Her-2/neu基因过表达与胃癌生物学行为的关系研究

目的:了解Her-2/neu基因过表达与胃癌生物学行为的关系。方法:应用免疫组化法检测了具有随访资料的164例胃癌标本的Her-2/neu基因的表达状态。结果:164例胃癌的Her-2/neu基因过表达率为19·51%,其过表达与患者的性别、年龄、肿瘤生长的部位、分化程度、浸润深度、脉管内癌细胞的浸润、UICC分期均无关(P>0·05);仅与胃癌的病理类型密切相关(P<0·05);且Her-2/neu基因过表达与胃癌的预后无关,胃癌的预后仅与胃癌的浸润深度和UICC分期有关。结论:胃癌Her-2/neu基因过表达似与胃癌的病理类型密切相关,预后与肿瘤的浸润深度和UICC分期有关。     

Her-2基因与乳腺癌靶向治疗

近年来随着肿瘤分子生物学技术的发展,分子靶向药物治疗已成为众多学者关注的热点领域,对乳腺癌的治疗策略产生了重大影响.其中,人表皮生长因子受体-2(Her-2)已证实为一个有效的分子靶向治疗的靶标,针对乳腺癌Her-2的分子靶向治疗成为近来继化疗和内分泌治疗后又一重要的治疗手段.     

Her-2/neu和NF-κBp65在胃癌中的表达及其临床意义

目的：探讨Her-2/neu和NF-κBp65在胃癌组织中的表达及其临床意义.方法：应用免疫组织化学PV-9000法检测80例胃癌及30例癌旁正常胃组织中Her-2/neu和NF-κBp65蛋白的表达,并分析其与胃癌临床病理特征之间的关系.结果：Her-2/neu在胃癌和癌旁正常胃组织中的阳性表达率分别为17.3%和3.3%（P〈0.05）,Her-2/neu的过表达与胃癌组织分化程度、淋巴转移显著相关（P〈0.05）.而NF-κBp65在胃癌和癌旁正常胃组织中阳性表达率分别为58.7%和11.4%（P〈0.05）,NF-κBp65表达与胃癌的组织分化程度、浸润深度和淋巴转移显著相关（P〈0.05）.Her-2/neu和NF-κBp65在胃癌组织中表达呈显著正相关（P〈0.05）.结论：Her-2/neu和NF-κBp65在胃癌组织中高表达与胃癌的发生发展密切相关,联合检测Her-2/neu和NF-κBp65表达,对指导胃癌分子靶向治疗及患者预后评估具有重要意义.     

Her-2/neu与术后复发晚期胃癌临床病理及预后的相关性研究

摘 要：［目的］ 探讨术后复发晚期胃癌患者Her-2/neu表达及与临床病理特征和预后的相关性。［方法］ 分别采用免疫组织化学法（IHC）及荧光原位杂交法（FISH）对108例术后复发晚期胃癌患者进行Her-2/neu表达的检测,分析其与患者的年龄、性别、Lauren分型、组织学分级及与预后的相关性。［结果］ 108例患者中,IHC法检测Her-2/neu阳性表达13例,FISH法检测Her-2/neu阳性表达14例,两种方法均为阳性表达者10例,一致率为61.5 %。15例正常胃黏膜中未见阳性表达。Her-2/neu表达与患者的年龄、性别、肿瘤部位、组织学分级、TNM分期、浸润深度、有无脉管浸润无关（P＞0.05）,而与患者的Lauren分型、淋巴结转移有关（P＜0.05）。Her-2/neu阳性患者的中位疾病进展时间（TTP）为22.4个月（95%CI：23.44~26.55）,阴性患者的中位TTP为25.0个月（95%CI：17.02~27.77）,两者差异无统计学意义(P=0.215)。［结论］ Her-2/neu可能是胃癌预后不良的标志之一。     

乳腺癌患者血清与肿瘤组织中Her-2/neu表达的相关性研究

目的 :建立一种检测血清Her 2 /neu的快速、简单的方法 ,并从临床的角度探讨了血清Her 2 /neu与组织Her 2 /neu表达及其他因素的相关性。方法 :收集初治乳腺癌 5 3例 ,采用ELISA方法检测血清Her 2 /neu水平 ,并采用免疫组化方法对术后标本进行组织Her 2 /neu表达的检测 ;同时设立了 10例正常人、31例乳腺良性病变为对照。结果 :早期乳腺癌中 ,10 / 5 3(19% )血清Her 2 /neu水平高于正常 ,组织Her 2 /neu表达阳性者中 32 %血清Her 2 /neu阳性 ,而组织表达阴性者中仅7%血清阳性 ,二者有相关性 (P <0 0 5 )。血清Her 2 /neu水平与肿瘤大小有相关性 (P <0 5 ) ,与淋巴结、受体状况无关。结论 :血清Her 2 /neu与组织Her 2 /neu有一致性 ,前者可作为后者的补充。     

PEA3蛋白在乳腺癌组织中的表达及其与Her-2/neu的关系

背景与目的:Ets转录因子家族成员多瘤病毒增强子激活因子3基因(polyomavirus enhancer activator 3,PEA3)与肿瘤的侵袭和转移密切相关,其在乳腺癌发生、发展中的作用有待探讨.本研究旨在探讨PEA3蛋白在乳腺癌组织中的表达及其与Her-2/neu和乳腺癌临床病理因素的关系.方法:采用免疫组化法检测80例乳腺癌组织中PEA3及Her-2/neu的表达,对Her-2/neu(++)的病例采用显色原位杂交(coloration in situ hybridization,CISH)检测Her-2基因扩增情况.结果:80例乳腺癌组织中PEA3的阳性率57.5％(46/80),高于正常乳腺组织及乳腺纤维腺瘤,与肿瘤大小、组织学分级及腋淋巴结转移均有一定的相关性,且与Her-2/neu的表达呈正相关.PEA3蛋白的阳性表达与乳腺癌患者5年生存率呈负相关.结论:PEA3与乳腺癌浸润转移及预后密切相关,有望作为乳腺癌预后的一个参考指标,其作用机制可能与Her-2/neu相关.     

RNA干扰Her-2基因对乳腺癌治疗的研究进展

乳腺癌是严重威胁女性健康的恶性肿瘤之一,近年来发病率呈现逐年上升的趋势,大量的分子遗传学资料表明约25％-30％乳腺浸润性导管癌患者存在Her-2原癌基因扩增及其蛋白的过度表达。作为乳腺癌预后不良的一项独立危险因素,Her-2与肿瘤发生、转移、放化疗抵抗具有密切关系。因此针对Her-2基因治疗、基因疫苗等技术的探索为乳腺癌的治疗提供了新的思路,目前比较前沿的为RNA干扰技术。     

新型抗Her-2药物T-DM1

T-DM1是新型抗体-药物偶联物,具有曲妥珠单抗类似的生物活性,可特异性的将强效抗微管药物DM1释放至Her-2过表达的肿瘤细胞内。T-DM1单药疗效优于拉帕替尼联合卡培他滨,有望成为Her-2阳性晚期乳腺癌的标准二线治疗药物。比较T-DM1与曲妥珠单抗联合紫杉类药物一线治疗晚期乳腺癌的试验正在进行中。该药是继曲妥珠单抗之后又一种全新的抗Her-2药物。美国FDA正式批准T-DM1作为治疗Her-2阳性晚期乳腺癌患者的药物。      

乳腺癌Her-2基因扩增及其蛋白表达与ER、PR的关系及临床意义

目的:探讨乳腺癌中Her-2基因及其蛋白表达状况,并研究其与ER、PR的关系及临床意义。方法:采用荧光标记原位杂交(FISH)和免疫组化法(IHC)检测45例乳腺癌组织中Her-2基因及其蛋白表达并检测ER、PR表达。实验数据采用SPSS统计软件处理。结果:在45例乳腺癌中有17例出现Her-2基因扩增,阳性率为37.7%。Her-2蛋白总阳性率为66.7%。Her-2基因阳性率在ER阳性组为32.3%,在ER阴性组为50.0%,Her-2基因阳性率在PR阳性组为27.5%,在PR阴性组为56.2%。FISH法检测Her-2基因扩增与Her-2蛋白过表达之间相关(P<0.05),而与淋巴结转移、组织学分级及ER、PR的表达无关(P>0.05)。结论:FISH检测Her-2基因扩增和免疫组化检测Her-2蛋白一致性较好,ER、PR和Her-2三者在乳腺癌的发生发展中起重要作用。     

复方苦参注射液辅助治疗Her-2／neu过表达乳腺癌的疗效观察

 摘要】　目的　观察并探讨复方苦参注射液辅助多西紫杉醇治疗Her-2／neu过表达乳腺癌的治疗效果。方法　选择Her-2／neu过表达、改良根治术后乳腺癌患者,前期完成AC方案化疗,共38例,行随机、对照、双盲法试验。患者随机分为两组,A组17例,给予多西紫杉醇化疗,B组21例,行复方苦参注射液辅助多西紫杉醇化疗。所有患者检测血清Her-2／neu胞外配体域 （ECD）水平,观察化疗不良反应。结果　A、B两组患者化疗后Her-2／neu ECD水平分别为（3.74±2.26）和（2.73±2.18）ng／ml,化疗前分别为（4.33±2.98）和（3.92±2.59）ng／ml,化疗前后差异均无统计学意义（t＝0.65,P＞0.05;t＝1.61,P＞0.05）。B组患者骨髓抑制和消化系统反应较A组轻,差异有统计学意义（χ2＝8.610,P＜0.01;χ2＝5.828,P＜0.05）。结论　复方苦参注射液辅助多西紫杉醇化疗能增强对Her-2／neu过表达乳腺癌的抗肿瘤效应,减轻患者化疗不良反应。     

Her-2/neu、p53和P-gp在非小细胞肺癌中的表达

[目的]探讨非小细胞肺癌（NSCLC）中Her-2/neu、p53和P-gp的表达及临床意义。[方法]采用免疫组化EnVision法,对60例NSCLC及其20例正常肺组织中Her-2/neu、p53和P-gp进行检测。[结果]Her-2/neu、p53和P-gp相关蛋白在NSCLC中的表达分别是75%、70%和75%,而正常组织未见表达（P均〈0.01）。Her-2/neu的表达与病理类型和组织学分级呈相关性（P=0.031和P=0.047）;p53的表达与淋巴结转移、临床分期有关（P=0.024和P=0.003）;P-gp的表达与病理类型有关（P=0.020）;三者之间,Her-2/neu的阳性表达与p53和P-gp的阳性表达存在明显正相关性（P=0.025和P=0.000）,而p53的阳性表达与P-gp的阳性表达之间未见明显相关性（P=0.517）。[结论]Her-2/neu、p53和P-gp在NSCLC的发展过程中起了重要作用,联合检测该三项基因的表达将有助于判断是否存在肿瘤的原发耐药及治疗方案的选择。     

Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund’s adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors. Asim Saha and Smarajit Pal contributed equally to this work. This work was presented as abstract in the San Antonio Breast Cancer Symposium, 2005. Breast Cancer Research and Treatment 94, supplement 1:4093.     

Her-2/neu基因扩增及其蛋白表达与肺癌分化和转移的关系

应用荧光原位杂交技术（FISH）和免疫组化法观察50例肺癌中Her－2／neu基因扩增及其蛋白表达状况、组织学分级和淋巴结转移的关系。结果有Her－2／neu基因扩增者共2例（4％）。有Her－2／neu基因蛋白表达共12例（24％），其中鳞癌1例，肺泡细胞癌4例，腺癌6例，神经内分泌癌1例。肺癌组织学分级Ⅰ级与Ⅱ、Ⅲ级间该基因蛋白表达均有明显差异（P＜0．05），有肺门或支气管淋巴结转移与无淋巴结转移蛋白表达亦有明显差异（P＜0．05）。研究结果表明Her－2／neu基因编码的P185KD蛋白在肺癌分化及转移过程中起重要作用。     

乳腺癌患者血清Her-2/neu蛋白的临床意义

[目的]探讨血清Her-2/neu蛋白在乳腺癌患者诊疗中的临床意义.[方法]应用化学发光法(chemiluminescence immunoassay,CLIA)对60例健康人、100例其他肿瘤患者和195例乳腺癌患者样本进行Her-2/neu蛋白检测.[结果]健康对照组、其他肿瘤对照组和乳腺癌组血清Her-2/neu浓度分别为10.3± 1.7ng/ml、10.9±2.6ng/ml和23.7±38.8ng/ml,乳腺癌组浓度明显高于健康对照组(P=0.003)和其他肿瘤组(P=0.005).Ⅰ～Ⅱ期乳腺癌血清Her-2/neu浓度明显低于Ⅲ～Ⅳ期,差异有统计学意义(P=0.001).乳腺癌Her-2阴性、+、++和+++4组患者血清Her-2/neu蛋白浓度分别为32.3±56.2ng/ml、27.9±31.4ng/ml、17.7±29.2ng/ml和23.1 ±39.6ng/ml;血清Her-2/neu蛋白阳性率分别为26.67％ 、33.33％、11.11％和15.38％.转移性乳腺癌患者血清Her-2/neu检测结果与临床状态总体符合率为82.98％(39/47).[结论]血清Her-2/neu蛋白水平与乳腺癌患者临床分期相关,化学发光法检测血清Her-2/neu蛋白在乳腺癌临床诊疗中有重要应用价值.     

EXPERIMENTAL RESEARCH OF EFFECTIVENESS OF siRNA- Her-2/neu ON DRUG SENSITIVITY OF Her-2/neu-OVEREXPRESSING LUNG ADENOCARCINOMA CELL LINE

Lung cancer is a potentially systemic disease. Despite improvements in the detection and treatment of lung cancer in the past two decades, the overall 5-year survival remains <15%. Constitutive overexpression for Her-2/neu gene is a frequent event in a variety of human tumors, including non-small cell lung cancer (NSCLC), but not small cell lungcancer[1-5]. In recent years, many studies have explored the effects on chemosensitivity resulting from altered expression and activation of the Her…     

Expression of ER,PR, and Her-2/neu in Endometrial Cancer: A Clinicopathological Study

Objective: To determine any association between expression of estrogen receptor (ER), progesterone receptor(PR), and Her-2/neu and clinicopathological features, including survival, of endometrial carcinoma (EMC)patients. Methods: Samples of formalin-fixed, paraffin-embedded tissue of 108 patients with EMC treated atour institution between January 1994 and December 2007 were immunohistochemically studied. Results: ER,PR, and Her-2/neu expression were positive in 59.3%, 65.7% and 2.8% of cases, respectively. Positive ERexpression was significantly associated with grade I-II tumor while PR expression was linked with endometrioidhistology, grade I-II tumor, less myometrial invasion (MI) and negative lymph node involvement. Her-2/neuexpression was significantly associated with deep MI, while positive ER and negative Her-2/neu expression incombination was significantly associated with longer disease-free and overall survival. Conclusion: ER expressionis a good prognostic factor while Her-2/neu expression appears to be a poor indicator for both disease-free andoverall survival, while PR tended to show favorable influence for only disease-free survival of Thai EMCs.     

Herceptin联合顺铂对高表达Her-2／neu卵巢癌体外作用的实验研究

 目的 筛选高表达Her-2／neu的卵巢癌细胞株，观察Herceptin联合顺铂（DDP）对该细胞株体外生长的抑制作用。方法 采用反转录-聚合酶链反应技术，检测人卵巢癌细胞株3AO，SKOV3，OVCAR Her-2／neu的表达情况，筛选出高表达Her-2／neu的人卵巢癌细胞株。采用四甲基偶氮唑蓝（MTT）法测定Herceptin，DDP以及联合用药对高表达Her-2／neu的人卵巢癌细胞株体外生长抑制率并进行比较。结果 人卵巢癌细胞株SKOV3 Her-2／neu呈高表达；Herceptin 可有效抑制SKOV3的生长，具有浓度依赖性（P = 0.001），联合用药组的生长抑制率为79.41 %，明显高于二者单独作用（P = 0.0001）。结论 人卵巢癌细胞株 SKOV3 Her-2／neu呈高表达。Herceptin，DDP均能有效抑制SKOV3的生长，联合用药组疗效更佳。