Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation

The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC₅₀) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.     

EBV-miR-BART10-3p facilitates epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma by targeting BTRC

Epstein-Barr virus (EBV) infection is closely associated with tumorigenesis and development of nasopharyngeal carcinoma (NPC), but the underlying molecular mechanisms remain poorly understood. It has been recently reported that EBV encodes 44 mature miRNAs, some of which were found to promote tumor development by targeting virus-infected host genes or self-viral genes. However, few targets of EBV encoded-miRNAs that are related to NPC development have been identified to date. In this study, we revealed that in NPC cells, EBV-miR-BART10-3p directly targets BTRC gene that encodes βTrCP (beta-transducin repeat containing E3 ubiquitin protein ligase). We found that EBV-miR-BART10-3p expression in clinical samples from a cohort of 106 NPC patients negatively correlated with BTRC expression levels. Over-expression of EBV-miR-BART10-3p and down-regulation of BTRC were associated with poor prognosis in NPC patients. EBV-miR-BART10-3p promoted the invasion and migration cabilities of NPC cells through the targeting of BTRC and regulation of the expression of the downstream substrates β-catenin and Snail. As a result, EBV-miR-BART10-3p facilitated epithelial-mesenchymal transition of NPC. Our study presents an unreported mechanism underlying EBV infection in NPC carcinogenesis, and provides a potential novel biomarker for NPC diagnosis, treatment and prognosis.     

新辅助化疗治疗肢体软组织肉瘤28例报告

目的分析探讨新辅助化疗治疗肢体软组织肉瘤(soft tissue sarcoma,STS)的临床疗效及价值。方法选取2009年5月至2012年6月,我科经新辅助化疗[术前顺铂+异环磷酰胺+阿霉素(cisplatin+ifosfamide+adriamycin,DDP+IFO+ADM,DIA)化疗2个周期+手术治疗+术后DIA化疗6个周期]治疗的28例肢体STS患者,其中男18例,女10例;年龄15~62岁,中位年龄35岁。DIA 1个周期的化疗方案为:第1天DDP 120 mg/m2,第7~9天每天按序均给予ADM 30 mg/m2、IFO 2.0 g/m2,第10~11天IFO2.0 g/m2。对所有患者进行随访,复查肺部CT及病变部位X线片,记录复发、转移、死亡情况。参照实体瘤疗效评价标准(response evaluation criteria in solid tumour,RECIST)1.1评价化疗疗效;按照化疗常见不良反应事件评价标准(common terminology criteria for adverse events,CTCAE)4.0对化疗期间的不良反应进行评价。结果本组28例手术均进行顺利,总失血量50~600 ml,平均260 ml,切口如期愈合。DIA化疗方案进行了术前2个周期、术后6个周期化疗,持续时间为38周,28例共进行了224个化疗周期。28例随访12~59个月,随访结束时,存活23例,其中无瘤生存20例,带瘤生存3例。本组2年无瘤生存率71.4%,2年总生存率82.1%。术后转移5例,均肺部转移而死亡;4例术后复发,复发率12.3%。4例复发患者与3例肺转移患者,于发现后先辅助三维适行放疗。经过术前化疗,肿瘤体积平均缩小(30.2±11.3)%,尤其肿瘤直径>15 cm的22例,肿瘤体积平均缩小(42.7±7.8)%;28例中完全缓解(complete remssion,CR)0例,部分缓解(partial remission,PR)12例,稳定(stable disease,SD)14例,疾病进展(progression diseas,PD)2例,客观缓解率(objective response rate,ORR)为42.9%,疾病控制率(disease control rate,DCR)为92.9%;患者对化疗耐受性良好,主要化疗不良反应均为一过性,经用药对症处理后症状消失。结论新辅助化疗方案治疗肢体STS,术前化疗可明显缩小STS的体积,减轻肿瘤周围的软组织水肿,可控制微小转移灶,很好地配合STS的手术切除;能够提高患者的总生存率及无瘤生存率,有利于肢体STS的保肢治疗;其近、中期疗效满意,不良反应可耐受,是治疗STS重要有效的方法。     

产妇健康教育需求与全程助产达标率的研究

目的 有效开展产程健康教育,提高一对一全程助产责任制可控达标率.方法 抽查300名产妇对产程中健康教育的需求;将2004年(413例)与2005年(368例)住院分娩产妇全程助产可控达标率及人力资源情况进行对照.结果 健康教育主要需求为产程中减轻疼痛的知识、介绍产程中应注意的问题;两年对比全程助产可控达标率及人力资源情况有显著差异性(P＜0.01).结论 建立基层医院一对一全程助产模式有利于提高产程健康教育质量,提高可控达标率,确保母婴安康.     

Cyclin D_1蛋白的表达与鼻咽癌放射治疗的疗效

目的探讨CyclinD1基因蛋白的表达与鼻咽癌放射治疗疗效的相互关系。方法应用抗CyclinD1基因蛋白单克隆抗体 ,采用免疫组化S P法 ,检测 76例鼻咽癌组织标本中CyclinD1基因蛋白的表达情况。将CyclinD1基因蛋白的表达程度分 4个级别 ,应用 χ2 检验放射治疗与基因蛋白表达程度是否相关。结果CyclinD1基因蛋白的表达与鼻咽癌放射治疗疗效明显相关。结论CyclinD1基因蛋白的表达与鼻咽癌放射治疗疗效之间具有明显相关性 ,CyclinD1基因蛋白的表达可作为指导鼻咽癌临床治疗及预后判定的一项参考指标     

影响便携式输液泵氟尿嘧啶化疗流速相关因素分析

[目的]探讨影响便携式输液泵流速的相关因素.[方法]观察273例次病人使用便携式输液泵进行5-FU化疗液体流速,对可能影响流速的7个因素进行分析.[结果]流速正常153例次,占56.04%,流速异常120例次,占43.96%(其中流速增快21例次,占17.50%,流速减慢99例次,占82.50%).温度、溶液黏度与静脉通道是否通畅是影响流速的主要因素.[结论]护理人员应针对影响便携式输液泵流速的主要因素进行调整、完善,保证化疗药物准确、及时输注.