三阴性乳腺癌中miRNA-124表达与E-钙黏蛋白及雄激素受体的关系

目的 研究三阴性乳腺癌(Triple-negative breast cancer,TNBC)中miRNA-124(miR-124)的表达与E-钙黏蛋白(E-cadherin)及雄激素受体(Androgen receptor,AR)的关系。方法 采用RT-PCR在TNBC组织和癌旁正常乳腺组织中检测miR-124的表达,免疫组化检测TNBC中E-cadherin及雄激素受体(AR)的表达。结果 与癌旁正常乳腺组织相比,TNBC组织中miR-124表达明显降低(P＜0.05);TNBC组织中,miR-124表达与组织分级、E-cadherin表达有关(P＜0.05),与AR表达无关(P＞0.05)。结论 在TNBC中,miR-124可能通过调节E-cadherin的表达发挥抑癌作用。     

E-钙黏蛋白在胃癌中的研究进展及临床应用

摘 要：E-钙黏蛋白(E-cadherin)是一种由CDH1基因编码的跨膜糖蛋白,在维持细胞黏附中起着至关重要的作用。由于E-钙黏蛋白参与调节细胞增殖、侵袭和迁移等信号通路,E-钙黏蛋白缺失可导致胃上皮细胞功能障碍,促进胃癌发生、发展。全文就E-钙黏蛋白在胃癌发生发展中的作用及临床应用价值等内容,总结了E-钙黏蛋白的生物学功能及其在胃癌发生、侵袭、转移和耐药中的调控作用,同时揭示了E-钙黏蛋白在胃癌早期诊断、预后、治疗等方面的应用,以及E-钙黏蛋白激活剂作为抗肿瘤药物的开发现状等,为胃癌的精准治疗提供新思路。     

上皮钙黏附素和连环素复合物在肿瘤中的研究

上皮钙黏附系统对细胞黏附和维持组织结构完整性发挥重要作用。钙黏蛋白一连环素复合物不仅仅是黏附分子，对其深入研究有助于阐明肿瘤发生的早期分子改变以及开发肿瘤防治的新策略。     

E-钙黏蛋白在结肠癌侵袭转移机制中的研究进展

结肠癌的侵袭行为与侵袭抑制因子——E-钙黏蛋白表达减少、缺失密切相关。E钙黏蛋白通过与肿瘤相关抗原RCAS1、抗黏附蛋白dysadherin、β-酪蛋白肽等相互作用,与结肠癌侵袭转移机制密切相关,其间涉及免疫逃避机制、肿瘤转移的细胞分子机制、肿瘤信号传导通路、细菌与肿瘤关系等近年研究热点。     

Syndecan-2及E-钙黏蛋白在I型子宫内膜样腺癌中的表达及与转移的关系

目的:检测I型子宫内膜样腺癌组织中syndecan-2和E-钙黏蛋白的表达情况,探讨二者在I型子宫内膜样腺癌发生发展及侵袭转移中的作用。方法:应用免疫组织化学SP法同步检测65例I型子宫内膜样腺癌中的syndecan-2和E-钙黏蛋白的表达,取同期65例正常子宫内膜组织做对照。数据采用SPSS 13.0软件处理,等级资料进行秩和检验。结果:Syndecan-2及E-钙黏蛋白在I型子宫内膜样腺癌中阳性表达率分别为43%及66%,均低于正常子宫内膜组（100%）。同时,syndecan-2阳性表达与I型子宫内膜样腺癌的组织学分级无明显相关,但与FIGO分期、淋巴结转移、肌层浸润深度呈正相关。相反,E-钙黏蛋白阳性表达与I型子宫内膜样腺癌的组织学分级、FIGO分期、淋巴结转移、肌层浸润深度呈负相关。结论:与正常子宫内膜相比,syndecan-2和E-钙黏蛋白在I型子宫内膜样腺癌中表达减少,syndecan-2高表达、E-钙黏蛋白低表达提示I型子宫内膜样腺癌分期晚、预后不良。     

E-钙黏蛋白在三阴性乳腺癌组织中的表达

目的检测E-钙黏蛋白（E-cad）在三阴性乳腺癌（TNBC）组织中的表达,探讨其评估预后的价值。方法采用免疫组化方法检测经手术病理确诊的147例TNBC患者的E—cad的表达情况。结果TNBC组织中E．cad的阳性率为32％（47／147）。E-cad阳性表达与肿块大小、组织学分级、淋巴结转移均有关（P均〈0．05）。E—cad阴性患者的5a总生存率和无病生存率均低于E-cad阳性患者（61％vs89％,27％vs65％,P均〈0．05）。结论TNBC中E-cad阳性者预后好,上调E—cad表达可能成为TNBC新的治疗手段。     

黏附分子与肿瘤侵袭和转移的研究进展

恶性肿瘤死亡多数是由转移所致,肿瘤转移是涉及恶性肿瘤侵袭和转移形成的全过程与临床有密切关系,但此过程在分子水平的研究很少,阐明这些机制在肿瘤研究和应用上是一个重要挑战。最近的研究证实了许多黏附分子,如上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)、整合素(Integrin)等与肿瘤侵袭、转移的发生发展密切关联。     

黏附分子与肿瘤侵袭和转移的研究进展

恶性肿瘤死亡多数是由转移所致,肿瘤转移是涉及恶性肿瘤侵袭和转移形成的全过程与临床有密切关系,但此过程在分子水平的研究很少,阐明这些机制在肿瘤研究和应用上是一个重要挑战。最近的研究证实了许多黏附分子,如上皮钙黏蛋白（E-cadherin）、神经钙黏蛋白（N-cadherin）、整合素（Integrin）等与肿瘤侵袭、转移的发生发展密切关联。     

E-钙黏蛋白及Ki67在三阴性乳腺癌中的表达及临床意义

目的探讨E-钙黏蛋白、Ki67在三阴性乳腺癌(TNBC)中的表达及临床意义。 方法回顾性分析陆军军医大学新桥医院2010年1月至2013年12月收治的77例女性TNBC患者临床资料。采用免疫组织化学方法检测E-钙黏蛋白和Ki67的表达情况,通过χ²检验分析其与患者临床病理资料的关系。由于77例患者中有5例失访,本研究仅对随访资料完整的72例患者采用Kaplan-Meier法、Log-rank检验、Cox逐步回归模型进行生存分析和危险因素分析。 结果在77例患者中,E-钙黏蛋白的表达与淋巴结状态有关(χ²＝16.428,P<0.001),而Ki67表达与组织学分级有关(χ²＝7.218,P＝0.007)。中位随访59个月,72例患者的DFS率和OS率分别为58.3%、68.1%。其中,E-钙黏蛋白高表达者DFS率和OS率均高于低表达者(DFS率：75.9%比46.5%,χ²＝7.553,P＝0.006;OS率：82.8%比58.1%,χ²＝5.132,P＝0.023),而Ki67低表达者DFS率和OS率均高于高表达者(DFS率：84.0%比44.7%,χ²＝9.486,P＝0.002;OS率：92.0%比55.3%,χ²＝9.006,P＝0.003)。Cox逐步回归模型分析显示,淋巴结转移、组织学分级高是患者DFS的独立危险因素(OR＝4.030, 95%CI：1.854～8.757, P<0.001; OR＝2.879,95%CI：1.359～6.100,P＝0.006),Ki67高表达、淋巴结转移是OS的独立危险因素(OR＝5.067,95%CI：1.179～21.768, P＝0.029; OR＝6.253,95%CI：2.296～17.034, P<0.001)。 结论E-钙黏蛋白高表达和Ki67低表达的TNBC预后良好,这对于乳腺癌的个体化治疗具有一定的指导意义。     

钙黏蛋白超家族新成员ODH17与胃癌关系的研究现状

目的：总结肝肠钙黏蛋白（CDH17）结构与功能的特点,探讨其与胃癌的关系。方法：应用PubMed、万方数据资源及CNKI期刊全文数据库,以“CDH17、胃肿瘤、肿瘤发生”等为关键词,检索2000～2010年相关文献。粗选78篇相关文献,精选24篇纳入分析。文献纳入标准：1）CDH17基因结构．与功能;2）CDH17在肿瘤中表达的研究;3）CDH17在胃癌中表达的研究。结果：CDH17是钙黏蛋白超家族的新成员,与经典的钙黏蛋白不同,在结构上其胞质区仅由18个氨基酸组成,胞外域7个同源染色体重复序列片段,与细胞黏附功能有关的基序为AAL序列,在功能上其不依赖于链蛋白（β-catenin）而独立发挥细胞黏附作用;CDH17在胃癌中表达上调,与胃癌的发生、发展、转移及预后均有着密切的联系。结论：CDH17可能成为一种新型胃癌标志,为胃癌的诊断、预后评估和治疗提供帮助。     

Enhancement of taxol,doxorubicin and zoledronate anti-proliferation action on triple-negative breast cancer cells by a PTHrP blocking monoclonal antibody

Triple-negative breast cancers (TNBCs) are heterogeneous cancers that present tumors without the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Because of the absence of these receptors, there are currently no known specific molecular targets for treatment, and although TNBC tumors are chemosensitive, prognosis is poor because this type of cancer relapses more frequently and more aggressively than hormone receptor-positive cancers. The mechanisms by which TNBCs escape control by chemotherapy are not clear, and it is crucial to identify novel molecular drivers that can be targeted in order to develop more efficient therapeutic approaches. We recently highlighted a pleiotropic role for parathyroid hormone-related protein (PTHrP) in all stages of breast cancer, and used our neutralizing anti-PTHrP monoclonal antibody (mAb M158) to efficiently inhibit progression and metastasis of human breast cancer xenografts in athymic mice. In the present study, we present evidence for a strong in vitro anti-proliferative effect of our blocking anti-PTHrP mAb M158 as a single agent on TNBC lines of various subtypes that are known to express PTHrP (MDA-MB-231, BT-549, MDA-MB-435). The same mAb is inactive in a TNBC line without detectable PTHrP expression (MDA-MB-468). In in vitro combination studies, the mAb enhances the effect of the chemotherapeutic drugs taxol and doxorubicin in PTHrP-positive TNBC cells in an additive manner. When combined with the bisphosphonate zoledronate, M158 can act in additive or antagonistic fashion in vitro depending on the cell line. Our observations identify PTHrP as a novel target against TNBC cell proliferation, and suggest that combination therapies that include an anti-PTHrP approach might increase treatment efficacy in patients with PTHrP-positive TNBC.     

Differential optineurin expression controls TGFβ signaling and is a key determinant for metastasis of triple negative breast cancer

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to its aggressive characteristics and low response to the existing clinical therapies. Distant metastasis is the main cause of death of TNBC patients. Better understanding of the mechanisms underlying TNBC metastasis may lead to new strategies of early diagnosis and more efficient treatment. In our study, we uncovered that the autophagy receptor optineurin (OPTN) plays an unexpected role in TNBC metastasis. Data mining of publicly available data bases revealed that the mRNA level of OPTN in TNBC patients positively correlates with relapse free and distance metastasis free survival. Importantly, in vitro and in vivo models demonstrated that OPTN suppresses TNBC metastasis. Mechanistically, OPTN inhibited the pro-oncogenic transforming growth factor-β (TGFβ) signaling in TNBC cells by interacting with TGFβ type I receptor (TβRI) and promoting its ubiquitination for degradation. Consistent with our experimental findings, the clinical TNBC samples displayed a negative correlation between OPTN mRNA expression and TGFβ gene response signature and expression of proto-typic TGFβ target genes. Altogether, our study demonstrates that OPTN is a negative regulator for TGFβ receptor/SMAD signaling and suppresses metastasis in TNBC.     

Treatment of triple negative breast cancer

Triple negative breast cancer (TNBC) is a special type of breast cancer. Its special clinical pathological characteristic and molecule expression type make the treatment of TNBC become an international problem. In recent years, a variety of attempts and explorations to the treatment of TNBC have made some initial results, which provides a direction for the treatment of TNBC and offers hope for patients with TNBC.     

Clinicopathological features and treatment strategy for triple-negative breast cancer

Breast cancers are divided into at least 4 subtypes on the basis of gene expression profiles and expression of receptors (hormone receptors (HR) and HER2) as measured by immunohistochemistry. These subtypes have different prognoses and responses to treatments such as endocrine manipulation, anti-HER2 therapy, and chemotherapy. Triple-negative breast cancer (TNBC) is immunohistochemically defined as lacking estrogen and progesterone receptors and not overexpressing HER2. TNBC accounts for approximately 15% of breast cancer patients, and is more chemosensitive but has a worse prognosis than the HR-positive/HER2-negative phenotype. TNBC is a heterogeneous disease that does not offer specific targets in the same way as HR-positive and HER2-positive breast cancers, and is similar to basal-like breast cancer and BRCA1-related breast cancer. At present, the lack of highly effective therapeutic targets for TNBC leaves standard chemotherapy, for example the combination of anthracycline and taxane, as the only medical treatment, but this is insufficiently efficacious. Novel approaches for TNBC, for example DNA damaging agents, PARP-1 inhibitors, receptor tyrosin kinase inhibitors (TKIs), and antiangiogenesis agents, have been examined in clinical settings. Concerning therapeutic strategies for TNBC, it is most important to develop novel effective approaches for TNBC treatment and high-throughput predictive tools for standard chemotherapy and novel agents.     

miR-34c-3p与M2型肿瘤相关巨噬细胞在三阴性乳腺癌中的表达及意义

目的:检测miR-34c-3p与M2型肿瘤相关巨噬细胞（tumor-associated macrophage,TAM)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达，并探讨其在乳腺癌发病中的意义。方法:选择2017年2月至2018年1月于西京医院就诊的68例TNBC患者作为实验组(A组)，以同期就诊的70例乳腺纤维腺瘤患者作为对照组(B组)。采用Real-time RT-PCR 检测组织标本中miR-34c-3p的表达；流式细胞检测M2型TAM的表达；ELISA法检测血清中IL-10的表达。并进一步分析miR-34c-3p的表达与乳腺癌M2型TAM及血清IL-10水平的相关性。结果:A、B组miR-34c-3p的相对表达量分别为0.84±0.08、1.29±0.71，A组明显低于B组，差异有统计学意义(P<0.05)。与B组比较，A组M2型TAM(CD68+CD163+)细胞比例显著升高(P<0.05)。A组血清IL-10的表达［(19.69±4.93) pg/ml］较B组［(17.26±3.51) pg/ml］显著升高，差异有统计学意义(P<0.05)。TNBC组织中miR-34c-3p的表达与M2型TAM比例及血清IL-10表达均呈显著负相关(r=-0.508，r=-0.656，P<0.05)。结论:TNBC组织中miR-34c-3p的表达下调，M2型TAM比例及血清IL-10表达均显著升高，促进TNBC进展。     

Systemic treatment for triple negative breast cancer in older patients: A Young International Society of Geriatric Oncology Review Paper

Breast cancer is the most common type of cancer affecting women worldwide and its risk increases with age. Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) behaves more aggressively, with earlier relapses and poorer survival outcomes. Although the incidence of TNBC decreases with age, it still affects about 10% of older women with breast cancer. The management of TNBC in older patients is particularly challenging as chemotherapy is the main treatment choice in both early and advanced diseases and older patients are often prone to increased treatment-related toxicities. This review highlights the specific considerations in this vulnerable group of patients and summarizes the current evidence for TNBC management in older adults from early to late stage of disease.     

Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

三阴性乳腺癌患者磁共振成像征象与临床病理特征的分析

目的 探讨三阴性乳腺癌（TNBC）的磁共振成像（MRI）特征性表现.方法 将符合纳入标准的患者分为TNBC（19例）及非三阴性乳腺癌（non-TNBC）（63例）两组.回顾性分析病变的形态学、MRI血流动力学、表观扩散系数（ADC）值（b=600 s/mm2）及临床病理资料,采用SPSS17.0软件进行统计学分析.结果 TNBC与non-TNBC患者在病理类型、腋窝淋巴结转移及组织学分级、肿块的形态、边缘、强化方式、ADC值方面,差异均有统计学意义（均P＜0.05）;病理类型上,髓样癌、鳞状细胞癌、基底样癌为TNBC特有;TNBC腋窝淋巴结转移率达78.9％（15/19）;TNBC更易表现为Ⅲ型时间-信号曲线（TIC）类型（89.4％）;TNBC病灶增强后肿块更易表现为分叶状、边缘光滑、环形强化,分别占TNBC组的52.6％、36.8％、42.1％;有更高的ADC值;而在发病年龄、是否绝经、是否有乳腺癌家族史及肿块最大径、病灶的个数、肿块类型及TIC类型方面,两组差异无统计学意义（P＞0.05）.结论 TNBC的MRi征象与临床病理特征有利于其正确诊断.     

Clinicopathological characters of triple negative breast cancer

Objective:To study the clinicopathological characters of triple negative breast cancer (TNBC).Methods:A total of 629 patients with breast cancer were reviewed, who were treated from 2003 to 2007 in Chongqing Cancer Institute. The comparison of clinicopathological features including TNM classification, histological type, tumor location, axillary lymphonodes status and neoadjuvant chemotherapy between TNBC and nontriple negative breast cancer (NTNBC) was performed. The overall response was evaluated by whether the patients achieve complete remission (CR) and partial remission (PR) after chemotherapy. Results:There were 69 TNBCs in the 629 patients with breast cancer. The premenopausal patients, which was found in 49/69 of TNBCs, was more than NTNBCs. The average diameter of tumor in TNBC group was 4.1 em, lager than NTNBC group. TNBC with axillary nodes metastasis occurred in 21 cases, and the axillary nodes metastasis rate was lower than NTNBC. The positive expression rate of p53 in TNBC was 44.9%, and the overall response (CR+PR) was 72.2%. No statistical differences were found regarding the positive expression rate of p53 and the overall response between TNBC and NTNBC. Conclusion:TNBC were a group of primary breast cancers with triple negative, tending to occur in premenopausal women, with larger tumors, lower axillary nodes metastasis rate. TNBC had worse clinical prognosis and currently lacked effective targeted therapies.     

Recent Progress in Triple Negative Breast Cancer Research

Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.