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Firenze, Italy

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. Source

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. Source

Fortunato P.,Viale Pieraccini | Pillozzi S.,University of Florence | Tamburini A.,Viale Pieraccini | Pollazzi L.,Orthoptist Ophthalmology Assistant | And 3 more authors.
BMC Cancer | Year: 2010

Background: Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K +channels.Case presentation: Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the vegf-a, flt-1, kdr, and hif1-α transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K +channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.Conclusions: We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the vegf-a, flt-1, kdr and hif1-α transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the herg1 gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A. © 2010 Fortunato et al; licensee BioMed Central Ltd. Source

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. Source

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