Dolara P.,Viale Pieraccini |
Bigagli E.,Viale Pieraccini |
Collins A.,University of Oslo |
Collins A.,University of Auckland
European Journal of Nutrition | Year: 2012
Purpose: Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials. Results: A: Effects of antioxidant-containing food and supplements on oxidation damage in humans. Intervention trials employing a variety of biomarkers have shown either a slight decrease in oxidation damage or no effect. B: Effects of selected antioxidants on mortality and cancer incidence. β-carotene and α-tocopherol, alone or in combination, increase cardiovascular and all-cause mortality or have no effect. In some studies, β-carotene and retinyl palmitate significantly increase the progression of lung cancer and aggressive prostate cancer. Protection against cardiovascular mortality or no effect of vitamin E has been reported, with an increase of all-cause mortality at dosages greater than 150 IU/day. Selenium showed beneficial effects on gastrointestinal cancer and reduced the risk of lung cancer in populations with lower selenium status. For multivitamin and mineral supplementation, no significant reduction of mortality or cancer incidence was observed, but some reports indicate a possible preventive effect in cervical cancer. Conclusions: The majority of supplementation studies indicate no variation of general mortality and of cancer incidence or a detrimental effect on both. Antioxidant supplements so far tested seem to offer no improvement over a well-balanced diet, possibly because of the choice of the substances tested or of an excessive dosage. However, new natural or synthetic compounds effective in vitro and in experimental studies might still be worth investigating in human trials. © Springer-Verlag 2012.
Rombouts K.,University of Florence |
Carloni V.,University of Florence |
Mello T.,Viale Pieraccini |
Mello T.,University of Florence |
And 7 more authors.
Cancer Letters | Year: 2013
Several actin-binding proteins have been shown to be altered in metastatic cell lines and tumours and, in particular, Myristoylated Alanine-Rich protein Kinase C substrate (MARCKS) has been implicated in the pathogenesis of various highly metastatic epithelial malignancies. Considering that a large percentage of deaths due to colorectal cancer (CRC) are consequent to hepatic metastasization, aim of this study was to elucidate the involvement and mechanism of MARCKS in CRC by employing in vitro and in vivo approaches. Loss-of and-gain-on function approaches of MARCKS were employed in two human CRC cell lines: Clone A cells expressing MARCKS and LoVo cells known to have a frameshift mutation of MARCKS i.e. typically for MSI-H CRC. The data unveiled that altering MARCKS expression suppresses cell motility and invasion in human colon carcinoma cells when conditioned medium of liver-specific stromal cells (hepatic stellate cells) was used as chemoattractant. Depletion or re-expression of MARCKS inhibited proliferation with a reduction in expression of the mitotic regulator Aurora B kinase (AURKB), whereas AURKB-depletion did not modify MARCKS expression. In murine colon carcinoma CT26 cells, shRNA MARCKS-depletion reduced motility and invasion, and induced an aberrant, prolonged mitotic process. Significantly less metastases were produced in a syngeneic model of colon metastasis by MARCKS-depleted CT26 in comparison to CT26-tumour challenged mice. In conclusion, MARCKS plays an articulated role in the progression of colorectal cancer and might represent a suitable target to interfere and overcome the invasive behaviour of colon carcinoma cells at primary and distant sites. © 2013 Elsevier Ireland Ltd.
Bellando-Randone S.,Viale Pieraccini |
Guiducci S.,Viale Pieraccini |
Matucci-Cerinic M.,Viale Pieraccini
International Journal of Clinical Rheumatology | Year: 2010
Systemic sclerosis is often well established at diagnosis, when the disease has already evolved to an obliterative vasculopathy with fibrosis and significant end-organ damage. The present classification criteria perform poorly when attempting to make an early diagnosis, limiting the possibility of early treatment and of preventing disease evolution and tissue damage, leading to loss of function and impairment of quality of life. Recently, experts have identified Raynauds phenomenon, antinuclear antibodies and puffy fingers as 'red flags that can be used as signs of suspected early systemic sclerosis. The positivity of other signs such as specific antibodies (anticentromere antibodies and anti-topoisomerase I) and capillaroscopy may allow a diagnosis of very early systemic sclerosis and prompt further investigation at the internal organ level. These red flags can help to track patients in the earliest phase of the disease and those at risk of progressing to overt disease. This 'window of opportunity may allow treatment of the disease while it is still reversible when safe, efficacious and curative treatments will be available. © 2010 Future Medicine Ltd.