早期Her-2阳性乳腺癌的替代靶向治疗

大约20％的早期乳腺癌过度表达Her-2(erbB-2)受体,在历史上被认为是预后不佳的一种类型[1].抗Her-2靶向治疗显著地提高了罹患此类乳腺癌女性的预后,此治疗现在标准方案为12个月的曲妥单抗治疗(一种可以抗Her-2细胞外结构域的单克隆抗体).有4组随机对照试验显示曲妥单抗能明显提高患者的无瘤生存期和总生存期,其中2组试验(美国乳腺与肠道外科辅助治疗研究计划[NSABP]试验B-31和美国北方中心癌症治疗组试验N9831)的联合分析显示曲妥单抗能减低33％的病死率且差异具有统计学意义[2-5].在标准的新辅助治疗及辅助化疗后,1年期的曲妥单抗化疗与安慰剂相比,前者可提高总生存率,危险比为0.66 (95％ CI=0.47-0.91).在中期报告及继续随访后,因为52％的对照组交叉影响,在继续随访过程中风险比将减低[5].患者对曲妥单抗耐受性普遍较好,但和其他Her-2靶向治疗一样,均可造成无症状的左心射血分数减低,罕见情况下可出现充血性心功能衰竭.最新证据表明使用非蒽环类的联合用药可在对预后无明显影响的情况下减低上述风险[4].     

我国HER-2阳性乳腺癌预后影响因素的Meta分析

目的:系统评价影响HER-2阳性乳腺癌预后的因素。方法:检索国内公开发表的关于HER-2阳性乳腺癌预后相关的文献,依据纳入标准和排除标准,纳入符合要求的文献,并提取相应观测指标的5年生存率,利用Revman 5.3软件行Meta分析。结果:纳入4篇文献。558例患者纳入研究。各指标5年生存率的Meta结果显示,年龄≥35岁患者优于年龄35岁患者(OR=0.01,95%CI=0.01~0.02,P0.00001)、无家族史的优于有家族史的患者(OR=0.00,95%CI=0.00~0.00,P0.00001)、肿瘤5 cm的患者优于肿瘤≥5 cm的患者(OR=14.83,95%CI=1.03~212.53,P=0.05)、无淋巴结转移的患者优于有淋巴结转移的患者(OR=0.47,95%CI=0.27~0.82,P=0.007)、组织学分级为I、II级的患者优于分级为III级的患者(OR=2.84,95%CI=1.63~4.97,P=0.0002)、病理分型为其他癌的患者优于病理分型为浸润性导管癌的患者(OR=35.5,95%CI=21.71~58.03,P0.00001);绝经状态对患者预后无明显影响(OR=0.64,95%CI=0.26~1.59,P=0.34)。结论:年龄、家族史、肿瘤大小、淋巴结转移、组织学分级、病理分型与HER-2阳性乳腺癌预后有关。绝经状态对预后的影响有待进一步证明。     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

目的 评价雌、孕激素受体和Her-2表达均阴性乳腺癌(triple-negative breast cancer,TNBC)的临床病理特征及其对预后的影响.方法 500例乳腺癌采用免疫组化筛选TNBC,观察TNBC的临床病理特征,并对其中243例乳腺癌进行临床随访. 结果 500例乳腺癌中TNBC占17.6%(88/500).组织学类型主要为浸润性导管癌(NOS)、化生性癌和髓样癌.组织分级Ⅲ级占72.7%(64/88),高于激素受体阳性组和Her-2高表达组(P=0.000).TNBC中CK5/6阳性率30.7%(27/88),EGFR阳性率34.1%(30/88).TNBC中ERCC1和KIT阳性率分别为28.4%(25/88)和34.1%(30/88),均分别高于激素受体阳性组和Her-2高表达组(P=0.032和P=0.026).TNBC 3年累积生存率为71.5%,低于激素受体阳性组(P=0.021),与Her-2高表达组差异无统计学意义(P=0.474). 结论 TNBC是一类具有高侵袭性病理特征和预后不良的乳腺癌;部分病例表达EGFR和ERCC1.     

首诊HER-2阳性局部晚期年轻乳腺癌行改良PCH方案新辅助治疗的临床观察

背景与目的：HER-2阳性乳腺癌,特别是HER-2阳性局部晚期年轻乳腺癌患者,推荐采用PCH方案（紫杉醇+卡铂+曲妥珠单抗）行新辅助治疗。然而,临床中常用的溶剂型紫杉醇被聚氧乙稀蓖麻油包裹,会导致不同程度的过敏反应,骨髓抑制及外周神经毒性等不良反应。因此,本研究探讨改良PCH方案（白蛋白结合型紫杉醇+卡铂+曲妥珠单抗）新辅助治疗首诊HER-2阳性局部晚期年轻乳腺癌的临床疗效及安全性。 方法：采用前瞻性方法选取2016年6月—2018年12月于徐州医科大学附属宿迁医院乳腺外科就诊的首诊HER-2阳性局部晚期年轻女性乳腺癌患者（18~40岁）。将患者采用随机数字法分为两组,分别应用PCH方案（PCH组）与改良PCH方案（改良PCH组）行新辅助化疗,所有患者化疗6个周期化疗后评价临床疗效及不良反应,并均行改良根治术,术后继续应用曲妥珠单抗治疗满1年,对两组患者的无进展生存（PFS）与总生存（OS）进行比较。 结果：共纳入62例患者,其中PCH组30例,改良PCH组32例,两组患者术前一般资料具有可比性。新辅助治疗后,PCH组患者临床完全缓解（cCR）6例,病理完全缓解（pCR）2例,部分缓解（PR）22例;改良PCH组患者cCR 14例,pCR 8例,PR 10例,改良PCH组的cCR、pCR率均明显高于PCH组（43.8% vs. 20.0%,χ2=3.997,P=0.046;25.0% vs. 6.7%,χ2=4.098,P=0.043）。所有患者治疗期间未出现治疗相关死亡事件。改良PCH组患者中性粒细胞减少发生率为明显低于PCH组（31.3% vs. 60%,χ2=5.168,P=0.023）,改良PCH组患者中周围感觉神经毒性发生率明显高于PCH组（40.6% vs. 20.0%,χ2=3.997,P=0.046）,但均表现为手足麻木和刺痛,两组患者均未发生3~4度的神经毒性反应,其他常见不良反应,如恶心呕吐、脱发、皮疹等,两组间比较差异无统计学意义（均P>0.05）。两组患者治疗期间心功能测定均在正常范围内。改良PCH组中位PFS时间为13.1个月,中位OS时间为35.4个月,PCH组中位PFS时间为7.8个月,中位OS时间为21.6个月,差异有统计学意义（χ2=8.302、8.557,P=0.005、0.004）。 结论：对于首诊HER-2阳性局部晚期年轻乳腺癌患者,采用改良PCH方案较PCH方案不但提高了患者的cCR率,同时也一定程度上提高了pCR率,患者近期疗效满意,不良反应较轻,推荐临床应用。     

浸润性乳腺癌HER-2基因扩增与蛋白表达的关系研究

目的 了解HER-2基因与蛋白在乳腺癌中表达状况,探讨HER-2基因与Ki-67、P53、ER、PR、年龄、淋巴结转移、TNM分期的相关性及其临床意义.方法 收集150例浸润性乳腺癌组织石蜡标本,用荧光原位杂交( FISH)技术和免疫组化(IHC)法分别检测标本中的HER-2基因及HER-2、Ki-67、P53、ER、PR蛋白表达情况.结果 150例浸润性乳腺癌标本HER-2基因扩增率为32.68％ (49/150);其中,在HER-2蛋白(+++)的病例中HER-2基因扩增率为90.32％ (28/31);HER-2蛋白(++)的病例中扩增率34.78％ (16/46);HER-2蛋白(+)和(-)的扩增率分别为11.54％(3/26)、4.25％(2/47).HER-2基因与ER、PR表达及TNM分期相关,而与年龄、Ki-67、P53、淋巴结转移无关.结论 FISH技术和IHC技术检测HER-2基因和蛋白表达在(+++)和(-)的病例中一致性较好,IHC可作为替代FISH检测HER-2基因状态的方法.     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.     

雌、孕激素受体和Her-2阴性乳腺癌的临床病理特征

Objective To study the clinicopathologic characteristics of triple-negative breast cancer (TNBC) and its value in the prediction of prognosis. Method In this study,500 cases of female breast cancers were examined immunohistochcmically for the TNBC. The clinicopathologic characteristics of the 243 TNBC cases were inspected. Results TNBC accounted for 17.6% (88/500) of the 500 breast cancers. The histological types of the TNBC included mainly infihrative ductal carcinoma, metaplastic carcinoma and medullar carcinoma. Among those, histological grade Ⅲ accounted for 72.7% (64/88) of all the TNBC and was more common than that in hormone receptor positive breast cancers (HR+ group ) and Her-2 overexpression breast cancers (Her-2 group)(P=0.000). The positive rates of CK5/6 and EGFR in the TNBC were 30.7% (27/88) and 34.1% (30/88), respectively. The positive rates of ERCC1 and KIT in the TNBC were 28.4% (25/88) and 34.1% (30/88), respectively, Both of which were higher than those in the HR + group and Her-2 group, respectively (P=0.032 and P=0.026). 3-year survival rate of the TNBC was 71.5% and it was lower than that of HR group (P=0.021) and not significantly different from that of Her-2 group (P=0.474). Conclusions TNBC is the breast cancer with high aggressive pathologic futures and poor prognosis. EGFR and ERCC1 expression were positive in a portion of TNBC cases.     

乳腺癌干细胞含量及其耐药相关蛋白表达的临床病理意义

目的：探讨乳腺癌中癌干细胞含量与临床病理参数的关系,以及P-糖蛋白（P-gp）,谷胱甘肽S转移酶π（GST-π）,肺耐药蛋白（LRP）和拓扑异构酶II（TOPO-II）在乳腺癌干细胞和分化细胞中的表达及其意义。 方法：选取乳腺浸润性导管癌新鲜标本30例制备成单细胞悬液,通过免疫磁珠两步法从中分离出癌干细胞（CD44+/CD24-细胞）和分化细胞（CD24+和CD44-CD24-细胞）并计数,分析癌干细胞含量与乳腺癌患者临床病理参数的关系;应用免疫细胞化学方法检测以上两种细胞P-gp,GST-π,LRP和TOPO-II的表达情况。 结果：乳腺癌干细胞含量与患者的年龄、肿块大小、组织学分级及淋巴结转移均无明显关系（均P>0.05）。乳腺癌干细胞P-gp的阳性表达率明显高于分化细胞（73.3% vs. 40.0%）,而TOPO-II的阳性表达率明显低于分化细胞（40.0% vs. 76.7%）（P<0.05或P<0.01）;GST-π和LRP的表达在两种细胞间无统计学差异（均P>0.05）。 结论：乳腺癌干细胞含量与患者的临床病理参数无关,但乳腺癌干细胞中P-gp高表达与TOPO-II低表达可能是导致乳腺癌化疗失败和复发的重要原因。     

不同分子亚型乳腺癌中癌干细胞量的研究

目的研究乳腺癌不同分子亚型中癌干细胞量的差别。方法根据分子亚型将乳腺癌组织标本分为A(乳腺腔内A型),B(乳腺腔内B型),C(HER-2过表达型),D(基底样型),E(正常细胞样型)5组,通过集落细胞法计数各组癌干细胞球,分析乳腺癌干细胞量与乳腺癌不同分子亚型的关系。结果 A,B两组的癌干细胞球数分别为(1.1±0.2)/1 000细胞和(1.3±0.1)/1 000细胞,组间差异无统计学意义(P>0.05);C组的癌干细胞球数为(8.6±1.0)/1 000细胞,明显多于A,B组(均P<0.05);D,E两组的癌干细胞球数分别为(22.4±1.2)/1 000细胞和(17.7±2.0)/1 000细胞,两组间差异无统计学意义(P>0.05),但均明显多于前3组(均P<0.05)。结论不同分子亚型乳腺癌组织中含有不同量的癌干细胞,对预测乳腺癌预后可能有一定意义。     

siRNA干扰叉头框C2对乳腺癌中肿瘤干细胞标志物CD44的影响

目的：探讨siRNA干扰叉头框C2（FOXC2）对乳腺癌中肿瘤干细胞（CSC）标志物CD44 mRNA及蛋白表达的影响。 方法：常规培养乳腺癌MCF-7细胞株，再通过乳腺球形成实验培养、筛选乳腺癌CSC；将FOXC2-siRNA或阴性对照siRNA慢病毒载体转染至乳腺癌CSC，同时将转染载体的CSC作为空白对照。通过real time RT-PCR和Western blot检测FOXC2-siRNA对FOXC2的干扰效应，再通过real time RT-PCR和Western blot分别检测CD44 mRNA和蛋白在各组细胞中的表达，结果均以空白对照的表达量作为参照进行分析。 结果：从MCF-7细胞株中成功培养出乳腺癌CSC。与转染阴性对照siRNA的乳腺癌CSC比较，转染FOXC2-siRNA的乳腺癌CSC中FOXC2 mRNA和蛋白表达均明显降低（P=0.00509；P=0.00001），同时CD44 mRNA及蛋白的表达也均明显降低（P=0.00848；P=0.00218）。 结论：干扰乳腺癌CSC中FOXC2基因的表达能够抑制乳腺癌CSC中CD44 mRNA及蛋白的表达，FOXC2信号转导通路可能通过调控CD44来介导乳腺癌CSC的增殖、分化。     

胰腺癌干细胞研究进展

胰腺癌干细胞（PCSC）在胰腺癌的发生、发展过程中起着重要作用,且与胰腺癌的耐药、转移机制关系密切。PCSC的表面标志物、分离、鉴定、信号通路、微环境、耐药、转移和靶向治疗等方面的研究,将为临床胰腺癌的治疗提供新的方向。     

甲状腺癌肿瘤干细胞的研究进展

肿瘤干细胞(CSC)学说得到了越来越多的关注,已有研究证实在甲状腺癌中存在CSC。甲状腺癌CSC可能是甲状腺癌发生、转移、复发及耐药的根源,因此,甲状腺癌CSC的研究对甲状腺癌的诊断、治疗及预防具有重要意义。笔者对甲状腺癌CSC的最新研究进展进行综述。     

下调CD133表达对肝癌细胞恶性生物学行为的影响

目的:探讨下调CDl33基因的表达对肝癌细胞生物学行为的影响。方法:将合成的CDl33小干扰核糖核酸分子(si RNA)转染至肝癌SMMC7721细胞并检测转染效率;分别以无转染与转染随机si RNA序列的SMMC7721细胞为空白对照和阴性对照,观察CDl33 si RNA转染后CDl33基因沉默效果,以及SMMC7721细胞主要生物学行为的变化。结果:转染24 h后,转染效率可达到(80.8±9.1)%;与空白对照组比较,CDl33 si RNA转染后的SMMC7721细胞CD133 m RNA及蛋白表达量分别降至空白对照组的10%与35%、细胞增殖活性明显降低、细胞凋亡率明显增加(41.3%vs.25.3%)并出现明显的S期阻滞,集落形成能力明显降低(均P0.05)。阴性对照组与空白对照组各指标无统计学差异(均P0.05)。结论:CDl33在肝癌细胞中可能起了癌基因作用,下调其表达能抑制肝癌的恶性生物学行为。     

microRNA调控胰腺癌干细胞的作用研究进展

胰腺癌干细胞在胰腺癌的发生、发展、转移及治疗抗性与复发中起着重要作用,但是其中的调节机制仍不清楚。深入研究特定微小RNA调控胰腺癌干细胞的作用,对于阐明胰腺癌发生发展的关键机制具有重要意义,同时有望为胰腺癌的诊治提供新的靶点。     

乳腺癌中ALDH1的表达与其分子亚型及ABCG2的关系

目的探讨乙醛脱氢酶1(ALDH1)表达在乳腺癌中的表达及与各分子亚型、ATP结合膜转运蛋白超家族G成员2(ABCG2)的关系。方法根据免疫学标志物(ER,PR,HER2,CK5/6)把179例乳腺癌标本分为5类分子亚型:管腔A型,管腔B型,HER2过表达型,基底样型和正常乳腺样型。应用免疫组织化学检测ALDH1及ABCG2表达情况,并分析两者之间的相互关系以及两者与乳腺癌各临床病理因素之间的关系。结果 179例乳腺癌中43例(24.0%)呈ALDH1阳性表达。ALDH1的表达率在乳腺癌各分子亚型有明显差异(P=0.003),在管腔A型,管腔B型,HER2过表达型,基底样型和正常乳腺样型中的阳性表达率分别为16.7%(17/102),21.4%(3/14),54.5%(13/22),33.3%(8/24)和17.6%(3/17)。ALDH1阳性表达与ABCG2的表达之间无明显关系(P=0.052)。ALDH1和ABCG2的表达均与术前化疗与否有关(P=0.027和P=0.033),ALDH1的表达与HER2表达有关(P=0.006)。结论小部分乳腺癌呈ALDH1阳性表达,且ALDH1表达率在乳腺癌各分子亚型中表...     

胃肠道肿瘤干细胞生长相关信号转导通路

根据目前肿瘤的干细胞起源理论,肿瘤的生长是极少量肿瘤干细胞增殖的结果,而肿瘤干细胞的生长调控与多种信号转导通路有关.笔者就胃肠道肿瘤干细胞生长相关信号转导通路的研究进展做一综述.