2,272 research outputs found
Ricordo di Matteo Dell'Olio
No full textL'A. ricorda il profilo scientifico ed accademico del prof. Matteo Dell'Olio, esaminandone i contributi più significativi
Re: Using Deep Learning To Differentiate Among Histology Renal Tumor Types in Computed Tomography Scans
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New deals on the transcriptional and post-transcriptional regulation of TRP channel target genes during the angiogenesis of glioma
No full textTriggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents
No full textThe aggressive behavior of Glioblastoma multiforme (GBM) is mainly due to high invasiveness and proliferation rate as well as to high resistance to standard chemotherapy. Several chemotherapeutic agents like temozolomide (TMZ), carmustine (BCNU) or doxorubicin (DOXO) have been employed for treatment of GBM, but they display limited efficacy. Therefore, it is important to identify new treatment modalities to improve therapeutic effects and enhance GBM chemosensitivity. Recently, activation of the transient receptor potential vanilloid type 2 (TRPV2) has been found to inhibit human GBM cell proliferation and overcome BCNU resistance of GBM cells. Herein, we evaluated the involvement of cannabidiol (CBD)-induced TRPV2 activation, in the modulation of glioma cell chemosensitivity to TMZ, BCNU and DOXO. We found that CBD increases TRPV2 expression and activity. CBD by triggering TRPV2-dependent Ca(2+) influx increases drug uptake and synergizes with cytotoxic agents to induce apoptosis of glioma cells, whereas no effects were observed in normal human astrocytes. Moreover, as the pore region of transient receptor potential (TRP) channels is critical for ion channel permeation, we demonstrated that deletion of TRPV2 poredomain inhibits CBD-induced Ca(2+) influx, drug uptake and cytotoxic effects. Overall, we demonstrated that co-administration of cytotoxic agents together with the TRPV2 agonist CBD increases drug uptake and parallelly potentiates cytotoxic activity in human glioma cells
Tendenza e lavoro in Germania e in Italia. Le sfide dell’ordinamento europeo
No full textSommario: 1. Il contributo di Francesco Santoni allo studio del lavoro nelle organizzazioni di tendenza. – 2. L’esperienza paradigmatica della Germania: i rapporti di lavoro nelle istituzioni gestite dalle confessioni religiose. – 3. L’incontro-scontro con il diritto europeo. – 4. L’esperienza italiana dall’influenza tedesca al diritto antidiscriminatorio europeo: appunti da un viaggio senza bussola. – 5. Qualche riflessione conclusiva e di prospettiva.The article deals with employment relationships in ideologically oriented organisations, with particular attention to religiously oriented ones. The author, taking the cue from a book of Francesco
Santoni on this theme, written in 1983, points out continuity and distances in the present scholar debate and case-law. In the first part, after a description of the German experience, the article focuses
upon some milestone decisions of the European Court of Human Rights and of the European Court of Justice. These rulings are actually forcing the German system to give up strong prerogatives that
it has always granted to religiously oriented organisation in managing labour relations with their employees. The final part of the essay is devoted to the Italian experience, by now dominated by
anti-discriminatory law, which is eliminating any peculiarities of labour law in religiously oriented organisations. In conclusion, the author proposes to strike a better balance between collective freedom
of religion, enjoyed by religiously oriented organisations, and right not to be discriminated against, to which individual employees in these organisations are entitled
Insulin potentiates FcepsilonRI-mediated signaling in mouse bone marrow-derived mast cells.
No full textFactors contained in physiological microenvironments in tissues where mast cells differentiate and reside may influence mast cell responsiveness and modify antigen-dependent activation. A possible direct or indirect role of mast cell responses in diabetes mellitus prompted us to study the impact of insulin treatment on antigen triggered signaling pathways downstream of FcepsilonRI in bone marrow-derived mouse mast cells (BMMCs). We found that insulin alone stimulates tyrosine phosphorylation of tyrosine kinases Lyn, Syk, Fyn, the adapter protein Gab2 (Grb2-associated binding protein 2), Akt and activates ERK, JNK and p38 kinase. Effect of insulin on FcepsilonRI signaling pathways was marked by enhanced phosphorylation of Lyn, Fyn, Gab2 and Akt. Furthermore, BMMC stimulated with antigen in the presence of insulin responded with enhanced protein kinase theta (PKCtheta) activity and increased JNK phosphorylation when compared to BMMC triggered with antigen alone. Functional studies reveal enhanced degranulation and altered cytoskeletal rearrangement when BMMCs were treated simultaneously with insulin and antigen. Our results suggest that insulin tunes antigen-mediated responses of mast cells. (c) 2009 Elsevier Ltd. All rights reserved
Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons
No full textAn increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms
play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all
multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition
receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular
patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and
function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a
major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many
physiological and pathological processes.
In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels
of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP
channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation
to generate the mature caspase-1 that cleaves pro-interleukin-1β cytokine into the mature interleukin-1β.
Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and
irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus,
they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction
of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement
of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative
pathologies. This field is still at its beginning and further studies may be required.
Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory,
autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific
TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated
inflammatory signals
Calcium Signaling and the Regulation of Chemosensitivity in Cancer Cells: Role of the Transient Receptor Potential Channels
No full textCancer cells acquire the ability to modify the calcium signaling network by altering the expression and functions of cation channels, pumps or transporters. Calcium signaling pathways are involved in proliferation, angiogenesis, invasion, immune evasion, disruption of cell death pathways, ECM remodelling, epithelial-mesenchymal transition (EMT) and drug resistance. Among cation channels, a pivotal role is played by the Transient Receptor Potential non-selective cation-permeable receptors localized in plasma membrane, endoplasmic reticulum, mitochondria and lysosomes. Several findings indicate that the dysregulation in calcium signaling induced by TRP channels is responsible for cancer growth, metastasis and chemoresistance. Drug resistance represents a major limitation in the application of current therapeutic regimens and several efforts are spent to overcome it. Here we describe the ability of Transient Receptor Potential Channels to modify, by altering the intracellular calcium influx, the cancer cell sensitivity to chemotherapeutic drugs
TUTELA DEL LAVORO E LIBERTA' D'IMPRESA NEI PROCESSI DI ESTERNALIZZAZIONE
No full textL’elaborato analizza le conseguenze lavoristiche della successione fra imprenditori, muovendo da una ricognizione delle varie tipologie di esternalizzazione con le relative esigenze e principali criticità.
L’indagine si concentra in primo luogo sul trasferimento d’azienda, esaminando la normativa e la giurisprudenza europee per passare poi alla disciplina di diritto interno, alle procedure sindacali e a uno specifico focus sul trasferimento delle aziende in crisi.
Successivamente l’autore si sofferma sull’appalto, prendendone in particolare considerazione gli indici di genuinità, i criteri di distinzione dalla somministrazione illecita di manodopera e la tutela delle maestranze in caso di avvicendamento fra imprese.
Da ultimo, la ricerca approfondisce le c.d. “clausole sociali”, sia di prima che di seconda generazione, valutandone la compatibilità con il diritto eurounitario e con la costituzione nonché riflettendo sui possibili rimedi in caso di loro violazione.The author analyzes the labour consequences of the succession between entrepreneurs, starting from a recognition of the various types of outsourcing with the related needs and main critical issues.
The survey focuses primarily on the transfer of businesses, examining European legislation and case-law and then moving on to internal legislation, trade union procedures and a specific focus on the transfer of companies in crisis.
The author then dwells on the contract, taking into account in particular the indications of authenticity, the criteria of distinction from the illicit administration of labour and the protection of workers in the event of turnover between companies.
Finally, the research deepens the "social clauses", both first and second generation, assessing their compatibility with European law and with the constitution and reflecting on possible remedies in case of their violation
Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression
No full textTransient receptor potential (TRP) cation channel superfamily plays important roles in a variety of cellular processes such polymodal cellular sensing, adhesion, polarity, proliferation, differentiation and apoptosis. The expression of TRP channels is strictly regulated and their de-regulation can stimulate cancer development and progression.In human cancers, specific miRNAs are expressed in different tissues, and changes in the regulation of gene expression mediated by specific miRNAs have been associated with carcinogenesis. Several miRNAs/TRP channel pairs have been reported to play an important role in tumor biology. Thus, the TRPM1 gene regulates melanocyte/melanoma behaviour via TRPM1 and microRNA-211 transcripts. Both miR-211 and TRPM1 proteins are regulated through microphthalmia-associated transcription factor (MIFT) and the expression of miR-211 is decreased during melanoma progression. Melanocyte phenotype and melanoma behaviour strictly depend on dual TRPM1 activity, with loss of TRPM1 protein promoting melanoma aggressiveness and miR-211 expression supporting tumour suppressor. TRPM3 plays a major role in the development and progression of human clear cell renal cell carcinoma (ccRCC) with von Hippel-Lindau (VHL) loss. TRPM3, a direct target of miR-204, is enhanced in ccRCC with inactivated or deleted VHL. Loss of VHL inhibits miR-204 expression that lead to increased oncogenic autophagy. Therefore, the understanding of specific TRP channels/miRNAs molecular pathways in distinct tumors could provide a clinical rationale for target therapy in cancer
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