Laminin gene LAMB4 is somatically mutated and expressionally altered in gastric and colorectal cancers

Laminins are important in tumor invasion and metastasis as well as in maintenance of normal epithelial cell structures. However, mutation status of laminin chain‐encoding genes remains unknown in cancers. Aim of this study was to explore whether laminin chain genes are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). In a public database, we found that laminin chain genes LAMA1, LAMA3, LAMB1 and LAMB4 had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI). We analyzed the genes in 88 GC and 139 CRC [high MSI (MSI‐H) or stable MSI/low MSI (MSS/MSI‐L)] by single strand conformation polymorphism analysis and DNA sequencing. In the present study, we found LAMB4 (11.8% of GC and 7.6% of CRC with MSI‐H), LAMA3 (2.9% of GC and 2.5 of CRC with MSI‐H), LAMA1 (5.9% of GC with MSI‐H) and LAMB1 frameshift mutations (1.3% of CRC with MSI‐H). These mutations were not found in MSS/MSI‐L (0/114). We also analyzed LAMB4 expression in GC and CRC by immunohistochemistry. Loss of LAMB4 expression was identified in 17–32% of the GC and CRC. Of note, the loss expression was more common in the cancers with LAMB4 mutation or those with MSI‐H. Our data show that frameshift mutations of LAMA1, LAMA3, LAMB1 and LAMB4, and loss of LAMB4 may be features of GC and CRC with MSI‐H.     

不同空间排列静电纺丝对RSC96细胞表达NGF及Laminin的研究

目的：研究不同空间排列静电纺丝对雪旺细胞株(RSC96)神经营养因子（NGF）及层粘连蛋白（Laminin,LN）的表达情况。方法根据培养条件不同分3组,即平行静电纺丝培养组（A）、随机静电纺丝培养组（B）及膜上培养组（C）培养3天后用Trizol法提取细胞总RNA,用Oligo(dT)逆转录酶得到cDNA。经特定引物PCR扩增,取相同量的逆转录产物进行qPCR反应,检测NGF及LN的表达差异。结果平行静电纺丝组,随机静电纺丝组,膜上培养组上NGF基因表达依次递增,各组间差异明显;LN基因的表达依次递减,各组间差异明显。结论不同空间排列的静电纺丝对RSC96细胞表达NGF和Laminin影响不同,平行的静电纺丝有促进细胞向成熟分化的可能。     

Meningeal/vascular alterations and loss of extracellular matrix in the neurogenic zone of adult BTBR T+ tf/J mice,animal model for autism

Autism spectrum disorders are characterized by impaired social and communication skills and seem to result from altered neural development. We sought to determine whether the anatomy of the meninges and extracellular matrix (ECM) is altered in an animal model of autism, the BTBR T+ tf/J mouse. This mouse displays white matter tract anatomical defects and exhibits several symptoms of autism. Immunofluorescence cytochemistry for laminin, a major ECM marker, was performed on series of coronal sections of the adult BTBR T+ tf/J brain and the anatomy was analyzed in comparison to B6 wild type mice. Laminin immunoreactivity visualized meninges, blood vessels and the subventricular zone (SVZ) stem cell-associated ECM structures, which I have named fractones. All BTBR T+ tf/J mice observed showed the same forebrain defects. The lateral ventricle volume was severely reduced, the falx cerebri elongated, the arteries enlarged and the choroid plexus atrophied. Compared to B6 mice, fractone numbers in BTBR T+ tf/J mice were reduced by a factor three in the SVZ of the anterior portion of the lateral ventricle. This represents the primary neurogenic zone during adulthood. Fractones were reduced by a factor 1.5 in posterior portions of the lateral ventricle. Moreover, fractone size was reduced throughout the lateral ventricle SVZ. These results show hitherto unsuspected alterations in connective tissue/vasculature and associated ECM in the adult BTBR T+ tf/J mouse. The drastic changes of the connective tissue and ECM in the neurogenic zone of the lateral ventricle may contribute to incorrect neurogenesis during developmental and adult stages.     

抗p200类天疱疮7例临床及免疫血清学特征分析

【摘要】 目的 总结抗p200类天疱疮患者的临床和免疫血清学特征。方法 收集2015年1月至2021年10月在中国医学科学院皮肤病医院确诊为抗p200类天疱疮的患者资料,回顾性分析其临床和免疫血清学特征。结果 纳入7例抗p200类天疱疮患者,盐裂皮肤-间接免疫荧光实验显示,7例患者血清IgG抗体均结合于盐裂皮肤的真皮侧,以真皮提取物为底物的免疫印迹显示,在相对分子质量200 000蛋白处有条带。4例呈经典型大疱性类天疱疮样损害,2例初起呈湿疹样损害,1例类似线状IgA大疱性皮病。6例循环IgG抗体可识别层粘连蛋白γ1-C端重组蛋白。4例患者接受不同剂量系统糖皮质激素治疗,其中1例对高剂量系统糖皮质激素（相当于泼尼松1.4 mg·kg-1·d-1）治疗抵抗;2例对米诺环素、氨苯砜治疗反应好;1例失访。4例患者在随访平均22.5个月时达到完全缓解停药;2例在随访平均8个月时达到最小剂量治疗保持完全缓解。结论 抗p200类天疱疮临床表现多样,重组Lnγ1-C端可作为可靠的抗原底物用于检测抗p200类天疱疮患者自身抗体;部分患者最终可达到完全缓解并停药。