Figure 2 Forest plot summarizes a pooled analysis of G2 or more fibrosis/fat necrosis distinguishing patients with/without XRCC1 399Gln. The mutation is toxic or protective when OR is higher or lower than 1, respectively. Figure 3 Forest plot summarizes a pooled analysis of G2 or more fibrosis/fat necrosis distinguishing patients with/without het/mut GSTP1. The OSI 906 mutation is toxic or protective when OR is higher or lower than 1, respectively. Discussion Recently partial breast irradiation has been proposed in a particular subgroup of patients

at low risk of local recurrence. In agreement with this approach, we tested a new schedule at our Institute naming it SSPBI after BCS [8, 28]. Due to the major expected killing efficacy of the single dose, unfortunately a incidence of fibrosis/fat necrosis was observed in 44% of our patients. Generally the moderate-to-severe fibrosis after conventional fractionation is generally observed in 13.5% [35] of patients at 10 years; thus a lot of patients to obverse the same number of complications observed in our cohort (44%). Moreover, the single dose is expected to be more difficult to be repaired, enhancing the scenarios in which the mechanism of protect against ROS damage or DNA repair

fails. It is for this reason, we focused our attention on SNPs evaluation that may help design Selleck eFT508 a clinical approach and explain basic phenomena such as subcutaneous fibrosis or fat necrosis. Fibrosis is a complex tissue response characterized by a massive deposition of extra cellular matrix (ECM) molecules (collagens, non collagenous glycoproteins, glycosaminoglycans, proteoglycans) and excessive fibroblast proliferation. Under oxidative stress generated by ionization radiation, ROS levels can increase dramatically,

and this Selleck Depsipeptide may result in significant damage to cell structures. Accordingly, in the cellular compartments, the response to oxidative stress can activate a series of processes including DNA repair, antioxidant enzymes, cell cycle Selleck LY333531 arrest and secretion of pro-inflammatory cytokines such as TNF-α,TGF-β1,IL1, IL6 and many growth factors in the irradiated tissue. Some authors reported that a coordinated cellular response after radiation occurs, like the involvement antioxidant enzymes (such as superoxide dismutases, catalases, lactoperoxidases, glutathione peroxidases and peroxiredoxins) to protect themselves against ROS damage [11–13]. Reduced mechanisms of cell protection resulting from functional polymorphisms in several genes involved in these processes may be associated with the development of late side effects following RT [36]. For these reasons, we decided to investigate genetic variation in enzymes involved in the detoxification process of oxidative stress products, such as GSTP1, and its possible correlation with susceptibility to late complications after RT [37, 38].