Her2 positive breast cancer: practices

The molecular classification of Perou and Sørlie breast tumors has to streamline, systematize and make effective use of targeted therapies against specific molecular subtypes, including breast HER2 positive. Trastuzumab and lapatinib are currently the two therapies targeting HER2, which have demonstrated their effectiveness in clinical practice. This literature review aims to make the data points on pertinent and useful data for physicians in daily     

Targeting metastatic upper gastrointestinal adenocarcinomas

Upper gastrointestinal (GI) tumors, including adenocarcinoma of the esophagus, stomach, pancreas, and biliary tree, have traditionally been difficult to treat with cytotoxic chemotherapeutic agents. There has been little drug development success in treating these cancers over the last 20 years, perhaps a reflection of a combination of the aggressive biology of these tumors, the void in effective and specific drug development for these varied tumors, and the lack of properly designed, biologically-based clinical trials. Recently, so called "targeted agents" have risen to the forefront in the care of cancer patients and have made strong impacts in many areas of oncology, particularly gastrointestinal stromal tumors (GIST), colon, breast, and lung cancers. Unfortunately, slow progress has been made using such agents in upper GI tumors. However, more recently, trials in some tumor types have demonstrated gains in progression free survival and overall survival. In this review, we discuss the drugs and pathways that have been most successful in the treatment of upper GI tumors and present the relevant data supporting their use for each tumor site. Additionally, we will explore a few novel pathways that may prove effective in the treatment of upper GI malignancies in the near future.     

利用噬菌体随机七肽库技术筛选人膀胱癌相关表面标志物Her2、Survivin表位模拟肽

目的 利用噬菌体随机七肽库技术筛选人膀胱癌相关表面标志物Her2、Survivin表位模拟肽.方法 分别以Her2、Survivin多克隆抗体为固相筛选分子,对噬菌体随机七肽库进行3轮生物淘洗,随机挑选单克隆噬菌体进行酶联免疫吸附试验(ELISA)分析检测其结合力,竞争抑制实验鉴定其阳性克隆,对结合力较好的噬菌体提取DNA并测序,寻找比较保守的核心序列,合成多肽,最后鉴定合成多肽的结合力.结果经噬菌体随机七肽库3轮淘洗后,特异性噬菌体模拟肽得到富集,分别挑选Her2、Survivin20个克隆,经DNA测序分析,Her2较保守的序列为ACT ACG GCT GAG AAT AAT GAG,Survivin为TCT CCT CCT CAT CTT TCG CAG,合成多肽,Her2为Thr-Thr-Ala-Glu-Asn-Asn-Glu(TTAENNE),Survivin为Ser-Pro-Pro-His-Leu-Ser-Gln(SPPHLSQ),ELISA分析具有良好结合力.结论 利用噬菌体随机七肽库成功筛选到人膀胱癌相关表面标志物Her2、Survivin表位模拟肽,从而为今后膀胱癌多肽疫苗的研制提供良好的基础和条件.     

Her2／Neu和EGFRvⅢ与乳腺癌发生及浸润的相关性研究

目的探讨表皮生长因子受体2型（Her2／Neu）和表皮生长因子受体3型突变体（EGFRvⅢ）在乳腺癌发生及其浸润过程中的作用。方法采用免疫组织化学染色法（SP法）检测30例正常乳腺组织（NB）、导管原位癌（DCIS）和乳腺浸润性导管癌（IDCNOS）符50例石蜡标本中Her2／Neu和EGFRvⅢ的表达情况。结果Her2／Neu和EGFRvIII在NB、DCIS和IDCNOS组中的阳性表达率均呈上升趋势,且差异均有显著性意义（P〈0．01）。IDCNOS组巾EGFRvⅢ的表达水平明显高于DCIS组（P〈0．01）。各组乳腺组织中Her2／Neu和EGFRvⅢ的表达情况呈正相关（r=0．597,P〈0．001）。结论Her2INeu和EGFRvIII均可能参与乳腺癌的发生,且EGFRvIII可能在乳腺癌的浸润过程中起重要作用。     

TOPOIIα and HER‐2/neu overexpression/amplification in Barrett’s oesophagus,dysplasia and adenocarcinoma

Rossi E, Villanacci V, Bassotti G, Donato F, Festa A, Cengia G, Grisanti S & Cestari R
(2010) Histopathology 57, 81–89
TOPOIIα and HER‐2/neu overexpression/amplification in Barrett’s oesophagus, dysplasia and adenocarcinoma Aims: Topoisomerase IIα (TOPOIIα) and HER‐2/neu are chromosome 17q genes coamplified in various cancers; no data exist for Barrett’s oesophagus (BO) and BO adenocarcinoma (ADC). The aim was to investigate gene amplification and protein overexpression of TopoIIα and Her‐2/neu in non‐dysplastic BO, dysplastic BO, Barrett ADC, and chromosome 17 aneusomy. Methods and results: Forty‐four patients [18 BO, 13 BO with dysplasia (five low‐grade dysplasia, eight high‐grade dysplasia) and 13 ADC in BO] were evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). Genes (HER‐2/neu and TOPOIIα) and chromosome 17 were evaluated by FISH. Patients with BO, dysplasia and ADC were compared. A significant association was found between TOPOIIα protein overexpression and TopoIIα gene amplification, chromosome 17 aneusomy, HER‐2/neu gene amplification and HER‐2 protein overexpression as well as between HER‐2 protein and HER‐2/neu gene, TopoIIα gene and aneusomy for chromosome17, and between the genes TOPOIIα and HER‐2/neu. Gene amplification (HER‐2/neu, TOPOIIα), protein overexpression (HER‐2/TOPOIIα), and chromosome 17 aneusomy were associated with dysplasia or ADC. Most BO patients showed no amplification/overexpression/aneusomy for the above genes, proteins and chromosome, with no differences between dysplasia and ADC. Conclusions: HER‐2/neu and TOPOIIα amplification/overexpression might discriminate between BO and dysplasia/ADC. Chromosome 17 aneusomy is associated with dysplasia or ADC in BO.     

乳腺癌患者血清Her2-ECD、CA15-3、TPS检测的临床意义

为了评价血清Her2-ECD、CA15-3、TPS检测在各期乳腺癌中的应用价值,通过测定45例乳腺癌患者、30例乳腺良性病变患者和30名正常人血清Her2-ECD、CA15-3、TPS水平,分析其在辅助诊断、疗效观察和预后判断中的价值。结果表明,早期乳腺癌患者血清CA15-3、Her2-ECD与良性乳腺疾病患者及正常对照组之间无显著性差异,TPS在早期乳腺癌患者中虽有升高,但诊断灵敏度和特异性过低（44.00%,33.33%）;晚期、复发转移乳腺癌病人三项指标均明显高于其他各组,但相互间无明显相关性。Wilcoxon检验结果表明,三项指标术后均明显低于术前（P〈0.05）,个别术后指标升高者预后不佳。绝经与否、肿瘤直径、淋巴结转移、ER、PR等5项因素对三项肿瘤标志物的血清水平没有影响,晚期乳腺癌患者CA15-3和Her2-ECD阳性率明显高于早期患者,而TPS水平与肿瘤分期无关。血清Her2-ECD水平与组织Her2 IHC结果较为一致。结论：CA15-3、TPS和Her2-ECD三项血清学指标都不具备乳腺癌早期诊断的价值,但是三项指标从肿瘤生物活性的不同侧面提供了有价值的信息,对于上述指标升高的早期乳腺癌患者,连续动态监测将有助于判断疗效、疾病进展和预后。血清Her2-ECD作为Her2 IHC和FISH检测的有效补充和延续手段,可对各期乳腺癌的治疗、疗效观察和判断预后提供其独立而客观的参考信息。     

Molecular and magnetic resonance imaging: The value of immunoliposomes

Molecular imaging has the potential to transform the field of diagnostic imaging through enabling far more detailed investigation and characterisation of disease processes than is currently possible. Magnetic resonance imaging (MRI) is capable of three-dimensional non-invasive imaging of opaque tissues at near cellular resolution. Among the imaging techniques available today, MRI has, perhaps, the greatest potential to exploit the possibilities that molecular imaging presents. Nanoparticles are the focus of intense research, due to a wide variety of potential applications in the biomedical, optical, and electronic fields. In this article we examine the progress made in the development of nanoparticles as targeted contrast agents for molecular magnetic resonance imaging. In particular, we will examine the potential of antibody-targeted liposomes (immunoliposomes) as vehicles for delivering MRI contrast agents to cellular biomarkers, thus enabling visualisation of structures and processes at the molecular level. We will address some of the challenges that must be faced by researchers in this field before the progress made in the laboratory can be translated into improved clinical diagnostics and therapeutics.     

Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer

Background: Brain metastases are frequently encountered in Her2 positive advanced breast cancer. It is still not clear, if trastuzumab treatment should be continued following their diagnosis. In this analysis we evaluated if trastuzumab was able to influence time to in-brain progression (TTP) and overall survival (OS). For this reason, we compared patients who continued on trastuzumab with a historical control group. Patients and Methods: Seventeen Her2 positive patients receiving whole brain radiotherapy for brain metastases and continuing on trastuzumab were identified. As historical control group, thirty-six patients treated before 2002 were identified from a breast cancer database. We performed a multivariate analysis (Cox regression) to explore which factors were potentially able to significantly influence TTP and OS. Results: Median TTP was 6 months, range 1–33+ months. Median OS was 7 months, range 1–38 months. Seventeen patients received trastuzumab after WBRT. Factors associated with prolonged TTP were KPS (p = 0.001), and intensified local treatment (p = 0.004). A trend towards longer TTP was observed in patients treated with trastuzumab (p = 0.068). OS was significantly influenced by KPS (p < 0.001), and continued antibody therapy (p = 0.001). Conclusion: Two parameters were significantly associated with prolonged OS: KPS and trastuzumab. While there was a trend towards prolonged TTP in patients with trastuzumab treatment after WBRT, this did not reach statistical significance. It appears therefore reasonable to suggest continuation of antibody therapy in patients with good performance status despite disease spreading to the brain. Concerning activity of trastuzumab in brain metastases themselves, no final conclusion is possible.     

Cyclin A2 和Her2 结合可更好预测早期乳腺癌的复发风险

摘要：目的: 评价281例浸润性乳腺癌cyclin A2 和Her2 的表达,对预测复发风险的关系;方法：用免疫组化检测了北医三院281例乳腺癌患者cyclin A2 和Her2 的表达,以及用基因芯片和RT-PCR技术检测了12例患者的cyclin A2 和Her2 的扩增,用Kaplan-Meier,和Cox regression 分析两者与乳腺癌生存的关系;结果：cyclin A2 在76.5%的患者中有表达,65例≦5%, 110 例6～25%, 75 例26～50% , 30例﹥50% 。cyclin A2 和Her2 过表达的患者有明显低的 DFS (分别为P=0.047 和 p=0.05, )。但用Kappa分析,两者是独立的预测因子,为0.37。基因表达谱和RT-PCR也验证了cyclin A2 在早期复发的患者上调,平均上调3.69和2.74倍。结论：cyclin A2 和Her2一样均能将患者分成不同的预后,但两者并不吻合,而是互为补充,所以两者结合可以更好地预测乳腺癌的复发风险,特别是在Her2 阴性的患者;cyclin A2 作为核内蛋白更容易检测。     

人工栽培黄花石蒜乙醇提取物HPLC指纹图谱研究

目的:建立人工栽培黄花石蒜乙醇提取物HPLC指纹图谱。方法:黄花石蒜乙醇提取物的分析采用ZORBAX Eclipse XDB-C18色谱柱(4.6×250 mm,5μm);流动相:甲醇(A)-水(含0.1%磷酸,B),梯度洗脱见表2;柱温:30℃;紫外检测波长:238 nm;流速:1.0 mL/min。结果:以加兰他敏为参照峰,确定了13个特征峰,10批样品指纹图谱相似度均在0.9以上。结论:此方法操作简单,准确可靠,可为黄花石蒜鉴别及内在质量评价提供参考依据。