阿帕替尼对Her2阴性晚期胃癌患者的治疗效果及毒副作用分析

目的:探究Her2阴性晚期胃癌患者采用阿帕替尼进行治疗的疗效及毒副作用。方法:按照不同治疗方法将本院就诊的Her2阴性晚期胃癌患者分为阿帕替尼组(AP组)和替吉奥组(TI组),各46例,分析比较两组患者的临床疗效、生活质量、毒副作用及远期疗效。结果:治疗后,AP组11例、TI组6例患者出现部分缓解,AP组患者RR、DCR数值明显比TI组高(P<0.05);AP组患者生活质量明显优于TI组(P<0.05)。AP组和TI组患者均出现血小板减少、蛋白尿、肝功能异常等不良反应,但未出现Ⅳ级毒副作用,其中AP组患者高血压、血小板减少的发病率分别为63.52%、76.73%,TI组患者发病率分别为62.45%、78.11%, AP组出现毒副作用的患者人数与TI组比较无明显差异(P>0.05)。随访3年结果显示,AP组患者3年生存率为10.86%,TI组患者为0,AP组患者总生存率明显高于TI组(P<0.05)。结论:阿帕替尼对Her2阴性晚期胃癌患者的临床疗效及远期治疗效果较佳,虽然治疗后也会出现一定的毒副作用,但与替吉奥治疗后出现的毒副作用相近,且患者身体承受程度较佳。阿...     

Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival

BackgroundTo understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors.Materials and methodsWe conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS).Results1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes.ConclusionsSurgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.     

不同产地忽地笑的叶绿体基因psb A-trn H序列分析

目的通过叶绿体基因psb A-trn H序列分析,探讨我国忽地笑种质资源的系统进化关系及分子鉴定方法。方法分别提取15省(市)52个忽地笑居群的DNA,经PCR扩增叶绿体基因psb A-trn H序列及测序,并用Mega5.0等软件对测序结果进行分析。结果 52条psb A-trn H序列长度为544～656 bp,GC含量为35.8%～37.0%,遗传距离为0.000 00～0.009 47;核苷酸变异(多态性)位点数共33个,其中简约信息位点9个,单一突变位点18个,插入/缺失片段6个;单倍型数量(H)10个,单倍型多态性水平(Hd)0.749,核苷酸多态性(π)0.002 63,收集的忽地笑资源具有较高的遗传多样性。最大简约法(maximum parsimony,MP)系统树中52个居群聚为4类,并且该聚类结果与其地理分布基本一致。结论不同产地忽地笑居群的遗传变异较大,psb A-trn H序列可作为忽地笑种源分子鉴定的依据;我国忽地笑种质资源在进化上具有明显的地域性特征。     

Breast Carcinoma in Young Women: No Evidence of Increasing Rates of Metastatic Breast Carcinoma in a Single Tertiary Center Review

Breast carcinoma in young women aged less than 40 years attracts a high level of mainstream media coverage, and there is a gap between societal perceptions of the disease as a growing problem and epidemiological trends. Several population studies have reported that the overall incidence of breast carcinoma in young women is stable, while one recent article suggested that the relative proportion of breast carcinoma in young women that is metastatic at diagnosis is growing. We sought to establish whether these trends were apparent at our institution. In this study, the clinical database at a breast carcinoma tertiary center was reviewed in terms of clinicopathologic data on patient age, diagnosis, clinical and pathologic stage, hormone receptor status, and HER‐2 overexpression status for the period 2000–2011. Over the study period, young patients represented a decreasing proportion of all breast carcinoma cases (10.8% [2000–2003] to 8.7% [2008–2011]; p < 0.0001) treated at our institution. Young patients were more likely than patients aged 40 years or older to present with metastatic (M1) disease (5.4% versus 4.4%; p = 0.009), to be triple negative (21.6% versus 13%; p < 0.001), or to be HER‐2 positive (24.3% versus 14.8%; p < 0.01). Young patients with HER‐2‐positive cancers were significantly more likely to present with metastatic disease (8.3% versus 4.8%; p = 0.004). This study showed no demonstrable increase in the relative proportion of breast cancer occurring in patients aged <40 years over the 12‐year period 2000–2011 and no increase in the proportion of young patients presenting with metastatic disease.     

Chromogenic in situ hybridization for Her‐2/neu‐oncogene in breast cancer: comparison of a new dual‐colour chromogenic in situ hybridization with immunohistochemistry and fluorescence in situ hybridization

Aims: Her‐2/neu testing is used as a marker for Herceptin^® therapy. The aim was to investigate new dual‐colour chromogenic in situ hybridization (CISH), in a large number of breast carcinomas (n = 205) with DNA‐specific dual‐colour probes (ZytoVision, Bremerhaven, Germany) and to compare the results with immunohistochemistry (n = 205) and fluorescence in situ hybridization (FISH) (n = 129). Methods and results: Paraffin‐embedded tissue of 205 patients was used. After immunohistochemistry with a focus on immunohistochemically uncertain cases, Her‐2/neu amplification using dual‐colour CISH (ZytoVision^®) was analysed. Validation by FISH was performed. The results were: immunohistochemistry, 27.8% with strong expression, 53.7% with uncertain overexpression and 18.5% with no expression; FISH, 25.6% amplified and 74.4% negative; CISH, 35.6% amplified, 62.9% negative and 1.5% not evaluable. Comparison of immunohistochemistry with CISH: CISH negative in 100% with immunohistochemistry 0/1+, amplified in 82.5% with immunohistochemistry 3+; 5.9% contradictory results: 4.4% immunohistochemistry 3+ and negative by CISH, 1.5% negative in immunohistochemistry but amplified by CISH; FISH (129 cases), 8.5% contradictory results to immunohistochemistry, 6.2% immunohistochemistry 3+ and negative by FISH, 2.3% negative by immunohistochemistry and amplified by FISH; comparison of CISH and FISH, 94.6% same results, 3.9% different ones, 1.6% CISH not analysable. Conclusions: CISH, using dual‐colour probes (ZytoVision^®) is as good as FISH for Her‐2/neu analysis. The few discrepant results are likely to be caused by polysomy or tumour heterogeneity.     

Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against Her-2/neu antigen

The Her-2/neu oncogene, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. Antibodies directed to this molecule have been previously shown to have an antitumor effect in vivo. In an attempt to understand the mechanisms of the antitumor activity, we generated 2 monoclonal antibodies (mAbs), HRO G1 and HRT G1, that recognize different epitopes on Her-2/neu. Both of the mAbs bound HER2/neu on the tumor surface, resulting in phosphorylation of HER2/neu. We also generated IgG2a and IgG2b mAbs from these 2 mAbs, respectively. The results of in vitro studies showed that these anti-Her-2/neu mAbs could not inhibit the growth of the tumor cells that express Her-2/neu molecules by themselves. However, in an antibody-dependent cellular cytotoxicity study using mouse splenocytes as effector cells, HRT mAbs had antitumor activities superior to those of HRO mAbs, indicating that the epitope specificity may also partake in antibody-dependent cellular cytotoxicity with antibody isotype. In a complement-dependent cytotoxicity study, the IgG2a and IgG2b mAbs showed stronger effects than IgG1 isotype mAbs irrespective of the epitope specificities. The results of in vivo studies also showed that HRT mAbs had superior antitumor activity to those of HRO mAbs. The antitumor activity was most prominent in the HRT G2b isotype among HRT mAbs. HRT G1 also showed a moderate antitumor effect, while HRT G2a showed only slight inhibition effect. These data indicate that both the epitope specificity and the differences in Fc region of mAbs could play important roles in the antitumor activities.     

Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast

BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen. METHODS: The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status. RESULTS: Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis. CONCLUSION: Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.     

Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.