BRCA1在乳腺肿瘤中的表达及其临床意义

目的探讨乳腺癌易感基因（BRCA1）在乳腺癌和乳腺良性肿瘤中的表达及其临床意义。方法应用ABC免疫组化法检测52例乳腺癌、30例乳腺纤维腺瘤并上皮增生活跃和10例乳腺增生症患者中的BRCA1的表达。结果BRCA1在乳腺癌中的阳性表达率为38％（20／52），在乳腺纤维腺瘤中的阳性表达率为73％（22／30），而10例乳腺增生症患者BRCA1阳性率为90％（9／10）（Χ^2=14．78，P〈0．01），在乳腺癌患者中腋窝有淋巴结转移组的表达率明显低于无淋巴结转移组（Χ^2=15．42，P〈0．01），BRCA1的表达与肿瘤的组织学类型（Χ^2=0．156，P〉0．05）、肿块大小（Χ^2=0．587，P〉0．05）无关。结论BRCA1在乳腺癌的发生发展过程中有重要作用，可能成为临床对乳腺癌诊断和判断预后的一个重要指标，可能对乳腺癌的早期诊断及预防有重要意义。     

雄激素受体在膀胱尿路上皮癌中的表达及其临床意义

目的 观察雄激素受体(AR)在膀胱癌中的表达及其与临床病理特征的关系,探讨其临床意义.方法 采用免疫组织化学SP法检测AR蛋白在123例膀胱尿路上皮癌和18例正常膀胱黏膜中的表达.结果 AR蛋白的阳性表达主要定位于细胞核中,其在膀胱癌组织中阳性表达率为46.3%,在正常膀胱黏膜组织阳性表达率为5.6%,差异有统计学意义(P＜0.05).AR的表达率随着膀胱癌病理分级和临床分期的升高而增高(P＜0.05),而与年龄和性别无明显相关(P＞0.05),有淋巴结转移者AR表达率也显著升高(P＜0.05).结论 AR在膀胱癌组织中有广泛表达,且与膀胱癌的分化和浸润性进展密切相关,提示AR蛋白可能在膀胱癌的发生发展中起重要作用.     

表皮生长因子受体在525例消化系统肿瘤中的表达及其临床意义

目的研究表皮生长因子受体（EGFR）在525例消化系统肿瘤中的表达及其临床意义。方法应用免疫组织化学法检测525例消化系统肿瘤组织中EGFR的表达,分析EGFR表达与患者的性别、年龄、肿瘤的原发部位、肿瘤大小、组织学类型、分化程度、临床TNM分期和淋巴结转移的关系。结果 525例消化系统肿瘤组织中,EGFR阳性率为17.1%,其中男性EGFR阳性率明显高于女性的（P=0.014）;EGFR表达与分化程度呈负相关（P=0.033）,其中低分化的EGFR阳性率明显高于高分化的（P=0.035）;EGFR表达与淋巴结转移呈负相关（P=0.015）;EGFR表达与消化系统肿瘤患者的年龄、肿瘤的原发部位、肿瘤大小、组织学类型和临床TNM分期均无关（P〉0.05）。结论 EGFR表达和消化系统肿瘤的恶性程度有关。     

p75在乳腺肿瘤中的表达

目的 探讨神经牛长因子低亲和力受体p75在乳腺肿瘤中的表达及其意义.方法 采用PV-9000免疫组织化学方法检测101例乳腺疾病患者病灶组织中p75的表达.结果 p75在乳腺肿瘤肌上皮细胞中均有表达,而在乳腺癌中的表达率明显低于纤维腺瘤、小叶增生、导管内乳头状瘤(P＜0.05),各类乳腺痛中的p75表达未见明显差异(P＞0.05).结论 p75可能抑制乳腺肿瘤细胞的增生,诱导瘤细胞的分化.     

直肠癌及其癌旁粘膜中维生素D受体表达的研究

目的探讨直肠癌及其近旁粘膜组织中维生素D受体(VDR)的表达.方法采用免疫组化结合显微光度测量图像分析技术,对21例直肠癌及其近旁粘膜中VDR表达与正常大肠粘膜比较.结果直肠癌组织中VDR表达(2.4±0.7)显著低于正常大肠粘膜;癌旁2 cm粘膜中VDR表达(4.6±0.5)介于癌组织与正常粘膜(6.0±0.6)之间,与2者差异均有显著意义.癌组织中VDR的表达在不同的年龄、性别、Dukes分期、组织学分型、肿瘤生长方式、浸润深度之间差异无显著意义;VDR表达与癌组织分化程度之间有显著联系,高、中、低分化3组VDR表达依次降低且差异有显著意义(P＜0.05).其中癌旁2 cm粘膜DNA异倍体者占57.1%,增殖指数显著高于正常粘膜.结论直肠癌及其近旁粘膜组织中VDR表达下降.癌旁2     

维生素D在妇科肿瘤患者中的表达变化

目的探讨维生素D在妇科肿瘤患者中的表达变化,研究其作用。方法检测62例妇科肿瘤患者（观察组）及62例常规体检的妇女（对照组）的空腹静脉血维生素D含量,并进行比较。结果观察组维生素D的平均水平为（20.54±10.16）ng/mL,明显低于对照组为（49.22±21.76）ng/mL（P〈0.05）。结论在妇科肿瘤患者中维生素D的表达下降,提示维生素D可能对妇科肿瘤的发生发挥一定的作用。     

生长抑素在乳腺癌中的表达及其临床意义

目的 探讨生长抑素（ｓｓｔ）在乳腺癌中诊断和治疗的价值。方法 应用免疫组织化学方法对３０例原发性乳腺癌患者行ｓｓｔ和ＥＲＰＲ的表达。结果 有同侧腋窝淋巴结转移患者１１例,其中８例ｓｓｔ（＋）;无同侧腋窝淋巴结转移者１９例,其中７例ｓｓｔ（＋）,两组差异有显著性（χ＾２＝３．６,Ｐ〈０．０５）。良性乳腺瘤１０例;其中４例ｓｓｔ（＋）与２０例乳腺癌ｓｓｔ（＋）相比,两组差异有非常显著性（χ＾２＝９．２２,Ｐ〈０．０１）。结论 ｓｓｔ对原发性乳腺癌诊断及治疗有一定的潜力。     

雌激素受体-β在膀胱尿路上皮癌中的表达及其临床意义

目的 观察雌激素受体β(ER-β)在膀胱癌中的表达及其与临床病理特征的关系,探讨其临床意义.方法 采用免疫组织化学SP法检测ER-β蛋白在146例膀胱尿路上皮癌和25例正常膀胱黏膜中的表达.结果 ER-β蛋白在膀胱癌组织中阳性表达率为44.5%,在正常膀胱黏膜组织阳性表达率为20.0%,差异有统计学意义(P＜0.05).ER-β的表达率随着膀胱癌病理分级和临床分期的升高而增高(P＜0.05),而且与患者性别明显相关,女性阳性率显著高于男性患者(P＜0.05).结论 ER-β在膀胱癌组织中表达有明显的性别差异,且与膀胱癌的分化和浸润性进展密切相关,提示ER-β蛋白可能在膀胱癌的发生发展中起重要作用.

Abstract：

Objective To investigate the expression of estrogen receptor beta (ER-β) in bladder urothelial carcinoma and to explore its clinical significance.Methods Immunohistochemical SP method was employed to detected the expression of ER-β in bladder cancer tissue ( 146 cases) and the normal controls (25 cases).In addition,clinicopathological data of them were analyzed.Results The positive expression rate of ER-β in bladder cancer tissue was 44.5%,but low positive expression rate (20.0% )was found in normal bladder tissue.The expression of ER-β was markedly associated with tumor pathological grade and clinical stage ( P＜0.05).Moreover,the expression of ER-β was observed more frequently in female (59.6%) than male (37.4%) (P＜0.05 ).Conclusion The sex difference in expression of ER-β is associated with differentiation and invasion in bladder urothelial carcinoma,it implies that ER-β might play important roles in the development and progression of bladder cancer.     

Ki-67在乳腺癌中的表达及其临床意义

目的 研究Ki 67在乳腺癌中的表达与临床病理特征的关系.方法 应用免疫组织化学方法检测120例女性乳腺癌患者中Ki-67、ER、PR、C-erbB-2的表达,分析Ki-67与ER、PR 、C-erbB-2、肿瘤大小、淋巴结转移情况、年龄、月经状况、病理组织学分级等临床病理特征的关系.结果 120例患者乳腺癌组织中Ki-67表达(-)6例(5％);Ki-67表达(+)36例(30％);Ki-67表达(++)31例(25.83％);Ki-67表达(+++)47例(39.17％).Ki-67表达与乳腺癌组织中C-erbB-2表达、肿瘤大小、淋巴结转移情况、患者年龄、月经状况之问差异无统计学意义(P＞0.05);与ER、PR受体表达、肿瘤组织学分级相关(P＜0.05).结论 Ki-67不能作为评估乳腺癌预后和指导临床治疗的重要指标.     

趋化因子受体7在膀胱癌组织中的表达及其临床意义

目的 探讨趋化因子受体7(CXCR7)蛋白在膀胱癌中的表达情况,并分析其与临床生物学行为及复发的关系.方法 选择148例膀胱移行细胞癌标本,30例正常膀胱组织标本:肿瘤标本中非肌层浸润性癌104例,肌层浸润性癌44例;G147例、G2 73例、G3 28例;单发肿瘤89例,多发肿瘤59例;非肌层浸润性癌中未复发40例,复发64例.采用LSAB免疫组织化学方法,检测膀胱癌和正常组织中CXCR7蛋白的表达,并结合临床资料进行分析. 结果正常组织中CXCR7蛋白的表达水平为10.0%(3/30),肿瘤组织为85.1%(126/148);单发及多发肿瘤CXCR7蛋白高表达率分别为49.4%(44/89)和71.2%(42/59),G1、G2、G3膀胱癌CXCR7蛋白高表达阳性率分别为34.0%(16/47)、65.8%(48/73)、78.6%(22/28),差异均有统计学意义(P＜0.01).非肌层浸润性肿瘤和肌层浸润性肿瘤中CXCR7蛋白高表达阳性率为51.9%和72.7%,组间差异有统计学意义(P＜0.05).非肌层浸润性膀胱癌中,复发组与未复发组中CXCR7蛋白高表达阳性率为64.1%和32.5%,差异有统计学意义(P＜0.01).Kaplan-Merier曲线显示,CXCR7蛋白高表达组患者和CXCR7蛋白低表达组患者术后无复发生存率比较,差异有统计学意义(P＜0.01). 结论CXCR7蛋白高表达与膀胱移行细胞癌的恶性程度及预后相关,提示CXCR7与膀胱癌的发生发展存在相关性.

Abstract：

Objective To explore the expression of CXCR7 in bladder cancer and analyze its clinical significance and relationship with bladder cancer recurrence. Methods The expressions of CXCR7 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues were detected by immunohistochemical staining and its clinical significance was then analyzed. Results The expression of CXCR7 protein was higher in bladder cancers than in the adjacent normal tissues (P＜0.01). CXCR7 protein expression rates were 49. 4% and 71.2% in mutifocal tumors and unifocal tumors, while 34.0%, 65.8% and 78. 6% in G1, G2, and G3 tumors, respectively (P＜0. 01). Expression of CXCR7 protein was higher in muscle invasive bladder cancers than in non-muscle invasive bladder cancers (72. 7% versus 51.9% ,P＜0.05). In patients followed up for 2-95 months, CXCR7 protein expression was significantly higher in patients with recurrence than with non-recurrence (64. 1% versus 32.5%, P＜0.01). Kaplan-Meier analysis and the log-rark test showed that the recurrence-free survival was significantly different between the group of lower CXCR7 expression group and the higher expression group (P＜0.01). Conclusions The expression of CXCR7 protein is high in bladder cancer and the analysis of CXCR7 protein expression is potentially valuable in prognostic evaluation of bladder cancers. CXCR7 may play a role in the development of bladder urothelial cell cancer.     

Renal vitamin D receptor expression and vitamin D renoprotection

Therapy to enhance the renoprotective actions of vitamin D receptor (VDR) activation should safely overcome the distinct VDR content along the nephron to effectively control renal calcium reabsorption, control renal klotho levels for the phosphaturic actions of FGF23, and inhibit proteinuria and the activation of the renin-angiotensin system.     

Vitamin D receptor expression in human brain tumors.

Vitamin D receptor (VDR) has important effects not only on physiological processes related to Ca2+ metabolism but also on cell growth and differentiation. VDR is a member of the Steroid-Thyroid Receptors Superfamily (STRS). Work in our and other laboratories has shown that several other members of the STRS (androgen, estrogen, glucocorticoid, and progesterone receptors) are present in astrocytomas and glioblastomas. We now report the finding of VDR-like mRNA in human anaplastic astrocytomas and glioblastomas. VDR mRNA levels, as determined by a method, developed in our laboratory, based on the polymerase chain reaction, are significantly higher in glioblastomas compared to both low and high grade astrocytomas. We discuss the biological and clinical implications of our results.     

Characterization of vitamin D receptor immunoreactivity in human bone cells

The present study examined the expression of the vitamin D receptor (VDR) in adult human bone by immunohistochemical analysis. Antiserum from goats immunized with an N-terminal rat VDR peptide was purified by affinity chromatography. The purified antiserum recognized both endogenous rat and recombinant human VDR in Western blots. The purified antiserum was also able to specifically supershift the recombinant human VDR when analyzed in mobility shift assays. Immunohistochemical analysis of MG-63 cells, a human osteoblastic cell line known to express the VDR, revealed prominent staining over the nuclei of these cells. Immunostaining was greatly attenuated in the presence of an excess of the immunizing peptide. Analysis of bone biopsy samples from 16 normal human subjects immunostained for VDR protein showed strong, immunopositive staining over bone cells, particularly osteoblasts, in keeping with prior studies. In addition, there was significant immunoreactivity observed in nuclei of osteoclasts, lining cells and scattered bone marrow stromal cells of the adult human bone. Results showed that 298 osteoblasts out of 808 (36.9%) examined were immunopositive. It was also observed that 29 osteoclasts out of 125 (23%) contained VDR immunoreactivity. The ability to detect VDR in osteoclasts and stromal cell populations suggests that in addition to regulating osteoblast function, these other cell types are also direct targets of the hormone's action. These results demonstrate the utility of this purified antiserum in detecting the VDR in a variety of molecular techniques and should prove useful in examining receptor expression in various pathological conditions.     

Cyclin D1和p16在肥大乳房腺体组织中的表达及意义

目的：探讨Cyclin D1以及p16蛋白在肥大乳房乳腺组织中的表达及意义。方法：采用免疫组化SP法,检测35例肥大乳房及16例正常体积乳房乳腺组织中cyclinD1及p16蛋白的表达情况及相互联系。结果：35例肥大乳房腺体组织中Cyclin D1蛋白阳性表达率51.4%（18/35）,16例正常体积乳房标本腺体组织中无一例Cyclin D1呈阳性表达（0/16）,两组间比较差异有统计学意义（P〈0.05）。肥大乳房组腺体组织中p16蛋白阴性表达率为77.2%（27/35）,正常体积乳房腺体组织中阴性率为31.3%（5/16）,两组间比较差异有统计学意义（P〈0.05）。在Cyclin D1阳性表达的18例样本中,p16阴性表达者17例,阳性表达者1例,Cyclin D1阴性表达的17例样本中,p16阴性表达者10例,阳性表达者7例。Pearson相关性分析显示,Cyclin D1与p16的表达呈负相关（P〈0.05）。结论：①Cyclin D1在肥大乳房腺体中呈高表达,p16呈低表达,提示其可能参与了肥大乳房的发生和发展;②Cyclin D1和p16在肥大乳房组织中的表达呈负相关,提示二者存在着一定的调控关系。     

MCM2在前列腺癌中的表达及临床意义

目的探讨MCM2在前列腺癌中的表达情况及其意义。方法采用免疫组化法检测MCM2与ki-67在49例前列腺癌（PCa）及20例良性前列腺增生组织（BPH）标本中的表达,计算其标记指数（LI）,同时分析MCM2表达与临床病理间的关系。结杲MCM2与ki-67中位数在前列腺增生组织分别为：0．1、0．08,腺癌细胞中为0．33、0．22;MCM2的u除良性腺上皮外均显著高于ki-67的u值（P〈0．01）,MCM2的表达与肿瘤的分化程度（P〈O．01）和临床分期有显著相关性（P〈0．05）,ki-67只与肿瘤分化相关,MCM2和n67的表达呈正相关（n=0．596,P〈0．01）。结论MCM2蛋白是前列腺癌组织的一种新的可靠增殖标志物,其表达与前列腺癌的发生发展密切相关。     

胰腺癌组织中类肝素酶的表达及其临床意义

目的 探讨类肝素酶1(heparanasel,Hpal)在胰腺癌中的表达及其与胰腺癌发生、发展的关系.方法 采用real-time PCR、Western blot法检测37例胰腺癌组织中Hpal基因和蛋白的表达情况,并分析其与胰腺癌临床病理参数之间的关系.结果 real-time PCR检测结果 显示,Hpal mRNA在胰腺癌中相对表达量为23.53±4.13、在正常胰腺组织中为4.08±2.14、在癌旁组织中为16.93±3.06(P<0.01).Western blot检测结果 显示,Hpal蛋白在正常胰腺组织中的相对表达量为0.36±0.14、在胰腺癌旁组织中为1.21±0.37、在胰腺癌组织中为1.76±0.28(P<0.05).胰腺癌组织中Hpal mRNA与Hpal蛋白表达均高于癌旁组织和正常胰腺组织.胰腺癌组织中Hpal mRNA表达与胰腺癌TNM分期、浸润神经和血管以及淋巴转移有关(P<0.05),但是与组织学分化程度、肿瘤大小无关(P>0.05).结论 胰腺癌组织中Hpal蛋白呈高表达,Hpal蛋白的高表达可能与胰腺癌的发生及发展有关.     

Regulation of parathyroid vitamin D receptor expression by extracellular calcium

Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production. This study began with the hypothesis that the parathyroid cell response to CTR may be modulated by extracellular Ca concentration through an effect on parathyroid cell vitamin D receptor (VDR). In the present study, rat parathyroid glands were incubated in low (0.6 mM) and high (1.5 mM) Ca concentration. The parathyroid VDRmRNA was higher in 1.5 than 0.6 mM Ca. Furthermore, this effect was not observed in incubated slices of kidney cortex and medulla, tissues which also possess both Ca and vitamin D receptors. Experiments were also performed to evaluate the effect of Ca on VDR expression in vivo. Male Wistar rats received intraperitoneal injections of CaCl(2) or a single intramuscular injection of EDTA to obtain 6 h of hypercalcemic (ionized Ca, 1.4 to 1.6 mM) or hypocalcemic (ionized Ca, 0.85 to 0.95 mM) clamp; a third group of rats was used as control. A small dose of CTR was administered to hypercalcemic rats to match the serum CTR levels of hypocalcemic rats. Parathyroid gland VDRmRNA and VDR protein were increased in hypercalcemic rats as compared with hypocalcemic rats. Increasing doses of CTR upregulated VDRmRNA and VDR only in hypercalcemic rats. Additional experiments showed that the decrease in VDR in hypocalcemic rats prevented the inhibitory effect of CTR on PTHmRNA. In conclusion, our study shows that extracellular Ca regulates VDR expression by parathyroid cells independently of CTR and that by this mechanism hypocalcemia may prevent the feedback of CTR on the parathyroids.     

趋化因子受体CXCR4在结肠直肠癌中的表达及意义

目的：研究趋化因子受体CXCR4在结肠直肠癌中的表达及其临床意义。方法：采用RT-PCR法检测8种结肠直肠癌细胞株中CXCR4mRNA表达,应用蛋白印迹法检测细胞株中CXCR4蛋白表达。应用免疫组化染色法、结合组织芯片检测正常结肠直肠黏膜组织54例、结肠直肠癌组织49例中之CXCR4蛋白表达情况,并探讨其与结肠直肠癌临床病理特征的关系。结果：在8种结肠直肠癌细胞株中,CXCR4基因在HT29中表达水平最高。COL0205及SW480次之,HCTll6最低。CXCR4蛋白在结肠直肠癌组织中的表达高于结肠直肠正常黏膜组织,差异具有统计学意义（P=0．000）;在伴发转移的结肠直肠癌组织中,其表达比未发生转移者增强,差异具有统计学意义（P=0．024）。结论：CXCR4表达与结肠直肠癌转移存在密切关系,可能成为结肠直肠癌转移潜在治疗靶点。