组织COX 2的表达与临床分期、周围组织浸润和淋巴结转移密切相关 ,(P <0 .0 5 ,P <0 .0 5 ,P <0 .0 0 1) ,与患者年龄和肿瘤大小无明显相关性。结论　COX 2蛋白表达可能在乳腺浸润癌的发生、发展中起重要作用。     

运用原位杂交和二步法技术检测乳腺癌PTTG基因表达

目的　研究PTTG基因在乳腺癌组织中表达的临床意义。方法　应用原位杂交和二步法 ,检测 66例乳腺癌、2 7例乳腺小叶增生及 5 4例乳腺正常组织中PTTGmRNA和PTTG蛋白的表达。结果　PTTGmRNA在乳腺癌、乳腺小叶增生和乳腺正常组织中表达阳性率分别为 71.2 % (4 7/66)、5 1.9% (14 /2 7)和 11.1% (6/5 4) ,而PTTG蛋白表达阳性率分别为 63 .6% (4 2 /66)、48.1% (13 /2 7)和 7.4% (4 /5 4)。乳腺癌、乳腺小叶增生与乳腺正常组织之间的PTTGmRNA及PTTG蛋白阳性率比较均有显著性差异 (P <0 .0 5 ) ;PTTGmRNA的表达与PTTG蛋白表达呈正相关 (P <0 .0 5 ) ,而与淋巴结转移无关 (P >0 .0 5 )。结论　PTTG基因的过度表达可能参与了人乳腺癌的发生发展过程     

间隙连接蛋白Cx43在乳腺癌组织中表达的研究

目的　探讨间隙连接蛋白connexin43 (Cx43 )表达与乳腺癌恶性程度的关系及其生物学意义。方法　应用S -P免疫组织化学方法 ,检测 66例乳腺癌组织和 3 5例良性病变组织中Cx43的表达。结果　Cx43蛋白阳性染色主要位于乳腺癌和乳腺良性病变组织细胞的细胞质和细胞膜上 ,阳性表达率分别为 3 4.8% ( 2 3 /66)和 91.2 % ( 3 2 /3 5 ) ,两者有非常显著性差异 ( χ2 =2 9.3 8,P<0 .0 1) ;Cx43基因表达与肿瘤分化程度呈正相关 (γ =0 .85 2 ,P <0 .0 5 ) ,而与肿瘤恶性进程和转移呈负相关 (γ =-0 .83 1,γ =-0 .73 ,P <0 .0 5 )。结论　Cx43基因表达下调 ,可能是乳腺肿瘤发生发展和恶性进程的 1个重要环节 ,也是乳腺肿瘤的生物学行为特征之一。     

植物相关人肿瘤抗原在乳腺癌中表达的研究

目的　检测一种植物相关人肿瘤抗原在乳腺癌、乳腺良性病变和正常乳腺组织中的表达 ,并探讨其临床意义。方法　采用S P免疫组织化学方法 ,检测该抗原在 5例正常乳腺组织、2 0例乳腺纤维腺瘤和 136例原发性乳腺癌中的表达。结果　植物相关人肿瘤抗原在乳腺正常组织中无表达 ;在乳腺纤维腺瘤中 ,表达阳性率为 2 0 .0 % ,且表达强度较低 ;在乳腺癌组织中 ,该抗原阳性表达率为 85 .3% ,与前两者相比 ,差异有极显著性 (P <0 .0 1) ,其表达水平与乳腺癌的组织学分级 (P <0 .0 5 )、浸润 (P <0 .0 1)和复发 (P <0 .0 5 )密切相关。结论　植物相关人肿瘤抗原在乳腺癌的发生发展过程中可能起重要作用 ,是一种具有潜在乳腺癌诊断价值的肿瘤标志物。     

STS和EST在乳腺癌患者中的表达及临床意义

目的 探讨硫酸酯酶(steroid sulfatase,STS)、雌激素硫酸转移酶(estrogen sulfotransferase,EST)在乳腺癌组织和正常乳腺组织中的表达与临床病理特征的关系,及STS与EST相互之间的关系.方法 选取术前未行放疗、化疗及内分泌治疗的乳腺癌患者82例,取其术后肿瘤组织和距肿瘤边缘＞5 cm的乳腺组织.应用免疫组织化学法,检测STS、EST在乳腺癌组织及正常乳腺组织中的表达,采用卡方检验和spearman法分析其表达及相关性.结果 乳腺癌组织中STS蛋白表达水平高于正常乳腺组织,差异有统计学意义(P=0.000).EST在乳腺癌和正常乳腺组织中的表达差异无统计学意义(P =0.367).在乳腺癌组织中STS与EST的表达水平无差异,两者无相关性(r =0.078,P=0.487).结论 STS、EST的表达与乳腺癌的发生、发展相关.     

Expression and significance of ERK protein in human breast carcinoma

Breast carcinoma is one of the most commonmalignancies affecting women. The etiology andpathogenesis of breast carcinoma remain unclear, butseveral observations suggest a prominent role for themitogen-activated protein kinase signal pathway inthe development of breast carcinoma. Extracellularsignal-regulated kinase pathway is one of theimportant, best characterized and human cancer closerelated pathway among MAPK regulatory network.ERK is the first discovered member of MAPK family.ERK1 an…     

ERK-1和p27在三阴乳腺癌中的表达及意义

目的：检测三阴乳腺癌（TNBC）组织中ERK-1和p27的表达并探讨其意义.方法：采用免疫组织化学SP法检测56例TNBC组织和30例癌旁正常乳腺组织ERK-1和p27的表达情况.结果：TNBC组织中ERK-1和p27表达定位于细胞核,其表达率分别为55.36％ （31/56）和30.36％ （17/56）,分别高于和低于癌旁正常组织（P ＜0.05）;56例TNBC组织中,ERK-1和p27蛋白在组织学分级G3级表达率高于G1＋G2级（P＜0.05）,ERK-1的病理分期Ⅲ期的表达率高于Ⅰ-Ⅱ期（P＜0.05）,ERK-1的表达与淋巴结转移、病理组织类型无关（P＞0.05）,而p27与淋巴结转移有关（P＜0.05）.相关性分析显示,二者之间呈负相关（P＜0.05）.结论：ERK-1和p27在TNBC中分别呈高表达和低表达,提示ERK-1、p27与TNBC的发生、发展和转移密切相关.     

Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro.

BACKGROUND: Chemotherapeutic management of breast cancers is a difficult task as they show significant differences in chemosensitivity. The present study was undertaken to determine the usefulness of the apoptosis-related factors as indicators of tumor sensitivity to 5'-deoxyfluorouridine (5'-DFUR) in breast cancers. METHODS: (1) Forty-six breast cancer patients were randomly assigned to a group in which oral 5'-DFUR (1200 mg/day) was administered for more than 5 days before operation (24 patients) and a control group who received no preoperative chemotherapy (22 patients). Surgical specimens were examined for the frequency of apoptotic cells [apoptotic index (AI)] by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and for the expression of p53, BCL-2 and BAX by immunohistochemical staining. (2) Normal human diploid fetal lung fibroblast, IMR90 and SV40 transformed IMR90 were exposed to 5-FU. Apoptotic cells were detected by flow cytometry and BCL-2 and BAX mRNAs by real-time quantitative RT-PCR analysis. RESULTS: (1) No significant difference in the AIs or in BCL-2 and BAX scores was observed between the 5'-DFUR-treated and control groups. However, in the p53 negative subgroup (n = 36), AI and BAX scores were higher and BCL-2 scores lower in the 5'-DFUR group than in the control group (P = 0.006, 0.008 and 0.050, respectively). (2) The sensitivity of IMR90 was significantly decreased by SV40 transformation and the 5-FU-induced cytotoxicity was mainly due to induction of apoptosis. The BCL-2/BAX mRNA ratio was decreased in response to 5-FU in IMR90. These results correlated with our clinical data. CONCLUSIONS: Preoperative treatment with 5'-DFUR induced apoptosis and changes in BCL-2 and BAX expression in p53 negative breast cancers. p53 status, AI and the BCL-2/BAX ratio may be useful information for the choice of postoperative chemotherapy for breast cancer.     

细胞外信号调节激酶在直肠癌发生发展中的意义

Objective： To study the ERK expression and its significance in the development of human rectal carcinoma. Methods： Samples were obtained from 62 patients with rectal carcinoma, including tumor tissue and adjacent normal rectal tissue. Western blot was used to measure the expression of ERK-1 and ERK-2. S-P immunohistochemical method was used to count the microvessel density （MVD）. Results： ERK-1 and ERK-2 protein levels were increased in rectal carcinoma tissue compared with those in adjacent normal tissues （t = 2.980 and 2.194, P 〈 0.01 and 0.05 respectively）. The MVD was higher in patients with higher ERK-1 and/or ERK-2 protein levels than that in cases with lower ERK-1 and/or ERK-2 levels. Conclusion： Overexpression of ERK-1 and/or ERK-2 may play an important role in the development of human rectal carcinoma, the overexpression can enhance the growth of tumor microvessel and promote the development of human rectal carcinoma.     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.     

Thymidine phosphorylase expression and efficacy of adjuvant doxifluridine in advanced colorectal cancer patients

To clarify the correlation between the expression level of thymidine phosphorylase (TP) and efficacy of doxifluridine (5'-DFUR) and 5-fluorouracil (5-FU), samples from 177 colorectal cancer patients who underwent curative resection were evaluated by immunohistochemical staining using a newly developed monoclonal antibody 1C6-203. Patients were randomly given either oral 5'-DFUR or 5-FU as postoperative adjuvant chemotherapy. In Dukes' C staged colon cancer patients treated with 5'-DFUR, better survival was observed in the high TP patients than the low TP patients (P=0.025 by the log-rank test). The observed 5-year survival rates were 91.2 and 74.8%, respectively. No correlation between TP expression and patient prognosis was detected in the 5-FU group. In Dukes' C stage colon patients with high TP expression, the 5'-DFUR group had slightly better survival than the 5-FU group. These findings suggest that TP may be a chemosensitive marker for 5'-DFUR as postoperative adjuvant chemotherapy for advanced colon cancer patients.     

Long-term outcome of preoperative chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer

We performed a multicenter clinical trial of preoperative chemotherapy for gastric cancer. Patients aged 75 years or less with advanced gastric cancer were enrolled and randomized into the following groups: Group I, which received oral 5'-DFUR (610 mg/m2/day x 10 days or over) preoperatively, and Group II, which received no treatment preoperatively. Patients in both groups also received intravenous MMC 1 and 2 days after surgery and were orally administered 5'-DFUR for two years postoperatively. There were 171 patients (Group I: 91, Group II: 80) enrolled and analyzed, and the 5-year survival rate was 63.4% in Group I and 64.9% in Group II (p = 0.698). Among patients classified as having curability B, the 5-year survival rate of each group was 51.8% and 36.8%, respectively (p = 0.426). However, the 5-year survival rate of patients showing good compliance with oral 5'-DFUR therapy was significantly higher than that of patients with poor compliance (53.3% vs 22.0%, p = 0.010). The pyrimidine nucleoside phosphorylase (PyNPase) activity in gastric carcinoma tissue from Group I was lower than that from Group II, and Group II patients tended to die of hematogeneous metastases. In conclusion, although this clinical trial failed to demonstrate a significant benefit of preoperative chemotherapy because of the low dose of 5'-DFUR, we believe that good compliance with oral anticancer treatment contributes to long-term survival and that 5'-DFUR reduces hematogeneous metastasis of gastric carcinoma.     

High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients

The mitogen-activated protein kinase (MAPK) signaling pathway is known to be activated in triple-negative breast cancer (TNBC). Extracellular signal-related kinase (ERK), a member of the MAPK pathway, promotes cell proliferation, angiogenesis, cell differentiation, and cell survival. To assess the prognostic impact of ERK in TNBC patients, relative quantities of ERK (ERK-2 and pMAPK) and direct targets of the ERK pathway (MAPK/ERK kinase 1, phospho-enriched protein in astrocytes [PEA]-15, phosphorylated (p)PEA-15, tuberous sclerosis protein 2, p70S6 kinase, and p27) were measured using reverse-phase protein arrays in tumor tissue from patients with TNBC (n = 97) and non-TNBC (n = 223). Protein levels in patients with TNBC were correlated with clinical and tumor characteristics and outcome. The median age of patients with TNBC was 55 years (range, 27-86 years). Disease stage was I in 21%, II in 60%, and III in 20% of the patients. In a multivariate analysis, among patients with TNBC, those with ERK-2-overexpressing tumors had a lower overall survival rate than those with low ERK-2-expressing tumors (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.19-6.41). However, high pMAPK levels were associated with a significantly higher relapse-free survival rate (HR, 0.66; 95% CI, 0.46-0.95). In conclusion, ERK-2 and pMAPK are valuable prognostic markers in TNBC. Further studies are justified to elucidate ERK's role in TNBC tumorigenicity and metastasis.     

ERK5在胃癌中的表达及临床意义

目的:分析细胞外信号调节激酶5（ERK5）在胃癌及癌旁正常黏膜组织中的表达情况及其与胃癌临床病理参数的关系,探讨ERK5的临床意义。方法:采用免疫组织化学方法检测80例胃癌组织和35例癌旁正常组织中ERK5的表达,分析ERK5表达与胃癌临床病理参数及预后的相关性。结果:35例癌旁正常组织中,ERK5低表达29例（82.9%）、高表达6例（17.1%）;80例胃癌组织中ERK5低表达51例（63.8%）、高表达29例（36.3%）;两者中ERK5蛋白表达有显著有统计学意差异（P＜0.05）。在80例胃癌组织中,癌组织中ERK5蛋白的表达水平与淋巴结转移和临床分期有关（P＜0.05）,与患者性别、年龄、肿瘤浸润深度和分化程度无明显相关性（均P＞0.05）。生存分析显示,胃癌组织中ERK5高表达的患者总体5年生存率明显低于低表达组。结论:ERK5可能是一个促进肿瘤转移的因子。