Practical uses of contrast‐enhanced spectral mammography in daily work: A pictorial review

Contrast‐enhanced spectral mammography (CESM) has a number of uses including the work‐up of inconclusive findings on mammography, assessment of breast symptoms, cancer staging, evaluation of response to neoadjuvant chemotherapy and recently as an alternative to magnetic resonance imaging (MRI) in high‐risk screening. CESM can be swiftly incorporated into the workflow of busy breast clinics. We share our experiences with CESM at a large breast assessment centre in Western Australia.     

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm²) was higher compared to iRBD (0.07 ± 0.07 cm²; p < 0.0001) and controls (0.05 ± 0.03 cm²; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.     

Current status of first-line therapy,anti-angiogenic therapy and its combinations of other agents for unresectable hepatocellular carcinoma

Globally, hepatocellular carcinoma (HCC) is a frequently diagnosed malignancy with rapidly increasing incidence and mortality rates. Unfortunately, many of these patients are diagnosed in the advanced stages when locoregional treatments are not appropriate. Before 2008, no effective drug treatments existed to prolong survival, until the breakthrough multi-tyrosine kinase inhibitor (TKI) sorafenib was developed. It remained the standard treatment option for advanced HCC for 10 years, with a battery of other candidate drugs in clinical trials failing to produce similar efficacy results. In 2018, the REFLECT trial introduced another multi-TKI, lenvatinib, which has non-inferior overall survival compared with sorafenib. Thus, offering patients and their treating physicians two effective treatment options. Recently, immunotherapy-based drugs, such as atezolizumab and bevacizumab, have shown promising results in patients with unresectable HCC. This review summarizes clinical trial and real-world data studies of sorafenib and lenvatinib in patients with unresectable HCC. We offer guidance on the optimal choice between the two treatments and discuss the potential of immunotherapy-based combination; when more data become available, this will likely make the choice between sorafenib and lenvatinib somewhat obsolete.     

肝细胞癌中miR-942-5p的表达及其与患者恶性特征及不良预后的关系

目的:探讨微小RNA-942-5p(miR-942-5p)在肝细胞癌(HCC)组织中的表达及其功能。方法:用实时定量PCR检测西安交通大学第一附属医院样本库保存的73例HCC组织和对应癌旁组织中miR-942-5p的表达。分析miR-942-5p表达与HCC患者临床病理资料的关系,同时分析TCGA数据库中miR-942-5p表达与HCC患者总生存率的关系。Transwell小室检测干扰miR-942-5p表达后HCC细胞迁移和侵袭能力的变化,StarBase V3.0网站和荧光素酶报告基因质粒预测分析miR-942-5p的下游靶点,并用Western blot验证。结果:miR-942-5p表达量在HCC组织中明显高于对应癌旁组织(2.390 vs. 1.764,P0.05)。miR-942-5p表达量与HCC患者肿瘤数目、血管浸润和临床分期明显有关(均P0.05)。miR-942-5p高表达HCC患者总生存率明显低于miR-942-5p低表达HCC患者(19.535%vs. 53.873%,P0.05)。沉默miR-942-5p表达后,肝癌HCCLM3和MHCC97H细胞迁移和侵袭能力明显减弱(均P0.05)。预测与分析结果显示,扣针蛋白5(FBLN5)是miR-942-5p的直接下游靶点(P0.05),沉默miR-942-5p表达导致HCCLM3和MHCC97H细胞中FBLN5表达增加。结论:miR-942-5p在HCC组织中表达异常升高并与恶性临床特征和不良预后密切相关,机制可能与miR-942-5p抑制FBLN5表达促进HCC细胞迁移和侵袭有关。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.