乳腺癌超声征象与肿瘤干细胞及上皮间质转化标志物表达水平的相关性

目的探讨乳腺癌超声征象与肿瘤干细胞及上皮间质转化标志物表达水平的相关性及其意义。方法选择在我院行乳腺癌手术的患者组织标本98例,分析每位患者对应的乳腺超声征象,包括肿块周边是否有毛刺、边缘是否有高回声晕、纵横比、后方回声情况、微小钙化、内部血流显像分级;并采用免疫组化方法检测组织样本中CD24、CD44、E-cadherin、N-cadherin、β-catenin、Vimentin的表达情况,分析其与超声表现的相关性。分析其它可能影响肿瘤干细胞及上皮间质转化标志物表达的因素;对肿瘤干细胞及上皮间质转化标志物表达相关性进行多因素logistic回归分析。结果肿瘤周边是否有毛刺与CD44、E-cadherin、N-cadherin、β-catenin的表达水平差异有统计学意义（P < 0.05）。肿块边缘是否有高回声晕与CD44和E-cadherin的表达水平差异有统计学意义（P < 0.05）。肿块纵横比、后方回声变化均与E-cadherin的表达水平差异有统计学意义（P < 0.05）。血流分级、腺体类型与CD44的表达水平差异有统计学意义（P < 0.05）。腺体背景类型是CD24表达的独立相关因素（P < 0.05）。血流情况、雌孕激素受体表达情况是CD44表达的独立相关因素（P < 0.05）。有无高回声晕、肿块后方回声特征、腋窝淋巴结是否有转移是E-cadherin表达的独立相关因素（P < 0.05）。临床分期是N-cadherin表达的独立相关因素（P < 0.05）。边缘有无毛刺是β- catenin表达的独立相关因素（P < 0.05）。结论乳腺癌超声征象与肿瘤干细胞及上皮间质转化标志物表达之间存在联系,超声征象可作为无创性预测乳腺癌患者肿瘤干细胞及上皮间质转化标志物表达水平的方式,并可为预测乳腺癌潜在的侵袭能力提供更多依据。     

YKL-40 promotes invasion and metastasis of bladder cancer by regulating epithelial mesenchymal transition

ObjectiveThis study aims to explore the relevance between YKL-40 and recurrence and progression of bladder cancer, and determine whether YKL-40 can be used as a potential target in patients with bladder cancer.MethodsWe analyzed the invasion and metastasis ability of BIU-87, UMUC3, J82, T24, 5637 and immortalized human bladder epithelial cells SVHUC1 by Transwell method. The YKL-40 expression levels in cell lines were analyzed by Western blot and qPCR.ResultsThe increase of YKL-40 level, especially in tumour group, was related to tumour pathological stage and tumour invasion and metastasis. The cell lines with YKL-40 high expression had stronger invasion and metastasis ability. Overexpression of YKL-40 in SVHUC1 with the lowest YKL-40 expression can enhance the invasion and migration of cells. In T24 cells with YKL-40 high expression, transfection of shRNA plasmid targeting YKL-40 can down regulate the invasion and migration. The expression levels of N-cadherin and Vimentin in YKL-40 overexpressed SVHUC1 cells were increased, the E-cadherin expression was decreased, the Twist, Snail and Slug expression levels were increased, but they were opposite in T24 cells with down-regulation of YKL-40 expression.ConclusionsYKL-40 promoted the migration and invasion of bladder cancer cells by up regulating the EMT gene expression. The YKL-40 expression is closely related to the invasion and migration of bladder cancer.     

胃癌微环境中肥大细胞的临床病理学意义

目的初步探讨肥大细胞（mastcell,MC）在胃癌微环境中的生物学意义。方法采用免疫组织化学方法对31份胃癌标本、20份胃良性病变标本中的MC进行标记,并分析MC数目与胃癌及临床病理资料之间的关系。结果胃癌组中MC数目显著高于胃良性病变组,且差异有统计学意义（P〈0．05）。高、中、低分化胃癌组织中MC数目差异无统计学意义（P〉0．05）。胃癌患者高龄组与低龄组间MC数目差异有统计学意义（P〈0．05）,而在性别比例、TNM分期、浸润深度、分化级别、局域淋巴结转移、神经、脉管浸润各临床病理因素分组中差异均无统计学意义（P均〉0．05）。结论MC参与肿瘤微环境及肿瘤的形成与发展,但与重要临床病理资料无明显相关性。     

乳腺癌Hpa表达与淋巴管生成的相关性

目的 探讨乙酰肝素酶(Hpa)在乳腺正常组织、不典型增生、导管内癌、浸润性导管癌组织中的表达水平,分析其与浸润性乳腺癌临床病理指标及肿瘤淋巴管生成之间的关系.方法 收集西安交通大学第一附属医院2005年1月至2007年12月经手术切除的23例不典型增生组织,34例导管内癌组织,80例浸润性导管癌组织标本,以及距离肿瘤边...     

New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.     

乳腺癌相关抗原在乳腺癌辅助诊断中的应用

目的 探讨乳腺癌相关抗原CA15-3动态检测对乳腺癌的早期诊断价值.方法 运用SEROZYME系统检测了疑有乳房疾患和妇女健康普查的妇女512人外周血CA15-3数值,并对CA15-3值高于27.4 IU/mL的患者1～3月后再次复查CA15-3.结果 CA15-3动态增高组PVPT为85.7%.CA15-3相近和降低组6例,病理检查证实为乳腺癌1例,阳性预测值(PVPT)为16.7%.结论 CA15-3动态检测对乳腺癌早期诊断有重要价值,尤其是CA15-3高于40IU/ml的动态升高组在乳腺癌早期诊断中具有不可替代的预测作用.     

乳腺癌肿瘤细胞检测及其临床意义

目前,在部分未见转移的乳腺癌患者中,通过免疫细胞化学和分子生物学的方法能检测到骨髓中的微转移细胞和外周血中的循环肿瘤细胞,而且研究证实检测肿瘤细胞的存在与否,对预后判断和治疗效果监测都有一定的意义,本文就目前所采用的检测微转移细胞和循环肿瘤细胞的方法和它们的临床意义作一简要综述。     

The breast tumor microenvironment: role in cancer development,progression and response to therapy

Introduction: Numerous clinical and pre-clinical studies have provided ample evidence supporting that the tumor microenvironment plays a significant role during breast cancer development, progression and in determining the therapeutic response.

Areas covered: This review focuses on the evolving concept of the microenvironment as the critical participant in each step of the multi-stage process of malignant progression. Currently, only a small number of molecules form part of routine molecular diagnostics in breast caner, but microenvironment-derived biomarkers are potential additions to existing predictive and prognostic marker panels. The authors discuss the dependency of the breast tumor cells on different components of the microenvironment for their survival, dissemination, dormancy and establishment in secondary sites to form overt metastasis, as well as the potential as a therapeutic target to improve breast cancer outcome.

Expert commentary: Despite the importance in the development of breast cancer, the contribution of the microenvironment is not considered in routine diagnostic testing or informing therapeutic decisions. However, introduction of immunotherapy will increasingly require patient selection based on the stromal composition of the primary breast tumor. Better understanding of the role of specific microenvironment-derived molecules is likely to inform personalized therapy, leading to improved patient outcome.     

PEBP4 silencing inhibits hypoxia-induced epithelial-to-mesenchymal transition in prostate cancer cells

Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family and has been reported to be upregulated in various cancer types. The definite function of PEBP4 in regulating the EMT of prostate cancer, however, is still unclear. Here, we examined the functional role of PEBP4 and the underlying molecular mechanisms in hypoxia-induced EMT in prostate cancer cells. Our results showed that PEBP4 mRNA and protein expression was markedly increased in the human prostate cancer tissues and cell lines. Knockdown of PEBP4 significantly inhibited hypoxia-induced migration/invasion and EMT program. Furthermore, knockdown of PEBP4 prevented hypoxia-induced the expression of p-Akt and p-mTOR in prostate cancer cells. Taken together, this study reported here provided evidence that knockdown of PEBP4 inhibited hypoxia-induced EMT in prostate cancer cells. Our study uncovered a novel role for PEBP4 in prostate cancer progression, which might support the potential for PEBP4 targeting in prostate cancer therapy.     

MicroRNA与乳腺癌关系的研究进展

MicroRNAs（miRNAs）是一类广泛存在于真核细胞中的长约21-22 nt的单链、非编码小RNA,具有转录后基因调控的功能,参与调控胚胎发育、细胞生长和凋亡、细胞分化、细胞能量代谢等多种生理过程以及糖尿病、心血管疾病、神经系统疾病、肿瘤等多种病理过程。近些年来研究发现,miRNAs与乳腺癌之间的关系十分密切。本文综述与乳腺癌发生、发展密切相关的miRNAs。     

骨髓间充质干细胞缺氧后促红细胞生成素信号通路的改变

目的研究骨髓间充质干细胞缺氧后细胞死亡情况及促红细胞生成素信号通路成分的表达改变。方法从Wistar大鼠股骨提取骨髓分离培养骨髓间充质干细胞并在体外扩增。取第4至6代接近融合的骨髓间充质干细胞置于氧浓度为0．5％的缺氧箱内培养24、48、72、96h后行台盼蓝染色计数阳性细胞并提取蛋白行Western blot检测促红细胞生成素、促红细胞生成素受体、HIF-1α、ERK、磷酸化ERK表达改变,另取0．5％缺氧培养48h的细胞免疫荧光染色观察EPO表达改变,Hoechst 33342染细胞核。结果常氧浓度培养对照组骨髓间充质细胞组台盼蓝染色阳性率为3．5％±0．4％,缺氧培养24、48、72、96h组分别为3．9％±0．2％、5．0％±0．4％、5．9％±0．5％、7．1％±0．5％。Western blot和免疫荧光染色发现EPO表达在缺氧48h后开始明显上调。F20R表达在缺氧后24h即开始显著上调且倍数更高。总ERK在对照组和不同缺氧时间组表达改变不明显,但HIF-1α和磷酸化ERK缺氧24h后即上调,72h达高峰。结论骨髓间充质干细胞对单纯缺氧损害较耐受,缺氧后促红细胞生成素信号通路的主要成分均显著上调,提示促红细胞生成素信号通路在骨髓间充质干细胞耐缺氧和旁分泌保护能力中起着重要作用。     

Closer to Nature: The Role of MSCs in Recreating the Microenvironment of the Hematopoietic Stem Cell Niche in vitro

BackgroundThe stem cell niche in human bone marrow provides scaffolds, cellular frameworks and essential soluble cues to support the stemness of hematopoietic stem and progenitor cells (HSPCs). To decipher this complex structure and the corresponding cellular interactions, a number of in vitro model systems have been developed. The cellular microenvironment is of key importance, and mesenchymal stromal cells (MSCs) represent one of the major cellular determinants of the niche. Regulation of the self-renewal and differentiation of HSPCs requires not only direct cellular contact and adhesion molecules, but also various cytokines and chemokines. The C-X-C chemokine receptor type 4/stromal cell-derived factor 1 axis plays a pivotal role in stem cell mobilization and homing. As we have learned in recent years, to realistically simulate the physiological in vivo situation, advanced model systems should be based on niche cells arranged in a three-dimensional (3D) structure. By providing a dynamic rather than static setup, microbioreactor systems offer a number of advantages. In addition, the role of low oxygen tension in the niche microenvironment and its impact on hematopoietic stem cells need to be taken into account and are discussed in this review.SummaryThis review focuses on the role of MSCs as a part of the bone marrow niche, the interplay between MSCs and HSPCs and the most important regulatory factors that need to be considered when engineering artificial hematopoietic stem cell niche systems.ConclusionAdvanced 3D model systems using MSCs as niche cells and applying microbioreactor-based technology are capable of simulating the natural properties of the bone marrow niche more closely than ever before.     

腹腔微环境与卵巢上皮性癌腹腔转移关系的研究

目的：探讨腹腔微环境与卵巢上皮性癌腹腔转移关系的研究。方法采用 RT-PCR 法及免疫组化法检测卵巢上皮性癌组织相应趋化因子受体及其配体的表达情况,腹膜组织相应配体的表达情况,以揭示趋化因子介导上皮性卵巢癌腹腔内转移机制。结果趋化因子受体 CXCR4在卵巢上皮性癌组织中表达明显高于其他趋化因子受体表达（P ＜0．01）;趋化因子受体 CX-CR4的配体 SDF-1在上皮性卵巢癌组织和腹膜中均高表达。结论趋化因子 SDF-1及其受体 CXCR4在卵巢癌组织中高表达,通过自分泌作用,可能刺激卵巢癌细胞的过度生长;SDF-1在腹膜组织高表达,通过旁分泌作用,可能介导表达 CXCR4的卵巢癌细胞向腹腔内转移。     

乳腺特异性伽马成像半定量指标与乳腺癌临床特征的相关性

目的:探讨乳腺特异性伽马成像(BSGI)半定量分析指标与乳腺癌常见临床特征的相关性。方法:收集2016年1月至2017年7月在复旦大学附属中山医院住院的668例乳腺疾病患者。BSGI检查基于目测分析法和半定量分析法。其中,半定量分析的具体方法为:首先计算可疑病灶与邻近正常组织放射度的比值(T/N),分别在轴位(craniocaudal,CC)与内外侧斜位(mediolateral oblique,MLO)中各获取1个T/N值,选取最大值为半定量分析结果。比较不同病理状态下T/N值的差异。结果:668例患者中,恶性肿瘤患者505例、良性肿瘤患者163例,均可获得T/N值。受试者工作特征曲线(receiver operating characteristic curve,ROC)显示,临界T/N=1.81,AUC为0.83(SD=0.844,95%CI 0.812~0.872),BSGI敏感性为84.53%、特异性为74.02%。不同肿瘤大小(P=0.000)、Ki-67水平(P=0.039)、腋窝淋巴结转移情况(P=0.02)患者T/N值差异有统计学意义。结论:T/N值与肿瘤大小、Ki-67和腋窝淋巴结转移等临床病理因素相关,可用于预测乳腺癌的侵袭性,有助于医师进行临床决策。     

乳腺癌DBT征象与不同分子亚型之间的相关性

目的探讨乳腺癌数字乳腺断层摄影(DBT)征象与不同分子亚型相关性。方法回顾性分析经病理证实的260例乳腺癌患者的资料。采用单因素和多因素Logistic回归分析,以评估乳腺癌DBT征象与其分子亚型的关联。结果Luminal A、B型多表现为不规则的毛刺状肿块,毛刺与Luminal A型(OR 3.77,P<0.001)关系密切;肿块边缘清楚、形态规则高度提示三阴型(OR 12.53,P<0.001);HER-2型(OR 2.42,P=0.015)、Luminal B型(OR 1.69,P=0.047)与微钙化相关,其中单纯钙化多见于HER-2型(P=0.005),肿块伴钙化多见于Luminal B型(P=0.017);不同亚型间钙化形态有统计学差异(P=0.027),Luminal A型(12,52.2%)多表现为无定形钙化,HER-2型(10,55.6%)多表现为细小多形性钙化。结论乳腺癌某些DBT征象可用于预测特定的亚型,并帮助指导临床治疗策略。     

乳腺癌化疗患者疾病不确定感与应对方式的相关性研究

目的 探讨乳腺癌化疗患者疾病不确定感和应对方式的相关性.方法 描述性相关性研究设计,使用一般资料调查表、Mishel疾病不确定感量表(MUIS-A)和医学应对方式问卷(MCMQ)对147例乳腺癌化疗患者进行调查,所有资料使用SPSS 11.5进行统计分析.结果 乳腺癌化疗患者的疾病不确定感得分(87.46±9.92),与面对(19.63±4.02)和回避(14.81±2.26)的应对方式呈显著负相关(P＜0.01),与屈服(9.68±2.67)的应对方式呈显著正相关(P＜0.01).结论 较多使用面对和回避应对方式的乳腺癌化疗患者疾病不确定感较低,较多使用屈服应对方式的患者疾病不确定感较高.建议医护人员在临床工作中指导乳腺癌化疗患者使用有效的应对方式以降低疾病不确定感,促进身心健康.     

肿瘤抑制基因PTEN在乳腺癌中的表达及其临床意义

目的研究肿瘤抑制基因PTEN在乳腺癌组织中的表达及临床意义。方法采用免疫组化法检测83例乳腺癌组织PTEN蛋白的表达情况。结果83例乳腺癌组织的PTEN阳性表达率为61.4%（51/83）,PTEN阴性表达率为38.6%（32/83）。PTEN表达与乳腺癌原发肿瘤的大小（P〈0.05）、临床分期（P〈0.05）、淋巴结转移（P〈0.05）以及雌激素受体（ER）（P〈0.05）有关。PTEN高表达的乳腺癌患者5年总生存率明显高于低表达者（P〈005）。结论乳腺癌组织中存在肿瘤抑制基因PTEN的表达缺失或减弱,可能与乳腺癌的发生、发展有关。PTEN可以作为一个判断乳腺癌预后的指标。     

不同分子亚型乳腺癌的MRI特征研究

目的探讨不同分子亚型乳腺癌的MRI特征。方法收集2015年3月~2016年12月行3.0 T MRI检查并经病理证实的乳腺癌病例187例,所有病例都能区分不同分子亚型。比较各型乳腺癌在年龄、组织学分类、病理分级、病灶形态、肿块数目、肿块大小、肿块形状、肿块边缘、肿块强化特征、病灶T_2WI信号、TIC曲线、ADC值、瘤周血管上的差异,并采用单因素及多因素分析法进行统计学分析。结果 Luminal A组45例(24.1%),Luminal B组91例(48.7%),HER-2过表达组26例(13.9%),三阴性乳腺癌(TNBC)组25例(13.4%)。TNBC多表现为边缘光整、圆形肿块、环形强化、T_2WI高信号;而TNBC和HER-2过表达型共同表现为具有较高的ADC值、瘤周血供丰富及较高病理分级;Luminal A型则多表现为瘤周血供较少,病理分级较低。结论不同分型乳腺癌特别是TNBC具有一定的MRI特征。     

阿片受体及其药物与乳腺癌的关系的研究进展

阿片类药物是癌症患者常用的麻醉镇痛药,但有许多研究提示阿片受体及其药物与乳腺癌之间存在紧密关联。本文对阿片类药物对乳腺癌和阿片受体对乳腺癌以及μ阿片受体多态性A118G与乳腺癌的关系做一综述。