50-Hz extremely low frequency electromagnetic fields enhance cell proliferation and DNA damage: possible involvement of a redox mechanism

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Cyclin E correlates with manganese superoxide dismutase expression and predicts survival in early breast cancer patients receiving adjuvant epirubicin-based chemotherapy.

Anthracycline-based chemotherapy represents a milestone in the treatment of breast cancer. We previously demonstrated in an in vitro model that cyclin E overexpression is associated with increased expression of manganese superoxide dismutase (MnSOD) and resistance to doxorubicin. In the present study, immunohistochemical expression of cyclin E and MnSOD was evaluated in 134 early breast cancer patients receiving adjuvant epirubicin-based chemotherapy regimens containing epirubicin. Both parameters were correlated with the available clinicopathological parameters and with the outcome of patients. Overexpression of cyclin E and MnSOD was detected in 46 (34.3%) and 56 (41.8%) patients, respectively, and expression levels of the two proteins were related. Disease-free and alive patients displayed a lower mean percentage of cyclin E-expressing cells than relapsed and dead patients, respectively. Kaplan-Meier survival analysis demonstrated a significant separation between high versus low cyclin E-expressing tumors in terms of overall survival (P = 0.038 by log-rank). Similar results were obtained considering the subset of node-negative patients separately. No significant relationship with patient outcome was observed for MnSOD expression levels. At multivariate analysis cyclin E failed to demonstrate an independent prognostic value. In conclusion, the results of the present study support previous evidence that increased cyclin E expression is associated with higher MnSOD expression levels and poorer outcome, at least as evaluated in terms of overall survival. Further studies are warranted to evaluate the usefulness of cyclin E as a prognostic marker to identify breast cancer patients at higher risk of death from the disease when treated with adjuvant anthracycline-based therapy

Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence.

lmost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer

Loss of nuclear p27kip1 and α-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma

Expression levels of p27kip1, a negative regulator of the G1 phase of the cell cycle, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were assessed by immunostaining in a series of renal cell carcinomas (RCCs) and their prognostic significance was evaluated. Expression of p27kip1 as well as of the α-subunit of the dystroglycan (DG) complex, previously reported to be altered in RCC, was also evaluated by western blot analysis. Nuclear expression of p27kip1 was reduced in a significant fraction of tumors and low p27kip1 staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27kip1-low expressing tumors and Kaplan–Meier curves showed a significant separation between high vs low expressor groups for both disease-free (P = 0.011) and overall (P = 0.002) survival. Low nuclear expression of p27kip1 as well as loss of α-DG were confirmed to be independent prognostic parameters at a multivariate analysis and the simultaneous loss of both molecules defined a "high-risk" group of patients with increased risk of recurrence (RR = 28.7; P = 0.01) and death (RR = 12.9; P = 0.03). No significant correlation with clinical or pathological parameters was found for 8-OHdG staining. Western blot analyses suggested a post-translational mechanism for the loss of α-DG expression and demonstrated that cytoplasmic dislocation of the protein contributes to the loss of active nuclear p27kip1. Loss of nuclear p27kip1 is a frequent event in human RCCs and is a powerful predictor of poor outcome which, in combination with low DG expression, could help to identify high-risk patients with clear cell RCC. (Cancer Sci 2010; 00: 000–000

M tuberculosis in the adjuvant modulates time of appearance of CNS-specific effector T cells in the spleen through a polymorphic site of TLR2

DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called "immunoscope") mostly reach the spleen by day 28 after immunization ("late relocation") in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis ("early relocation"). The C57Bl/6 background confers a dominant "early relocation" phenotype to F1 (SJL 7C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for "early/late" relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand

Lycopene as a guardian of redox signalling

It has been suggested that lycopene, the major carotenoid found in tomato, exhibits health-beneficial effects by virtue of its antioxidant activity. However, recent literature suggests that lycopene can actually \u201cperform\u201d roles independent of such capacity and involving a direct modulation of redox signalling. Reactive oxygen species are known to act as second messengers in the modulation of cellular signalling leading to gene expression changes and pharmacological responses. Lycopene may control redox-sensitive molecular targets, affecting enzyme activities and expressions and modulating the activation of MAPKs and transcription factors, such as NF-\u3baB and AP-1, Nrf2