OBJECTIVEThe aims of this study were to determine the effects of heavy metals such as manganese on nicotinamideN-methyltransferase (EC 2.1.1.1) (NNMT) activity and to consider the possibility of involvement of NNMT activation in the pathogenesis of heavy metal induced Parkinson's disease.

METHODSNNMT activity in supernatants separated from brain, liver and kidney homogenates of 5 elderly male Wistar rats by centrifugation were measured by high performance liquid chromatography system with fluorescence. NNMT activity under the conditon of 0.5 or 5.0 mM Mn(2+), Fe(2+), Cu(2+) or Cd(2+) was compared with control (no metal ion existence).

RESULTSNNMT activities in rat brain, liver and kidneys were significantly decreased by Cu(2+), and those in the liver and kidneys were significantly decreased by Cd(2+). Mn(2+) reduced NNMT activity only in the liver. Fe(2+) had no effect on NNMT activity.

CONCLUSIONSNo metal increased NNMT activity in this study, contrary to our hypothesis. Further study is needed to clarify the reason why the effects of Mn(2+) and Fe(2+) which have a high relevance to Parkinson's disease on NNMT activity differ from those of Cu(2+) and Cd(2+).

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution.Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed.Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41–91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1–49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1–39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors.Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option.