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Luigi Rossi,1 Federica Tomao,2 Giuseppe Lo Russo,1 Anselmo Papa,1 Federica Zoratto,1 Raffaella Marzano,3 Enrico Basso,1 Erika Giordani,1 Monica Verrico,1 Fabio Ricci,4 Giulia Pasciuti,5 Edoardo Francini,6 Silverio Tomao11Oncology Unit, ICOT Hospital, 2Department of Gynecology and Obstetrics, Policlinico Umberto I Hospital, University of Rome, 3Institute of Hematology and Blood Transfusion, 4Department of Surgery, S Maria Goretti Hospital, Latina, 5Oncology Unit, Don Luigi Liegro Hospital, Gaeta, 6Oncology Unit, Policlinico Umberto I Hospital, University of Rome, ItalyBackground: Neutropenia is a common toxicity in patients receiving myelosuppressive chemotherapy. In this prospective pilot study, we compared the efficacy and safety profiles of pegfilgrastim administered subcutaneously once per cycle and lenograstim administered subcutaneously daily six times per cycle, for primary neutropenia prophylaxis in women with breast cancer receiving adjuvant anthracycline-based chemotherapy.Materials and methods: Twenty women were enrolled. All patients received epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and every 21 days thereafter, according to the FEC 100 chemotherapy regimen. Eight patients received a single dose of pegfilgrastim on day 2, while 12 patients were treated with daily administration of lenograstim from days five to ten. Absolute neutrophil count and duration of grade 3–4 neutropenia were monitored using seriated blood samples. The incidence of bone pain was evaluated using the visual analog scale (VAS).Results: The incidence of grade 3–4 neutropenia was 75% in patients who received pegfilgrastim, and 25% in patients who received lenograstim. One case of febrile neutropenia was shown in pegfilgrastim patients. The mean duration of grade 3–4 neutropenia was 2 days in pegfilgrastim group versus 1.4 days in the lenograstim group. Bone pain was present in 37.5% of pegfilgrastim patients versus 58.3% of lenograstim patients. The mean duration of bone pain in the pegfilgrastim group was 4 days versus 6 days in the lenograstim group.Conclusion: In our experience, a single injection of pegfilgrastim was less effective for controlling neutropenia than six daily injections of lenograstim. The safety profiles of pegfilgrastim and lenograstim were similar with a lower incidence of bone pain in patients treated with pegfilgrastim.Keywords: lenograstim, pegfilgrastim, neutropenia, bone pain, breast cancer, adjuvant anthracycline-based chemotherapy

Luigi Rossi, Foteini Vakiarou, Federica Zoratto, Loredana Bianchi, Anselmo Papa, Enrico Basso, Monica Verrico, Giuseppe Lo Russo, Salvatore Evangelista, Guilia Rinaldi, Francesca Perrone-Congedi, Gian Paolo Spinelli, Valeria Stati, Davide Caruso, Alessandra Prete, Silverio TomaoDepartment of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, ItalyAbstract: Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.Keywords: metastatic colorectal cancer, patient clinical features, tumor biology, multidisciplinary approach

Both human and non-human animals frequently deal with risky decisions in a social environment. Nevertheless, the influence of the social context on decision-making has been scarcely investigated. Here, we evaluated for the first time whether the presence of a conspecific influences risk preferences in rats and in tufted capuchin monkeys. Subjects received a series of choices between a constant, safe option and a variable, risky option, both alone (Alone condition) and when paired with a conspecific (Paired condition). The average payoff of the risky option was always lower than that of the safe option. Overall, the two species differed in their attitude towards risk: whereas rats were indifferent between options, capuchins exhibited a preference for the safe option. In both species, risk preferences changed in the Paired condition compared to the Alone condition, although in an opposite way. Whereas rats increased their risk preferences over time when paired with a conspecific, capuchins chose the risky option less in the Paired condition than in the Alone condition. Moreover, whereas anxiety-like behaviours decreased across sessions in rats, these behaviours where more represented in the Paired condition than in the Alone condition in capuchins. Thus, our findings extends to two distantly-related non-human species the evidence, so far available for human beings, that a decrease in anxiety corresponds to an increase in risk preferences, and vice versa . This suggests that the modulation of risk preferences by social influences observed in rats and capuchin monkeys may rely on a common, evolutionarily ancient, mechanism. [ABSTRACT FROM AUTHOR]

Gambling disorder is associated to an increased impulsivity, a high level of novelty-seeking and a dysregulation of the forebrain neurotransmission systems. However, the neurobiological mechanisms of this addictive disorder are not fully understood and no valid pharmacological approach has yet been approved. The present study aimed to investigate the effect of 5-HT7 receptor (5-HT7R) stimulation with a brain penetrant and selective agonist, LP-211 (0.25 and 0.50 mg kg−1 i.p.) during post-experience consolidation, (i) acutely in a novelty-preference test (Exp. 1) or (ii) sub-chronically in the Probabilistic-Delivery Task (rPDT, commonly used to measure individual differences in risk proneness of rats; Exp. 2). Results of Exp. 1 showed that 5-HT7R activation improves consolidation of chamber-shape memory in the novelty-preference test, leading to significant novelty-induced hyperactivity and recognition, in conditions where controls displayed a null-preference. These results suggest that 5-HT7Rs may be involved in the consolidation of information inherent to spatial environments, facilitating the recognition of novelty. Furthermore, in the operant rPDT (Exp. 2), 5-HT7R activation shifts the choice towards a larger yet unlikely reward and turns the propensity of rats towards risk-prone behavior. Thus, 5-HT7Rs stimulation apparently strengthens the consideration of future, bigger rewards, also enhancing the seeking of it by operant pokes. These effects may well be explained by LP-211 actions on hippocampal versus prefrontal cortex-mediated regulations, leading to improved (though suboptimal) strategy formation. However, further experiments are necessary to determine more in depth the serotonergic pathways involved. [ABSTRACT FROM AUTHOR]

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo , we investigated the connectivity of neuronal networks belonging to limbic vs . cortical loops in NHE and NRB rats (n = 10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. [ABSTRACT FROM AUTHOR]