Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins

Cancer Stem Cells (CSCs) are self-renewing cancer cells responsible for expansion of the malignant mass in a dynamic process shaping the tumor microenvironment. CSCs may hijack the host immune surveillance resulting in typically aggressive tumors with poor prognosis. In this review, we focus on neurotrophic control of cellular substrates and molecular mechanisms involved in CSC-driven tumor growth as well as in host immune surveillance. Neurotrophins have been demonstrated to be key tumor promoting signaling platforms. Particularly, Nerve Growth Factor (NGF) and its specific receptor Tropomyosin related kinase A (TrkA) have been implicated in initiation and progression of many aggressive cancers. On the other hand, an active NGF pathway has been recently proven to be critical to oncogenic inflammation control and in promoting immune response against cancer, pinpointing possible pro-tumoral effects of NGF/TrkA-inhibitory therapy. A better understanding of the molecular mechanisms involved in the control of tumor growth/immunoediting is essential to identify new predictive and prognostic intervention and to design more effective therapies. Fine and timely modulation of CSCs-driven tumor growth and of peripheral lymph nodes activation by the immune system will possibly open the way to precision medicine in neurotrophic therapy and improve patient's prognosis in both TrkA- dependent and independent cancers

Enzymatic spermine metabolites induce apoptosis associated with increase of p53, caspase-3 and mir-34a in both neuroblastoma cells, SJNKP and the N-Myc-amplified form IMR5

Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down-or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis

A virtual reality extended neuropsychological assessment for topographical disorientation: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Topographical disorientation represents one of the main consequences of brain injury. Up to now several methodological approaches have been used in the assessment of the brain injured patient's navigational abilities showing a moderate correlation with the impairments observed in everyday contexts.</p> <p>Methods</p> <p>We propose a combination of standardized neuropsychological tests and a more situated virtual reality-based assessment for the evaluation of spatial orientation in brain injured patients.</p> <p>Results</p> <p>When tested with this virtual reality integrated procedure patients showed performance and execution times congruent with their neuropsychological evaluation. When compared to a control group, patients revealed significantly slower times and greater errors in solving virtual reality based spatial tasks.</p> <p>Conclusion</p> <p>The use of virtual reality, when combined with classical neuropsychological tests, can provide an effective tool for the study of topographical disorientation.</p

Nerve growth factor serum levels in treatment-resistant schizophrenic patients following electroconvulsive therapy

Background Electroconvulsive Therapy (ECT) has been widely applied to treat schizophrenia (SCZ) in the presence of resistance to pharmacotherapy. The mechanism of action of ECT in schizophrenia has not been fully clarified, though its intrinsic mechanism presents analogies with some neurobiological processes mediated by nerve growth factor (NGF). Objectives. The aim of this study was to investigate in patients with treatment-resistant schizophrenia (TRS) the effect of ECT on acute and long-term NGF serum levels and the association with the clinical outcomes. Methods. Twelve male inpatients with TRS underwent eight sessions of ECT. Blood samples were collected during the first and the eighth ECT at the following time points: 5 minutes before the induction of seizure and then at 0, 5, 15 and 30 minutes after seizure. Results. Following ECT treatment, a substantial clinical improvement in symptom severity was indicated by a significant reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscales scores. Even though the baseline NGF levels showed an increase over time, there were no statistical differences in NGF at time 0 at the first and the eighth ECT session. Furthermore, no correlation was observed between the severity of schizophrenic symptoms and NGF levels. Conclusions. This is the first study addressing peripheral NGF during ECT treatment in TRS, as well as the first study in which NGF has been evaluated in different ECT sessions at various time points. These findings may potentiate the knowledge about the neurotrophic effects of ECT and the role of NGF in synaptic plasticity related to possible mechanisms of schizophrenia treatment.