SDN Foundation

Napoli, Italy

SDN Foundation

Napoli, Italy
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Sahani D.V.,Harvard University | Jiang T.,Harvard University | Jiang T.,Shanghai University | Hayano K.,Harvard University | And 6 more authors.
Journal of Hematology and Oncology | Year: 2013

Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC). Methods. In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm 2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated. Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min -1 to 0.94 min-1 (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10-3 mm 2/s to 0.98 × 10-3 mm2/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P < 0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035). Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST. Trial registration. ClinicalTrials.gov: NCT00361309. © 2013 Sahani et al.; licensee BioMed Central Ltd.


PubMed | S. Orsola Malpighi University Hospital, Erasmus Medical Center, Marche Polytechnic University, University of Bologna and 6 more.
Type: Journal Article | Journal: La Radiologia medica | Year: 2016

It is unclear whether (and, to what extent) radiologists look at and report cardiovascular abnormalities on non-cardio-synchronized standard chest computed tomography (CT). In this study, the frequency and the reporting rate of cardiovascular findings in chest CT examinations were retrospectively assessed.This study was approved by the institutional review board of each participating center. Four academic centers provided data on 447 subjects who underwent non-ECG-synchronized chest CT examinations for evaluating pulmonary fibrosis (161/447, 36%), suspected pulmonary embolism (140/447, 31.3%), or lung cancer staging (146/447, 32.7%). A total of 220/447 (53.7%) and 227/447 CT (46.3%) examinations were evaluated and reported by junior and senior chest radiologists, respectively. Two radiologists with training in cardiac imaging reviewed the same chest CT images looking for the presence of incidental cardiovascular abnormalities using a preformatted score sheet. Inter-observer agreement was assessed using the kappa coefficient of agreement (k).Inter-observer agreement between the study reviewers was moderate to good (0.4-0.73) for most of the incidental cardiovascular findings. At least one incidental cardiovascular finding not documented in the original report was identified by the study reviewers in 225/409 (55%) of chest CT examinations. A total of 168/266 (63.2%) potentially clinically significant cardiovascular findings were unreported in the original reports of 177/447 (39.6%) subjects (p<0.0001). Senior radiologists tended to more frequently report coronary artery calcification (p=0.0006), cardiac valves calcification (p=0.0003), and ascending aorta enlargement (p=0.01) compared to junior radiologists.Several cardiovascular abnormalities can be reliably identified on standard chest CT. Yet, they are often under-reported, even when they might be relevant to the patients work-up.


Castellone M.D.,University of Naples Federico II | Castellone M.D.,SDN Foundation | Langella A.,SDN Foundation | Cantara S.,University of Siena | And 6 more authors.
Antioxidants and Redox Signaling | Year: 2014

Aims: Rat sarcoma virus (RAS)-induced tumorigenesis has been suggested to follow a three-stage model consisting of an initial RAS activation, senescence induction, and evasion of p53-dependent senescence checkpoints. While reactive oxygen species act as second messengers in RAS-induced senescence, they are also involved in oncogenic transformation by inducing proliferation and promoting mutations. In the current work, we investigated the role of extracellular superoxide dismutase (SOD3) in RAS-induced senescence and immortalization in vitro and in vivo. We used a mouse embryonic fibroblast (MEF) primary cell model along with immortalized and transformed human cell lines derived from papillary and anaplastic thyroid cancer. Results: Based on our data, sod3 RNA interference in H-RasV12-transduced cells markedly inhibited cell growth, while sod3 over-expression in MEFs initially caused a proliferative burst followed by the activation of DNA damage checkpoints, induction of p53-p21 signal transduction, and senescence. Subsequently, sod3-transduced MEF cells developed co-operative p21-p16 down-regulation and acquired transformed cell characteristics such as increased telomerase activity, loss of contact inhibition, growth in low-nutrient conditions, and in vivo tumorigenesis. Interestingly, as previously reported with RAS, we showed a dose-dependent response to SOD3 in vitro and in vivo involving transcriptional and non-transcriptional regulatory mechanisms. Innovation: SOD3 may mediate H-RasV12-induced initiation of primary cell immortalization. Conclusions: Our results indicate that SOD3 influences growth signaling in primary and cancer cells downstream of the ras oncogene and could serve as a therapy target at an early tumorigenesis phase. © Mary Ann Liebert, Inc.


Babiloni C.,University of Rome La Sapienza | Del Percio C.,IRCCS S. Raffaele Pisana | Vecchio F.,IRCCS S. Raffaele Pisana | Sebastiano F.,IRCCS Neuromed | And 12 more authors.
Clinical Neurophysiology | Year: 2016

Objective: In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. Methods: ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. Results: Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. Conclusion: Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. Significance: Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients. © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.


PubMed | Catholic University of Sacro Cuore, Parthenope University of Naples, University of Rome La Sapienza, IRCCS Neuromed and 3 more.
Type: Journal Article | Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology | Year: 2016

In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas.ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter.Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation.Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution.Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients.


Castellone M.D.,University of Naples Federico II | Laukkanen M.O.,SDN Foundation | Teramoto H.,U.S. National Institutes of Health | Bellelli R.,University of Naples Federico II | And 4 more authors.
Oncogene | Year: 2014

Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth factors. Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli through its downstream Gαq and Gα12/13 GTPases, and consistently, other Gαq and Gα13 coupled receptors (such as muscarinic receptor, m1, and thrombin receptor, PAR-1) and constitutively active GαqQL and Gα12/13QL mutants stimulated Gli. By using cells null for Gαq and Gα12/13, we demonstrate that these G proteins are strictly necessary for Gli activation by BBS. Moreover, by using constitutively active Rho small G-protein (Rho QL) as well as its inhibitor, C3 toxin, we show that Rho mediates G-protein-coupled receptor (GPCR)-, Gαq- and Gα12/13-dependent Gli stimulation. At the molecular level, BBS caused a significant increase in Shh gene transcription and protein secretion that was dependent on BBS-induced GPCR/Gαq-12/13/Rho mediated activation of nuclear factor κB (NFκB), which can stimulate a NF-κB response element in the Shh gene promoter. Our data identify a novel molecular network acting in SCLC linking autocrine BBS and Shh circuitries and suggest Shh inhibitors as novel therapeutic strategies against this aggressive cancer type.Oncogene advance online publication, 21 April 2014; doi:10.1038/onc.2014.104.


PubMed | University of Pisa, University of Naples Federico II, SDN Foundation and U.S. National Institutes of Health
Type: Journal Article | Journal: Oncogene | Year: 2015

Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth factors. Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli through its downstream Gq and G/ GTPases, and consistently, other Gq and G coupled receptors (such as muscarinic receptor, m1, and thrombin receptor, PAR-1) and constitutively active GqQL and G/QL mutants stimulated Gli. By using cells null for Gq and G/, we demonstrate that these G proteins are strictly necessary for Gli activation by BBS. Moreover, by using constitutively active Rho small G-protein (Rho QL) as well as its inhibitor, C3 toxin, we show that Rho mediates G-protein-coupled receptor (GPCR)-, Gq- and G/-dependent Gli stimulation. At the molecular level, BBS caused a significant increase in Shh gene transcription and protein secretion that was dependent on BBS-induced GPCR/Gq-//Rho mediated activation of nuclear factor B (NFB), which can stimulate a NF-B response element in the Shh gene promoter. Our data identify a novel molecular network acting in SCLC linking autocrine BBS and Shh circuitries and suggest Shh inhibitors as novel therapeutic strategies against this aggressive cancer type.


Prinster A.,National Research Council Italy | Prinster A.,SDN Foundation | Quarantelli M.,National Research Council Italy | Lanzillo R.,University of Naples Federico II | And 8 more authors.
Multiple Sclerosis | Year: 2010

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing-remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing-remitting multiple sclerosis (Expanded Disability Status Scale range 1.0-6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.


Cademartiri F.,Erasmus Medical Center | Cademartiri F.,Cardiovascular Imaging Unit | Maffei E.,Cardiovascular Imaging Unit | Arcadi T.,Cardiovascular Imaging Unit | And 2 more authors.
European Radiology | Year: 2013

Computed tomography coronary angiography (CTCA) has reached very high standards both in terms of diagnostic performance and radiation dose reduction. This commentary follows a report on CTCA using less than 0.1 mSv in selected patients. This is an extraordinary accomplishment, both for technology and for medicine. The difficult task is now to implement this tool in clinical practice so it can play the best possible role. CTCA can improve diagnostic pathways, can save money for healthcare systems and could even improve pharmacological therapy. All of this may happen, but it will require the combined effort of all the experienced operators in this field, including the referring clinicians. In times of financial constraint, CTCA may also help to restrict ineffective medical expenses. Key Points • CT coronary angiography provides high diagnostic standards in non-invasive cardiovascular medicine. • It should therefore replace other less effective diagnostic tools. • Inappropriate catheter angiography is costly to healthcare systems. • CTCA could help reduce costs of cardiac investigations by around 33 %. • Low radiation doses in CTCA lead to risk-free individualised pharmacological treatment. © 2013 European Society of Radiology.


PubMed | SDN Foundation
Type: Journal Article | Journal: World journal of radiology | Year: 2014

To evaluate the feasibility of coronary artery calcium score (CACS) on low-dose non-gated chest CT (ngCCT).Sixty consecutive individuals (30 males; 73 7 years) scheduled for risk stratification by means of unenhanced ECG-triggered cardiac computed tomography (gCCT) underwent additional unenhanced ngCCT. All CT scans were performed on a 64-slice CT scanner (Somatom Sensation 64 Cardiac, Siemens, Germany). CACS was calculated using conventional methods/scores (Volume, Mass, Agatston) as previously described in literature. The CACS value obtained were compared. The Mayo Clinic classification was used to stratify cardiovascular risk based on Agatston CACS. Differences and correlations between the two methods were compared. A P-value < 0.05 was considered significant.Mean CACS values were significantly higher for gCCT as compared to ngCCT (Volume: 418 747 vs 332 597; Mass: 89 151 vs 78 141; Agatston: 481 854 vs 428 776; P < 0.05). The correlation between the two values was always very high (Volume: r = 0.95; Mass: r = 0.97; Agatston: r = 0.98). Of the 6 patients with 0 Agatston score on gCCT, 2 (33%) showed an Agatston score > 0 in the ngCCT. Of the 3 patients with 1-10 Agatston score on gCCT, 1 (33%) showed an Agatston score of 0 in the ngCCT. Overall, 23 (38%) patients were reclassified in a different cardiovascular risk category, mostly (18/23; 78%) shifting to a lower risk in the ngCCT. The estimated radiation dose was significantly higher for gCCT (DLP 115.8 50.7 vs 83.8 16.3; Effective dose 1.6 0.7 mSv vs 1.2 0.2 mSv; P < 0.01).CACS assessment is feasible on ngCCT; the variability of CACS values and the associated re-stratification of patients in cardiovascular risk groups should be taken into account.

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