Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), a fast rise in pressure ( < 10 ns) and a short lifecycle (10 μs), are conveyed by an appropriate generator to a specific target area at an energy density ranging from 0.03 to 0.11 mJ/mm2. Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in orthopaedic diseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-time tissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keeping with this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Furthermore, clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, the biochemical mechanisms underlying these effects have yet to be fully elucidated. In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. We then go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing on the possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatory conditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that increased NO levels and the subsequent suppression of NF-κB activation may account, at least in part, for the clinically beneficial action on tissue inflammation.

STAT1 and STAT3 are nuclear transcription factors that regulate genes involved in cell cycle, cell survival and immune response. The cross-talk between these signaling pathways determines how cells integrate the environmental signals received ultimately translating them in transcriptional regulation of specific sets of genes. Despite being activated downstream of common cytokine and growth factors, STAT1 and STAT3 play essentially antagonistic roles and the disruption of their balance directs cells from survival to apoptotic cell death or from inflammatory to anti-inflammatory responses. Different mechanisms are proposed to explain this yin-yang relationship. Considering the redox aspect of STATs proteins, this review attempts to summarize the current knowledge of redox regulation of STAT1 and STAT3 signaling focusing the attention on the post-translational modifications that affect their activity.

The tumor microenvironment is a key factor in disease progression, local resistance, immune-escaping, and metastasis. The rapid proliferation of tumor cells and the aberrant structure of the blood vessels within tumors result in a marked heterogeneity in the perfusion of the tumor tissue with regions of hypoxia. Although most of the tumor cells die in these hypoxic conditions, a part of them can adapt and survive for many days or months in a dormant state. Dormant tumor cells are characterized by cell cycle arrest in G0/G1 phase as well as a low metabolism, and are refractive to common chemotherapy, giving rise to metastasis. Despite these features, the cells retain their ability to proliferate when conditions improve. An understanding of the regulatory machinery of tumor dormancy is essential for identifying early cancer biomarkers and could provide a rationale for the development of novel agents to target dormant tumor cell populations. In this review, we examine the current knowledge of the mechanisms allowing tumor dormancy and discuss the crucial role of the hypoxic microenvironment in this process.