Renin–angiotensin system inhibitors (RAS inhibitors) are antihypertensive agents with potential antitumor effects. However, various studies have yielded conflicting results on the influence of RAS inhibitors on survival of cancer patients. The aim of this study was to evaluate the effect of RAS inhibitors on recurrence, metastasis, and survival in cancer patients through a meta-analysis. PubMed, Web of Science, EMBASE, and Cochrane Library were systematically searched from inception to December 2016. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) was calculated to evaluate the association between RAS inhibitors and recurrence, metastasis, and survival in cancer patients. Fifty-five eligible studies were included in the present meta-analysis. Results showed that there were significant improvements in overall survival (OS) (HR = 0.82; 95% CI: 0.77–0.88; P < 0.001), progression-free survival (HR = 0.74; 95% CI: 0.66–0.84; P < 0.001), and disease-free survival (HR = 0.80; 95% CI: 0.67–0.95; P = 0.01) in RAS inhibitor users compared with nonusers. Subgroup analyses revealed that the effect of RAS inhibitors on OS depended on the cancer type or different RAS inhibitors. This meta-analysis suggests that RAS inhibitors could improve the survival of cancer patients and depend on cancer type and types of RAS inhibitors.

Peripheral neuropathy is the major dose-limiting side effect of paclitaxel (PTX), affecting both the quality of life and the survival of cancer patients. Nab-paclitaxel (nab-PTX) was developed to provide additional clinical benefits and overcome the safety drawbacks of solvent-based PTX. However, the prevalence of peripheral neuropathy induced by nab-PTX was reported higher than that induced by solvent-based PTX. Upon investigation, oxidative stress plays a major role in the toxicity of nab-PTX. In order to assess if the antioxidant alphalipoic acid (α-LA) could prevent the nab-PTX-induced peripheral neuropathy, Sprague-Dawley (SD) rats were treated with three doses of α-LA (15, 30, and 60 mg/kg in normal saline, i.p., q.d. (days 1-30)) and/or nab-PTX (7.4 mg/kg in normal saline, i.v., q.w. (days 8, 15, and 22)). Body weight and peripheral neuropathy were measured and assessed regularly during the study. The assessment of peripheral neuropathy was performed by the von Frey and acetone tests. A tumor xenograft model of pancreatic cancer was used to assess the impact of α-LA on the antitumor effect of nab-PTX. Results showed that α-LA significantly ameliorated the peripheral neuropathy induced by nab-PTX (p<0.05) without promoting tumor growth or reducing the chemotherapeutic effect of nab-PTX in a tumor xenograft model. Moreover, α-LA might significantly reverse the superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels altered by nab-PTX in the serum and the spinal cord of rats. Furthermore, α-LA could reverse the mRNA and protein expressions of Nrf2 (nuclear factor erythroid 2-related factor 2) and three Nrf2-responsive genes (HO-1, γ-GCLC, and NQO1) altered by nab-PTX in the dorsal root ganglion (DRG) of rats. In conclusion, our study suggests that α-LA could prevent oxidative stress and peripheral neuropathy in nab-PTX-treated rats through the Nrf2 signalling pathway without diminishing chemotherapeutic effect.

Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300–600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method. There were statistically significant variances in the steady-state IM trough plasma concentrations (from 272.22 to 4365.96 ng/mL). Subjects of GG in rs2242480, T allele carriers in rs1045642 and CC in rs3814055 had significantly higher steady-state IM dose-adjusted trough plasma concentrations. Subjects of CC in rs3814055 had significantly higher incidence rate of edema. The genetic polymorphisms of rs2242480, rs1045642, rs3814055 were significantly associated with IM plasma levels, and the genetic variations of rs3814055 were significantly associated with the incidence rate of edema in Chinese GIST patients. The current results may serve as valuable fundamental knowledge for IM therapy in Chinese GIST patients.