长链非编码RNA在乳腺癌中的研究进展

乳腺癌为女性最常见的恶性肿瘤，是女性癌症相关死亡的第二大原因。乳腺癌缺乏特异性的肿瘤标志物，目前影像学和传统的血清标志物难以及时有效的监测肿瘤的发生发展及耐药的发生，导致临床治疗效果不佳，因此早期诊断、早期治疗提高临床治疗效益，使患者生存率及生活质量提高尤其重要。多项研究证实长链非编码RNA(long non-coding RNA，lncRNA)在乳腺癌中异常表达，并与乳腺癌的发生发展、预后、耐药等密切相关，lncRNA可以作为治疗或是诊断乳腺癌新的生物靶点。本文通过总结lncRNA近年来的研究进展，旨在为乳腺癌的诊治过程提供新的方案。     

长链非编码RNA在三阴性乳腺癌中的作用

三阴性乳腺癌(TNBC)作为乳腺癌恶性程度高、异型性强的一类亚型,找到其有效作用靶点是亟待解决的问题。长链非编码RNA(lncRNA)在TNBC的发生过程中起重要的调控作用,有希望成为临床化疗反应新型预测分子。笔者介绍了lncRNA参与调控TNBC细胞增殖、侵袭、转移及肿瘤干性相关信号通路的作用机制和功能研究,并探讨了lncRNA作为TNBC治疗靶点及诊断和预后的生物标志物的潜力。     

雌激素受体阳性乳腺癌中长链非编码RNA与他莫昔芬耐药关系的研究进展

摘 要：长链非编码RNA（long non-coding RNA,lncRNA）是非编码RNA的一个大类,其在多种肿瘤中异常表达。近年来,不少研究发现lncRNA,如ROR、HOTAIR、UCA1、BCAR4,在雌激素受体阳性（ER+）乳腺癌的他莫昔芬耐药中发挥了重要作用。因此,了解lncRNA在他莫昔芬耐药中的生物学机制具有重要的临床意义。该文就lncRNA与ER+乳腺癌他莫昔芬耐药的相关研究展开综述,为ER+乳腺癌他莫昔芬耐药的预防及治疗提供新思路。     

乳腺癌相关长链非编码RNA的研究进展

长链非编码RNA(long non-coding RNA,lncRNA)是一类长度大于200 nt、不能编码蛋白质的RNA,参与基因调控的各个层面.近年来研究发现,多种lncRNA在乳腺癌的发生、发展过程中起着重要的调控作用.该研究就lncRNA在乳腺癌中的异常表达,与乳腺癌的增殖、凋亡、侵袭、转移的关系,以及在乳腺癌早期诊断、药物耐药、判断预后中的作用等相关进展做一综述,希望为乳腺癌的预测、诊断和个体化治疗提供新的靶点和思路.     

非编码RNA在骨肉瘤血管新生中的研究进展

骨肉瘤在发展的过程中需不断诱导血管新生来满足自身营养的供给,因此对骨肉瘤细胞诱导的血管新生为靶点进行抑制,已成为近年来研究的热点。尽管目前针对mRNA编码蛋白为靶点的血管抑制剂已运用于临床,但效果欠佳。而非编码RNA（ncRNA）是一类不参与蛋白编码的RNA分子,可以通过调节血管内皮生长因子、血管生成素2和缺氧诱导因子...     

长链非编码RNA在乳腺癌中的研究进展

乳腺癌是一种高度异质性的疾病,是全球女性发病率最高的恶性肿瘤.虽然手术、化疗、放疗、内分泌治疗、靶向治疗等综合治疗极大地改善了患者预后,但是耐药、转移和复发总是伴随着这些抗肿瘤策略.此外,缺乏早期诊断方法和生物标志物也是导致乳腺癌患者病死率较高的原因.因此,深入研究乳腺癌的发病、转移及耐药机制,寻找更为准确的生物标志物...     

乳腺癌分化拮抗非蛋白编码RNA表达及作用研究进展

摘 要：长链非编码 RNA(long non-coding RNA,lncRNA )是一种包含长于200个核苷酸序列且无法编码为蛋白的非编码RNA。已有较多研究证实lncRNA在乳腺癌中表达失调,参与乳腺癌的进展。分化拮抗非蛋白编码RNA是人类染色体4q12上编码的lncRNA,在乳腺癌中呈异常上调表达并广泛参与乳腺癌进展的多种信号通路。全文就分化拮抗非蛋白编码RNA在乳腺癌中的表达、功能及作用机制作简要综述。     

长链非编码RNA在宫颈癌中作用的研究进展

宫颈癌是妇科最常见的恶性肿瘤之一,严重威胁女性的生命健康。然而,目前尚未确定用于诊断和治疗宫颈癌的有效手段。长链非编码RNA（long non-coding RNA, lncRNA）是长度大于200个核苷酸且无蛋白质编码功能的RNA分子,近年来越来越多的研究发现,lncRNA可能是细胞多种生物学过程的关键调节剂。多种lncRNA在宫颈癌组织和细胞中表达异常,参与多条信号通路的调控,影响宫颈癌细胞的增殖、凋亡、迁移和侵袭等过程,在宫颈癌的发生发展中起抑制肿瘤或促进肿瘤的重要作用。本文在简要介绍lncRNA结构与功能的基础上,着重对近年来宫颈癌中异常表达的lncRNA和lncRNA基因中单核苷酸多态性与宫颈癌的关系、分子调节机制以及潜在的临床应用等研究进展进行综述。     

长链非编码RNA HCP5通过调控凋亡通路促进三阴性乳腺癌的研究

目的 探讨长链非编码RNA(lncRNA)HCP5在三阴性乳腺癌中的作用及其机制。方法 通过qPCR分析HCP5在乳腺癌细胞系和正常乳腺细胞系中的mRNA含量,RNA Scope方法分析HCP5在乳腺组织和癌组织中的表达;通过CCK-8实验和细胞存活/死亡实验分析敲低HCP5对三阴性乳腺癌细胞增殖能力的影响;裸鼠体内实验分析敲低HCP5对三阴性乳腺癌细胞成瘤能力的影响;抗体芯片技术分析敲低HCP5影响凋亡通路中BIRC3和Caspase-3蛋白的表达。结果 与正常乳腺细胞和其他类型乳腺癌细胞相比,HCP5在三阴性乳腺癌细胞系中表达上调(P＜0.05),与正常乳腺组织和其他亚型乳腺癌组织相比,HCP5在三阴性乳腺癌组织中表达上调(P＜0.05);与对照组相比,HCP5敲低组三阴性乳腺癌细胞增殖减少、凋亡增加,且原位移植瘤的生长受到抑制(P＜0.01);敲低HCP5引起凋亡通路中凋亡抑制因子BIRC3表达量降低、Caspase-3表达增加,差异具有统计学意义(P＜0.05),对MAPK信号通路蛋白的影响组间差异无统计学意义。结论 lncRNA HCP5通过调控细胞凋亡途径促进三阴性乳腺癌的恶性进展。     

长链非编码RNA及环状RNA在胆管癌中的研究进展

胆管癌起病隐匿且缺乏早期诊断标志物,大多数患者在确诊时已处于疾病晚期。目前手术治疗是胆管癌患者的首选方案,但手术也会面临着风险大、难点多等问题。近年研究发现,长链非编码RNA（lncRNA）和环状RNA（circRNA）具有调节胆管癌细胞增殖、转移、侵袭、上皮间质转化及耐药性等功能。文章综述lncRNA和circRNA...     

The p160 ER co-regulators predict outcome in ER negative breast cancer

The SRC family of ER co-regulators are frequently overexpressed in breast cancer. Overexpression of AIB1 appears to be linked to hormone resistance in HER2 positive breast cancer. However, the role of these co-regulators in ER negative disease is poorly understood. SRC1, SRC2 and AIB1 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate tumours that overexpress both HER2 and AIB1 were associated with markedly reduced relapse free, distant relapse free and overall survival compared to HER2 and AIB1 only overexpressing tumours irrespective of ER status. In ER negative disease both SRC1 and AIB1 were linked to early relapse and death. The SRC family of ER co-regulators is involved in early relapse and resistance in both ER negative and ER positive breast cancer challenging the conventional concept that this effect is mediated solely via the ER.     

P53 alteration correlates with negative ER,negative PGR,and high histologic grade in breast cancer

Seventy tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the RT-PCR-SSCP method. Sixty-five samples (92.9%) were investigated in the regions of codons 101–200 and 201–300. In total, 16 samples (24.6%) showed p53 gene alteration. We found that p53 gene alteration showed a correlation with (1) a negative ER status, (2) a negative PgR status, and (3) a high histologic grade (especially numerous mitotic figures) of the tumor. However, we found no correlation between p53 gene alteration and the lymph node status or clinical stage. Thus, p53 gene alteration in breast cancer may occur in highly malignant breast cancer other than advanced clinical stage cancer or node-positive cancer. © 1994 Wiley-Liss, Inc.     

Role of AMPK and Akt in triple negative breast cancer lung colonization

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 or Akt2 dramatically decreased metastatic colonization of lungs by inducing apoptosis or inhibiting invasion, respectively. Importantly, transient pharmacologic inhibition of Akt activity with MK-2206 or AZD5363 inhibitors did not prevent colonization of lung tissue by TNBC cells. Knockdown of AMPKα1, AMPKα2, or AMPKα1/2 also had no effect on metastatic colonization of lungs. Taken together, these findings demonstrate that transient decrease in AMPK isoforms expression alone or in combination with Akt1 in circulating tumor cells does not synergistically reduce TNBC metastatic lung colonization. Our results also provide evidence that Akt1 and Akt2 expression serve as a bottleneck that can challenge colonization of lungs by TNBC cells.     

Estrogen receptor alpha (ERα) mRNA copy numbers in immunohistochemically ERα-positive-, and negative breast cancer tissues

Background  

The presence of ERα is the basis for treating breast cancer patients with targeted molecular therapies that block estrogen stimulation of breast cancer cell division. To select patients for the above therapies, currently, the ERα presence in breast cancer tissues is determined in clinical laboratories by microscopically scoring the slides subjected to immunohistochemistry (IHC). This method is not quantitative, highly subjective and requires large amount of tumor tissue, therefore, cannot be applied to sterotactic and ultrasound guided biopsy samples. To circumvent these problems, we previously developed quantitative real-time PCR based molecular assay that can be applied to determine mRNA copies of ERα in picogram amounts of total RNA from tumor samples. However, it is not known how the mRNA copy numbers correlate to IHC positive and negative status.     

病理诊断在乳腺癌保乳手术中的作用

乳房对女性是非常重要的形体标志。因肿瘤而被切除一侧或双侧乳房不仅在肉体上，而且在精神上将对女性造成长久的创伤。改良根治术后的患肢酸痛、淋巴水肿、胸壁畸形等，亦严重影响患者的生活质量。伴随着诊疗水平的进步和生活水平的提高，仅采取乳腺部分切除的保乳手术和保乳手术后并用放射治疗的保乳疗法越来越多，使一些乳腺癌患者的生活质量得到了很大的提高。     

Role of high speed biopsy gun in breast cancer diagnosis

Preoperative diagnosis of histology and receptor status is important in management of breast cancer. Percutaneous automated core biopsy with biopsy gun (Gun biopsy) was done in fifty patients with palpable breast lump in whom fine needle aspiration cytology (FNAC) was either negative or not done In all patients adequate tissue for histology and receptor status studies was obtained forty-two patients had infiltrating duct carcinoma and eight patients had benign lesions on gun biopsy. There were no complications in this procedure. Twenty of the forty-two patients underwent mastectomy either per primum or after chemotherapy, had the diagnosis substantiated on histopathological examination Thirty-four samples were examined for receptor status and the specimen was found to be adequate and of good quality. We conclude that gun biopsy is a simple and safe procedure which is more sensitive and specific than FNAC.     

三阴性乳腺癌临床病理特征及诊治分析

目的研究三阴性乳腺癌的临床病理特征,探索合理的治疗策略。方法对2002年4月至2010年6月我院肿瘤中心收治的42例三阴性乳腺癌患者的临床资料进行回顾性研究。结果三阴性乳腺癌占同期乳腺癌总数的13.5%。本组患者均为女性,中位年龄53岁,平均肿瘤直径2.8cm。病理类型以浸润性导管癌为主,p53阳性率33.3%,临床分期主要为Ⅱ期。辅助化疗是其主要的全身治疗手段,手术方式以乳腺癌改良根治术为主。随访8～106个月,中位时间39个月,16例患者出现复发转移,其中局部复发转移5例,内脏转移11例,复发转移高峰期为1～3年。死亡11例,其中非肿瘤原因死亡1例,肿瘤进展死亡10例,死亡高峰期为2～5年。结论三阴性乳腺癌具有独特的生物学特性及临床、病理特征,其发病年龄较轻﹑肿瘤直径较大﹑临床分期较晚﹑复发风险较高、易发生远处转移且复发转移后死亡率较高。化学治疗为目前唯一的全身治疗手段,仍需探索更为合理有效的化疗方案;新的分子靶向治疗药物值得期待。