Drugging the R-loop interactome: RNA-DNA hybrid binding proteins as targets for cancer therapy

Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers.     

Apatinib for heavily treated patients with non-small cell lung cancer: Report of a case series and literature review

Although many strategies have been developed for non-small cell lung cancer (NSCLC), more secondary and further treatments are needed due to drug resistance or tumor recurrence. Apatinib is a novel oral antiangiogenic agent and in this study, we aim to investigate the clinical value of apatinib in heavily pretreated NSCLC. Here, we reported the characteristics, efficacy and adverse events of three patients treated with apatinib (500?mg/day). We also summarized the currently available evidence and ongoing clinical trials regarding the use of apatinib in NSCLC. Two cases of adenocarcinoma and one case of squamous cell carcinoma were treated with apatinib due to disease progression after previous treatments of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). All patients responded to apatinib rapidly and underwent drug resistance shortly afterwards. The patient with squamous cell carcinoma died of hemoptysis. Other adverse events were acceptable. All previous relevant studies were compared and showed similar results but a longer progression-free survival. Additionally, ongoing clinical trials were systematically searched and listed. In conclusion, apatinib shows some efficacy in heavily treated NSCLC and generally tolerable toxicity in non-squamous NSCLC. More solid evidence will be accessible in near future.     

林木种源速生丰产势的研究

在数学上可用林木种源收获量分布曲线中超过某一收获量标准（如对照种源的平均收获量)的积分面积来表示林木种源获得速生丰产的可能性大小，这种可能性可以用来衡量林木种源的优劣。在林木种源试验中，由于参试种源的平均收获量水平和稳定性能的差异,各个林木种源均有其独特的收获量分布曲线，并均可求出各个种源相应的速生丰产积分面积或累积概率。本文提出用林木种源超过对照平均收获量的收获量累积概率值作为林木种源速生丰产综合性能优劣的一个指标，在各种源参试地点完全相同时，可用一个相应的参数--林木种源速生丰产势--来衡量和评价林木参试种源的优劣。