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Laezza C.,National Research Council Italy | Laezza C.,University of Naples Federico II | Malfitano A.M.,University of Salerno | Di Matola T.,Centro Traumatologico Ortopedico ASLNA1 | And 2 more authors.
Molecular Carcinogenesis | Year: 2010

N6-isopentenyladenosine (i6A) inhibits the tumor cell growth by inducing cell apoptosis in various cancer cell lines. However, little is known regarding the mechanisms by which the drug induces cell apoptosis. In this study, we further explored the molecular mechanisms of i6A as an anticancer agent on a human breast cancer cell line MDA MB 231. Treatment with i6A decreased the cell proliferation of MDA MB 231 cells in a dose-dependent manner by arresting the cells at G0/G1 phase. This effect was strongly associated with concomitant decrease in the level of cyclin D1, cyclin E, cdk2, and increase of p21waf1 and p27kip. In addition i6A also induced apoptotic cell death by increasing the expression of Bax, and decreasing the levels of Bcl-2 and Bcl-xL, and subsequently triggered mitochondria apoptotic pathway (release of cytochrome c and activation of caspase-3). We observed that i6A suppressed the nuclear factor kappaB (NF-κB) pathway and inhibited the Akt activation. The results of this study indicate that i6A decreases cell proliferation and induces apoptotic cell death in human breast cancer cells, possibly by decreasing signal transduction through the Akt/NF-κB cell survival pathway. © 2010 Wiley-Liss, Inc. Source


Ricchi P.,Uoc Centro Delle Microcitemie A Mastrobuoni | Ammirabile M.,Uoc Centro Delle Microcitemie A Mastrobuoni | Costantini S.,Uoc Centro Delle Microcitemie A Mastrobuoni | Cinque P.,Uoc Centro Delle Microcitemie A Mastrobuoni | And 6 more authors.
Expert Opinion on Drug Safety | Year: 2010

Objective: Although IFN therapy is known to cause neutropenia, data on the risk of deferiprone (DFP)-induced haematological complications in patients receiving IFN are lacking. Research design and methods: This was a retrospective single-centre study to assess the association between exposure to IFN for hepatitis C virus treatment and haematological side effects of DFP therapy in patients with thalassemia major and intermedia using a large database spanning 2001 2008. During observation time, a total of 66 patients, including 63 affected by thalassemia major and 3 by thalassemia intermedia, were treated with chelation DFP-based regimens. A subset of 25 patients was treated at least for 3 months also with IFN (6 were cotreated and 19 were pretreated). Results: Overall, the incidence of neutropenia and agranulocytosis was 9.83 and 1.14/100 patient/year, respectively. Receipt of IFN was significantly associated with increased risk of haematological complications of DFP therapy: among patients receiving IFN, 48 and 12% experienced at least one episode of neutropenia and agranulocytosis, respectively. Conclusions: These results suggest that IFN therapy may increase the risk of complications of DFP-based iron chelation therapy in patients with thalassemia. Further research is needed to assess whether the association observed in this retrospective single-centre observational study is due to IFN or other factors. © 2010 Informa UK, Ltd. Source


Ricchi P.,Uoc Centro Delle Microcitemie A Mastrobuoni | Ammirabile M.,Uoc Centro Delle Microcitemie A Mastrobuoni | Spasiano A.,Uoc Centro Delle Microcitemie A Mastrobuoni | Costantini S.,Uoc Centro Delle Microcitemie A Mastrobuoni | And 4 more authors.
European Journal of Haematology | Year: 2010

Objectives: The benefits of combined chelation therapy with daily deferiprone (DFP) and subcutaneous desferrioxamine (DFO) have been widely reported in literature. We retrospectively evaluated the efficacy of different schedules of combined chelation therapy and the incidence of adverse events. Methods: We evaluated 36 patients affected by thalassemia major treated with combined chelation therapy. Patients were subdivided into four treatment arms according to severity of iron overload and previous onset of adverse events to DFP therapy: Group 1 (13 pts) DFP 75 mg/kg per d plus DFO (25-35 mg/kg per d for 5 d); Group 2 (6 pts) DFP 50 mg/kg per d plus DFO (25-35 mg/kg for 5 d), Group 3 (10 pts) DFP 75 mg/kg per d plus DFO (25-35 mg/kg for 3 d), and Group 4 (7 pts) DFP 50 mg/kg per d plus DFO (25-35 mg/kg for 3 d). Change in serum ferritin level was evaluated in all patients. Results: Overall, ferritin decreased from 2592 ± 1701 to 899 ± 833 ng/mL (P < 0.001). All treatments were able to reduce ferritin levels, but in patients of group 1 and group 2 the highest mean decrease in serum ferritin level and the greatest improvement in liver iron concentration (LIC) and in T2* values were observed. Conclusions: This study showed that the administration of DFO for 5 d a wk in combination with daily administration of DFP at 75 mg/Kg seemed to be the most efficacy and rapid method for reducing iron overload at liver and heart level. Furthermore, the use of different schedules of combined DFO and DFP administration was not associated with different incidence of adverse effects between the groups. © 2010 John Wiley & Sons A/S. Source


Ricchi P.,Uoc Centro Delle Microcitemie A Mastrobuoni | Ammirabile M.,Uoc Centro Delle Microcitemie A Mastrobuoni | Costantini S.,Uoc Centro Delle Microcitemie A Mastrobuoni | Di Matola T.,UOC Clinical Pathology | And 4 more authors.
Blood Cells, Molecules, and Diseases | Year: 2012

Few data are available on the prevalence and the risk factors for the presence of kidney stones and hyperuricemia in patients with thalassemia intermedia. We retrospectively reviewed the charts and radiological studies of 89 patients with thalassemia intermedia followed at our clinic with routine biochemical examination and radiological imaging of the urinary tract. Renal calculi were identified in 11 patients (12%) and 22 patients (25%) were under uricosuric treatment for hyperucemia. The prevalence of nephrolithiasis increased with age but not in a statistically significant manner. Major risk factors for renal stone formation were splenectomy (in 91% of the cases) and higher number of erythroblasts. Patients with renal stones had higher mean creatinine level and lower GFR value with respect to those observed in patients not affected. Our data suggest that splenectomy, by further increasing erythrocyte turnover and number, may be directly involved in the pathogenesis of hyperuricemia and nephrolithiasis observed in thalassemia intermedia patients. © 2012 Elsevier Inc.. Source

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