乳腺癌复发转移灶与原发灶中ER、PR、HER-2、p53、Ki-67的表达差异

目的 探讨ER、PR、HER-2、p53、Ki-67在乳腺癌复发转移灶与原发灶中的表达差异。方法 采用免疫组化En Vision两步法检测156例乳腺癌原发病灶及对应的复发或转移灶中ER、PR、HER-2、p53及Ki-67的表达,比较各指标的表达差异,并分析发生局部复发或远处转移的乳腺癌临床病理特征及与原发癌相比与各指标表达的一致性。结果 乳腺癌局部复发组和远处转移组与肿瘤分期(P=0.015)、肿瘤直径(P=0.005)差异有显著性;与患者年龄、组织学分级和腋窝淋巴结状态的差异无显著性(P0.05)。复发转移灶ER、PR阳性率比原发灶均有所下降,但差异无显著性;ER、PR表达不一致(分别为18.6%、19.2%),差异有显著性(P=0.024,P=0.043);原发灶与复发转移灶HER-2表达有较高的一致性,表达不一致占5.1%;原发灶与复发转移灶p53的阳性率差异不大,p53表达不一致占14.1%;复发转移灶Ki-67高表达者比原发灶多,Ki-67表达不一致占30.8%,差异有显著性(P0.001)。局部复发组和远处转移组各指标表达不一致的差异无显著性。结论 乳腺癌原发灶与复发转移灶ER、PR和Ki-67表达存在不一致性,HER-2表达有较高一致性。因此,检测乳腺癌复发转移灶中各指标表达对治疗方案选择和预后有重要意义。     

VEGF-C在晚期卵巢癌原发灶和转移灶中的表达比较

目的 研究血管内皮生长因子C（VEGV-C）在晚期卵巢癌原发灶和转移灶中的表达并进行比较,探讨其与晚期卵巢癌发生、发展及预后的关系。方法 应用SP免疫组织化学技术检测52例晚期卵巢癌原发灶以及相应的大网膜转移灶中VEGF-C的表达。结果 VEGF-C在52例卵巢上皮癌中原发灶的高表达率为21％（11／52）,其中透明细胞癌与黏液性癌相比有显著性差异（X^2=6．97,P〈0．01）;在转移灶的高表达阳性率为35％（18／52）,各种组织学类型之间无显著性差异（P〉0．01）。卵巢癌原发灶和转移灶之间VEGF-C表达无明显差异（P〉0．05）。结论 VEGF-C在晚期卵巢癌组织中表达增高,原发灶与转移灶之间无明显差异。     

乳腺癌原发灶与复发/转移灶HER2低表达状态变化

目的探讨乳腺癌原发灶与复发/转移灶HER2阴性患者中HER2低表达状态的变化及临床意义。方法收集河北医科大学第四医院2015年1月至2022年1月出现复发/转移且原发灶肿瘤HER2阴性的259例乳腺癌患者资料及存档切片, 以免疫组织化学(IHC)染色法确定原发灶及复发/转移灶HER2状态, 其中IHC 2+患者均行荧光原位杂交(FISH)法进一步明确HER2状态, 将HER2 IHC 0判定为HER2-0组, IHC 1+及IHC 2+且FISH无扩增患者判定为HER2低表达组, IHC 3+及IHC 2+且FISH扩增为HER2阳性组, 并对患者进行随访。对比乳腺癌原发灶与复发/转移灶中HER2低表达患者HER2状态的变化, 并分析其临床病理特征及预后。结果乳腺癌原发灶与复发/转移灶HER2状态总体一致率60.6%(157/259, κ=0.178), 共102例(102/259, 39.4%)患者原发灶和复发/转移灶HER2状态不一致, 其中56例(56/259, 21.6%)患者原发灶HER2低表达, 复发/转移灶为HER2-0, 37例(37/259, 14.3%)患者原发灶H...     

甲状腺乳头状癌 ALDH1A1表达与淋巴结转移的相关性

目的探讨甲状腺乳头状癌（ PTC）中ALDH1A1的表达情况及与淋巴结转移的相关性。方法收集首都医科大学附属北京同仁医院病理科2006年1月至2013年12月间PTC腺叶切除＋淋巴结清扫标本153例,在HE染色下观察其一般临床病理学特点（肿物直径、双侧、多灶、肿瘤边界、腺叶外浸润）,并采用免疫组织化学染色EnVision法,检测癌及癌旁组织中ALDH1A1的表达情况,分析ALDH1A1表达与淋巴结转移的关系。结果在153例PTC中,84例（54.9％）发生淋巴结内癌转移,126例癌组织高表达ALDH1A1,112例癌旁组织高表达ALDH1A1。通过单因素分析,发现年龄＜45岁、肿物直径＞10 mm、浸润性边缘及癌组织 ALDH1A1高表达与淋巴结转移明显相关（P＜0.05）。而性别、双侧、多灶、腺叶外浸润、癌旁组织ALDH1A1与淋巴结转移无关（P＞0.05）。进一步多因素分析发现浸润性边界和癌组织ALDH1A1高表达是PTC淋巴结转移的独立危险因素（P＜0.05）。在随访的82例PTC中,局部肿瘤复发4例,5年局部复发率为4.88％,包括淋巴结肿瘤复发3例和甲状腺肿瘤复发1例,无远处转移及疾病相关死亡病例。复发病例肿瘤组织ALDH1A1均为高表达。结论 ALDH1 A1在PTC癌组织内高表达与淋巴结转移明显相关,可作为PTC淋巴结转移的有效预测因子,有利于改善PTC患者治疗方法及随访方案。     

乳腺癌中雄激素受体的表达及与雌激素、孕激素受体表达的关系

目的 研究乳腺癌组织中雄激素受体(AR)表达的意义及其与雌激素受体(ER)、孕激素受体(PR)表达的关系.方法 应用免疫组化染色检测200例乳腺癌中AR及ER、PR的表达,并结合相关临床病理指标进行比较分析.结果 乳腺癌组织中有113例表达AR,121例表达ER,109例表达PR.在肿瘤＜2cm者中AR阳性率为66.67％(42/63),肿瘤2～5cm者中AR表达率为55.17％ (64/116),肿瘤＞5cm者AR表达率为33.33％(7/21).组织学分级Ⅰ级者肿瘤AR阳性表达率为67.8％(36/53),组织学分级Ⅱ级及Ⅲ级者肿瘤AR的阳性表达率分别为56.5％(61/108)及36.11％(13/36),Ⅰ级及Ⅲ级间比较差异有统计学意义(P =0.0031);AR表达差异与淋巴转移无相关性.AR在乳腺癌中的表达与ER的表达相关(P＜0.001),而与PR的表达无关(P=0.3280).结论 AR高表达的乳腺癌可能具有较好的预后.     

一种新型转移诱导蛋白AGR2在乳腺癌中的表达及其临床和预后意义

目的 研究转移诱导蛋白AGR2在人乳腺癌中表达和意义及其与患者预后的关系.方法 采用组织芯片,应用免疫组织化学方法检测160例乳腺癌和20例乳腺良性病变组织AGR2表达,以及乳腺癌ERα、PR和HER2表达状况,并用Kaplan-Meier曲线法和Log-rank检验对有随访资料的127例进行与AGR2的相关性分析.结果 乳腺癌AGR2表达量较乳腺良性病变显著性增高(68.3%和25.0%,P＜0.01);AGR2表达与乳腺癌组织学分级呈负相关(P＜0.05),与乳腺癌ERα和PR表达呈正相关(分别为P＜0.05和P＜0.01);Logistic回归模型显示AGR2和TNM分期是ERa阳性乳腺癌淋巴结转移重要的影响因子(均P＜0.01);Kaplan-Meier生存曲线显示ERα阳性乳腺癌患者中,AGR2阳性患者总生存率和无复发生存率均显著低于阴性患者(均P＜0.01),COX比例风险模型分析也证实AGR2蛋白表达是ERα阳性乳腺癌患者独立的预后影响因子(P＜0.01).结论 AGR2表达异常可能参与了乳腺癌的发生、发展过程,该机制可能部分依赖雌激素受体途径发挥其诱导肿瘤转移作用.AGR2可能是一个潜在的分子标记物,对雌激素受体阳性乳腺癌患者的预后评估有一定提示作用.     

Sox2、EpCAM在三阴乳腺癌及其癌症转移灶中的表达与临床意义

目的 检测Sox2、EpCAM在三阴乳腺癌及其癌症转移灶中的表达并探讨其临床意义.方法 选择2015年1月至2016年12月我院收治的30例发生癌症转移的三阴乳腺癌患者,作为观察组.并选取同期的非三阴乳腺癌患者30例作为对照组,对观察组和对照组癌症原发灶及转移灶进行 Sox2、EpCAM的表达分析.结果 观察组30例三阴乳腺癌中,TNM分期越高,Sox2的表达越高,Ⅲ期阳性率显著高于Ⅰ期和Ⅱ期,差异有统计学意义(P<0.05),而EpCAM的表达差异不具有统计学意义(P>0.05);组织学分级越高,Sox2、EpCAM的表达也越高,Ⅲ级阳性率显著高于Ⅰ级和Ⅱ级,差异有统计学意义(P<0.05).Sox2在观察组转移灶的阳性表达率(93.3%)高于原发灶(70.0%),且显著高于对照组(43.3%),差异具有统计学意义(P<0.05);EpCAM 在观察组转移灶中的阳性表达率(86.7%)与原发灶(80.0%)相比,差异无统计学意义(P>0.05),与对照组(53.3%)相比,差异具有统计学意义(P<0.05).结论 在三阴乳腺癌中SOX2、EpCAM蛋白均呈高表达,可作为临床检测三阴乳腺癌的一个参考指标,且在转移灶中显著表达,也可作为癌症转移的辅助诊断指标.     

非小细胞肺癌患者组织原发灶和转移灶中ROS1融合基因的研究

目的：研究晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)原发灶和转移灶ROS1融合基因阳性率,探讨其相关性。方法：收集2013年1月至2015年5月中国人民解放军北京军区总医院、军事医学科学院附属医院、浙江省肿瘤医院、大连大学附属中山医院和山西医学科学院山西大医院原发灶384例,其中配对转移灶246例,统计得出ROS1融合基因阳性率并分析原发灶与转移灶ROS1融合基因的一致性、ROS1融合基因阳性与临床基线资料间的关系。结果：ROS1融合基因阳性率原发灶为2.60%(10/384)。ROS1融合基因阳性率配对原发灶为2.85%(7/246),配对转移灶为1.63%(4/246),配对的246对原发灶、转移灶组织中,转移灶融合基因阳性而对应的原发灶融合基因阴性1例,原发灶融合基因阳性而对应的转移灶融合基因阴性4例,转移灶较原发灶检出ROS1融合基因阳性率高,两者差别有统计学意义(χ2=52.341,P=0.000);转移灶和原发灶ROS1融合基因阳性的一致率好(κ=0.536,P=0.000),通过转移灶判断原发灶融合阳性的情况,敏感性为42.86%(3/7),特异性为99.58%(238/239)。结论：非小细胞肺癌中转移灶可以预测原发灶ROS1融合基因情况,在难以取得原发灶的情况下转移灶可以作为ROS1融合基因测的备选手段。     

结直肠癌肿瘤原发灶与肝脏转移灶中PD-L1表达的差异性

目的探讨结直肠癌肿瘤原发灶与肝脏转移灶中PD-L1表达是否一致。方法收集结直肠癌肝转移病例,选取同时行原发灶与肝脏转移灶切除或活检的标本32例。肿瘤原发灶位于直肠7例,乙状结肠12例,降结肠2例,横结肠2例,升结肠9例。肿瘤病理类型:31例管状腺癌,1例黏液腺癌。采用免疫组化法检测结直肠癌原发灶和肝脏转移灶组织中PD-L1的表达。评估整个切片中的肿瘤区域,计数原发灶肿瘤细胞PD-L1阳性细胞百分比,计数原发灶肿瘤浸润免疫细胞PD-L1阳性细胞百分比。采用同样的方法评估转移灶中PD-L1的表达。结果结直肠癌原发灶肿瘤细胞PD-L1阳性率为9. 4%(3/32),原发灶间质免疫细胞的阳性率为21. 9%(7/32);肝脏转移灶瘤细胞PD-L1阳性率为15. 6%(5/32),转移灶间质免疫细胞PD-L1阳性率34. 4%(11/32)。PD-L1在原发灶肿瘤细胞和肿瘤浸润免疫细胞中的表达率均低于其对应转移灶(P=0. 020、0. 037)。结论结直肠癌原发灶和肝脏转移灶的免疫状态存在差别,转移灶可能存在更强的免疫抑制,为临床开展肿瘤免疫治疗提供一定的参考。     

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.     

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.     

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.     

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.     

纳米水平分子成像与诊疗一体化研究进展与挑战

分子成像能以非侵入性的方式重现活体细胞的生理功能和生物学过程,提高疾病的早期和特异性诊断水平。纳米颗粒/材料具有物理性质可控性高、易于表面修饰、血液循环时间长和可功能化等优点,在疾病诊断与治疗中显示出巨大潜力。但如何阐明纳米材料多功能间的内在联系、解决其代谢及安全性等关键机制难题、实现纳米颗粒/材料多功能性到临床多功能...