乳腺癌和癌旁乳腺组织中Notch1基因mRNA及蛋白的表达

目的 检测Notch1基因mRNA及Notch1蛋白在人乳腺癌和癌旁乳腺组织中的表达,分析其临床病理学意义.方法 应用逆转录聚合酶链反应(RT-PCR)方法榆测60例乳腺浸润性导管癌和60例癌旁乳腺组织中Notch1基因mRNA,应用免疫组织化学SP法检测60例乳腺浸润性导管癌、30例导管原位癌及60例癌旁乳腺组织Notch1蛋白的表达,分析Notch1表达水平与乳腺癌临床病理特征的相关性.结果 Notch1基因mRNA在人乳腺浸润性导管癌及癌旁乳腺组织中均有表达.Notch1蛋白在癌旁乳腺组织和导管原位癌中的阳性牢分别为55%(33/60)、70%(21/30),二者差异无统计学意义(P>0.05),在乳腺浸润性导管癌中的阳性率为90%(54/60),明显高于癌旁乳腺组织和导管原位癌的阳性率(P<0.05).乳腺浸润性导管癌Notch1蛋白的高表达与肿瘤的淋巴结转移(P=0.006)、病理学分级(P=0.001)和TNM分期(P=0.022)均呈显著正相关.结论 乳腺浸润性导管癌存在Notch1蛋白的高表达.Notch1蛋白高表达与乳腺癌的恶变演进有关.Notch1基因的表达可能影响乳腺癌的发生、发展.     

锰超氧化物歧化酶在乳腺浸润性导管癌中的表达及临床意义

目的检测锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)在乳腺浸润性导管癌组织及癌旁正常组织中的表达,探讨MnSOD在肿瘤的发生及肿瘤侵袭过程中的作用。方法采用RT-PCR和Western blot法分别对20例乳腺浸润性导管癌组织样本和20例癌旁正常组织样本的MnSOD mRNA及蛋白表达进行检测,以β-actin作为定量参考物,比较其在乳腺癌组织和癌旁正常组织中的表达差异,并结合临床特征淋巴结转移和TNM分期,分析MnSOD在肿瘤不同阶段表达的差异。结果乳腺浸润性导管癌组织MnSOD mRNA的表达值为0.61±0.15,癌旁组织为1.24±0.14,两者比较差异具有统计学意义(P<0.01);MnSOD蛋白在癌组织中表达值为0.40±0.04,癌旁组织为0.75±0.06,两者比较差异具有统计学意义(P<0.01)。乳腺浸润性导管癌中淋巴结转移与非淋巴结转移MnSOD mRNA及蛋白表达无统计学意义(P>0.05)。TNM分期:Ⅰ期4例MnSOD mRNA表达值为0.45±0.15,Ⅱ期9例MnSOD mRNA表达值为0.44±0.15,Ⅲ期7例MnSOD mRNA表达值为0.36±0.07,Ⅱ期与Ⅲ期及Ⅰ期与Ⅲ期的比较差异均有统计学意义(P<0.05);Ⅰ期与Ⅱ期比较差异无统计学意义(P>0.05);Ⅰ～Ⅲ期MnSOD蛋白表达三者相互间比较差异均无统计学意义(P>0.05)。结论乳腺浸润性导管癌组织中Mn-SOD mRNA和蛋白表达明显下降,检测MnSOD的表达可作为临床诊治及判定乳腺浸润性导管癌预后的指标。     

乳腺浸润性导管癌中Livin和MMP-7的表达及临床意义

目的检测凋亡抑制蛋白家族新成员Livin和基质金属蛋白酶-7(matrix metallo proteinase 7,MMP-7)在乳腺浸润性导管癌组织中的表达,探讨两者表达的相关性及其临床意义。方法采用免疫组化SP法检测Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的表达,并分析两者表达的相关性及其与乳腺浸润性导管癌患者临床病理特征的关系。进一步应用Western blot法检测乳腺浸润性导管癌及其相应的癌旁乳腺组织中Livin和MMP-7蛋白的表达水平。结果 Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的阳性率分别为65%vs 10%和73.3%vs 25%,且两者在乳腺浸润性导管癌组织中的阳性率均高于癌旁乳腺组织(P0.05)。统计学分析显示,Livin表达与乳腺浸润性导管癌患者的淋巴结转移和TNM分期具有正相关性(P0.05),MMP-7表达与乳腺浸润性导管癌的淋巴结转移、组织学分级均具有正相关性(P0.05)。Livin与MMP-7表达具有正相关性(r=0.322,P=0.007)。Western blot结果也表明,Livin与MMP-7蛋白在乳腺浸润性导管癌组织中的表达水平均高于癌旁乳腺组织。结论 Livin和MMP-7表达与乳腺浸润性导管癌的转移有关,两者可能具有协同作用促进乳腺浸润性导管癌的发展演进。     

乳腺浸润性导管癌中N-cadherin mRNA及蛋白的表达与预后分析

目的 探讨N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的表达及其临床意义.方法 采用原位杂交技术和免疫组化SP法检测70例乳腺浸润性导管癌中N-cadherin mRNA及蛋白表达,以30例乳腺不典型导管增生为对照组.结果 乳腺浸润性导管癌中N-cadherin mRNA及蛋白阳性率分别为61.4%(43/70)、68.6%(48/70),乳腺不典型导管增生中N-cadherin mRNA及蛋白阳性率分别为3.3%(1/30)、6.7%(2/30),差异有统计学意义(P<0.01);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达与淋巴结转移、TNM分期以及ER、PR表达有关,差异有统计学意义(P均<0.01);与患者年龄、肿瘤大小和组织学分级无关(P均>0.05);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达呈正相关(rs=0.73,P<0.01);N-cadherin mRNA阳性患者生存率明显低于阴性患者,差异有统计学意义(P<0.01).结论 N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的过表达提示其对乳腺癌发生、发展、浸润及转移起重要作用,并提示患者预后不良.     

LDHA对乳腺癌演变的影响及SUMO化修饰

目的 探讨LDHA在乳腺癌中的表达、临床意义及与SUMO1修饰的关系。方法 采用免疫组化和Western blot法检测乳腺癌组织中LDHA蛋白表达,并分析其与临床病理特征的关系。应用数据库预测LDHA表达与患者预后的关系。Co-IP鉴定LDHA分子SUMO化水平,软件筛选SUMO化位点。结果 LDHA在癌旁正常乳腺组织、普通型导管增生、导管不典型增生、导管原位癌和浸润性导管癌组织中的阳性率分别为26.0%、26.8%、31.4%、54.2%、64.3%。LDHA表达与乳腺癌组织学高分级、淋巴结转移、TNM III+IV期、ER阴性相关(P均<0.05),与患者总生存期、无瘤生存期呈负相关(P=0.009,P=0.008)。LDHA与SUMO1相互作用,致使乳腺癌中的SUMO化修饰水平降低。LDHA的SUMO化位点可信度最高的是K284、K59及K14。结论 LDHA高表达提示乳腺癌变、恶性进展及预后不良,同时LDHA蛋白发生SUMO化修饰。     

葡萄糖转运蛋白1在乳腺癌组织中表达的临床意义

目的 探讨葡萄糖转运蛋白1(glucose transporter 1,Glut-1)及其mRNA在正常乳腺组织、乳腺纤维腺病、乳腺纤维腺瘤和乳腺癌中的表达及其意义.方法 收集乳腺组织标本147例,其中乳腺浸润性导管癌92例、纤维腺瘤26例、腺病24例、正常乳腺组织5例,应用免疫组织化学EnVision法、Western blot以及RT-PCR分别定量检测不同病变组织中Glut-1蛋白及其mRNA表达水平.结果 在正常乳腺组织、乳腺腺病以及纤维腺瘤组织中难以检测到Glut-1阳性表达或仅呈轻微胞质着色.在乳腺癌组织中,Glut-1表达强度明显增高(P=0.0002),主要定位于瘤细胞膜,细胞质染色较淡.原发灶及转移灶中央的细胞Glut-1表达明显高于周边癌组织,转移灶Glut-1表达水平明显高于原发灶,浸润癌高于原位癌.Western blot定量分析结果显示,乳腺癌组织中Glut-1表达水平显著高于纤维腺瘤(P=0.001)和腺病(P=0.001),各病变组织间差异有统计学意义(P=0.0002).RT-PCR定量检测分析显示乳腺浸润性导管癌中Glut-1 mRNA的表达明显高于纤维腺瘤(P＜0.05)和腺病(P＜0.05),各病变组织间差异有统计学意义(P=0.0001).结论 乳腺癌组织中葡萄糖转运活性显著增高,Glut-1的表达水平与乳腺肿瘤的恶性程度、肿瘤细胞的浸润与转移密切相关;Glut-1高表达可作为细胞的恶性转化标志,并有望成为乳腺恶性肿瘤早期诊断、判断预后的一种新标记物及治疗的新靶点.     

泛素连接酶hHrd1在人乳腺癌组织表达的意义

目的探讨一种泛素连接酶hHrd1在人乳腺癌发病中的病理意义。方法应用免疫组织化学SP法研究正常人乳腺组织、乳腺增生症、乳腺纤维腺瘤、原发性乳腺癌组织中hHrd1的表达。结果人乳腺癌组织hHrd1蛋白表达水平明显强于正常人乳腺组织、乳腺增生症、乳腺纤维腺瘤。导管内癌（或伴早浸）与浸润性导管癌相比，表达水平低，差异有显著性意义（P〈0．05）。人乳腺浸润性导管癌组织hHrd1表达与肿瘤大小有关（P〈0．05），与组织学分级、淋巴结是否转移无关（P〉0．05）。结论泛素连接酶hHrd1参与人乳腺癌的发生。     

膜联蛋白A2在乳腺癌及乳腺纤维腺瘤中的表达及意义

目的 研究膜联蛋白A2 (Annexin Ⅱ,ANX A2)在乳腺浸润性导管癌和乳腺纤维腺瘤中表达,以探讨其在乳腺癌发生发展中的作用.方法 分别使用免疫组织化学染色(SP)法和逆转录聚合酶链反应(RT-PCR)法检测乳腺浸润性导管癌和乳腺纤维腺瘤中ANX A2的蛋白表达水平和mRNA表达水平,并分析其在不同病理分级、临床分期及有无淋巴结转移的乳腺浸润性导管癌组织中的表达情况.结果 免疫组化结果显示乳腺浸润性导管癌组织中ANX A2表达高于乳腺纤维腺瘤(P＜0.05),RT-PCR结果也显示乳腺浸润性导管癌中ANX A2 mRNA的表达高于乳腺纤维腺瘤(P＜0.05).乳腺癌中ANX A2的表达与年龄、病理分级、临床分期和淋巴结转移呈正相关.结论 乳腺浸润性导管癌中annexinA2表达明显高于乳腺纤维腺瘤,annexinA2可能是乳腺癌的生物学标记物之一,其在乳腺癌的发生发展中可能扮演重要的角色.     

受体酪氨酸激酶EphA7在乳腺癌中的表达及其临床意义

目的观察受体酪氨酸激酶EphA7在乳腺癌和正常乳腺组织中的表达,探讨EphA7蛋白表达的临床意义。方法应用免疫组化En Vision法染色检测乳腺正常细胞系、乳腺癌肿瘤细胞系和150例浸润性导管癌组织中EphA7的表达,分析其表达与临床病理特征的相关性。结果 EphA7蛋白在乳腺癌细胞系和浸润性导管癌中表达丢失,其表达水平与患者年龄(r_s=-0.157,P=0.055)、肿瘤分级(r_s=-0.331,P0.001)呈负相关;与淋巴结转移(r_s=0.245,P=0.002)、TNM分期(r_s=0.217,P=0.008)、HER-2表达(r_s=0.179,P=0.028)呈正相关。结论 EphA7在多数乳腺癌细胞中表达丢失,可能在乳腺癌发生和转移中发挥重要作用。     

泛素特异性加工酶2—69对乳腺癌细胞增殖的影响北大核心CSCD

目的探讨泛素特异性加工酶2—69（USP2—69）在乳腺浸润性导管癌中的表达及意义。方法收集2013至2015年复旦大学附属华山医院24例人乳腺浸润性导管癌组织,分别应用分子杂交技术、Western blot及免疫组织化学法检测其USP2-69mRNA和蛋白水平表达。采用体外人乳腺癌细胞株MCF-7瞬时转染USP2-69质粒,使其过表达USP2-69,检测细胞增殖能力。结果乳腺浸润性导管癌的肿瘤组织中,USP2—69在mRNA及蛋白水平均高表达,与癌旁组织相比差异有统计学意义（P〈0．01）。USP2—69蛋白高表达的组织其Ki-67的蛋白表达也升高,Western blot免疫印迹法检测发现人乳腺浸润性导管癌组织中USP2-69的蛋白表达显著高于癌旁组织。细胞实验中转染USP2-69质粒的MCF-7细胞中cyclin D1较空载组表达增高,p27表达下降。细胞增殖速度明显加快,S期比例明显增高,平板阳性克隆明显增加（P〈0．01）。结论乳腺浸润性导管癌组织中USP2-69表达升高,与促进肿瘤细胞增殖能力密切有关。实验结果为进一步研究调节乳腺癌增殖的分子机制提供重要的实验基础。     

Rates of oxygen consumption and of anaerobic glycolysis in renal cortex and medulla of adult and new-born rats and guinea-pigs

1. Rates of oxygen uptake and of anaerobic glycolysis were estimated in slices from the renal cortex and medulla (a) of adult rats and guinea-pigs, (b) of new-born (1-, 5- and 21-day-old) rats and of guinea-pigs of 1, 12, 21, 24 and 120 hr age.2. In the adult rat, Q(O2) values for the cortex were 12.55 +/- 0.20 (22) and for the medulla: 8.56 +/- 0.17 (22) mul./hr.mg dry weight, while in the new-born rat (24 hr old) they were 10.99 +/- 0.46 (12) and 9.33 +/- 0.18 (9) mul./hr.mg dry weight respectively.3. Values for Q(CO2) (N2) (anaerobic glycolysis) in the 14 hr old new-born rat were in the renal cortex 9.65 +/- 0.35 (5) and in the medulla 7.39 +/- 0.43 (5) mul./hr.mg dry weight; while in the adult they were 2.25 +/- 0.08 (16) and 5.76 +/- 0.14 (16) mul./hr.mg dry weight, respectively.4. In the adult guinea-pig values for Q(CO2) (N2) were of the same order as in the adult rat, though the rate of O(2) uptake was for the cortex 8.12 +/- 0.22 (12) and for the medulla 5.02 +/- 0.23 (11) mul./hr.mg dry weight.5. Though the Q(O2) values in the renal cortex and medulla were smaller in the 1 hr old new-born guinea-pig, they were already increasing in the 12 hr old neonate.6. The results are discussed in the light of enzyme changes occurring during the process of maturation of the nephron as indicated by histochemical observations.     

Modes of reinforcement and gender and culture of experimenter and subject: effects of "alien" and external reinforcement for Japanese and American men and women

In this study, we examined external and "alien" reinforcement (ER and AR. respectively) as a factor in social learning, and studied the combined effects of culture and reinforcement mode. A female (Experiment 1) and a male (Experiment 2) experimenters conducted experimental sessions. Both men and women, who grew up in the same culture as the experimenter, participated and performed the experimental task. A three-way interaction effect of experimenter gender, culture, and reinforcement mode was found on task performance. And the effect was more pronounced for a Japanese experimenter. A female and a male experimenters conducted Experiments 3 and 4, respectively; however participants this time were men and women who grew up in different cultures than the experimenter. Results indicated that the pattern of the subject gender and reinforcement mode interaction effect, when the experimenter was Japanese with American subjects, was exactly opposite to that when the experimenter was American. These experiments showed that AR was as effective for social learning as ER, and that the cultural backgrounds of experimenter and subject influenced AR and ER effectiveness.     

Timing and intensity of early fevers and the development of allergies and asthma

BACKGROUND: Early childhood fevers appear to protect against later allergies and asthma. What is not known is the time in which fevers exert this effect and whether the degree of temperature increase is important. OBJECTIVE: We sought to examine the relationship between the time and degree of early fevers and later allergies and asthma. METHODS: Eight hundred thirty-five children from southeast Michigan were enrolled at birth. Clinic records from their first 2 years were abstracted for episodes of fever. At age 6 to 7 years, children underwent allergy testing. We examined fevers occurring within 6-month intervals in the first 2 years of life and outcomes at age 6 to 7 years. The primary outcome measures were allergic sensitization, asthma, asthma with allergic sensitization, and asthma without allergic sensitization. RESULTS: In the unadjusted analysis each episode of fever between 7 and 12 months of age was associated with a lower odds of allergic sensitization (odds ratio [OR], 0.71; 95% CI, 0.54-0.93) and asthma with allergic sensitization (OR, 0.43; 95% CI, 0.21-0.90) at age 6 to 7 years. Likewise, every 1 degrees C increase in the maximum temperature between 7 and 12 months was associated with a lower odds of allergic sensitization (OR, 0.77; 95% CI, 0.61-0.96) and asthma with allergic sensitization (OR, 0.62; 95% CI, 0.40-0.94). After adjusting for potential confounders, each episode of fever between 7 and 12 months was associated with a lower likelihood of asthma with allergic sensitization (adjusted OR, 0.33; 95% CI, 0.11-0.94) at age 6 to 7 years. CONCLUSIONS: Both the timing and intensity of childhood fevers appear to be important factors in the development of allergies and asthma.     

Association between functional alterations of senescence and senility and disorders of gait and balance

OBJECTIVES:

Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil.

METHODS:

Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale.

RESULTS:

Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores.

CONCLUSIONS:

Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.     

男性乳腺发育症临床病理分析及雌,孕激素受体检测

对１１３例男性乳腺发育症进行临床病理分析。同时检测其中３０例乳腺组织中雌激素受体和孕激素受体分布情况，结果发现两者阳性率分别为８０．０％和８３．３３％。结合文献讨论了男性乳腺发育症的发生与高血清激素浓度及乳腺组织高受体水平的关系。