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91.
Gianluca Sala Ilario Giovanni Rapposelli Reza Ghasemi Enza Piccolo Sara Traini Emily Capone Cosmo Rossi Angela Pelliccia Annalisa Di Risio Maurizia D'Egidio Nicola Tinari Raffaella Muraro Stefano Iacobelli 《Translational oncology》2013,6(6):676-IN9
ErbB-3 (HER-3) receptor is involved in tumor progression and resistance to therapy. Development of specific inhibitors impairing the activity of ErbB-3 is an attractive tool for cancer therapeutics. MP-RM-1, a murine monoclonal antibody targeting human ErbB-3, has shown anticancer activity in preclinical models. With the aim to provide novel candidates for clinical use, we have successfully generated a humanized version of MP-RM-1. The humanized antibody, named EV20, abrogates both ligand-dependent and ligand-independent receptor signaling of several tumor cell types, strongly promotes ErbB-3 down-regulation, and efficiently and rapidly internalizes into tumor cells. Furthermore, treatment with EV20 significantly inhibits growth of xenografts originating from prostatic, ovarian, and pancreatic cancers as well as melanoma in nude mice. In conclusion, we provide a novel candidate for ErbB-3-targeted cancer therapy. 相似文献
92.
Dominic Bresser Elie Paillard Richard Kloepsch Steffen Krueger Martin Fiedler René Schmitz Dietmar Baither Martin Winter Stefano Passerini 《Liver Transplantation》2013,3(4):513-523
The preparation and electrochemical characterization of a new material consisting of carbon coated ZnFe2O4 nanoparticles is presented. This material, which offers an interesting combination of alloying and conversion mechanisms, is capable of hosting up to nine equivalents of lithium per unit formula, corresponding to an exceptional specific capacity, higher than 1000 mAh g?1. Composite electrodes of such a material, prepared using environmentally friendly sodium carboxymethyl cellulose as binder, showed the highest, ever reported, specific capacity and high rate performance upon long‐term testing. Furthermore, in situ X‐ray diffraction analysis allowed identifying the reduction process occurring upon initial lithiation. 相似文献
93.
Marian Cristian Stan Richard Klöpsch Aiswarya Bhaskar Jie Li Stefano Passerini Martin Winter 《Liver Transplantation》2013,3(2):231-238
Mechanochemical synthesis of Cu3P in the presence of n‐dodecane results in a material with a secondary particle size distribution of 10 μm, secondary particles which consist of homogeneously agglomerated 20 nm primary particles. The electrochemical performance of Cu3P with lithium is influenced by the reaction depth, in other words by the lower potential cut‐off. During the electrochemical reaction, the displacement of copper by lithium from the Cu3P structure until the formation of Li3P and Cu deteriorates the capacity retention. Improved performance was obtained when the charge potential was limited to 0.50 V (vs. Li/Li+) and the formation of the LixCu3‐xP phase (0 ≤ × ≤ 2). In this case, when the potential is limited to 0.5 V, the capacity is stable for more than 50 cycles. Acceptable electrochemical performances in Li‐ion cells within the voltage range 0.50–2.0 V (vs. Li/Li+) were shown when Cu3P was used as an anode and Li1.2(Ni0.13Mn0.54Co0.13)O2 and LiNi0.5Mn1.5O4 as positive electrode materials. 相似文献
94.
95.
Qiang Wei Stefano Costanzi Ramachandran Balasubramanian Zhan-Guo Gao Kenneth A. Jacobson 《Purinergic signalling》2013,9(2):271-280
The role of the A2B adenosine receptor (AR) in prostate cell death and growth was studied. The A2B AR gene expression quantified by real-time quantitative RT-PCR and Western blot analysis was the highest among four AR subtypes (A1, A2A, A2B, and A3) in all three commonly used prostate cancer cell lines, PC-3, DU145, and LNCaP. We explored the function of the A2B AR using PC-3 cells as a model. The A2B AR was visualized in PC-3 cells by laser confocal microscopy. The nonselective A2B AR agonist NECA and the selective A2B AR agonist BAY60-6583, but not the A2A AR agonist CGS21680, concentration-dependently induced adenosine 3′,5′-cyclic monophosphate (cyclic AMP) accumulation. NECA diminished lactate dehydrogenase (LDH) release, TNF-α-induced increase of caspase-3 activity, and cycloheximide (CHX)-induced morphological changes typical of apoptosis in PC-3 cells, which were blocked by a selective A2B AR antagonist PSB603. NECA-induced proliferation of PC-3 cells was diminished by siRNA specific for the A2B AR. The selective A2B AR antagonist PSB603 was shown to inhibit cell growth in all three cell lines. Thus, A2B AR blockade inhibits growth of prostate cancer cells, suggesting selective A2B AR antagonists as potential novel therapeutics. 相似文献
96.
Valeria Rimoldi Giulia Soldà Rosanna Asselta Silvia Spena Cristiana Stuani Emanuele Buratti Stefano Duga 《PloS one》2013,8(3)
Most pathological pseudoexon inclusion events originate from single activating mutations, suggesting that many intronic sequences are on the verge of becoming exons. However, the precise mechanisms controlling pseudoexon definition are still largely unexplored. Here, we investigated the cis-acting elements and trans-acting regulatory factors contributing to the regulation of a previously described fibrinogen gamma-chain (FGG) pseudoexon, which is activated by a deep-intronic mutation (IVS6-320A>T). This pseudoexon contains several G-run elements, which may be bound by heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H. To explore the effect of these proteins on FGG pseudoexon inclusion, both silencing and overexpression experiments were performed in eukaryotic cells. While hnRNP H did not significantly affect pseudoexon splicing, hnRNP F promoted pseudoexon inclusion, indicating that these two proteins have only partially redundant functions. To verify the binding of hnRNP F and the possible involvement of other trans-acting splicing modulators, pulldown experiments were performed on the region of the pseudoexon characterized by both a G-run and enrichment for exonic splicing enhancers. This 25-bp-long region strongly binds hnRNP F/H and weakly interacts with Serine/Arginine-rich protein 40, which however was demonstrated to be dispensable for FGG pseudoexon inclusion in overexpression experiments. Deletion analysis, besides confirming the splicing-promoting role of the G-run within this 25-bp region, demonstrated that two additional hnRNP F binding sites might instead function as silencer elements. Taken together, our results indicate a major role of hnRNP F in regulating FGG pseudoexon inclusion, and strengthen the notion that G-runs may function either as splicing enhancers or silencers of the same exon. 相似文献
97.
98.
Stefano Toldo Rachel W. Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T. Sumner Giuseppe G. L. Biondi-Zoccai Ignacio M. Seropian Benjamin W. Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F. Voelkel Antonio Abbate David A. Gewirtz 《PloS one》2013,8(3)
Purpose
The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.Methods
The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment.Results
In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin.Conclusion
This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin. 相似文献99.
Maria Antonella Burza Stefano Romeo Anna Kotronen Per-Arne Svensson Kajsa Sj?holm Jarl S. Torgerson Anna-Karin Lindroos Lars Sj?str?m Lena M. S. Carlsson Markku Peltonen 《PloS one》2013,8(3)
Background and Aim
Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals.Methods
The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups.Results
Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up.Conclusions
Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals. 相似文献100.
José Leopoldo Ferreira Antunes Tatiana Natasha Toporcov Maria Gabriela Haye Biazevic Antonio Fernando Boing Crispian Scully Stefano Petti 《PloS one》2013,8(7)
Alcohol drinking and tobacco smoking are assumed to have significant independent and joint effects on oral cancer (OC) development. This assumption is based on consistent reports from observational studies, which, however, overestimated the independent effects of smoking and drinking, because they did not account for the interaction effect in multivariable analyses. This case-control study sought to investigate the independent and the joint effects of smoking and drinking on OC in a homogeneous sample of adults. Case patients (N = 1,144) were affected by invasive oral/oropharyngeal squamous cell carcinoma confirmed histologically, diagnosed between 1998 and 2008 in four hospitals of São Paulo (Brazil). Control patients (N = 1,661) were not affected by drinking-, smoking-associated diseases, cancers, upper aero-digestive tract diseases. Cumulative tobacco and alcohol consumptions were assessed anamnestically. Patients were categorized into never/ever users and never/level-1/level-2 users, according to the median consumption level in controls. The effects of smoking and drinking on OC adjusted for age, gender, schooling level were assessed using logistic regression analysis; Model-1 did not account for the smoking-drinking interaction; Model-2 accounted for this interaction and included the resultant interaction terms. The models were compared using the likelihood ratio test. According to Model-1, the adjusted odds ratios (ORs) for smoking, drinking, smoking-drinking were 3.50 (95% confidence interval –95CI, 2.76–4.44), 3.60 (95CI, 2.86–4.53), 12.60 (95CI, 7.89–20.13), respectively. According to Model-2 these figures were 1.41 (95CI, 1.02–1.96), 0.78 (95CI, 0.48–1.27), 8.16 (95CI, 2.09–31.78). Analogous results were obtained using three levels of exposure to smoking and drinking. Model-2 showed statistically significant better goodness-of-fit statistics than Model-1. Drinking was not independently associated with OC, while the independent effect of smoking was lower than expected, suggesting that observational studies should be revised adequately accounting for the smoking-drinking interaction. OC control policies should focus on addictive behaviours rather than on single lifestyle risk factors. 相似文献