Selenium substituted axitinib reduces axitinib side effects and maintains its anti-renal tumor activity

Axitinib is a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, which has a strong inhibitory effect on the three isoforms of VEGFR 1–3. Having strong therapeutic efficacy, its broad use is limited by its side effects such as hypertension, proteinuria, cardiovascular damage, and liver and kidney dysfunction. Selenium compounds are broadly reported to have a good protective effect on cardiovascular disease, inflammation, infection, and immune function. In this study, a selenium substitute of axitinib was synthesized, and its anti-renal cell carcinoma activity and side effects were investigated. The results of the study indicated that Se-axitinib had potent antitumor activity on renal cell carcinoma (RCC), alleviated vascular hyperpermeability, and also alleviated axitinib-related side effects including hypertension, liver dysfunction and kidney dysfunction significantly. Therefore, we suggest that Se-axitinib could be a solution to the severe side effects of VEGFR inhibitors and provide evidence to improve the outcome of RCC treatment.

Se-axitinib is a selenium substitution of sulfur in axitinib, which reduced the side effect of VEGFR inhibitors and maintained the potent anticancer activity of the original drug.     

Socioeconomic status,individual behaviors and risk for mental disorders: A Mendelian randomization study

BackgroundThere is increasing attention on the association of socioeconomic status and individual behaviors (SES/IB) with mental health. However, the impacts of SES/IB on mental disorders are still unclear. To provide evidence for establishing feasible strategies on disease screening and prevention, we implemented Mendelian randomization (MR) design to appraise causality between SES/IB and mental disorders.MethodsWe conducted a two-sample MR study to assess the causal effects of SES and IB (dietary habits, habitual physical activity, smoking behaviors, drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on three mental disorders, including bipolar disorder, major depressive disorder and schizophrenia. A series of filtering steps were taken to select eligible genetic instruments robustly associated with each of the traits. Inverse variance weighted was used for primary analysis, with alternative MR methods including MR-Egger, weighted median, and weighted mode estimate. Complementary methods were further used to detect pleiotropic bias.ResultsAfter Bonferroni correction and rigorous quality control, we identified that SES (educational attainment), smoking behaviors (smoking initiation, number of cigarettes per day), risky behaviors (adventurousness, number of sexual partners, automobile speeding propensity) and reproductive behavior (age at first birth) were causally associated with at least one of the mental disorders.ConclusionsMR study provides robust evidence that SES/IB play broad impacts on mental disorders.     

Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein–Barr Virus-Associated Malignancies

The Epstein–Barr virus (EBV) can cause different types of cancer in human beings when the virus infects different cell types with various latent patterns. EBV shapes a distinct and immunosuppressive tumor microenvironment (TME) to its benefit by influencing and interacting with different components in the TME. Different EBV-associated malignancies adopt similar but slightly specific immunosuppressive mechanisms by encoding different EBV products to escape both innate and adaptive immune responses. Strategies reversing the immunosuppressive TME of EBV-associated malignancies have been under evaluation in clinical practice. As the interactions among EBV, tumor cells, and TME are intricate, in this review, we mainly discuss the epidemiology of EBV, the life cycle of EBV, the cellular and molecular composition of TME, and a landscape of different EBV-associated malignancies and immunotherapy by targeting the TME.     

Moderate Hypofractionated Helical Tomotherapy for Older Patients with Localized Prostate Cancer: Long-term Outcomes of a Phase I–II Trial

BackgroundOur previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up.Patients and methodsThe study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity.ResultsThe average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable.ConclusionsIn older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.Key words: helical tomotherapy, radiation dose hypofractionation, progression-free survival, follow-up studies, prostatic neoplasms, adenocarcinoma     

松茸不同提取部位的体外抗肿瘤作用

摘 要 目的： 研究松茸不同提取部位的体外抗肿瘤活性。 方法: 采用MTT法测定松茸乙醇提取物各部位及多糖部位对HepG-2细胞、Hela细胞和MCF-7细胞的抑制作用;采用流式细胞术检测多糖部位诱导HepG-2细胞和Hela细胞凋亡的作用。结果:松茸多糖部位体外对3种肿瘤细胞的IC₅₀分别为53.77μg·ml^-1(HepG-2)、40.04 μg·ml^-1(Hela)、100.65 μg·ml^-1(MCF-7),抑制作用均优于其他各部位,且对HepG-2细胞和Hela细胞抑制作用呈现良好的时间与浓度依赖性;松茸多糖部位能诱导HepG-2细胞和Hela细胞凋亡。结论: 松茸多糖部位能显著抑制HepG-2和Hela等肿瘤细胞的生长,具有诱导凋亡的作用,为松茸抗肿瘤的主要活性部位。     

中药饮片质量标准研究中的几个关键问题

中药饮片质量标准是中药炮制研究的重要内容,也是整个中药标准化体系的关键环节。尽管中药饮片有了国家标准,但是中药饮片标准化水平仍然处于较低水平。在中药饮片质量标准研究中,还存在一些实际问题需要我们加以重视和思考。本文结合作者长期的研究和生产实践,提出在中药饮片质量标准研究中要更加注重和传统炮制理论、炮制机理研究与药效物质研究的结合,努力构建更加全面、科学、合理的中药饮片质量标准。     

戊二酰辅酶A脱氢酶基因沉默及高浓度赖氨酸对BRL肝细胞活性的影响

目的探讨戊二酰辅酶A脱氢酶(GCDH)基因沉默和赖氨酸代谢物蓄积对肝细胞活性的影响。方法将BRL肝细胞分为正常对照组、阴性对照组和GCDH沉默组。构建含靶向沉默GCDH基因的sh RNA慢病毒载体,分别用该病毒和阴性对照病毒感染GCDH沉默组和阴性对照组BRL肝细胞。感染后细胞再用含5 mmol/L赖氨酸培养基培养。免疫荧光技术检测慢病毒感染效率;Western blot法检测GCDH蛋白表达水平;MTT法检测细胞活性,Hoechest 33342染色检测细胞凋亡,Western blot法检测细胞凋亡的经典指标Caspase3水平。结果构建的慢病毒可有效沉默肝细胞GCDH表达(P0.01)。MTT及Hoechest 33342染色检测各组间细胞活性及细胞凋亡比较差异无统计学意义(P0.05)。Caspase3蛋白表达在各组间比较差异亦无统计学意义(P0.05)。结论 GCDH基因沉默和赖氨酸代谢物蓄积对肝细胞无明显损伤作用。