The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease

Synthesis of novel cognition enhancer with pyrazolo[5,1-c][1,2,4]benzotriazine core acting at gamma-aminobutyric acid type A (GABAA) receptor.

Memory dysfunction associated with aging, neurodegenerative and psychiatric disorders represents an increasing medical need. Advances in research exploring the biological mechanisms underlying learning and memory have opened new potential approaches for development of memory-enhancing therapies addressed to selective neuronal targets. In this work, we synthesized some derivatives with a pyrazolo[5,1-c][1,2,4]benzotriazine core to identify ligands on GABA A receptors subtype (benzodiazepine site on GABAA- receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (γ-aminobutyric acid, type A receptor) subtype ligands have relevance in learning and memory. In vitro and in vivo tests have been performed. Pharmacological data indicate that compounds 7, 13, 14 and 22 act as dual functional modulators of GABA A-Rs (promnemonic and anxiolytic agents) while only compounds 3 and 10 stand out as selectively displaying good antiamnesic and procognitive activity (1 and 3 mg/kg, respectively). © 2013 Elsevier Ltd. All rights reserved

Absorption and scattering properties of carbon nanohorn-based nanofluids for direct sunlight absorbers

In the present work, we investigated the scattering and spectrally resolved absorption properties of nanofluids consisting in aqueous and glycol suspensions of single-wall carbon nanohorns. The characteristics of these nanofluids were evaluated in view of their use as sunlight absorber fluids in a solar device. The observed nanoparticle-induced differences in optical properties appeared promising, leading to a considerably higher sunlight absorption with respect to the pure base fluids. Scattered light was found to be not more than about 5% with respect to the total attenuation of light. Both these effects, together with the possible chemical functionalization of carbon nanohorns, make this new kind of nanofluids very interesting for increasing the overall efficiency of the sunlight exploiting device

Further studies on pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as potent and selective human A1 adenosine receptor antagonists.

A new series of pyrazolo[1',5':1,6]pyrimido[4,5-dlpyridazin-4(3H)-ones was synthesized and tested in radioligand binding assays on human A(1), A(2A) and A(3) adenosine receptors. Most of the compounds showed high selectivity of action towards A(1) receptor and high affinity with K-i values in the low nanomolar range. The pharmacological profile of the most active molecules towards A(1) adenosine receptors was evaluated in cAMP functional assay. Compounds demonstrated their ability to completely counteract the effect of the agonist NECA, thus demonstrating their antagonist profile. Moreover, the most interesting compound, tested in the mouse passive avoidance, exhibited an antiamnesic effect at the doses of 10 and 30 mg/kg. (C) 2014 Published by Elsevier Masson SAS

Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations

Objective. Polidocanol sclerotherapy of head and neck venous malformations (VMs) and lymphatic malformations (LMs) has been reported only in limited series. In this manuscript we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and neck venous and lymphatic malformations. Methods. This retrospective observational study analysed data on 20 head and neck VMs and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol microfoam sclerotherapy at our institution. Clinical response was ranked as excellent, moderate and poor based on volume reduction by MRI and resolution of symptoms. Results. The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4% of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of 76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic lymphatic ones. Conclusions. Polidocanol sclerotherapy appears to be an effective and safe treatment for venous and lymphatic head and neck malformations. We observed the best responses in macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response and microcystic lymphatic ones a poor response

L'impatto psicologico dell'amianto, killer invisibile del corpo e della mente.

Introduction: Exposure to asbestos causes the onset of various diseases, including lung plaques, asbestosis and malignant pleural mesothelioma (MPM). Living in a Contaminated Site can therefore represent for the entire community a real cumulative trauma that brings into the field disease and death due to a kind of "invisible killer": asbestos. In such circumstances, it is necessary to implement multidisciplinary protocols that can offer an integrated approach to care for both patients and their caregivers. Methodology: There is now a large body of scientific evidence in the literature substantiating the importance of the role that clinical psychology can play in oncology. The objective of this work is to describe specifically the situation in Casale Monferrato, the research carried out in the area and to outline the psychological-clinical intervention proposed there to respond to the quality of needs highlighted in patients suffering from asbestos-related diseases, including mainly MPM, and their caregivers. Results: The results of the research carried out in Casale Monferrato highlight what emerges in the international literature, namely that patients with asbestocorrelated diseases frequently manifest anxiety, depression, somatic disorders and a certain tendency to social withdrawal. The psychological-clinical work within the intervention of short-term group psychotherapy offers them a setting in which they can historicize the disease and process the many facets of pain that an inauspicious diagnosis brings to the field: from the one more related to the body, to the more purely psychic. Conclusion: The role of clinical psychology in oncology is of fundamental importance both for the patient and for his family, as it can facilitate the processing of suffering and anger related to the diagnosis of cancer disease or having to take care of a loved one who has been given an inauspicious diagnosis. Psychological intervention also allows to give name and meaning to the fear related to exposure to asbestos: a silent and invisible killer, which otherwise risks remaining unthought of and unthinkable

Chromosome anomalies in bone marrow as primarycause of aplastic or hypoplastic conditions andperipheral cytopenia: disorders due to secondaryimpairment of RUNX1 and MPL genes

Background Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. Results Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2-8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT). Conclusions A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias

Neuro-Oncology Multidisciplinary Tumor Board: The Point of View of the Neuroradiologist

Background: The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended to offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). The aim of the present paper is to describe our nMTB, to evaluate its impact on clinical management decisions, and to assess the role of neuroradiologists. Methods: The retrospective evaluation of the cases discussed at our nMTB from March 2017 to March 2020. From the electronic records, we extracted epidemiological, clinical and other specific data of nMTB. From the radiological records, we calculated data relating to the number, time for revision, and other specifications of MRI re-evaluation. Statistical analysis was performed. Results: a total of 447 discussions were analyzed, representing 342 patients. The requests for case evaluations came from radiation oncologists (58.8%) and neurosurgeons (40.5%), and were mainly addressed to the neuroradiologist (73.8%). The most frequent questions were about the treatment's changes (64.4%). The change in patient treatment was reported in 40.5% of cases, 76.8% of these were based on the neuroradiologic assessment. A total of 1514 MRI examinations were re-evaluated, employing approximately 67 h overall. The median of the MRI exams reviewed per patient was 3 (min-max 1-12). Conclusions: Our study supported that the multidisciplinary approach to patient care can be particularly effective in managing brain tumors. A review by an expert neuroradiologist impacts patient management in the context of nMTBs, but has costs in terms of the time and effort spent preparing for it