动态增强MRI成像在鼻咽癌诊疗中的应用价值

动态增强磁共振成像(Dynamic contrast enhanced MRI,DCE-MRI)是一种非常有价值的定量MRI技术,在提高肿瘤诊断的敏感度、良恶性肿瘤的鉴别、肿瘤分级等方面有良好的应用价值。本文就鼻咽癌分期、疗效评价、鉴别鼻咽癌放疗后瘢痕纤维化与肿瘤复发的DCE-MRI研究现状进行综述,供同道们在工作中参考。     

miRNA-325-3p通过下调细胞角蛋白13 的表达降低鼻咽癌细胞CNE1 的放疗敏感性

目的：探究miRNA-325-3p 及其靶基因细胞角蛋白13（cytokeratin 13，CK13）对鼻咽癌细胞CNE1 的放疗敏感性的影响。方法：通过miRBase、Targetscan 及Microcosm 三大数据库预测miRNA-325-3p 的潜在靶基因，并通过双荧光素酶活性检测实验进行验证，qPCR检测不同放射剂量下鼻咽癌细胞CNE1 中miRNA-325-3p 及其靶基因的表达水平变化，通过克隆形成实验观察不同放射剂量下过表达miRNA-325-3p 及敲低靶基因后CNE1 细胞克隆形成率的变化，流式细胞术验证过表达miRNA-325-3p及敲低靶基因后CNE1 在不同放射剂量下凋亡水平的变化，MTT法检测miRNA-325-3p 过表达和CK13 敲低组鼻咽癌细胞CNE1在不同放射剂量下的细胞存活率以验证其放疗敏感性的变化。结果：CK13 确认为miRNA-325-3p 的潜在靶基因，鼻咽癌细胞CNE1 经放射处理后，miRNA-325-3p 的表达水平显著升高、CK13 的表达水平显著降低（均P<0.05）。miRNA-325-3p 表达量上调和CK13 基因沉默均显著提高CNE1 细胞的存活率[miRNA上调时：（60.14±3.55）% vs（19.23±3.42）%，t=14.37、P<0.01；CK13 沉默时：（76.15±5.13）% vs（28.53±3.68）%，t=13.06、P<0.01]和克隆形成率，降低了凋亡率[miRNA 上调时：（27.95±2.67）% vs（51.68±3.47）%，t=9.39、P<0.01；CK13 沉默时：（20.31±2.62）% vs（38.14±3.83）%，t=6.66、P<0.01]。结论：miRNA-325-3p 能够通过下调靶基因CK13的表达降低鼻咽癌细胞CNE1 对放疗的敏感性。     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

范金茹教授治疗颈性眩晕经验举隅

范金茹教授为首批全国优秀中医临床人才,在诊治眩晕类疾病方面积累了丰富经验。颈性眩晕多表现为眩晕、头颈部疼痛、恶心、呕吐、耳鸣等,严重影响了人们的生活质量。范师认为颈性眩晕为本虚标实之证,病位在头颈,肝肾亏虚为本,病性因素多为痰瘀。强调分急性期、缓解期治疗,注重气之升降--引痰饮血瘀下行而出,津气上行以荣脑。自拟颈痹眩晕方,为升降散合泽泻汤加减而成,组方精当,临床运用每获良效。     

发泡胶在鼻咽癌放疗中对剂量分布的影响

目的：研究在鼻咽癌放射治疗中应用发泡胶进行体位固定对剂量分布的影响。方法：随机选取11例应用头颈肩热塑膜联合发泡胶进行体位固定的鼻咽癌患者，在Pinnacle计划系统中将空白CT值设置到发泡胶的CT值以下，以确保发泡胶的CT值被计算在内，作为第一组计划（Plan_F）。同时，复制第一组计划并在定位图像上勾画出发泡胶，设置发泡胶的CT值为0，在不改变射野分布、权重及计划跳数的情况下重新计算剂量分布，作为第二组计划（Plan_N）。比较两组计划的靶区及周围正常组织的剂量分布。结果：对于靶区（GTVnx、GTVnd、GTVrpn、PGTVnx、CTV1、PTV1、CTV2、PTV2）的最小剂量Dmin，最大剂量Dmax，平均剂量Dmean去除发泡胶之后，所测 255组数据中仅有6组数据出现减小（约占2.4%），Dmin、Dmax和Dmean的变化度（%）（X±SD）依次为0.215±0.969、 0.395±0.623和 0.442±0.178，其中除了GTVrpn的Dmin（P=0.727）和Dmax（P=0.142），PGTVnx的Dmin（P=0.623），CTV1 Dmin（P=0.713），CTV2 Dmax（P=0.066），其他评估指标皆显示发泡胶使用组剂量低于去除发泡胶组（P＜0.05）；而对于周围正常组织（脑干、脊髓、左右晶体、左右视神经和腮腺）的Dmean和Dmax去除发泡胶之后，所测的154组数据中仅有14组数据出现减小（约占9.1%），Dmax和Dmean的变化度（%）（X±SD）依次为0.194±0.192 和0.129±0.128，其中除了左、右晶体的平均剂量Dmean（P值分别为0.123和0.06），其余各项指标同样显示发泡胶使用组剂量低于去除发泡胶组（P＜0.05）。结论：发泡胶的使用降低了实际治疗过程中受照部位的剂量，但发泡胶对剂量变化的影响都在目前临床可接受的范围之内。     

Recurrent BRCA1 Mutation,but no BRCA2 Mutation,in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.     

SAMHD1通过调控p27表达抑制肝细胞癌细胞增殖的研究

背景与目的：不育α基序结构域和组氨酸/天冬氨酸残基双联体结构域包涵蛋白1（sterile alpha motif and histidine/aspartic acid domain-containing protein 1，SAMHD1）具有抑制多种肿瘤细胞生长的作用，但其调节肝细胞癌（hepatocellular carcinoma，HCC）细胞增殖的作用及机制尚未见报道。探究SAMHD1调控p27的表达对HCC细胞Huh7的增殖、凋亡和细胞周期的影响。方法：首先通过蛋白质印迹法（Western blot）检测正常肝细胞和不同类型HCC细胞中SAMHD1的表达情况。利用基因修饰技术构建过表达SAMHD1、dNTP酶活性位点突变体（SAMHD1-D207N）和磷酸化位点突变体（SAMHD1-T592E）的重组质粒，然后利用四甲基偶氮唑蓝（methyl thiazolyl tetrazolium，MTT）法检测过表达SAMHD1及其突变体或siRNA干扰沉默SAMHD1对HCC细胞增殖的影响，采用流式细胞术检测细胞周期与细胞凋亡情况。在癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中分析SAMHD1和p27表达的相关性。结果：HCC细胞中SAMHD1表达上调，过表达SAMHD1、SAMHD1-D207N和SAMHD1-T592E可以抑制Huh7细胞增殖，细胞周期停滞在G ₁ /G ₀ 期；相反，干扰SAMHD1后细胞增殖加快，细胞周期停滞在G ₂ /M期。机制研究表明，SAMHD1上调细胞周期蛋白激酶抑制因子p27的表达。在HCC组织中，p27的表达与SAMHD1表达呈正相关。结论：过表达SAMHD1可以上调p27的表达，导致细胞周期停滞在G ₁ /G ₀ 期，从而抑制HCC细胞增殖，这种抑制作用不依赖于其dNTP酶活性和磷酸化修饰。     

Oncologic outcome of mixed adenoneuroendocrine carcinoma (MANEC): A single center case series

IntroductionMixed adeno-neuroendocrine carcinomas (MANEC) are rare tumors of gastrointestinal tract mostly found in stomach. There are very few case reports and case series with location of colon and rectum. We aimed to report our results in the treatment of colorectal MANEC.MethodsWe performed a prospective analysis of patients with MANEC diagnosis from December 2011 to March 2019 at National Cancer Institute, Lithuania. The demographic information, tumor details, immunohistochemical markers, clinical data, stage, treatment modalities, clinical and oncological outcomes were collected.ResultsNine patients with a diagnosis of MANEC were found in our center. The average age at diagnosis was 64.8 (48–91) years. Seven out of nine (77.8%) patients underwent surgery. Distant metastases were observed in five (55.6%) patients. The adenocarcinoma and neuroendocrine tumor as a dominant component were equal in all cases. The most common tumor localizations were sigmoid colon in three patients (33.3%) and rectum – three patients, following two in an anal canal, and one in the hepatic flexure of colon. The adenocarcinoma component was poorly differentiated (G3) in six patients and moderately differentiated (G2) in three patients. The neuroendocrine component was G3 in seven patients (77.8%), G2 – in two patients (22.2%). Median follow-up was 17 months with a median survival time of 12.5 months.ConclusionMANEC is very rare, aggressive, rapidly spreading, usually with poor prognosis disease.