Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases

Abstract Folate receptors and transporters and one-carbon metabolism continue to be important areas of study given their essential roles in an assortment of diseases and as targets for treatment of cancer and inflammation. Reflecting this, every 2 years, the Folate Receptor Society organizes an international meeting, alternating between North America and Europe, where basic and translational scientists, clinical oncologists and rheumatologists from both academia and industry convene in an informal setting. The 7th International Symposium on Folate Receptors and Transporters was held in Sant’Alessio Siculo (ME), Taormina, Italy from 1st to 5th of October 2018, organized by Dr. Mariangela Figini from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Following the format of previous meetings, more than 50 scientists from 9 different countries attended the 2018 meeting to share ongoing developments, discuss current research challenges and identify new avenues in basic and translational research. An important feature of this meeting was the participation of young investigators and trainees in this area, two (A. Dekhne and N. Verweij) of whom were awarded fellowships to attend this meeting as a recognition of the high scientific quality of their work. This report provides a synopsis of the highlights presented in the following sessions: Barton Kamen Lecture; Targeting one-carbon metabolism in cytosol and mitochondria; Structure and biology of the one-carbon solute transporters; Physiology and pathophysiology of folate receptors and transporters; Folate receptors for targeting tumors and inflammatory diseases; Conventional and new anti-folate drugs for treating inflammatory diseases and cancer; Imaging; Ongoing clinical trials; and Chimeric Antigen Receptor cell therapies of cancer

Disease Outcome, Alexithymia and Depression are Differently Associated with Serum IL-18 Levels in Acute Stroke

Stroke has been shown to lead to depressive disorders, anxiety disorders and other emotional consequences. Although the cause of these disorders is a subject of debate, stroke has clearly been shown to lead to the production of pro-inflammatory cytokines, which we hypothesized to play a role in the production of post-stroke emotional disorders. Thus we investigated here whether acute stroke might be associated with changes in the normal serum levels of IL-18 and if these changes were related to stroke severity, as well as to the presence and severity of alexithymia and depression. Thirty patients with a first-ever symptomatic ischemic stroke were included. Alexithymia ( Toronto Alexithymia Scale; TAS-20), depression ( Hamilton Depression Rating Scale; HDRS-17) and serum IL-18 were assessed. Stroke patients showed serum levels of IL-18 significantly related to stroke severity. Furthermore, a strong positive correlation was observed between IL-18 levels and severity of alexithymia, particularly among patients with right-hemisphere lesions. Specifically, circulating concentrations of IL-18 were significantly increased in patients with categorical alexithymia (TAS-20 score 61), as compared with both non alexithymic patients and control subjects. In addition, stroke was more severe in alexithymic patients, as compared to non alexithymic patients. Following multivariate regression, serum IL-18 levels appeared to be specifically associated with alexithymia rather than with stroke severity in patients with right-hemisphere lesions only. These results suggest that IL-18 might be specifically implicated in the pathogenesis of post-stroke alexithymia, ultimately contributing to impaired recovery from stroke