乳腺癌组织中CD44v6和MMP-2的表达及其与淋巴结转移的关系

目的：检测CD44v6、MMP-2在乳腺浸润性导管癌中的表达情况,探讨它们与淋巴结转移的关系。方法：采用免疫组化SP法检测100例乳腺浸润性导管癌中CD44v6、MMP-2的表达情况。结果：CD44v6蛋白在正常乳腺组织及乳腺浸润性导管癌中的阳性表达率分别为12．5％（5／40）、87％（87／100）,CD44v6在淋巴结转移组中的阳性表达率（56／60）明显高于无淋巴结转移组（P〈0．05）。MMP-2蛋白在正常乳腺组织及乳腺浸润性导管癌中的阳性表达率分别为0（0／40）、94％（94／100）,MMP-2在淋巴结转移组中的阳性表达率（59／60）明显高于无淋巴结转移组（P〈0．05）。结论：CD44v6、MMP-2蛋白在乳腺浸润性导管癌组织高表达,且均与淋巴结转移有关（P〈0．05）,联合检测CD44v6与MMP-2有助于综合判断乳腺浸润性导管癌的恶性程度和转移潜能。     

胃癌及淋巴结转移灶中 CD44v5、 CD44v6 和上皮钙粘素的表达及意义

目的：探讨CD44v6、CD44v6和上皮钙粘素（epithelial cadherin,E-cd)在胃腺癌及淋巴结转移灶中的表达及其意义。方法：应用免疫组化SABC法检测20例正常胃粘膜、20例胃粘膜上皮异形增生组织、185例胃癌原发灶及117例淋巴结转移灶中CD44v5、CD44v6和E－cd表达。结果：CD44v5、CD44v6和E-cd在胃粘膜异型增生的阳性表达率依次为10．0％（2／20）、20．0％A（4／20）和85．0％（17／20）。胃癌原发灶及淋巴结转移灶中其阳性表达率依次分别为43．8％（84／185）、66．5％（123／185）、53．0％（98／185）和71．8％（84／117）、87．2％（102／117）、26．5％（31／117）。三者之间有显著差异（P＜0．01）。CD44v5阳性表达与胃癌生长方式、组织学类型、血管淋巴管内浸润及TNM分期密切相关,而CD44v6遇上述因素在统计学上则无显著性差异（P＞0．05）。E－cd阳性表达与胃癌生长方式、组织学类型及TNM分期显著相关。早期肠型胃癌CD44v6阳性表达率显著高于弥漫性（P＜0．05）。而在进展期胃癌,CD44v5的阳性表达则同弥漫性胃癌显著相关（P＜0．05）,E－cd的阳性表达率下降主要见于弥漫型胃癌。结论：CD44v5、CD44v6和E－cd阳性表达同胃癌分化及生物学行为密切相关,是预测其侵袭转移的价值指标。同时,此结果也支持胃癌两种不同起源的假说。     

胃癌中CA242和CD44v6蛋白的表达及其与临床病理的相关性

目的探讨CA242和CD44v6蛋白在胃癌中的表达及其意义。方法应用免疫组织化学技术检测120例胃癌、30例异型增生和20例正常胃黏膜组织中CA242和CD44v6蛋白表达,结合肿瘤的病理学行为和临床随访资料进行分析。结果在胃癌组织中,CA242和CD44v6阳性率分别为79．2％（95／120）和81．7％（98／120）,均显著高于异型增生和正常胃黏膜组织（P〈0．05）。CA242和CD44v6表达与胃癌浆膜浸润、淋巴结转移和患者预后密切相关（P〈0．05）。结论CA242和CD44v6表达与胃癌发生、转移和患者生存期相关,CA242和CD44v6蛋白表达可作为预测胃癌患者预后的参考指标。     

肿瘤相关蛋白与胃癌淋巴结转移的关系

目的：探讨与胃癌多步骤转移过程相关的蛋白上皮性钙粘素（E-cadhefin,E-Cad）,基质金属蛋白酶-9（metrix metalloproteinase-9,MMP-9）碱性成纤维细胞生长因子（basic Fibroblast Growth factor,bFGF）,和转移相关粘附分子拼接变异体（human matastasis molecule adhesion CD44 splice variant 6,CDd4v6）的表达及其与淋巴结转移的关系。方法：采用免疫组织化学SP方法检测E-Cad,MMP-9,bFGF,CD44、6在87例胃癌组织（其中淋巴结转移67例,无淋巴结转移20例）中的表达,并用多因素Cox比例风险模型分析患者的预后,结果：E-Cad,MMP-9．bFGF,CDd4v6在淋巴结转移胃癌组织中的表达率分别为44．83％、71．26％、72．41％、74．41％,存无淋巴结转移组胃癌组织中的表达率分别为91．67％、48.00％、41.67％、31．82％,各指标在淋巴结转移和无淋巴结转移两组之间均存在显著性差异（P〈0．05）。E-Cad高表达和CDd4v6低表达者生存时间长。结论：E-Cad,MMP-9,bFGF,CDd4v6的表达与胃癌淋巴结转移具有显著的相关性。检测这几种蛋白表达有助于判断胃癌转移的潜能及预后。     

肺癌骨桥蛋白和CD44v6的表达与转移关系的研究

目的：探讨骨桥蛋白（osteopontin，OPN）和粘附分子CD44v6在肺癌组织中的表达及其与肺癌转移的关系。方法：应用免疫组织化学技术（SP）检测57倒肺癌组织中OPN与CD44v6的表达水平，并将结果与30例良性肺部疾病组织中OPN及CD44v6水平相比较。结果：肺癌组织中OPN和CD44v6阳性表达率分别为57．9％（33／57）和54．4％（31／57），显著高于良性肺部疾病（肺部炎性假瘤）组织（P〈0．05），阳性表达率分别为16．7％和10．0％，肺癌组织中OPN与CD44v6的表斌足正相关.Kendall’s tau—b-0.503，P〈0．05；OPN与CD44v6在发生淋巴结转移的肺癌组织中阳性表达率分别达71．1％（27／38）和65．8％（25／38），显著高于无淋巴结转移的肺癌组织中阳性表达率（P〈0．05）。结论：OPN、CD44v6可能参与了肺痛的发生、发展和转移，联合检测它们的表达可作为肺癌生物学行为的一项评估指标。     

OPN、CD44v6及MMP-2在肺鳞癌、腺癌中的表达及其临床意义

背景与目的近年来关于细胞表面黏附分子（CD44）、基质金属蛋白酶（MMP）与肿瘤关系的研究比较多，而对骨桥蛋白（OPN）的研究却很少。本研究的目的是通过研究OPN、CD44v6及MMP-2在肺鳞癌、腺癌中的表达水平，了解它们与肺鳞癌、腺癌生长、浸润及转移的关系。方法采用免疫组化方法，对69例肺鳞癌、腺癌患者手术标本OPN、CD44v6和MMP-2进行检测。结果OPN、CD44v6和MMP-2表达率与患者组织学类型、TNM分期及淋巴结转移有密切关系（P〈0．05），与细胞分化程度则无明显关系（P〉0．05）。OPN与CD44v6、MMP-2的表达均呈正相关，CD44v6与MMP-2表达之间无相关性。结论OPN、CD44v6和MMP-2的表达同肺癌病理类型、分期、淋巴结转移有密切关系，可能作为临床评估肺鳞癌、腺癌进展及预测肿瘤转移潜能的指标。     

Ⅰ-Ⅱ期宫颈癌组织中CD44V6,MMP-2与VEGF-C蛋白的表达与预后的关系

目的探讨CD44V6，MMP-2与VEGF—C蛋白的表达与Ⅰ-Ⅱ期宫颈癌预后的关系。方法采用免疫组织化学方法（EnvisonTM）检测40例Ⅰ-Ⅱ期浸润性宫颈癌CD44V6、MMP．2与VEGF—C蛋白的表达情况。结果盆腔淋巴结转移与浸润宫颈深度≥2／3的患者中，CD44V6，MMP-2，VEGF—C同时过表达率（均为55．6％，5／9）明显高于无淋巴结转移及浸润宫颈深度〈2／3者（均为3．2％，1／31），P〈0．05。CD44V6，MMP-2与VEGF—C同时过表达的患者2年生存率为64．2％，明显低于其他非同时过表达患者（88．4％），P〈0．05。结论CD44V6，MMP-2与VEGF—C蛋白的过表达与Ⅰ-Ⅱ期浸润性宫颈癌浸润转移及预后密切相关。     

粘附因子CD44_S、CD44_V3、CD44_V6在乳腺癌中的表达及临床意义

目的：研究粘附因子CD44s、CD44v3、CD44v6蛋白在乳腺癌组织中的表达及其临床意义。方法：收集60例经根治性切除的乳腺癌标本，应用免疫组化S-P法检测CD44s、CD44v3、CD44v6。蛋白的表达，并分析与临床病理因素之间的相关性。结果：CD44s、CD44v3、CD44v6在乳腺癌中的阳性率分别为78．3％、75．0％、78．3％。CD44s、CD44v6的表达程度与淋巴结转移、临床分期、肿块的大小密切相关（P〈0．05）。CD44v3与乳腺癌的转移、临床分期无明显相关性。三者与患者的年龄均无明显相关性。结论：CD44s和CD44v6蛋白表达与乳腺癌转移、侵袭明显相关，而CD44v3则与之无明显相关性。     

MMP-2和CD44v6蛋白表达与胃癌生物学行为相关性的实验研究

目的探讨胃组织中基质金属蛋白酶-2(MMP-2)和黏附分子CD44拼接变异体V6(CD44v6)基因的表达与胃癌生物学行为的相关性.方法应用免疫组化S-P法,对40例胃癌手术切除标本进行抗人MMP-2和CD44v6单克隆抗体免疫组化染色,检测癌组织、癌旁组织、手术切缘区正常组织各区域MMP-2和CD44v6蛋白表达,并分析二者之间及二者的表达与胃癌临床病理特征之间的关系.结果 MMP-2蛋白表达在癌组织与手术切缘区正常组织、癌组织与癌旁组织之间差异有显著性,癌旁组织与手术切缘区正常组织之间其表达差异无显著性;CD44v6蛋白表达在癌组织与手术切缘区正常组织、癌组织与癌旁组织、癌旁组织与手术切缘区正常组织之间差异均具有显著性.癌组织中MMP-2和 CD44v6蛋白表达与患者性别和年龄无相关性;而与肿瘤分化程度、浸润深度、淋巴结转移、临床TNM分期呈正相关;CD44v6蛋白表达还与肿瘤有无远处转移有关.此两种蛋白表达彼此具有相关性,即同时表达阳性的胃癌病例具有更为恶性的生物学特征.结论 MMP-2和CD44v6在胃癌的发生和侵袭转移中可能起着重要作用,检测MMP-2和CD44v6的表达有望成为判断胃癌病变发展、预测肿瘤转移潜能的客观指标.     

CD44v6在乳腺癌患者化疗前后的表达及意义

背景与目的：CD44是粘附分子家族的成员,与肿瘤的形成及转移相关,尤其是变异型亚型CD44v6更是与多种肿瘤的侵袭和转移密切相关。本文旨在研究乳腺癌患者血、癌组织、淋巴结中CD44v6的表达及化疗对CD44v6表达的影响和意义。方法：用免疫组化方法检测癌组织CD44v6的表达,用流式细胞术检测血和淋巴结中CD44v6的表达。结果：乳腺癌组织中淋巴细胞（t=4.71,P＜0．05）和阳性淋巴结（t=5.11,P＜0．05）的CD44v6的表达与对照组相比显著增高,而患者外周血淋巴细胞CD44v6的表达也有所升高,但无统计学意义（t=0.98,P＞0．05）。乳腺癌细胞CD44v6的表达强阳性,且阳性率100％,而良性乳腺组织呈阴性表达。化疗后癌细胞CD44v6的表达仍是100％,血和淋巴结中淋巴细胞CD44v6的表达有所下降,但无意义,只有癌组织中淋巴细胞CD44v6的表达水平显著下降（t=4.13,P＜0．05）。结论：CD44v6的表达与乳腺癌患者的淋巴结转移和预后密切相关,化疗后癌组织中淋巴细胞CD44v6表达明显降低。     

Effects of cytotoxicity of 2-chloro-2'-deoxyadenosine and 2-bromo-2'-deoxyadenosine on cell growth, clonogenicity, DNA synthesis, and cell cycle kinetics

The cytotoxic effects of the adenosine deaminase resistant analogues 2-bromo-2'-deoxyadenosine (2-BrdAdo) and 2-chloro-2'-deoxyadenosine (2-CldAdo) have been compared with those of deoxyadenosine (dAdo). Like 2-CldAdo, 2-BrdAdo is highly effective in inhibiting the growth of many T-lymphoblastoid, B-lymphoblastoid, and myeloid cell lines in culture. Concentrations required to inhibit growth of CCRF-CEM human T-lymphoblastoid cells by 50% (IC50) are: 2-CldAdo, 0.045 microM; 2-BrdAdo, 0.068 microM; dAdo, 0.9 microM in the presence of 5 microM erythro-9-(2-hydroxy-3-nonyl)adenine. Like dAdo, 2-BrdAdo causes a much greater decrease in DNA synthesis than in RNA and protein synthesis. For each of the nucleosides the concentration required to cause 50% inhibition of DNA synthesis (as measured by thymidine incorporation) in an 18-h exposure is very similar to the IC50 for growth and to the concentration required to decrease viability (clonogenicity) over 18 h by 50% (EC50). A fraction of CCRF-CEM cells (approximately equal to 30%) is resistant to killing by exposure to 2-BrdAdo or 2-CldAdo for 4 h at concentrations 100 times the EC50, but 3% of cells are resistant to exposure for 4 h to a concentration of dAdo 3 times the EC50. Each of the three nucleosides causes accumulation of cells in S phase, the accumulation becoming more marked with longer periods of exposure and with higher concentrations of nucleoside. During exposures for 18-24 h at a concentration of nucleoside near the EC50 most cells accumulate in S, with most in early S, whereas exposure to concentrations greater than EC95 accumulates cells at the G1/S border. This suggests that loss of viability is associated with a blockade of some process specifically occurring at the initiation of S phase. At an optimum dosage schedule, 2-BrdAdo and 2-CldAdo have similar therapeutic effects against L1210 in vivo, both producing over 99% cell kill, but the optimum dosage of 2-CldAdo is lower.     

Expression of heparanase, Mdm2, and erbB2 in ovarian cancer

Ovarian cancer is the most lethal of gynecological malignancies. Yet early diagnosis and prognosis are far from being satisfactory. Degradation of heparan sulfate proteoglycans by heparanase appears to play an important role in the invasiveness of tumor cells through the basement membrane and into the extracellular matrix. Recent cloning of the heparanase gene and generation of monoclonal antibodies against the enzyme permit to examine tumor cell expression of the enzyme. The aim of the present study was to assess heparanase activity and localization in various subtypes of epithelial ovarian cancer in correlation with oncogene expression. Histologically confirmed malignant ovarian tissue from ten women and tissue from 2 benign ovarian tumors and 4 normal ovaries were assessed for heparanase presence, activity and localization, incidence of apoptosis and expression of the oncogenes erbB2 and Mdm2. Heparanase immunohistostaining and activity were present in mucinous carcinomas and were more intense than in endometrioid and in serous carcinomas. The lowest activity was observed in benign ovarian tumors and normal ovaries. In ovarian carcinomas the enzyme was intensely concentrated in the cytoplasm of the cancerous cells. In contrast, in normal ovaries and benign tumors the enzyme was predominantly localized in endothelial cells lining blood capillaries. The rate of apoptosis was considerably higher in mucinous and endometrioid carcinomas, and was lower in serous and primary peritoneal carcinomas. Extremely high concentration of heparanase was often demonstrated in apoptotic cells. Endometrioid and serous carcinomas showed high expression of Mdm2 and erbB2 while mucinous carcinomas showed low expression. In benign ovarian tumors and normal ovaries the expression of both oncoproteins was extremely low. In conclusion ovarian carcinomas demonstrate higher levels of heparanase than benign tumors and normal ovaries suggesting that the enzyme may play an important role in metastatic spread of the cancerous cells. Apoptosis may be a significant part of the mechanism of the enzyme release into the extracellular space. Although heparanase activity seems to play an essential role in tumor progression, expression of oncogenes, such as erbB2 and Mdm2 seems to play the dominant role in the development of ovarian cancer.     

1,1-双(4-氯苯)-2,2,2-三氯乙烷对大鼠神经系统的氧化应激作用

背景与目的：研究1,1-双(4-氯苯)-2,2,2-三氯乙烷（DDT）对大鼠大脑皮层、海马和小脑组织诱导的氧化应激作用。 材料与方法：SD大鼠共24只, 随机分为4组, 即溶剂对照组与低 （20mg/kg）、中 （40mg/kg）、高（80mg/kg）3个DDT剂量组,每组6只,大鼠经口灌胃染毒7 d后断头处死,测定大脑皮层、海马和小脑组织丙二醛（MDA）水平和总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-PX）和谷胱甘肽还原酶(GR)活力。 结果：①与溶剂对照组比较,随着DDT浓度的增加,大鼠大脑皮层、海马和小脑中MDA含量升高,T-SOD活性下降;② 大脑皮层GSH-PX活性在低剂量时升高,在中、高剂量组则显著下降,海马GSH-PX活性随着剂量的增加而显著下降,而小脑GSH-PX活性则在中、高剂量组出现显著下降;③ 海马GR活性在中、高剂量组随着剂量的增加而显著下降,在小脑则只有高剂量组出现了下降,皮层GR活性在各剂量组未观察到明显改变。结论：DDT可以引发神经组织的脂质过氧化反应增强。DDT导致机体组织的氧化损伤可能在动物神经毒性中起重要作用。     

Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study

Growth factors (GF) stimulate cell proliferation through binding to cell membrane receptors and are thought to be involved in cancer risk and survival. We examined how genetic variation in epidermal growth factor (EGF), neuregulin 2 (NRG2), ERBB2 (HER2/neu), fibroblast growth factors 1 and 2 (FGF1 and FGF2) and its receptor 2 (FGFR2), and platelet-derived growth factor B (PDGFB) independently and collectively influence breast cancer risk and survival. We analyzed data from the Breast Cancer Health Disparities Study which includes Hispanic (2,111 cases, 2,597 controls) and non-Hispanic white (1,481 cases, 1,586 controls) women. Adaptive rank-truncated product (ARTP) analysis was conducted to determine gene significance. Odds ratios (OR) and 95 % confidence intervals were obtained from conditional logistic regression models to estimate breast cancer risk and Cox proportional hazard models were used to estimate hazard ratios (HR) of dying from breast cancer. We assessed Native American (NA) ancestry using 104 ancestry informative markers. We observed few significant associations with breast cancer risk overall or by menopausal status other than for FGFR2 rs2981582. This SNP was significantly associated with ER+/PR+ (OR 1.66, 95 % CI 1.37–2.00) and ER+/PR? (OR 1.54, 95 % CI 1.03–2.31) tumors. Multiple SNPs in FGF1, FGF2, and NRG2 significantly interacted with multiple SNPs in EGFR, ERBB2, FGFR2, and PDGFB, suggesting that breast cancer risk is dependent on the collective effects of genetic variants in other GFs. Both FGF1 and ERBB2 significantly influenced overall survival, especially among women with low levels of NA ancestry (P _ARTP = 0.007 and 0.003, respectively). Our findings suggest that genetic variants in growth factors signaling appear to influence breast cancer risk through their combined effects. Genetic variation in ERBB2 and FGF1 appear to be associated with survival after diagnosis with breast cancer.