Tau基因表达与紫杉醇治疗胃癌敏感性的研究

目的:探讨胃癌细胞的Tau基因表达丰度与紫杉醇治疗敏感性间的关系,并分析其可能的耐药机制。方法:通过实时定量PCR筛选出Tau基因高表达和低表达的胃癌细胞株各一,然后观察两细胞株对紫杉醇的反应;并应用细胞增殖实验(CCK8方法)、流式细胞技术(AnnexinⅤ标记)检测紫杉醇在体外对胃癌细胞增殖、凋亡和周期的影响。对于Tau基因高表达的胃癌细胞,通过小干扰RNA(small interfering RNA,siRNA)等技术,观察其敲低Tau基因表达后,对紫杉醇的敏感性有无变化。结果:体外增殖实验显示,紫杉醇对Tau表达低的胃癌细胞的增殖生长抑制作用更为明显(P0.05)。而体外凋亡实验显示,紫杉醇更能促进Tau基因低表达胃癌细胞的凋亡(P0.05),在整个细胞周期中以G2/M期为主。而应用siRNA技术将Tau基因高表达的胃癌细胞降为低基因表达后,紫杉醇对其增殖的抑制作用明显增高(P0.05),更能促进转染后细胞的凋亡(P0.05);且对整个细胞周期,以作用于G2/M期为主。结论:紫杉醇对Tau基因表达低的胃癌细胞具有更强的增殖抑制作用,且更能促进其凋亡。而对干扰后的胃癌细胞,紫杉醇具有更强的抑制增殖作用,且更能促进其凋亡。     

microRNA与乳腺癌转移、复发的关系

miRNAs是一类广泛存在于真核细胞中的长约22 nt的单链、非编码的小分子RNAs,具有转录后基因调控的功能,能够调节细胞增生、凋亡以及分化等多种生物学过程.近年来研究发现,miRNA与肿瘤的侵袭、转移与复发关系密切.本文就miRNA的主要特点及其与乳腺癌转移、复发的关系的研究进展予以综述.     

血清VEGF监测术后复发转移性乳腺癌的临床意义

探讨术后复发转移性乳腺癌患者血清VEGF表达及其临床意义.用ELISA检测50例复发转移性乳腺癌,20例原发性乳腺癌,20例乳腺良性疾病及15例健康女性血清VEGF的浓度.结果:复发转移组血清VEGF浓度高于原发组(P＜0.05)、良性疾病及健康对照组(P＜0.01).血清VEGF表达阳性率高于CEA、CA15-3( P＜0.05),而与CEA、CA15-3联合表达差异无显著性(P＞0.05),与复发转移部位、原肿瘤病理类型、腋淋巴结转移状况、ER、PR、HER-2表达及月经状况无关(P＞0.05).结论:复发转移组血清VEGF表达水平明显升高.单项检测VEGF优于CEA、CA15-3,与CEA和CA15-3联合检测表达相似.血清VEGF有望作为乳腺癌复发转移的一项监测指标.     

84例乳腺癌复发转移因素分析

目的探讨复发、转移性乳腺癌的临床特点、治疗方法及个人素质等因素对复发转移的影响。方法采用自制＂乳腺癌复发转移因素调查表＂对所有复发、转移后入院的病例进行调查分析,调查内容主要有以下三个方面：疾病特征因素、个人素质因素、治疗因素,并对各因素在复发、转移病例的权重进行分析比较。结果通过调查发现,疾病期别较晚（Ⅲ、Ⅳ期）是主要因素;其次为病例类型：浸润性导管癌、病灶位于外侧、以疼痛为主要症状,免疫组化：ER（-）,PR（-）,C-erbB-2（-）的病例;再次为治疗方法不当和个人性格内向、偏食等。转移时间存在三个高峰期,分别为治疗后2、3、10年。结论乳腺癌复发、转移是由以下原因造成：医生的治疗不规范,疗程不足,方法不当;手术、放疗、化疗顺序颠倒,缺乏统一性;疾病分期较晚,组织分化差,病例类型不好,免疫组化为＂三阴＂;加之阳性家族史、月经紊乱史、性格内向、偏食等。因此,需针对上述因素采取积极有效地处理措施,才能降低复发及转移率。     

乳腺癌术后复发转移原因分析

目的探讨乳腺癌术后复发、转移的因素,寻求预防措施,以提高患者无瘤生存期。方法分析1998年1月至2006年12月收治87例乳腺癌术后复发、转移患者的相关资料。结果根据患者原来就诊时机,术后综合治疗不同而分别于术后8~72个月出现复发、转移。其中胸壁局部复发16例,肺转移28例,胸椎转移21例,远处骨转移12例,肝转移9例,锁骨上淋巴结转移19例,14例合并2个脏器以上转移。结论加强健康知识宣传,促使患者早期就诊,强调手术无瘤观念,规范、实施各项综合治疗措施,可收到预防乳腺癌术后复发、转移的良好效果。     

复发转移乳腺癌(附34例报告)

目的　探讨复发转移乳腺癌的临床病理特点 ,最佳治疗方法和治疗效果。方法　对3 4例复发转移乳腺癌病人 ,采取化疗 ,结合手术 ,放射治疗 ,术后继续化疗。结果　 2 3例伴有内脏转移的 2个部位以上复发转移病人 ,经化疗病灶缩小明显 (PR) 7例 ,病情稳定 (SD ) 8例 ,病情进展(PD) 8例 ,临床获益 (CR PR SD) 65 % (15 / 2 3 )。 1年生存率 65 % ,11例局部复发化疗后病灶缩小 (PR) 10例 ,病情进展 (PD) 1例 ,临床获益 90 % (10 / 11) ,2年无瘤生存率 90 %。结论　伴有内脏转移的复发转移应以化疗为主 ,病灶缩小者 ,局部手术切除 ,放疗 ,术后继续化疗。显著延长生存时间。局部复发无内脏转移 ,也应先化疗 ,再手术 ,可减少远隔器官转移。     

恩美曲妥珠单抗治疗复发转移性乳腺癌一例并文献复习

HER2阳性乳腺癌侵袭性高、易出现复发和转移。恩美曲妥珠单抗（ado-trastuzumab emtansine, T-DM1）是新型抗HER2靶向药物,具有靶向性和细胞毒杀伤双重抗肿瘤作用,2020年2月国家药品监督管理局正式批准其上市,而国内的应用报道较少。本文报道了1例局部晚期HER2阳性的乳腺癌患者使用T-DM...     

乳腺癌术后复发转移相关因素研究进展

正乳腺癌是当前女性发病率最高的恶性肿瘤。随着早期诊断、早期治疗以及乳腺癌辅助治疗的不断完善,乳腺癌术后无病生存率和总体生存率均明显提高,术后局部复发和远处转移仍然是导致乳腺癌患者死亡的重要原因。乳腺癌的复发转移是指乳腺癌经过治疗后在原发灶附近或远隔器官出现病理性质完全相同肿瘤的现象。乳腺癌术后肿瘤复发和转移的问题严重影响临床治疗的效     

乳腺癌空芯针穿刺活检术与局部复发的关系

乳腺癌已成为欧美国家最常见的女性恶性肿瘤;而随着我国人民生活水平的日益提高,越来越多的中国女性也正受其威胁。针吸细胞学（fine needle aspiration cytology,FNAC）与空芯针穿刺活检（core needle biopsy,CNB）的出现使得很大部分病人免去了不必要的手术切除活检。     

乳腺癌耐药蛋白的表达及其与核转录因子snail相关性的临床研究

目的：探讨乳腺癌耐药蛋白（BCRP）的表达,分析其与核转录因子snail的相关性及BCRP介导肿瘤耐药的分子机制。方法：应用免疫组化方法检测87例乳腺癌组织和35例癌旁组织中BCRP和snail的表达情况,分析其与乳腺癌临床病理因素的关系及BCRP与snail的相关性。结果：BCRP和snail在乳腺癌组织中的阳性率分别32．18％和85．06％,BCRP与年龄、肿瘤大小及TNM分期无关,与组织学分级、ER表达和淋巴结转移相关;snail与患者年龄、肿瘤大小、组织学分级、ER表达无关,而与TMN分期、淋巴结璜移正相关;相关分析显示BCRP与snail表达的存在密切相关性（x^2=35267,P〈001,r=O643）。结论：BCRP参与了乳腺癌的进展;snail是乳腺癌上皮-间质转换（EMT）过程中的一个重要调节因素,促进了EMT的发生,介导了BCRP介导的多药耐药。     

Treatment of locally recurrent and advanced breast cancer

The incidence of breast cancer in the UK continues to increase; however, the death rates continue to decline. Mortality rates have reduced by 19% in the UK in the last decade and are projected to fall by a further 26% in 2014–2035. Cancer research UK reports 55,176 new cases in 2015–2017 with 11,547 deaths from breast cancer reported from 2016 to 2018. Ten-year survival for all comers is reported at 76%. Largely, the improvements in outcomes is felt to be multi factorial in nature with earlier detection of cancers, increased axial imaging and the rapidly progressing and expanding radiotherapy and systemic therapy treatment options available. Irrespective of this, there are still a number of patients diagnosed with more advanced disease. Between 13% and 21% of patients are diagnosed with stage III/IV disease, with 7% of patients having metastatic disease at diagnosis. The following review discusses the treatment options available to patients with locally recurrent or metastatic breast cancer (MBC).     

Outcome and feasibility of palliative chemotherapy in very elderly patients with metastatic breast cancer

In the Netherlands, approximately 1300 women aged ≥75 years die every year of metastatic breast cancer (MBC). Data on palliative chemotherapy (CT) in very elderly patients are rare, and prospective studies appeared cumbersome. Therefore, we retrospectively analyzed the outcome and feasibility of chemotherapy in elderly MBC patients. Records of all patients with MBC aged ≥75 years who received first‐line palliative chemotherapy between January 2000 and December 2014 at two large teaching hospitals in the Netherlands were reviewed. We registered patient and tumor characteristics together with data on previous adjuvant treatment, palliative endocrine treatment, comorbidities, clinical benefit (defined as ≥6 months progression‐free survival), toxicity, and the reason for stopping chemotherapy. Patients with progressive disease (PD) or death within 30 days after starting CT were censored from analysis. A total of 54 patients with a median age of 77.6 years (range 75‐90) were treated with palliative chemotherapy for MBC. Of them, 20 patients (37%) were aged ≥ 80 years. There was clinical benefit in 28 patients (52%). Median progression‐free survival and median overall survival were 6.0 and 14.0 months, respectively. One year after the diagnosis of MBC, 27 patients (50%) were still alive and 15 patients (28%) lived longer than 2 years. Reasons for stopping CT were progressive disease (n = 32) or toxicity (n = 13). Most patients (n = 48) died of MBC while two patients died of toxicity. In selected patients with MBC aged 75 years or older, single‐agent palliative chemotherapy is feasible and may have clinical benefit.     

Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact

Background

One can consider as a standard neoadjuvant treatment for breast cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel. Based on the belief that the sequence order between anthracycline and taxane might be of interest, this study assessed the impact of the sequence order.

Methods

One hundred and twenty three patients with breast cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between 2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus another cohort of 58 patients treated with 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (cohort A).

Results

The overall dose intensity of docetaxel and clinical complete responses were significantly higher in cohort T. No statistically significant differences were observed in terms of conservative surgeries or histological responses. The sequence of chemotherapy did not significantly influence other treatment-related toxicities. Mild neurotoxicity was higher in patients treated in cohort T. Anemias (≥Grade 1) were higher in cohort A (52% versus 81%; p = 0.0008).

Conclusion

The present study failed to identify an impact of the sequence of taxane administration on the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces the occurrence of anemia. These findings might allow a selection of the sequence order based on the toxicity profile.     

Primary and secondary distant metastatic breast cancer: Two sides of the same coin

ObjectivesThis study evaluated the differences between breast cancer (BC) patients who present with primary distant metastatic disease (PMD) and those who develop distant metastases during the course of their illness (secondary metastatic disease [SMD]) with regard to clinicopathological characteristics, patterns of metastatic sites, palliative therapy and survival.Patients & methodsBased on a cohort of patients with newly diagnosed BC (n = 1459), we analyzed all patients who had PMD (n = 92, 6.3%) and those who developed SMD (n = 277, 20.3%).ResultsThere were no significant differences with regard to the patient's age in which metastatic disease had been diagnosed (PMD/SMD: 64 years/66 years, p = 0.19). The SMD group had more often triple-negative carcinomas (25.5%/7.3%, p = 0.019); there were no significant differences with regard to grading (p = 0.61), HER2 status (p = 0.67) and hormonal receptor status (p = 1.00). The mean number of metastatic locations was similar (2.3/2.3, p = 0.91). While patients with PMD usually initiated systemic therapy, patients with SMD received systemic therapy after diagnosis of metastatic disease less often (16.4%/2.6%, p < 0.001). Both groups received palliative chemotherapy similarly often (PMD/SMD: 62.8%/63.3%, p = 1.00). The mean number of palliative therapy lines was similar (PMD/SMD: 2.8/3.2, p = 0.39). Compared to patients with SMD, patients who had PMD had a significantly improved metastatic disease survival (p < 0.001). The one-year, two-year and five-year survival rates were as follows: 76.9%/60.3%, 58.2%/43.0%, 23.1%/10.6%. The median survival times were 18.5 months and 32 months.ConclusionThe poorer prognosis of patients with SMD may be explained by differences in clinicopathological features of the tumor, metastatic patterns, the use palliative therapy and drug resistance of the tumor cells which occurs in therapy-naïve PMD patients at a later phase of the disease course.     

Gemcitabine and vinorelbine combination in patients with metastatic breast cancer

Both gemcitabine and vinorelbine as single agents have significant activity against metastatic breast cancer, with an overall response rate ranging from 14% to 40%. Because each drug has different mechanisms of action and toxicity profile, we have evaluated the activity and tolerability as a combined regimen in metastatic breast cancer patients. Thirty-two breast cancer patients with prior chemotherapy for metastatic disease received a combination of gemcitabine and vinorelbine at 1,200 and 30 mg/m ², respectively. The drugs were administered on days 1 and 8 of every 21-day cycle. The study was designed to evaluate the response rate, the duration of response, the time to progression, and overall survival. Toxicity and tolerability of this combination were also evaluated. Out of 32 patients analyzed, a complete response was achieved in 2 patients (6.3%) and a partial response in 12 patients (37.5%), with an overall response rate of 43.8%. After a median follow-up of 7 months, the median duration of response was 5.3 months, and the time to progression was 5.0 months. Overall survival was not reached because the majority of the patients were alive at the time of analysis. The gemcitabine and vinorelbine combination was tolerable, with hematologic toxicity being the most common side-effect. Three patients suffered from grade 4 neutropenia, and none suffered from grade 4 thrombocytopenia. Nonhematologic toxicity was minimal and transient, with nausea and phlebitis being the most common. The gemcitabine and vinorelbine combination at the previously specified doses shows significant activity in metastatic breast cancer patients. The treatment is well tolerated and has an acceptable toxicity profile. In patients previously treated with anthracyclines and taxanes, this combination regimen offers an alternative treatment with preservation of a good quality of life.     

P-糖蛋白(Pgp)在乳腺癌中的表达及与预后的关系

目的探讨P-糖蛋白(P-glycoprotein,Pgp)在乳腺癌中的表达,评估其在乳腺癌预后中的作用。方法对我院1993年1月～1994年12月用免疫组织化学方法检测62例手术切除的乳腺癌组织中Pgp的表达的资料进行回顾分析,研究其与临床病理特征的关系及对预后的影响。结果(1)Pgp在乳腺癌组织中的阳性表达率为32.2%(20/62)。(2)Pgp表达与月经状况、肿瘤大小、腋淋巴结转移个数、组织学分级之间均无相关性(P>0.05)。(3)Kaplan-Meier生存分析结果表明Pgp阴性表达组的无病生存期(DFS)及总生存期(OS)均明显优于阳性表达组(P<0.05)。(4)Cox回归单因素分析显示腋窝淋巴结转移个数、组织学分级、肿瘤大小、TNM分期及Pgp表达与DFS及OS明显相关;Cox回归多因素分析表明除了腋窝淋巴结转移个数、组织学分级及肿瘤大小与DFS及OS明显相关外,Pgp表达与OS缩短有关,但和DFS无关。结论Pgp在乳腺癌组织中有一定程度的表达,Pgp阳性表达与乳腺癌患者生存期的缩短有关,有可能成为判断乳腺癌患者预后的指标。     

微小核糖核酸34a、糖类抗原15-3和糖类抗原125联合检测在乳腺癌复发转移监测中的价值

目的:探讨血清微小核糖核酸-34a(miR-34a)、癌抗原15-3(CA15-3)和癌抗原125(CA125)联合检测在乳腺癌复发转移监测中的价值。方法:根据患者影像学及病理组织学检查将2016年1月至2020年12月武汉科技大学附属普仁医院诊治的96例女性乳腺癌患者分为复发转移组(39例)与未复发转移组(57例),...     

血清HER-2/neu胞外域在复发转移性乳腺癌患者解救化疗中的临床意义

目的 探讨血清HER-2/neu胞外域(ECD)在复发转移性乳腺癌患者解救化疗中的临床意义.方法 酶联免疫吸附试验检测健康志愿者、良性乳腺疾病患者各27例的血清HER-2/neu ECD水平及27例复发转移性乳腺癌患者化疗前后的血清HER-2/neu ECD水平,结合其临床资料进行统计学分析.结果 健康志愿者与乳腺良性疾病患者血清HER-2/neu ECD水平均低于15μg/L,差异无统计学意义(P>0.05);复发转移性乳腺癌患者化疗前血清HER-2/neu ECD的平均浓度为(47.30±109.06)μg/L,显著高于健康志愿者及乳腺良性疾病患者(P<0.01).血清HER-2/neu ECD水平与原发肿瘤HER-2/neu的表达成正相关(r=0.752,P<0.01).解救化疗有效的患者,化疗3周后血清HER-2/neu ECD水平较化疗前明显降低(P<0.05),化疗3周后与化疗6周后血清HER-2/neu ECD水平差异无统计学意义(P>0.05).化疗前HER-2/neu ECD水平与患者总生存期呈负相关(r=-0.601,P<0.01),而与无进展生存期无明显相关(r=-0.374,P>0.05).化疗前血清HER-2/neu ECD>15 ug/L与HER-2/neu ECD<15 ug/L的患者比较,总生存率前者低于后者(P<0.05),无进展生存率两者间差异无统计学意义(P>0.05).结论 血清HER-2/neu ECD水平的监测,有助于早期发现乳腺癌的复发转移,指导解救化疗方案的选择,评估患者的疗效及预后.     

Metastatic disease of the breast and local recurrence of breast cancer

Breast cancer is a major health problem worldwide with over one million new cases diagnosed each year. The aim of treatment is to achieve good loco-regional control, provide appropriate adjuvant therapy and treat potential micro-metastasis. Good loco-regional control is essential to minimize local recurrence rates with histological clear margin being the most important factor. Several prognostic factors can be used to guide suitable adjuvant therapy. The most important is hormone sensitivity and the use of hormone manipulation has improved both recurrence rates and overall survival. Early detection with breast screening and better treatment options have improved outcome, but still 35–40% of patients will eventually present with metastatic disease. Metastatic disease is incurable, but several therapies have been shown to maintain a good quality of life whilst prolonging survival. A multidisciplinary team approach is essential to obtain the diagnosis and plan the appropriate treatment. The diagnosis of metastatic disease brings distress to patients and their relatives and support should be available from palliative care teams.