EMSY在乳腺癌中的功能研究进展

EMSY位于染色体11q13,编码约1 322个氨基酸,其N末端有保守的ENT结构域,此结构域可与BRCA2的第3外显子结合并抑制BRCA2的转录活性,自2003年首次报道以来,以EMSY与BRCA2相互作用为基础,EMSY的功能研究不断展开,研究发现EMSY与BRCA2的相互作用可能可以弥补BRCA2在散发性乳腺癌中作用机制的空白,同时EMSY可能与DNA的损伤修复及基因组的稳定性相关,其次,EMSY可能是染色体11q13扩增子的主要候选基因.此外,临床研究显示13%的散发性乳腺癌伴有EMSY扩增,并且在某些亚组中,EMSY扩增患者无病生存较差,提示其可能成为临床预后的一个预测指标.尽管关于EMSY的研究结果尚存在争议,不过作为一种新发现的蛋白,EMSY对散发性乳腺癌发生发展的影响有重要的研究价值.以EMSY与BRCA2相互作用为切入点,结合近年来EMSY的研究结果,对EMSY的结构功能作一简单介绍.     

EMSY links breast cancer gene 2 to the 'Royal Family'

Although the role of the breast cancer gene 2 (BRCA2) tumor suppressor gene is well established in inherited breast and ovarian carcinomas, its involvement in sporadic disease is still uncertain. The recent identification of a novel BRCA2 binding protein, EMSY, as a putative oncogene implicates the BRCA2 pathway in sporadic tumors. Furthermore, EMSY's binding to members of the 'Royal Family' of chromatin remodeling proteins may lead to a better understanding of the physiological function of BRCA2 and its role in chromatin remodeling.     

Amplification of the BRCA2 pathway gene EMSY in sporadic breast cancer is related to negative outcome.

DNA amplification at band q13 of chromosome 11 is common in breast cancer, and CCND1 and EMS1 remain the strongest candidate genes. However, amplification patterns are consistent with the existence of four cores of amplification, suggesting the involvement of additional genes. Here we present evidence strongly suggesting the involvement of the recently characterized EMSY gene in the formation of the telomeric amplicon. EMSY maps at 11q13.5, 100 kb centromeric to the GARP gene, which has been mapped within the core of the distal amplicon. The EMSY protein was shown to interact with BRCA2 and has a role in chromatin remodeling. This makes EMSY a strong candidate oncogene for the 11q13.5 amplicon. DNA amplification was studied in a total of 940 primary breast tumors and 39 breast cancer cell lines. Amplification profiles were consistent with the EMSY-GARP locus being amplified independently of CCND1 and/or EMS1. EMSY RNA expression levels were studied along with those of five other genes located at 11q13.5 by real-time quantitative PCR in the 39 cell lines and a subset of 65 tumors. EMSY overexpression correlated strongly with DNA amplification in both primary tumors and cell lines. In a subset of 296 patients, EMSY amplification was found by both uni- and multivariate analyses to correlate with shortened disease-free survival. These data indicate that EMSY is a strong candidate oncogene for the 11q13.5 amplicon.     

肿瘤反义治疗研究进展

肿瘤反义治疗是以反义寡核苷酸为基础的一种基因治疗方法,经过近二十几年的发展,反义寡核苷酸以其高特异性和低毒副作用等优良特性,正成为新一代抗肿瘤药物的主力军.现着重介绍反义技术的原理、反义寡核苷酸在临床应用的进展及具有临床应用前途的反义靶标.     

The development of hepatocellular cancer in humans

The biological characteristics of hepatocellular cancer vary appreciably in different parts of the world, but especially between regions with very high and low incidences of the tumour. Hepatocellular cancer is multifactorial in origin, and the pattern of its aetiological associations differs between populations at high and low risk. In Africans and Chinese, who have the highest incidences of hepatocellular cancer, the hepatitis B virus is the most important causal association. The viral carrier state is acquired during early childhood, and carries a relative risk for the development of the tumour of over 200. Integration of hepatitis B virus DNA probably acts as a genotoxic initiator in the multistep process of hepatocarcinogenesis, although the precise mechanisms involved have not been determined. Aflatoxin ingestion may also have an aetiological role in high incidence regions, probably as a genotoxic or epigenetic promoter to hepatitis B virus-initiated carcinogenesis. In low risk populations cirrhosis is the most important causal association of hepatocellular cancer. The cirrhosis is often the result of alcohol abuse, but the tumour may complicate all aetiological forms of this disease. Whether neoplasia is an inevitable consequence of the hyperplasia of cirrhosis, or the increased hepatocyte turnover rate acts as a promoter is not known. Hepatitis B virus infection plays a lesser part, and aflatoxin no part at all.     

lncRNAs在乳腺癌发生、发展中的作用及其潜在的临床意义

长链非编码RNA（lncRNAs）是长度在200～100 000核苷酸的非编码RNA分子,曾被认为是DNA转录的“噪音”,不具备生物学功能。近年研究表明lncRNAs广泛参与基因沉默、转录激活、细胞周期和分化、染色体构型修饰等众多生理功能,成为肿瘤研究领域的新热点。本文对lncRNAs在乳腺癌发生、进展、分子分型、治疗抵抗、上皮间质转化以及外泌体中表达作一系统阐述,将为深入理解lncRNAs在乳腺癌发生、发展中的精细分子调控机制以及探索乳腺癌新的诊断和特异性治疗靶点开拓思路。     

The function of poliamine metabolism in prostate cancer

In many developed countries prostate cancer is the second leading cause of cancer related death in human population. Prostate tissue is characterized by the highest level of polyamines among organs in human body, and it is even higher in prostate carcinomas. These ubiquitous molecules are synthesized by prostate epithelium and are involved in many biochemical processes including cell proliferation, cell cycle regulation and protein synthesis. In this review we made the attempt to discuss the functions of polyamines, their involvement in apoptosis and potential role as molecular biomarker for prostate cancer. Also we present recent data on generation of drugs, in particular, cyclin dependent kinase inhibitor, developed for therapy of prostate cancer.     

雄激素受体在去势抵抗性前列腺癌进展中的作用及研究进展

雄激素受体是前列腺癌发生发展的重要因素。雄激素去势疗法是目前治疗前列腺癌的标准疗法,在早期可以有效的抑制肿瘤生长。但2～3年内,肿瘤会复发或进展,形成去势抵抗性前列腺癌。目前关于雄激素去势疗法治疗后去势抵抗性前列腺癌发生发展机制研究的文献较多（其中包括类固醇激素代谢的变化、雄激素受体基因的扩增或过表达、雄激素受体辅助调节因子、雄激素受体剪接变异体、生长因子和／或细胞因子、雄激素受体突变等等机制）,但还没有对具体机制完全了解并形成共识。目前普遍认为在去势抵抗性前列腺癌中,雄激素和雄激素受体在其发生发展中起到了关键的作用。本文就雄激素受体在前列腺癌进展为去势抵抗性前列腺癌的机制中的作用加以综述。     

The future development of bevacizumab in colorectal cancer

Bevacizumab (Avastin), the first approved therapy designed to inhibit tumor angiogenesis, has significant clinical benefits in the management of colorectal cancer (CRC). When bevacizumab is added to IFL (5-fluorouracil [5-FU]/leucovorin [LV]/irinotecan [Camptosar)]) as first-line therapy for metastatic CRC, significant overall and progression-free survival benefits are obtained. Similar survival benefits may be achieved when bevacizumab is added to 5-FU/LV alone. In addition, additive and synergistic effects with a range of chemotherapeutic agents illustrate that bevacizumab has considerable potential in combination with existing therapeutic options. Clinical data indicate that bevacizumab is the only agent in addition to chemotherapy that has demonstrated survival benefit in the first- and second-line settings. In addition, bevacizumab is expected to produce clinical benefit in the adjuvant setting: inhibition of vascular endothelial growth factor should prevent the angiogenic switch in micrometastases, which is a key factor in malignancy. The clinical program is examining the activity of bevacizumab in combination with the likely future standard of care in both the metastatic and adjuvant treatment settings. Phase III trials (NO16966C, CONcePT and TREE-2) are studying the benefit of combining bevacizumab with oxaliplatin (Eloxatin)-based regimens. Similarly, in the adjuvant setting, phase III trials are assessing the efficacy and tolerability of bevacizumab in combination with oxaliplatin-based chemotherapy (AVANT, NSABP C-08).     

The development of neoadjuvant chemotherapy in breast cancer

In the beginning, neoadjuvant chemotherapy (NAC) is part of the multidisciplinary treatment of locally advanced breast cancer. Many clinical trials in the past have developed the usefulness of anthracycline containing NAC for operable breast cancer. The majority of trials have proven survival rates equivalent to adjuvant chemotherapy with increased breast conservation rates, and have also shown that a pathological complete response (pCR) after NAC is associated with improved survival. Taxanes have been introduced into clinical trials of NAC with increased pCR rates. However, there was no significant difference in overall survival among the regimens which added taxanes to neoadjuvant anthracycline. In this paper, the problems of NAC up to the present and the development of new regimens are discussed. We also discuss the new concept of NAC which might revolutionize what we know about NAC.     

LncRNA在结直肠癌中的研究进展

随着基因研究的进步,现已发现长链非编码RNA(Long non-coding RNA,LncRNA)在很多肿瘤的发生发展中起到关键的调节作用,其自身的各个片段能具有各不相同的调节效果;某些LncRNA甚至能在多种肿瘤中起到不同的调控作用。那么诸多新近发现的LncRNA在结直肠癌的表达情况如何？本文就LncRNA在结直肠癌中的研究进展做一综述。     

LncRNA在头颈肿瘤中的研究进展

长链非编码RNA(long non-coding RNA,lncRNA)是指转录本长度超过200个核苷酸的不编码蛋白的RNA.lncRNA参与了各种各样的生物学过程且发挥重要调控功能,如:细胞凋亡、侵袭、转移等.近年来大量研究表明lncRNA的异常调节可以导致各种疾病,特别是肿瘤.本文结合国内外最新报道对lncR-NAs在头颈肿瘤中的研究进展作一综述.     

The development of androgen-independent prostate cancer

The normal prostate and early-stage prostate cancers depend on androgens for growth and survival, and androgen ablation therapy causes them to regress. Cancers that are not cured by surgery eventually become androgen independent, rendering anti-androgen therapy ineffective. But how does androgen independence arise? We predict that understanding the pathways that lead to the development of androgen-independent prostate cancer will pave the way to effective therapies for these, at present, untreatable cancers.     

Reproductive function of women and risk of the development of breast cancer

The relationship between risk for breast cancer and certain factors of reproductive function was studied on a "case-control" basis. It was demonstrated that the traditional and well-known index of age at first birth cannot be considered a universal factor for all females who have borne different numbers of children. Indexes which take into account age at all births proved more reliable in evaluating risk of cancer in bi-, tri- and multiparae. Indexes of relative risk and the role of characteristics of reproductive function are discussed.     

TTK1在卵巢癌铂类耐药中的生物学功能分析

背景与目的:苏氨酸酪氨酸激酶1(threonine tyrosine kinase 1,TTK1)是纺锤体组装检查点的一个组成部分,确保染色体的正确分离,可能是与化疗敏感性相关的潜在目标分子,但TTK1在铂类药物耐药方面的作用机制仍不清楚.卵巢癌是女性常见的生殖系统恶性肿瘤之一,发病率在妇科恶性肿瘤中排名第三,死亡率排...     

mTOR功能及其抑制剂研究进展

哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin mTOR）是一种丝／苏氨酸蛋白激酶，mTOR在肿瘤细胞生长、增殖过程中起重要作用，mTOR信号通路活动异常与肿瘤的发生有密切关系，mTOR足肿瘤药物治疗作用的理想靶点，目前新的mTOR抑制剂不断出现。本文对mTOR蛋白的结构、功能和mTOR信号通路及其抑制剂进行了综述。