Disparities between Uptake of Germline BRCA1/2 Gene Tests and Implementation of Post-test Management Strategies in Epithelial Ovarian,Fallopian Tube,or Primary Peritoneal Cancer Patients

BackgroundTo assess the rate of germline BRCA gene tests in epithelial ovarian cancer (EOC) patients and uptake of post-test risk management strategies in BRCA1/2-mutated patients.MethodsInstitutional databases were searched to identify patients who were diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) between 2009 and 2019 in two academic hospitals. Retrospective review on medical records was performed to collect clinico-pathologic variables, including performance of germline BRCA gene test and its results, as well as conduct of breast cancer screening tests and cascade testing. If annual mammography +/− breast ultrasonography was performed, it was considered that regular breast cancer surveillance was done.ResultsA total of 840 women with EOC were identified during the study period. Of these, 454 patients (54.0%) received BRCA gene testing and 106 patients (106/454, 23.3%) were positive for BRCA1/2 mutations. The rate of BRCA tests has markedly increased from 25.8% in 2009-2012 to 62.7% in 2017-2019. Among the 93 patients with BRCA1/2 mutation without previous personal breast cancer history, 20 patients (21.5%) received annual mammography with or without breast ultrasonography for regular surveillance. Among the 106 BRCA1/2-mutated EOC patients, cascade testing on family members was performed only in 13 patients (12.3%).ConclusionAlthough BRCA1/2 gene tests have been substantially expanded, the uptake of post-test risk management strategies, including breast cancer screening for BRCA1/2-mutated patients and cascade testing for family members, has remained low. Strategies to increase its uptake and education about the importance of post-test risk managements are needed.     

Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma

BackgroundEpigenetic changes play a key role in the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor.MethodsWe explore the therapeutic potential of BMI1 and MAPK/ERK inhibition in BMI1^High;CHD7^Low MB cells and in a preclinical xenograft model.ResultsWe identify a synergistic vulnerability of BMI1^High;CHD7^Low MB cells to a combination treatment with BMI1 and MAPK/ERK inhibitors. Mechanistically, CHD7-dependent binding of BMI1 to MAPK-regulated genes underpins the CHD7-BMI1-MAPK regulatory axis responsible of the antitumour effect of the inhibitors in vitro and in a preclinical mouse model. Increased ERK1 and ERK2 phosphorylation activity is found in BMI1^High;CHD7^Low G4 MB patients, raising the possibility that they could be amenable to a similar therapy.ConclusionsThe molecular dissection of the CHD7-BMI1-MAPK regulatory axis in BMI1^High;CHD7^Low MB identifies this signature as a proxy to predict MAPK functional activation, which can be effectively drugged in preclinical models, and paves the way for further exploration of combined BMI1 and MAPK targeting in G4 MB patients.     

胶原-壳聚糖复合支架用作组织工程心瓣膜的可行性

目的:构建组织工程心脏瓣膜的先决条件之一是构建最佳解剖结构和性能的支架材料,拟证明胶原-壳聚糖复合支架可以作为组织工程心脏瓣膜的最佳支架材料。方法:实验于2004-03/2005-02在中国科学院昆明动物研究所完成。将胶原与壳聚糖分别按7∶1,5∶1,3∶1质量比混合,冷冻干燥法成膜,碾压平整后制成胶原-壳聚糖复合多孔支架。将复合支架制成直径1.0cm的圆片,依次经过固定、冲洗、脱水、透明、浸蜡、包埋、切片、展片与烘片行一般物理性状观察、苏木精-伊红染色和Masson染色观察内部结构;再将另一圆片依次经过固定、洗涤、脱水、置换、浸透、包埋后聚合、临界点干燥、喷镀、安置处理后制成超薄切片进行电镜扫描,观察其超微结构特性。结果:胶原-壳聚糖复合支架外观呈微黄色,半透明状,可见微孔状结构,柔韧适度,富有弹性,抗张强度约为4.0MPa,孔径大小基本一致,保持在80～260μm,孔隙率在95%以上,且孔与孔相互贯通,呈立体网状结构。结论:胶原-壳聚糖复合支架的结构和物理性状符合组织工程心瓣膜材料的要求。     

A Review on Surface Finishing Techniques for Difficult-to-Machine Ceramics by Non-Conventional Finishing Processes

Ceramics are advanced engineering materials in which have been broadly used in numerous industries due to their superior mechanical and physical properties. For application, the industries require that the ceramic products have high-quality surface finishes, high dimensional accuracy, and clean surfaces to prevent and minimize thermal contact, adhesion, friction, and wear. Ceramics have been classified as difficult-to-machine materials owing to their high hardness, and brittleness. Thus, it is extremely difficult to process them with conventional finishing processes. In this review, trends in the development of non-conventional finishing processes for the surface finishing of difficult-to-machine ceramics are discussed and compared to better comprehend the key finishing capabilities and limitations of each process on improvements in terms of surface roughness. In addition, the future direction of non-conventional finishing processes is introduced. This review will be helpful to many researchers and academicians for carrying out additional research related to the surface finishing techniques of ceramics for applications in various fields.