To investigate the status of insulin resistance, metabolic syndrome, dyslipidemia, and serum adiponectin levels in patients with uveal melanoma and choroidal nevus were investigated. Our study included 86 patients with uveal melanoma, 38 patients with choroidal nevus, and 86 controls. Uveal melanomas were classified as small, medium, and large on the basis of Collaborative Ocular Melanoma Study (COMS) criteria. Patients with uveal melanoma had significantly higher homeostatic model assessment scores compared with patients with choroidal nevus (P<0.001). Patients with uveal melanoma and choroidal nevus had significantly lower levels of serum adiponectin compared with controls (P<0.001). Patients with uveal melanoma who developed systemic metastases had significantly lower levels of serum adiponectin levels compared with patients with nonmetastases during follow-up (P=0.018). When the largest tumors (COMS III) were compared, ciliary body melanomas were associated with significantly lower levels of serum adiponectin than choroidal melanomas. In patients who were treated with enucleation, epitheloid predominant and mixed cell-type tumors were associated with lower levels of serum adiponectin compared with tumors with spindle cell type, but this did not reach statistical significance. By providing an antiapoptotic and proangiogenic environment, low serum adiponectin levels and insulin resistance may play a role in promoting the growth of uveal melanocytic tumors and may contribute toward a more aggressive clinical course, adversely affecting the prognosis.

Therapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39 × 10−12 M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24 hours tested by liquid chromatography-mass spectrometry (LC–MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.

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