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Giordano C.,University of Calabria | Chemi F.,University of Calabria | Panza S.,University of Calabria | Barone I.,University of Calabria | And 16 more authors.
Oncotarget | Year: 2016

Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patientderived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSCmediated disease progression.

Maione L.,University of Naples Federico II | Cantone E.,University of Naples Federico II | Nettore I.C.,University of Naples Federico II | de Brasi D.,R.O.S.A. | And 8 more authors.
Endocrine | Year: 2015

In Kallmann syndrome (KS), congenital hypogonadism is associated with olfactory impairment. To evaluate flavor perception-related disability in KS patients, 30 patients with KS, 12 with normosmic hypogonadism (nIHH), 24 with acquired anosmia (AA), and 58 healthy controls entered the study. All participants completed questionnaires concerning dietary habits, olfaction-related quality of life (QoL), and self-determined olfactory, flavor, and taste abilities prior to undergoing standardized olfactometry and gustometry. Each subject underwent flavor testing, using orally administered aqueous aromatic solutions, identifying 21 different compounds by choosing each out of 5 alternative items. Flavor score (FS) was calculated as the sum of correct answers (range 0–21). Flavor perception by self-assessment was similar between KS, nIHH, and controls, and was mostly reduced only in AA. FS was similar between KS (5.4 ± 1.4) and AA (6.4 ± 1.9), and lower than in nIHH (16.2 ± 2.4, p < 0.001) and controls (16.8 ± 1.7, p < 0.0001). FS showed strong reproducibility, and correlated with olfactory scores in the overall population. KS and AA patients identified aromatics eliciting trigeminal stimulation better than pure odorants. Olfaction-related QoL was more impaired in AA than in KS. We report significant flavor impairment in KS. This contrasts with routine clinic evidence; KS patients, in contrast with AA, do not complain of flavor perception impairment, perhaps owing to the congenital nature of the dysfunction. Flavor perception impairment should be considered a specific KS disability, because of important detrimental effects on physical and mental health and on QoL. KS patients should also be advised of this impairment in order to prevent accidental and life-threatening events. © 2015 Springer Science+Business Media New York

Babiloni C.,University of Foggia | Triggiani A.I.,University of Foggia | Marzano N.,Istituto di Ricerca Diagnostica e Nucleare | Valenzano A.,University of Foggia | And 5 more authors.
International Journal of Psychophysiology | Year: 2011

Here we tested the hypothesis that compared with normal weight non dieting (control) subjects, normal weight successful dieters submitted to a rigorous and continuous monitoring of body weight (i.e. karate athletes) are characterized by an increase of cortical responses to oddball visual stimuli depicting the enlargement of faces or foods, as neural underpinning of attention processes related to the control of weight and eating. Electroencephalographic (EEG) data were recorded in 18 successful dieters (5 females) and 24 non dieting subjects (9 females). The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL). The task was to click the mouse after the rare stimuli. The rare stimuli depicted the frequent stimuli graphically dilated by 25% along the horizontal axis. Cortical responses accompanying attention processes were probed by the difference between positive event-related potentials peaking around 400-500. ms post-stimulus for the rare minus frequent stimuli (P300). The popular freeware LORETA estimated P300 cortical sources. The results showed that in the FACE condition, the amplitude of left frontal (BA 6) and medial parietal (BA 5) P300 sources was higher in the successful dieters (karate athletes) than non dieting subjects. These results disclose that frontal-parietal responses to "oddball" stimuli depicting enlarged faces (i.e. representing face fattening) are enhanced in successful dieters (karate athletes). Future studies should evaluate this effect in other populations of successful dieters (i.e. boxers, top models etc.). © 2010 Elsevier B.V.

Babiloni C.,University of Foggia | Vecchio F.,Fatebenefratelli for Research AFaR | Infarinato F.,IRCCS San Raffaele Pisana | Buffo P.,University of Rome La Sapienza | And 7 more authors.
Cortex | Year: 2011

Here we describe a methodological approach for the simultaneous electroencephalographic (EEG) recording in musicians playing in ensemble. Four professional saxophonists wore pre-wired EEG caps (30 electrodes placed according to an augmented 10-20 system; cephalic reference and ground). Each cap was connected to a single multi-channel amplifier box [Brain Explorer (BE), EB-Neuro©]. The four boxes converged to a single workstation equipped with a software (GALILEO NT, EB-Neuro©) allowing the simultaneous recording of sounds, digital trigger, and EEG-electrooculographic (EOG)-electromyographic (EMG) data, and providing a separate output file for each individual. Noteworthy, the subjects were electrically decoupled to satisfy international safety guidelines. The quality of the EEG data was confirmed by the rate of artifact-free EEG epochs (about 80%) and by EEG spectral features. During the resting state, dominant EEG power density values were observed at alpha band (8-12Hz) in posterior cortex. The quality of EMG can be used to identify " on" and " off" states of the musicians' motor performance, thus potentially allowing the investigation of the relationships between EEG dynamics and different characteristics of the specific performance. During the music performance, alpha power density values decreased in amplitude in several cortical regions, whereas power density values enhanced within narrow high-frequency bands. In conclusion, the present methodological approach appeared to be suitable for simultaneous EEG recordings in musicians playing in ensemble. © 2011 Elsevier Srl.

Del Percio C.,IRCCS San Raffaele Pisana | Infarinato F.,IRCCS San Raffaele Pisana | Marzano N.,Istituto di Ricerca Diagnostica e Nucleare | Iacoboni M.,University of Rome La Sapienza | And 10 more authors.
International Journal of Psychophysiology | Year: 2011

In the present study, we tested the hypothesis that compared with non-athletes, elite athletes are characterized by a reduction of reactivity of electroencephalographic (EEG) alpha rhythms (about 8-12. Hz) to eyes opening in the condition of resting state, as a possible index of spatially selective cortical activation (i.e. "neural efficiency"). EEG data (56 channels; Eb-Neuro©) were recorded in 18 elite karate athletes and 28 non-athletes during resting state eyes-closed and eyes-open conditions. The EEG data were spatially enhanced by surface Laplacian estimation. Cortical activity was indexed by task-related power decrease (TRPD), namely the alpha power during the eyes-open referenced to the eyes-closed resting condition. Low-frequency alpha TRPD (about 8-10. Hz) was lower in the elite karate athletes than in the non-athletes in frontal (p < 0.00002), central (p < 0.008) and right occipital (p < 0.02) areas. Similarly, high-frequency alpha TRPD (about 10-12. Hz) was lower in the elite karate athletes than in the non-athletes in frontal (p < 0.00009) and central (p < 0.01) areas. These results suggest that athletes' brain is characterized by reduced cortical reactivity to eyes opening in the condition of resting state, in line with the "neural efficiency" hypothesis. The present study motivates future research evaluating the extent to which this general functional brain feature is related to heritable trait or intensive visuo-motor training of elite athletes. © 2011 Elsevier B.V.

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