Genetic variants at 9p21.3 are associated with risk of esophageal squamous cell carcinoma in a Chinese population

Genome‐wide association studies have linked genetic variants at 9p21.3 to the risk of multiple cancers. However, the roles of genetic variants at 9p21.3 in esophageal squamous cell carcinoma (ESCC) development are largely unknown. We evaluated the genetic variants at 9p21.3 reported in cancer genome‐wide association studies with a case–control study including 2139 ESCC cases and 2273 controls in a Chinese population, and measured the mRNA expression levels of MTAP, CDKN2A, CDKN2B, and CDKN2B‐AS1 in paired ESCC tumor and adjacent normal tissues. We found that the G allele of rs7023329 was significantly associated with a decreased risk of ESCC with a per‐allele odds ratio of 0.84 (95% confidence interval, 0.77–0.91; P = 2.95 × 10^?5). The rs7023329‐G allele was related to a high expression of MTAP (P = 0.020). The rs1679013‐C allele was independently associated with an increased risk of ESCC with a per‐allele odds ratio of 1.12 (95% confidence interval, 1.01–1.24; P = 0.039). We also found that the carriers of the risk allele rs1679013‐C had lower expression of CDKN2B than non‐carriers (P = 0.035). CDKN2B was also significantly downregulated in ESCC tumor tissues compared with adjacent normal tissues (P = 3.50×10^?5). Therefore, our findings indicate that genetic variants at 9p21.3 may modulate the expression of MTAP and CDKN2B and contribute to ESCC susceptibility. This may further advance our understanding of the 9p21.3 locus in cancer development.     

晚期非小细胞肺癌初始治疗后再次应用EGFR-TKI的疗效观察

背景与目的表皮生长因子受体酪氨酸激酶抑制剂(epidermalgrowthfactorreceptortyrosinekinaseinhibi-tor,EGFR-TKI)是化疗失败的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准二三线治疗方案,亦是EGFR突变患者一线治疗的最佳选择,但对初始治疗后进展的患者,在治疗过程中能否再次使用TKI是目前的关注热点。本研究旨在探讨晚期NSCLC初始治疗后再次应用EGFR-TKI的疗效。方法本研究回顾性分析了71例晚期或术后复发的NSCLC初始EGFR-TKI治疗后,再次应用TKI的疗效。结果 71例再次应用TKI的患者中,部分缓解(par-tial response,PR)为7%,稳定(stable disease,SD)为36.6%,(progressive disease,PD)为56.3%,疾病控制率(diseasecontral rate,DCR)为43.7%,无进展生存期(progression free survival,PFS)>3个月者26例(36.6%)。EGFR21外显子突变、初始TKI缓解期6个月、两次TKI的间隔期3个月与更长的PFS相关,单因素COX回归分析,P值分别为0.034、0.013、0.046。结论 TKI治疗失败的NSCLC患者再次应用TKI,部分患者仍可获得疾病控制。EGFR21外显子突变、初始TKI缓解期6个月、两次TKI间隔期3个月的患者更可能从再次应用TKI中获益。     

305例非小细胞肺癌骨转移的诊断、治疗及预后分析

背景与目的骨转移是肺癌最常见转移部位之一，可引起疼痛、病理性骨折等，严重影响患者生活质量。本研究拟探讨骨扫描、MRI、CT、X线对非小细胞肺癌（NSCLC）骨转移的诊断价值，骨转移的治疗及预后相关因素分析。方法回顾分析16年我组连续诊治的561例晚期NSCLC的骨扫描检查，并与MRI、CT、X线检查骨转移方法对比。结果561例骨扫描中阳性455例，155例经临床排除骨转移，300例经临床、MRI／CT／X线证实或病理等证实为骨转移，假阴性5例，共305例骨转移。骨扫描总敏感性为98．36％，特异性为39．45％，准确度为71．48％。305例骨转移患者中有症状者138例，无症状者144例（47．21o．4），未记载者23例。多因素回归分析显示：转移在周围扁骨，骨磷治疗，无症状为有益的预后因素（P〈0．05）。结论骨扫描对于肺癌骨转移筛查具有肯定的临床价值。核素骨扫描可成为肺癌分期检查的筛查手段。骨扫描的不典型阳性病灶。可辅以CT或MRI检查。     

Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin‐bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.     

缝隙连接蛋白26在肺腺癌相关成纤维细胞中的表达及临床意义

目的 探讨缝隙连接蛋白26(connexin 26,Cx26)在肺腺癌相关成纤维细胞中的表达及其临床意义.方法 收集2018年11月至2019年5月于广西医科大学附属肿瘤医院6例手术切除肺腺癌癌组织及相应癌旁组织,分离原代肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)和正常肺...     

Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, Human cervical cancer proto-oncogene (HCCR) aberrantly expressed in a number of malignant tumors, including HCC. HCC is associated with Hepatitis B virus (HBV) infection in a large percentage of cases. To explore the regulation and function of HCCR expression in the development of HCC, we detected HCCR expression in HBV expressing hepatocytes. Results showed that the expression of HCCR was higher in HBV-expressing hepatocytes than that in control cells. Examining different components of HBV revealed that the HBx promotes HCCR expression in hepatocytes via the T-cell factor (TCF)/β-catenin pathway. HCCR expression in HBx transgenic mice increased with as the mice aged and developed tumors. We also found that overexpression of HCCR in hepatocytes promoted cell proliferation, migration, and invasion and reduced cell adhesion. Suppressing HCCR expression abolished the effect of HBx-induced hepatocyte growth. In addition, HCCR represses the expression of E-cadherin by inhibition its promoter activity, which might correlate with the effects of HCCR in hepatocytes. Taken together, these results demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. They also imply that HCCR is a potential risk marker for HCC and/or a potential therapeutic target.     

Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis

To identify genes that are differentially over-expressed in Small Cell Lung Carcinoma (SCLC) we have used a combination of suppression subtractive hybridization and cDNA microarray to analyse the expression profiles of 2400 cDNAs clones. Genes that are over-expressed in SCLC were identified using 32 pairs of fluorescence-labeled cDNA samples representing various lung tumors and normal tissues. This comprehensive approach has resulted in the identification of 209 genes that are differentially over-expressed in SCLC. Quantitative real-time PCR was used to further validate the expression of 43 genes in SCLC tumors and various normal tissues. Discussed in this report are nine genes, which showed the most promising SCLC tumor to normal tissue differential expression profiles, including seven known and two novel genes. The large number of differentially expressed genes identified from this analysis and the characterization of these genes will provide valuable information in better understanding the biology of SCLC and help us in developing these gene products as potential targets for diagnostic as well as therapeutic usage.     

Association between asymmetry in cataract and asymmetry in age-related macular degeneration. The Beijing Eye Study

Background  

To examine in an intra-individual comparison whether cataract is associated with age-related macular degeneration (AMD).     

Persistent maternal anxiety affects the interaction between mothers and their very low birthweight children at 24 months

Background

Parental distress following the birth of a premature infant diminishes the parent's ability to be sensitive to the infant's cues, and this may affect infant developmental outcomes.

Aims

The present study examined the effects of maternal anxiety during infant hospitalization in the Neonatal Intensive Care Unit (NICU) on the interactive behavior of mothers with their very low birthweight (VLBW) children in toddlerhood.

Subjects

A sample of 56 mothers and their VLBW infants were recruited in the NICU.

Study design

During the infant's NICU stay, mothers completed a self-report measure of trait anxiety. These mothers and their infants were followed when the infants were 24 months corrected age, when mothers and their children were videotaped during free play at home. These videotapes were then coded using the Emotional Availability Scales.

Results

Maternal anxiety was not found to be related to severity of neonatal illness. Maternal anxiety in the NICU was associated with less sensitivity and less structure in interaction with their toddlers at 24 months corrected age, even controlling for maternal education and child birthweight. Children of mothers with higher anxiety scores in the NICU were less likely to involve their mothers in their play at 24 months corrected age.

Conclusions

Maternal anxiety in the NICU predicted adverse interactive behaviors when the children were 24 months corrected age. Early identification of anxious mothers in the NICU is needed in order to initiate preventive intervention to support the mother-infant relationship.     

表皮生长因子受体基因扩增在非小细胞肺癌预后中作用的meta分析

背景与目的 研究表明探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)基因扩增与非小细胞肺癌预后的可能相关,但各研究结论不一.本研究通过meta分析,评价了EGFR基因扩增在不同人种以及不同治疗情况下的预后意义.方法 检索PubMed、Cochrane图书馆以及CNKI中文数据库中研究细胞EGFR基因扩增与非小细胞肺癌预后关系的文献,根据欧洲肺癌工作组提供的专门的评分标准对纳入的文献进行质量评估,收集每个文献的风险比(hazard ratio,HR)及95%可信区间(confidence interval,CI),应用meta分析对文献进行定量综合分析.结果 共入选17篇文献,应用表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)治疗的12项研究共入选病例1 221例,结果显示扩增阳性患者预后优于扩增阴性患者(HR=0.82,95%CI:0.68-0.99,P-0.04);欧美人种基因扩增阳性对EGFR-TKI疗效有明显的预测作用(Hg=0.42,95%CI:0.31-0.57,P<0.001).未应用EGFR-TKI治疗的8项研究共入选病例658例,结果显示扩增阳性与阴性患者死亡风险相当(HR=1.1 4, P=0.12);其中亚洲人中基因扩增者较未扩增者预后差(HR=1.88,95%CI:1.21-2.93,P=0.00s).结论 EGFR基因扩增在欧美人中可能是EGFR-TKI治疗的阳性疗效预测指标,对于亚洲人预测意义不明显.另外,在未接受EGFR-TKI治疗的亚洲人中,EGFR基因扩增阳性者预后较差.