Emerging Therapeutic Targets in Oncologic Photodynamic Therapy.

BACKGROUND: Reactive oxygen species sustain tumorigenesis and cancer progression through deregulated redox signalling which also sensitizes cancer cells to therapy. Photodynamic therapy (PDT) is a promising anti-cancer therapy based on a provoked singlet oxygen burst, exhibiting a better toxicological profile than chemo- and radiotherapy. Important gaps in the knowledge on underlining molecular mechanisms impede on its translation towards clinical applications. AIMS AND METHODS: The main objective of this review is to critically analyse the knowledge lately gained on therapeutic targets related to redox and inflammatory networks underlining PDT and its outcome in terms of cell death and resistance to therapy. Emerging therapeutic targets and pharmaceutical tools will be documented based on the identified molecular background of PDT. RESULTS: Cellular responses and molecular networks in cancer cells exposed to the PDT-triggered singlet oxygen burst and the associated stresses are analysed using a systems medicine approach, addressing both cell death and repair mechanisms. In the context of immunogenic cell death, therapeutic tools for boosting anti-tumor immunity will be outlined. Finally, the transcription factor NRF2, which is a major coordinator of cytoprotective responses, is presented as a promising pharmacologic target for developing co-therapies designed to increase PDT efficacy. CONCLUSION: There is an urgent need to perform in-depth molecular investigations in the field of PDT and to correlate them with clinical data through a systems medicine approach for highlighting the complex biological signature of PDT. This will definitely guide translation of PDT to clinic and the development of new therapeutic strategies aimed at improving PDT.

Effects of zearalenone on oxidative stress and inflammation in weanling piglets.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by the fungi of Fusarium genera. Piglets were fed for 18 days with a control or a ZEN (316 ppb) contaminated diet. At the end of the experiment tissue samples were taken for assessment of: lymphocyte proliferation, monocytes and granulocytes respiratory burst, inflammatory cytokine synthesis in blood and liver, expression of genes involved in oxidative stress or in inflammation, plasma biochemical parameters, total antioxidant status and nitric oxide synthesis. In blood, ZEN increases the respiratory burst of monocytes and the inflammatory cytokine (TNF alpha, IL-1 beta, IFN gamma) synthesis, while in liver, ZEN decreases the synthesis of all inflammatory cytokines investigated. In liver and spleen, different effect on the expression of genes involved in oxidative stress and inflammation was observed. While in liver, ZEN decrease the expression of cyclooxigenase gene, but increase the expression of glutathione peroxydase and catalase genes; in spleen, ZEN induces a decrease of the superoxide dismutase gene expression together with an increase of the cyclooxigenase. In conclusion, our results showed that liver, spleen and blood may also be target tissues in weanling piglets fed ZEN contaminated diet, with different effects on oxidative stress and inflammation.