miR-133通过Notch1信号通路调控BCAR4对乳腺癌迁移和侵袭的影响

目的:探讨微小核糖核酸-133(miR-133)调控乳腺癌雌激素耐受基因4(breast cancer anti-estrogen resistance4,BCAR4)对乳腺癌细胞迁移和侵袭的影响及其机制.方法:采集2006年1至12月在郑州大学附属肿瘤医院接受手术切除治疗的80例乳腺癌患者的乳腺癌和相应癌旁组织.RT-PCR检测乳腺癌和癌旁组织BCAR4和miR-133的表达;双荧光素酶检测BCAR4和miR-133之间的关联;划痕实验和Transwell实验分别检测沉默BCAR4或沉默BCAR4和miR-133后乳腺癌MCF-7细胞的迁移和侵袭能力;Western blotting检测Notch1信号通路相关蛋白的表达;裸鼠皮下成瘤实验检测沉默BCAR4对MCF-7细胞成瘤能力的影响;生物统计学分析BCAR4表达和乳腺癌患者临床病理参数及生存率的关系.结果:乳腺癌组织中BCAR4表达显著高于癌旁组织(P＜0.05);双荧光素酶实验显示BCAR4可以调控miR-133的表达;沉默BCAR4表达可以抑制乳腺癌MCF-7细胞的迁移和侵袭;沉默miR-133和BCAR4表达的MCF-7细胞的迁移率和穿膜细胞数显著高于仅沉默BCAR4表达的MCF-7细胞[迁移率(92.31±8.64)％ vs(52.61±5.12)％,P＜0.05;穿膜细胞数:(171.38±12.61) vs (28.54±3.29),P＜0.01],抑制miR-133可以逆转BCAR4抑制乳腺癌MCF-7细胞迁移、侵袭能力;沉默BCAR4组裸鼠成瘤的体积和质量都显著减小;沉默BCAR4的MCF-7细胞的Notch1通路相关蛋白表达水平明显下调;BCAR4表达与乳腺癌的病理分期及淋巴结转移显著相关,BCAR4高表达患者生存率较BCAR4低表达患者低.结论:乳腺癌MCF-7细胞的侵袭和迁移受到BCAR4和miR-133的双重调控,miR-133可能通过Notch1信号通路调节BCAR4对乳腺癌细胞迁移和侵袭的影响,可为乳腺癌分子靶向治疗及乳腺癌耐药机制的研究提供思路.     

BCAR1基因与乳腺癌抗雌激素药物耐药的相关研究

乳腺癌抗雌激素药物耐药是导致雌激素受体阳性患者内分泌治疗失败的重要原因之一。BCAR1／p130Cas蛋白能在活体外诱导雌激素依赖性乳腺癌细胞对抗雌激素药物产生耐药,是内分泌治疗的重要耐药因子,其诱导机制尚不能确定。但研究表明检测BCAR1／p130Cas蛋白表达水平可以提示乳腺癌临床内分泌治疗的效果。     

乳腺癌组织中BCAR1 p130Cas 蛋白的表达及其临床意义*

目的:探讨BCAR1/p 130Cas蛋白在乳腺癌组织中的表达及其与乳腺癌内分泌治疗耐药及预后的关系。方法:选择ER阳性且经过规范化内分泌治疗和随访5 年资料完整的乳腺癌患者67例，应用免疫组化方法检测其BCAR1/p 130Cas蛋白表达情况，回顾性分析BCAR1/p 130Cas蛋白表达与乳腺癌的临床生物学特征及预后的关系。结果:在发生局部复发或远位转移的29例患者中，25例呈现BCAR1/p 130Cas蛋白高表达，占86.2% ，无复发转移的38例中，BCAR1/p 130Cas 蛋白高表达仅为21.1% ，两组差异显著（χ2=27.935，P=0.000）；乳腺癌组织中BCAR1/p130Cas蛋白表达与高组织学分级（r=0.270，P=0.027）、C-erbB-2 蛋白高表达（r=0.492，P=0.000）以及绝经状况（χ2=13.77，P=0.003）呈现正相关；与肿瘤大小（P=0.548）、病理类型（P=0.177）、淋巴结状况（P=0.720）、TNM分期（P=0.524）无统计学差异（P>0.05）。 结论:BCAR1/p 130Cas蛋白的表达水平与肿瘤的侵袭性显著相关，BCAR1/p 130Cas蛋白的表达水平越高肿瘤的恶性程度越高，所以BCAR1/p 130Cas蛋白高表达患者的复发、转移风险增加；BCAR1/p130Cas蛋白高表达与三苯氧胺治疗耐药密切相关；芳香化酶抑制剂是绝经后ER阳性乳腺癌患者内分泌治疗的最佳选择。BCAR1/p 130Cas蛋白的表达水平和腋淋巴结转移状况、肿瘤大小、病理类型、TNM分期无关。因此认为，BCAR1/p 130Cas蛋白可以作为独立判定乳腺癌预后的一个重要参数，为监测乳腺癌的转移提供了一个有价值的指标，有助于乳腺癌复发转移的诊断及治疗。      

视网膜毛细血管瘤合并肾细胞癌的von Hippel-Lindau病

目的重视并提高对von Hippel-Lindau（VHL）病的诊治水平.方法回顾性分析2例视网膜毛细血管瘤合并肾细胞癌的VHL病并结合文献分析.结果 2例患者均在发现视网膜血管瘤数年后出现肾细胞癌.其中1例双侧肾癌患者行右侧肾癌根治、左侧保留肾单位治疗,术后20个月随访肾功能正常、无复发和远处转移.结论视网膜毛细血管瘤是VHL病最早且最常出现的临床表现,一旦出现要警惕VHL病可能,密切随访对VHL病早期诊断和改善预后非常重要.能保证彻底切除病灶情况下,保留肾单位手术是一种可行的治疗手段.     

BCAR1基因与乳腺癌抗雌激素药物耐药的相关研究

乳腺癌抗雌激素药物耐药是导致雌激素受体阳性患者内分泌治疗失败的重要原因之一。BCAR1/p130Cas蛋白能在活体外诱导雌激素依赖性乳腺癌细胞对抗雌激素药物产生耐药,是内分泌治疗的重要耐药因子,其诱导机制尚不能确定。但研究表明检测BCAR1/p130Cas蛋白表达水平可以提示乳腺癌临床内分泌治疗的效果。     

神经胶质瘤组织BCAR4的表达及临床意义

目的 探讨长链非编码RNA乳腺癌抗雌激素耐药基因4(BCAR4)在神经胶质瘤组织中的表达及其临床意义。方法 采用实时定量PCR检测60例胶质瘤组织和癌旁正常组织的BCAR4表达水平,采用Kaplan-Meier检验分析BCAR4表达与胶质瘤患者总生存期(OS)的关系,Cox比例风险模型对患者预后进行风险因素分析。结果 与癌旁组织相比,胶质瘤组织中BCAR4表达水平显著升高(2.25±0.46 vs. 1.01±0.69,P<0.05);胶质瘤组织BCAR4表达与患者的WHO分级和肿瘤大小有关(P<0.05);根据随访资料绘制胶质瘤患者OS曲线,BCAR4低表达患者的中位OS为38个月,优于BCAR4高表达患者的19个月(P<0.05);多因素分析显示,BCAR4表达是影响神经胶质患者预后的危险因素(HR=2.651,95%CI:1.516～4.635,P<0.001)。结论 BCAR4表达在胶质瘤中升高,可作为胶质瘤患者诊断及预后预测的潜在分子标志物。     

肺鳞状细胞癌视网膜转移1例

肺癌是临床上常见的恶性肿瘤,发病率和死亡率居肿瘤首位,严重威胁人类的健康.由于早期缺乏有效的、特异性强的筛查方法,多数患者发现时已处于中晚期,常合并骨、脑、肝、肾上腺等部位的转移.通常,患者多因原发病灶、扩散转移或副肿瘤综合征等引起临床症状而就诊.对由于远处转移相关症状作为首发表现就诊的患者,诊断是一个非常大的挑战.视网膜转移作为肺鳞癌的首发症状极其罕见.本文回顾性分析了我院收治的一例肺鳞癌患者的诊治经过,以眼部症状为首发表现,基于临床表现、影像学检查和手术病理诊断,给予患者手术、化疗等多学科综合治疗,目前短期预后良好,随访观察中.我们总结了本病例诊疗过程的特点,为临床医生提供经验.同时复习肿瘤眼内转移的相关文献,为我们对于肺癌罕见表现的深入了解提供了一个窗口.     

恶性肿瘤伴糖尿病视网膜病变患者的社会支持状况分析调查

目的:通过调查恶性肿瘤伴糖尿病视网膜病变患者的社会支持状况,为有针对性地对患者进行有效的治疗提供理论依据。方法:应用社会支持评定量表(social support rate scale,SSRS)对26例恶性肿瘤伴糖尿病视网膜病变和25例恶性肿瘤伴无视网膜病变糖尿病患者的社会支持状况进行调查。结果:恶性肿瘤伴糖尿病视网膜病变组在主观支持(Z=2.14,P<0.01)、对支持的利用度(Z=1.99,P<0.01)和总分(Z=1.48,P<0.05)明显低于恶性肿瘤伴糖尿病无视网膜病变组,差异有统计学意义。结论:恶性肿瘤伴糖尿病视网膜病变患者获得的社会支持低于恶性肿瘤伴糖尿病无视网膜病变的患者,在恶性肿瘤伴糖尿病视网膜病变患者的治疗过程中应给予重点关注。     

急性白血病眼底改变与血液学参数的关系

目的探讨初诊急性白血病患者视网膜病变的发病率,视网膜改变与血液学参数的关系。方法123例急性白血病中急性髓性白血病86例和急性淋巴细胞白血病37例,年龄14~77岁。由眼科医师用直接或间接检眼镜在白血病诊断的5 d内对视网膜变化进行检查。包括视网膜内出血（IRH）、白色中心出血（WCH）、棉絮状斑（CW S）。结果视网膜损害见于61例患者（49.6%）,高白细胞计数,低血小板数和红细胞压积减低与视网膜病变发生有显著相关（P〈0.001）。有网膜病变者血清乳酸脱氢酶（LDH）水平明显增高（527.79±125.20对218.70±87.31,P〈0.001）。结论红细胞压积减低和较高的白细胞计数在急性白血病的发病机制中是重要的因素。     

鼻咽癌放射治疗性视网膜病变跟踪研究

目的探讨鼻咽癌(NPC)放射治疗的眼部并发症,提高患者生存质量.方法对254例NPC住院首程放射治疗患者在放射治疗前、中及后观察其视功能改变,包括远视力、裂隙灯显微镜、眼底、自动电脑视野及视诱发电位检查.视网膜损伤分级参照国际放射治疗晚期并发症(视网膜损伤)评分标准.结果 241例患者照射剂量≥70 Gy,发生视网膜损伤22例.观察时间30～61个月,平均46.8±14.4个月.发现视网膜损伤后早期进行治疗的9例患者病情获得控制,7例接受治疗较晚的患者,以后均发生视神经病变;其中3例患者在发生视网膜病变以后,观察14～20个月发现放射性脑病.NPC放射治疗性视网膜病变与患者年龄之间,差异无显著性意义(P>0.05).照射剂量在75～79 Gy组视网膜损伤发生率明显比70～74 Gy组高,差异有显著性意义(13.6%∶5.6%,χ2=4.54,P<0.05).结论 NPC放射治疗性视网膜病变与照射剂量和患者对射线的个体敏感性差异有关.NPC放射治疗后发生视网膜病变,提示视神经及脑组织可能已受损害,应及时做头颅CT或MRI及其他相关检查,对放射性脑病的早期发现可能有一定意义.发生视网膜损伤应及早发现并积极进行中西医结合治疗,对其视功能保护以及提高生存质量有积极意义.     

癌症相关性视网膜病变在乳腺癌中的研究进展

Cancer-associated retinopathy (CAR) typically has a sudden or progressive onset of severe visual loss and an ominous association with an occult malignancy which contains breast cancer. Pathologically, CAR is the degeneration of photoreceptors. But the precise mechanism has not been fully established, CAR may result from autoimmune mediated apoptosis. And in recent years, there also have been some results demonstrating that tumor derived angiogenic factors such as VEGF may also confer the development of CAR, which may offer novel avenues for the therapeutic intervention in CAR. Early initiation of immunosuppressive therapy is critical for vision preservation. Future developments in rapid identification and longitudinal quantification of antibody levels would enable individualized management in these patients. The goal of this review was to analyze the epidemiology, the clinical features, the diagnosis and management of retinopathy in the context of recent advances in the elucidation of breast cancer-associated retinopathy (BCAR) pathogenesis.     

Two cases of cancer-associated retinopathy combined with small-cell lung cancer

Cancer-associated retinopathy is a rare paraneoplastic syndrome that is often associated with small-cell lung cancer. It is caused by an autoantibody to the 23 kDa photoreceptor protein, recoverin. A small number of reports have described effective treatment for the disease. We report two cases of cancer-associated retinopathy with small-cell lung cancer whose visual symptom preceded the diagnosis of cancer. Their visual acuity and visual field were slightly improved after steroid and anticancer therapy. Steroid therapy was effective, although the period from visual symptom onset to therapy was comparative longer. When cancer-associated retinopathy is suspected, a comparatively large quantity of steroids and anticancer treatment should be combined immediately.     

胸腔积液中BCAR1检测的临床意义研究

目的 探讨BCAR1表达对癌性和结核性胸腔积液鉴别诊断价值.方法 收集结核性胸水患者40例和肺癌胸腔积液患者40例,另取我院中心健康体检者30例作为对照.BCAR1表达的测定采用ELISA法.结果 肺癌患者胸腔积液中BCAR1表达水平为(71.52±22.61) μg/L,显著高于肺结核胸腔积液中BCAR1的[(13.67±5.24)μg/L] (P＜0.01).对照组、肺结核组和肺癌组血液中BCAR1的表达水平分别为(12.52±4.18)、(14.21±6.55)和(84.63±30.27) μg/L,统计学分析显示:肺癌组血液中BCAR1的表达水平显著高于肺结核患者和健康对照人群(JP＜0.01),而肺结核组与对照组比较则无显著性差异(P＞0.05).相关性分析显示胸腔积液中BCAR1的表达与血液中BCAR1的表达呈显著正相关(γ =0.637,P＜0.01).结论 肺癌患者胸水中存在BCAR1蛋白的异常表达,BCAR1蛋白的高表达有可能作为胸水良恶性鉴别的一个有效的分子标记.     

The substrate domain of BCAR1 is essential for anti-estrogen-resistant proliferation of human breast cancer cells

To unravel the mechanisms underlying failure of endocrine therapy of breast cancer, we have previously executed a functional genetic screen and identified the adaptor protein BCAR1 to be causative for tamoxifen resistance. As a consequence of the manifold of interactions with other proteins, we characterized the contribution of individual protein domains of BCAR1 to anti-estrogen-resistant proliferation of human breast cancer cells. We took advantage of the observation that the closely related family member HEF1 was unable to support long-term anti-estrogen-resistant cell proliferation. Chimerical proteins containing defined domains of BCAR1 and HEF1 were evaluated for anti-estrogen-resistant growth. Exchange of the SH3 and C-terminal domains did not modify the capacity to support cell proliferation. Full support of anti-estrogen resistant proliferation was observed for chimerical molecules containing the central part of BCAR1. The bi-partite SRC-binding site or the Serine-rich domain did not explain the differential capacity of BCAR1. These findings indicate that the differences between BCAR1 and HEF1 with respect to support of anti-estrogen resistance reside in the substrate domain which contains multiple sites for tyrosine phosphorylation. The crucial interactions required for anti-estrogen resistance occur within the substrate domain of BCAR1. Further deciphering of these interactions may resolve the growth regulatory mechanism and provide an explanation for the observation that primary tumors with high levels of BCAR1 are likely to fail on tamoxifen therapy. This information may also help to devise alternative personalized treatment strategies with improved outcome for breast cancer patients.     

Up-regulated BCAR4 contributes to proliferation and migration of cervical cancer cells

OBJECTIVES

Recently, thousands of long non-coding RNAs (lncRNAs) involved in development and metastasis of malignant tumors have been identified. Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) has been proved to promote proliferation and metastasis in multiple tumors. However, the function and significance of BCAR4 in cervical cancer are still unclear.