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1.
A. G. Douglas-Jones H. Navabi J. M. Morgan B. Jasani 《Virchows Archiv : an international journal of pathology》1997,430(5):373-379
Immunocytochemically detectable MT and p53 have been found more commonly in comedo DCIS of the breast with high-grade cytology.
The aim of this study is to confirm these findings and to investigate the relationship between MT and p53 in a single large
series of cases of DCIS of the breast. To this end, 127 cases of DCIS were classified histologically according to architecture,
cytonuclear differentiation (grade), presence and extent of intraduct necrosis, and using the Van Nuys system. Sections were
immunostained for p53 and MT (E9) using established techniques, and the extent and intensity of staining were assessed semi-quantitively.
The results confirmed that there was generally more MT and p53 positivity in poorly differentiated (grade 3) DCIS with extensive
necrosis and that MT expression was greater in grade 2 lesions than p53 expression. However, overall there was no statistically
significant correlation between p53 and MT staining. The results indicate that MT and p53 overexpression may arise from independent
mechanisms in early breast neoplasia.
Received: 3 July 1996 / Accepted: 5 November 1996 相似文献
2.
The mechanisms associated with metallothionein (MT) gene regulation are complex and poorly understood. Only a modest increase in brain MT expression levels is attained by exposure to metals, MT gene transfection, and MT gene knock-in techniques. Accordingly, in the present study, MT null astrocytes isolated from transgenic mice deficient in MT-I and MT-II genes were introduced as a zero background model of MT expression. MT protein levels were determined by western blot analysis. MT proteins in MT-I and MT-II null astrocytes were undetectable. Transient MT-I gene transfection increased the levels of foreign MT expression in MT-I and MT-II null astrocytes by 2.3-fold above basal levels in wild-type astrocytes. Intracellular Na(2)51CrO(4) efflux and D-[2,3-3H]aspartate uptake were studied as indices of acute methylmercury (MeHg) (5 microM) cytotoxicity. In MT-I and MT-II knockout astrocytes MeHg led to significant (p<0.01) increase in Na(2)51CrO(4) efflux and a significant (p<0.05) decrease in the initial rate (1 min) of D-[2, 3-3H]aspartate uptake compared to MT-I and MT-II knockout controls. Transfection of the MT-I gene in MT-I and MT-II null mice significantly (p<0.01) decreased the effect of MeHg on Na(2)51CrO(4) efflux in MT null, as well as wild-type astrocytes. MT-I gene transfection in MT-I and MT-II null astrocytes reversed the inhibitory effect of MeHg on D-[2,3-3H]aspartate uptake, such that initial rates of uptake in MT-I transfected cells in the presence and absence of MeHg (5 microM) were indistinguishable. These results demonstrate that: (1) astrocytes lacking MTs are more sensitive to MeHg than those with basal MT protein levels, (2) the MT-I gene can be overexpressed in MT-I and MT-II null astrocytes by transient MT-I gene transfection, and (3) that foreign MT expression endows astrocytes with increased resistance to MeHg. 相似文献
3.
金属硫蛋白在食管鳞癌中的表达及其与增殖凋亡的关系 总被引:2,自引:0,他引:2
目的:探讨金属硫蛋白在食管鳞癌中的表达及其与癌细胞增殖、凋亡的关系。方法:采用免疫组化法检测92例食管鳞癌组织中的金属硫蛋白(MT)、增殖细胞核相关抗原(Ki-67抗原)的表达,并用TUNEL法检测细胞凋亡指数。结果:92例食管鳞癌标本中65例MT呈阳性表达,阳性率为70.6%,明显高于正常食管粘膜上皮组织(3/20,P<0.01);MT表达与食管鳞癌患者年龄、性别、浸润深度及病变长度无关,而与组织分化程度、TNM分期、淋巴结转移密切相关,MT与Ki-67抗原表达强度呈正相关,Pearson列联系数=0.227(P<0.05)。随MT表达强度的增加,癌组织凋亡指数逐渐降低。结论:MT表达与食管鳞癌的发生、发展密切相关,MT能促进癌细胞增殖,抑制细胞凋亡,可作为食管鳞癌治疗的新靶点。 相似文献
4.
金属硫蛋白在肝细胞癌中表达的临床意义 总被引:9,自引:0,他引:9
目的 探讨金属硫蛋白(metallothionein,MT)在肝细胞癌(hepatocellular carcinoma,HCC)组织中、癌旁组织和正常肝组织中的表达及其临床意义。方法 对30例HCC病人的癌组织、10例癌旁组织和10例正常肝组织标本进行免疫组化染色,观察MT的表达状况,分析MT在HCC中的表达与癌旁组织、正常肝组织、细胞分化和预后等的关系。结果 正常肝组织有很强而稳定的MT染色;癌旁组织(包括肝硬化结节)有较高的MT着色;癌组织中MT染色很弱,甚至无MT染色。相互比较有显著性差异(P<0.05)。MT在肝细胞癌组织中的表达与生存率之间存在着正相关关系(P<0.05)。结论 MT在正常肝组织、癌旁组织和肝细胞癌组织中的表达呈递减趋势,肝细胞癌组织中MT表达与癌细胞分化无关,而与瘤体组织坏死及肝切除术后病人生存状况相关。 相似文献
5.
Metallothionein in bladder cancer: correlation of overexpression with poor outcome after chemotherapy 总被引:2,自引:0,他引:2
Wülfing C van Ahlen H Eltze E Piechota H Hertle L Schmid KW 《World journal of urology》2007,25(2):199-205
We examined metallothionein (MT) expression in bladder cancer and its relationship to clinicopathologic factors, survival
data, and outcome of chemotherapy. In 97 patients who underwent radical cystectomy for bladder cancer, 34 of whom received
cisplatin-based chemotherapy, MT expression was evaluated immunohistochemically. Results were correlated with histopathologic
data, survival rates, and outcome of chemotherapy. MT overexpresison was present in 33 patients (34.0%): strong in 7 (7.2%)
and focal in 26 (26.8%). Overexpression was an independent prognostic factor and was significantly associated with poor survival.
Patients undergoing chemotherapy showed worse survival if their tumours were MT-positive than if they were MT-negative. MT
overexpression predicts unfavorable survival in bladder cancer patients. In those treated with cisplatin chemotherapy, survival
is significantly poorer if tumours express MT. Our results show that MT overexpression may mediate resistance to alkylating
agents. Therefore, further studies are warranted to define those patients who need a more aggressive therapy. 相似文献
6.
目的探讨诱导金属硫蛋白(MT)在未成熟心肌中的表达对缺血-再灌注未成熟心肌和心肌间质的影响。方法将24只兔(14~21d)按随机数字表法分为4组,每组6只,对照组:腹腔注射蒸馏水0.3ml,24h后取离体心脏行Langendorff灌注;组1、组2和组3在腹腔注射3.6%ZnSO4(1.5ml/kg),分别于注射后12h、24h和48h取离体心脏行Langendorff灌注。测定心肌细胞中MT含量、血流动力学、生化指标,观察心肌超微结构改变。结果组2、组3与对照组、组1比较,MT含量、三磷酸腺苷(ATP)含量、超氧化物歧化酶活性、羟脯氨酸含量、心肌线粒体[Ca2+-ATPase]m、心肌线粒体合成ATP的能力明显增高(P<0.01),心肌含水量、丙二醛含量、心肌肌酸激酶、乳酸脱氢酶漏出率、心肌线粒体Ca2+含量、心肌线粒体[Ca2+]m和内皮素含量明显降低(P<0.01),心肌超微结构损伤明显减轻。结论腹腔注射ZnSO4可诱导心肌MT长时间表达,MT可减轻未成熟心肌和心肌间质的缺血-再灌注损伤。 相似文献
7.
目的 探讨金属硫蛋白(Mr)与离体心脏细胞凋亡和一氧化氮(NO)、一氧化氮合酶(NOS)的关系。方法 Wistar大鼠16只,分为2组:对照组(c),腹腔注射蒸馏水0.5ml24h后取离体心脏灌注HTK心脏保护液,4℃保存3h后建立Langendorff灌注模型,灌注KH液2h;实验组(E)腹腔注射3.6%ZnSO4(1.5ml/ks)24h后取离体心脏,处理方法同C组。测定心肌MT含量、心肌细胞凋亡率、NO、NOS的含量。结果 MT含量E组明显较C组增高(P〈0.05),心肌细胞凋亡率E组明显低于C组(P〈0.01),琼脂糖凝胶电泳检测DNA片段梯E组与C组比较,光密度明显减弱(P〈0.01),E组与C组比较,NO、NOS的含量明显增多(P〈0.01)。MT含量与凋亡细胞率呈负相关(r=-0.96,P〈0.01),与心肌组织中NO含量呈正相关(r=0.97,P〈0.01)。结论 心肌MT可增加心肌中NO、NOS的表达,减少再灌后心肌细胞凋亡的发生。 相似文献
8.
The expression and distribution of metallothionein (MT) in frozen sections of normal and pathological human skin was studied using the monoclonal antibody L2E3 directed against MT derived from human fetal liver. Immunohistochemical staining of normal fetal and adult skin revealed strong reactivity in basal keratinocytes of epidermis and outer hair root sheath, hair matrix cells and the secretory coil, but not the exocrine portion of eccrine glands; myoepithelial cells around apocrine sweat glands were similarly stained. In epidermal hyperplasia, variable numbers of suprabasal keratinocytes were stained, whereas in interface dermatitis, interrupted staining was found in the basal layer. Weak or scattered staining was observed in squamous tumours, whereas basal cell carcinomas did not show consistent staining. The distribution of MT in normal skin was in line with the germinative role of basal keratinocytes and hair matrix cells, whereas its distribution in hyperplastic epidermis was in line with experimental animal data, and reflected the increase in the germinative pool in these conditions. It is concluded that monoclonal antibody L2E3 may serve as a valuable immunohistochemical marker in diagnostic cutaneous pathology since it labels basal keratinocytes selectively, and since it discriminates between eccrine and apocrine sweat glands. 相似文献
9.
目的:探讨人参皂甙Rg1对镉诱导的大鼠睾丸损伤的保护作用及作用机制。方法:30只雄性wistar大鼠随机分为对照组、氯化镉组和Rg1+氯化镉组。氯化镉组大鼠按0.5mg(/kg·d)氯化镉腹腔染毒,Rg1+氯化镉组大鼠在0.5mg(/kg·d)氯化镉腹腔染毒2h前进行按100mg(/kg·d)Rg1灌胃处理,连续14天后将动物处死,分离附睾,测定精子数量和质量。分离睾丸,测定金属硫蛋白(MT)含量,TUNEL法检测睾丸切片凋亡情况。结果:氯化镉引起附睾中精子数量减少,质量降低,金属硫蛋白表达增加,睾丸中精细胞凋亡指数增加,而Rg1可以改善附睾中精子质量和数量,减少精细胞凋亡指数,并进一步上调金属硫蛋白表达。结论:人参皂甙Rg1对镉诱导的大鼠睾丸损伤具有保护作用,机制可能与上调金属硫蛋白表达有关。 相似文献
10.
金属硫蛋白抑制同型半胱氨酸诱导的大鼠血管平滑肌细胞增殖 总被引:4,自引:1,他引:3
目的:研究金属硫蛋白(MT)对同型半胱氨酸(Hcy)诱导大鼠血管平滑肌细胞(vascularsmoothmusclecells,VSMCs)增殖的影响及其作用机制。方法:以[3H]-TdR掺入法测定VSMCs增殖程度,免疫沉淀法测定VSMCs内丝裂素活化蛋白激酶(MAPK)活性,[109Cd]-血红蛋白饱和法测定MT含量,硫代巴比妥酸法测定丙二醛(MDA)含量,NADH氧化法测定乳酸脱氢酶(LDH)漏出量。结果:Hcy(10-6-10-4mmol/L)呈浓度依赖性的刺激培养大鼠VSMCs[3H]-TdR掺入,0.1mmol/LHcy刺激[3H]-TdR掺入比对照组高4.2倍(P<0.01)。Hcy亦呈浓度依赖性地激活VSMCsMAPK活性、增加细胞MDA的生成和LDH的漏出(P均<0.01)。单独MT孵育,对VSMCs的上述指标均无明显影响(P>0.05)。但MT(10-6-10-4mol/L)呈浓度依赖性抑制100μmol/LHcy的促增殖效应(r=0.98,P<0.01)。MT显著抑制Hcy对VSMCs的MAPK活性、MDA生成和LDH漏出的激活作用(均P<0.01)。以0.5mmol/LZnCl2预孵育6h后,VSMCsMT含量比非诱导细胞高5.7倍(P<0.01),这种内源性MT高表达的细胞,显著抵抗Hcy刺激的-TdR掺入和MAPK激活;抑制Hcy的促细胞MDA生成与LDH漏出效应(均P<0.01)。结论:MT能有效抑制Hcy促大鼠VMSCs增殖作用,其机制可能与MT拮抗Hcy对MAPK的激活和其抗氧化作用有关。 相似文献