Sesamin Metabolites Suppress the Induction of Cellular Senescence

Cellular senescence induces inflammation and is now considered one of the causes of organismal aging. Accumulating evidence indicates that age-related deterioration of mitochondrial function leads to an increase in reactive oxygen species (ROS) and DNA damage, which in turn causes cellular senescence. Thus, it is important to maintain mitochondrial function and suppress oxidative stress in order to inhibit the accumulation of senescent cells. Sesamin and its isomer episesamin are types of lignans found in sesame oil, and after being metabolized in the liver, their metabolites have been reported to exhibit antioxidant properties. However, their effects on cellular senescence remain unknown. In this study, the effects of sesamin, episesamin, and their metabolites SC1 and EC1-2 on replicative senescence were evaluated using human diploid lung fibroblasts, and TIG-3 cells. The results showed that sesamin and episesamin treatment had no effect on proliferative capacity compared to the untreated late passage group, whereas SC1 and EC1-2 treatment improved proliferative capacity and mitigated DNA damage of TIG-3 cells. Furthermore, other cellular senescence markers, such as senescence-associated secretory phenotype (SASP), mitochondria-derived ROS, and mitochondrial function (ROS/ATP ratio) were also reduced by SC1 and EC1-2 treatment. These results suggest that SC1 and EC1-2 can maintain proper mitochondrial function and suppress the induction of cellular senescence

Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes