Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS

Background

Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values.

Methods

Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated.

Results

The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC.

Conclusion

Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.     

Angelchik prosthesis with oesophageal adenocarcinoma: our surgical approach

The Angelchik prosthesis is an incomplete doughnut-shaped device composed of silicone elastomer used in the treatment of gastro-oesophageal reflux disease (GORD). It is used to encircle the lower oesophagus at the gastro-oesophageal junction (GOJ). The ease of the operation led to the insertion of over 25,000 such prostheses world-wide. However, a variety of major complications including intractable dysphagia, prosthesis migration and gastric erosion required a quarter of these devices to be removed. Development of adenocarcinoma in patients with Angelchik prosthesis is a rare occurrence. This article describes two patients who developed adenocarcinoma above their prosthesis and whose cardio-oesophagectomy was technically challenging due to the formation of a dense inflammatory capsule around the prosthesis. Our surgical approach to curative oesophageal resection with the Angelchik prosthesis in situ is also discussed.     

Burn injury induces an early activation response by lymph node CD4+ T cells

Several reports have shown that burn injury primes the immune system for an early and vigorous proinflammatory CD4 T cell response, suggesting that injury might signal CD4 T cell activation. We addressed this possibility by investigating changes in CD4 T cell activation marker expression, proliferation, and T cell receptor (TCR) usage at several early time points after burn injury. Using a sensitive flow cytometry approach to measure changes in the expression of Ki-67 antigen, a nuclear protein detected only in proliferating cells, we observed an early burst of proliferation by lymph node, but not spleen, CD4 T cells 12 h after burn injury. In contrast, mice that were treated with the bacterial superantigen staphylococcal enterotoxin B (SEB) as a positive control for in vivo T cell activation did not show this early proliferation. Instead, we observed a significant increase in proliferating lymph node and spleen CD4 and CD8 T cells by 3 days after SEB treatment. Burn injury induced higher cell surface CD25 and CD152 expression on lymph node CD4 T cells, whereas SEB treatment increased CD25 and CD69 expression on CD4 and CD8 T cells. Finally, we found that burn injury induced a proliferative response at 12 h by an oligoclonal subset of TCR Vbeta-chain-expressing CD4 T cells (Vbeta4, Vbeta6, Vbeta11, and Vbeta14). Interestingly, CD4 T cells expressing the Vbeta11-TCR remained significantly increased in the lymph nodes 3 days after burn injury. Taken together, these findings indicate that burn injury induces an early proliferation and activation of CD4 T cells in the regional lymph nodes and that these proliferating cells show restricted TCR Vbeta-chain usage consistent with the idea that injury triggers an early T cell activation signal.     

培养基对兔骨髓间充质干细胞扩增与分化的影响

目的:考察α-MEM,DMEM-HG,DMEM-LG3种培养基对兔骨髓间充质干细胞体外贴壁、增殖与分化的影响。方法:实验于2005-04/2005-12在华东理工大学生物反应器工程国家重点实验室完成。①兔骨髓间充质干细胞的获取:从1个月龄新西兰大白兔股骨中用全骨髓分离法分离得到兔骨髓间充质干细胞,体外培养,将第4代兔骨髓间充质干细胞分别在α-MEM,DMEM-HG,DMEM-LG三种培养基中以1×107L-1的密度培养于24孔板中,观察细胞形态,测生长曲线和贴壁率。②为消除贴壁差异,在α-MEM培养基中待接种的细胞贴附后,分别更换DMEM-HG或α-MEM培养基进行培养;在DMEM-HG培养基中贴附的细胞以同样方法处理,比较其生长速率和细胞密度。③以100个细胞/孔的密度将细胞接种于3种培养基的6孔板中,测克隆形成率。④细胞以0.5×107L-1的密度接种于24孔板,分别在3种培养基中扩增至50%汇合后,改用成骨诱导培养液进行诱导培养,茜素红染色测其矿化能力。结果:①3种培养基中细胞在α-MEM中贴壁率最高,达(41.7±1.4)%,第1天即进入对数生长期,平均比生长速率最大,为0.57d-1,平均倍增时间最短,为2d,培养期最大扩增倍数为27.9倍,克隆形成率最多,达(30.9±2.6)%。②消除贴壁差异后,细胞在不同培养基中生长无明显差别,两条生长曲线基本重合。③3种培养基中扩增的细胞经成骨诱导后,茜素红染色皆为阳性,其中DMEM-HG培养基中阳性最明显。结论:α-MEM培养基适合于骨髓间充质干细胞体外培养和扩增,引起细胞在不同培养基中生长差异的主要原因在于贴壁率的不同。     

大鼠抗组胺药敏感性细胞色素P450基因的克隆及其反转录病毒载体的构建和鉴定

目的:构建反转录病毒表达载体pLXSN-HP450。方法:实验于2004-12/2006-05在广西医科大学生化药理实验室完成。提取正常的Wistar大鼠肝组织的总RNA,反转录-聚合酶链反应技术扩增出抗组胺药敏感性细胞色素P450(HP450)基因。并克隆到pMD18-T载体,经蓝白斑筛选后进行聚合酶链反应,酶切,测序鉴定。BamHI,EcoRI双酶切构建好的重组质粒和反转录病毒载体pLXSN在16℃下经T4连接酶连接过夜,并转化到感受态细胞DH5α,以菌液为模板做聚合酶链反应,结合酶切筛选及鉴定阳性重组反转录病毒载体pLXSN-HP450。结果:反转录-聚合酶链反应扩增出HP450基因。重组质粒pMD18-HP450经双酶切后得到1461bp的酶切产物。测序的结果用ClustalW在线与Genebank对比,此目的基因与基因库中的H1基因100%同源。阳性重组载体pLXSN用其菌液聚合酶链反应扩增出目的条带。对重组体pLXSN-HP450进行双酶切得到1461bp和5900bp两条特异性条带。结论:克隆了HP450基因,并成功构建了重组反转录病毒载体pLXSN-HP450,为进一步研究肝癌的基因治疗奠定了基础。     

中国卫生地理信息系统基础数据库的构建

目的：构建可用于中国卫生地理信息系统（GIS）应用研究的基础数据库，以合理应用已有的数据资源，并成为一个空间决策系统。方法：采集不同资料来源，经统一标化后构成基本资料源。主要的资料源包括：（1）覆盖中国地区的卫星遥感图片库；（2）GIS数字化地图库；（3）疾病资料库与相关模型库。结果：已获卫星遥感图片库中的植被指数遥感图片、地面温度遥感图片、数字化高程图片、数字化土地利用图片等；GIS数字化地图库中的中国行政区划数字化地图、环境数据矢量地图、人口分布图、气象资料分布图等；疾病资料库与相关模型库中包括了多种疾病的调查报告、疾病防治年报表等资料，以及疾病的传播模型和媒介／中间宿主潜在自然孳生地模型，及恶性肿瘤发病因素相关图。结论：该数据库的构建使不同来源的数据达到统一性，数据库收集的数据量以足能为国内卫生专业人员应用为前提，希望通过更多疾病的应用，使数据库得以完善。     

川芎嗪对复氧后损伤心肌细胞的影响

目的：观察川芎嗪对大鼠心室肌细胞缺氧－复氧损伤的作用,方法：在缺氧－复氧条件下,测量对照组和不同浓度川芎嗪组对杆形心肌细胞百分比,心肌细胞释放乳酸脱氢酶（LDH）和心肌细胞类脂过氧化产物－丙二醛（MDA）含量。结果：缺氧－复氧对大鼠心室肌细胞有损伤作用。浓度为4umol/L的川芎开始对缺氧－复氧损伤细胞有保护作用,它能抑制损伤细胞挛缩,提高损伤细胞生存率,抑制细胞LDH的释放,减少MDA的生成,且剂量越大,保护作用越好,即川芎嗪对缺氧－复氧损伤细胞的保护呈剂量依赖性,结论：川芎嗪对缺氧一复氧损伤的心肌细胞具有保护作用。它能显著地对抗缺氧－复氧对心室肌细胞的损伤。