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Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural Mesothelioma cells

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Cancer Drug Resistance 2022年第3期5卷 814-828页

作者： Mario Cioce Daniela Rutigliano Annamaria Puglielli Vito michele fazio department of Medicine Laboratory of Molecular Medicine and BiotechnologyUniversity Campus Bio-Medico of RomeRome 00128Italy Institute of Translational Pharmacology National Research Council of Italy(CNR)Rome 00133Italy

Aim:Malignant pleural mesothelioma is a chemoresistant tumor,and biphasic and sarcomatoid histologies portend the worst prognosis for malignant pleural mesothelioma(MPM)*** obtained the microRNA expression profile of three biphasic-sarcomatoid MPM cell lines to identify commonly expressed microRNAs and evaluate the effect of butein,a chemo-sensitizing compound,on this microRNA ***:Nanostring-based microRNA profiling and analysis through the ROSALIND platform were employed to identify the commonly modulated microRNAs and their ***-mimic transfection,Luciferase assay,and Western blotting were employed to show specific perturbation of TWIST1 levels by ***-forming assays,invasion assay,and metabolic profiling were used to assess the biological consequences of the butein-instigated miR-186-5p-mediated perturbation of TWIST1 *** analysis was used to search for the correlation between TWIST1 and miR-186-5p levels in biphasic and epithelioid MPM ***:We identified a set of perturbed microRNAs,common to three biphasic/sarcomatoid MPM cell lines,after butein *** focusing on miR-186-5p,we unraveled a butein-ignited and miR-186-5p-mediated modulation of TWIST1 levels which affected the 3D anchorage-independent growth,cisplatin resistance,invasion,and bioenergetics of the MPM cell lines *** showed that miR-186-5p and TWIST1 levels are anti-correlated in biphasic MPM specimens from ***:We unraveled a novel mechanism of action of butein,which attenuated the pro-tumorigenic features of MPM at least through a miR-186-5p-TWIST1 *** suggest that those activities converge into the chemo-sensitizing effect of this compound and may be of translational relevance.

关键词： Mesothelioma butein miR-186-5p TWIST1 pithelial-to-mesenchymal transition(EMT) chemoresistance cancer metabolism invasion anchorage-independent growth

Targeting menin: a promising therapeutic strategy for susceptible acute leukemia subtypes

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5141-5142页

作者： Pietro Di fazio department of Visceral Thoracic and Vascular SurgeryPhilipps University of MarburgBaldingerstrasse35043MarburgGermany

Two recent studies published in Nature focused on the clinical efficacy of the menin inhibitor revumenib(SNDX-5613)in KMT2A(histone-lysine N-methyltransferase 2A)-rearranged or NPM1(Nucleophosmin1)-mutant acute myeloid leukemia.1,2 These studies indicate that menin inhibition and its acquired resistance to long-term exposure to revuminib are key points for future treatment,emphasizing the role of menin as a challenging and promising target for the current treatment of leukemia.

关键词： acute clinical therapeutic

Effects of sampling frequency on node mobility prediction in dynamic networks: A spectral view

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Digital Communications and Networks 2023年第4期9卷 1009-1022页

作者： Peppino fazio Miralem Mehic Miroslav Voznak DSMN Ca’Foscari University of VeniceVia Torino 15530172MestreVEItaly department of Telecommunications Faculty of Electrical EngineeringUniversity of Sarajevo Zmaja od Bosne bb71000SarajevoBosnia and Herzegovina VSB–Technical University of Ostrava 17.listopadu 2172/1570800OstravaCzech Republic

The field of mobility prediction has been widely investigated in the recent past,especially the reduction of the coverage radius of cellular networks,which led to an increase in hand-over *** the cell coverage very frequently,for example,may lead to service disruptions if a predictive approach is not deployed in the *** several works examined mobility prediction in the new-generation mobile networks,all of these studies focused on studying the time features of mobility traces,and the spectral content of historical mobility patterns was not considered for prediction purposes as *** the present study,we propose a new approach to mobility prediction by analyzing the effects of a proper mobility sampling *** proposed approach lies in the mobility analysis in the frequency domain,to extract hidden features of the mobility ***,we proposed a new methodology to determine the spectral content of mobility traces(considered as signals)and,thus,the appropriate sampling frequency,which can provide numerous *** considered several types of mobility models(***,urban,and vehicular),containing important details in the time and frequency *** simulation campaigns were performed to observe and analyze the characteristics of mobility from real traces and to evaluate the effects of sampling frequency on the spectral content.

关键词： Mobile networking Frequency domain Mobility spectrum

Harnessing the value of TCTP in breast cancer treatment resistance: an opportunity for personalized therapy

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Cancer Drug Resistance 2023年第3期6卷 447-467页

作者： Gianluca Santamaria Mario Cioce Antonia Rizzuto Vito michele fazio Giuseppe Viglietto Maria Lucibello department of Experimental and Clinical Medicine “Magna Graecia”University of CatanzaroCatanzaro 88100Italy department of Medicine Laboratory of Molecular Medicine and BiotechnologyUniversity Campus Bio-Medico of RomeRome 00128Italy Institute of Translational Pharmacology National Research Council of Italy(CNR)Rome 00133Italy department of Medical and Surgical Sciences “Magna Graecia”University of CatanzaroCatanzaro 88100Italy department of Biomedical Sciences Institute for Biomedical Research and InnovationNational Research Council of Italy(CNR)Catanzaro 88100Italy

Early identification of breast cancer (BC) patients at a high risk of progression may aid in therapeutic and prognostic aims. This is especially true for metastatic disease, which is responsible for most cancer-related deaths. Growing evidence indicates that the translationally controlled tumor protein (TCTP) may be a clinically relevant marker for identifying poorly differentiated aggressive BC tumors. TCTP is an intriguing protein with pleiotropic functions, which is involved in multiple signaling pathways. TCTP may also be involved in stress response, cell growth and proliferation-related processes, underlying its potential role in the initiation of metastatic growth. Thus, TCTP marks specific cancer cell sub-populations with pronounced stress adaptation, stem-like and immune-evasive properties. Therefore, we have shown that in vivo phospho-TCTP levels correlate with the response of BC cells to anti-HER2 agents. In this review, we discuss the clinical relevance of TCTP for personalized therapy, specific TCTP-targeting strategies, and currently available therapeutic agents. We propose TCTP as an actionable clinically relevant target that could potentially improve patient outcomes.

关键词： Breast cancer metastasis TCTP stem cells therapy resistance biomarker

Reaction mechanisms in massive nuclei collisions and perspectives for synthesis of heavier superheavy elements

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Nuclear Science and Techniques 2013年第5期24卷 98-106页

作者： GIARDINA G NASIROV A K MANDAGLIO G CURCIARELLO F de LEO V fazio G ROMANIUK M Dipartimento di Fisica e di Scienze della Terra dell'Università di Messina Istituto Nazionale di Fisica Nucleare Sezione di Catania Joint Institute for Nuclear Research Institute of Nuclear Physics Centro Siciliano di Fisica Nucleare e Struttura della Materia Catania 95125Italy

We discuss a hardship in synthesis of heaviest super heavy elements in massive nuclei reactions due to the hindrance to complete fusion of reacting nuclei caused on the onset of quasifission process which strongly competes with complete fusion and due to the strong increase of fission yields along the de-excitation cascade of the compound nucleus in comparison with the evaporation residue *** hindrance to formation of compound nucleus and evaporation residue is determined by the characteristic of the entrance channel.

关键词：超重元素反应机制合成碰撞聚变反应残余物复合核核反应

Central Schemes and Second Order Boundary Conditions for 1D Interface and Piston Problems in Lagrangian Coordinates

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Communications in Computational Physics 2010年第9期8卷 797-822页

作者： Riccardo fazio Giovanni Russo department of Mathematics University of MessinaSalita Sperone 3198166 MessinaItaly department of Mathematics and Computer Science University of CataniaViale Andrea Doria 695125 CataniaItaly

We study high-resolution central schemes in Lagrangian coordinates for the one-dimensional system of conservation laws describing the evolution of two gases in slab geometry separated by an *** using Lagrangian coordinates,the interface is transformed to a fixed coordinate in the computational domain and,as a consequence,the movement of the interface is obtained as a byproduct of the numerical *** main contribution is the derivation of a special equation of state to be imposed at the interface in order to avoid non-physical *** boundary conditions at the piston that guarantee second order convergence are *** compare the solution of the piston problem to other results available in the literature and to a reference solution obtained within the adiabatic approximation.A shock-interface interaction problem is also *** results on these tests are in good agreement with those obtained by other methods.

关键词： Lagrangian central schemes Euler equations interface conditions boundary conditions

Elucidating the molecular responses of apple rootstock resistant to ARD pathogens:challenges and opportunities for development of genomics-assisted breeding tools

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Horticulture Research 2014年第1期1卷 110-117页

作者： Yanmin Zhu Gennaro fazio Mark Mazzola USDA ARS Tree Fruit Research Lab WenatcheeWA 98801USA USDA-ARS Plant Genetic Resources UnitGenevaNY 14456USA

Apple replant disease(ARD)is a major limitation to the establishment of economically viable orchards on replant sites due to the buildup and long-term survival of pathogen *** soilborne necrotrophic fungi and oomycetes are primarily responsible for ARD,and symptoms range from serious inhibition of growth to the death of young *** fumigation has been the primary method used for control of ARD,and manipulating soil microbial ecology to reduce pathogen density and aggressiveness is being *** date,innate resistance of apple rootstocks as a means to control this disease has not been carefully explored,partly due to the complex etiology and the difficulty in phenotyping the disease *** defense responses of plant roots to soilborne necrotrophic pathogens are largely elusive,although considerable progress has been achieved using foliar disease *** defense responses to necrotrophic pathogens consist of several interacting modules and operate as a *** pathogen detection by plants,cellular signals such as the oscillation of Ca^(2+)concentration,reactive oxygen species(ROS)burst and protein kinase activity,lead to plant hormone biosynthesis and *** acid(JA)and ethylene(ET)are known to be fundamental to the induction and regulation of defense mechanisms toward invading necrotrophic *** hormone crosstalk modulates the fine-tuning of transcriptional reprogramming and metabolic redirection,resulting in production of antimicrobial metabolites,enzyme inhibitors and cell wall refortification to restrict further *** profiling of apple roots in response to inoculation with Pythium ultimum demonstrated that there is a high degree of conservation regarding the molecular framework of defense responses compared with those observed with foliar *** is conceivable that the timing and intensity of genotype-specific defense responses may lead to different outcome

关键词： pathogens breeding roots

Characterizing traditional rice varieties grown in temperate regions of Italy:free and bound phenolic and lipid compounds and in vitro antioxidant properties

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Food Quality and Safety 2018年第2期2卷 89-95页

作者： Pierluigi Plastina Bartolo Gabriele Alessia fazio department of Pharmacy Health and Nutritional SciencesUniversity of CalabriaArcavacata di Rende(CS)Italy department of Chemistry and Chemical Technologies University of CalabriaArcavacata di Rende(CS)Italy

Objectives:A comparative study regarding the fatty acid profiles and antioxidant properties of the two most common varieties of rice(Carnaroli and Karnak)cultivated in Sybaris(Southern Italy)was *** variety from Pavia district(Northern Italy)was also ***:Free and bound lipids were separately *** acid composition was determined by high resolution gas chromatography(HRGC).Free and bound phenolic acids were determined using high performance liquid chromatography(HPLC).The antioxidant properties were assessed using 2,2’-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging ***:The total lipid content was found to be higher in both Sybaris species with respect to the Pavia *** lipid distribution was also significantly *** particular,the amount of bound lipids(14.2-16.3 mg g−1)was higher than the free lipids(7.2-7.5 mg g−1),and unsaturated fatty acids(USFA)were significantly higher in the free-FA fraction than in bound-FA in both Sybaris *** contrast,Carnaroli variety from Northern Italy displayed a higher content of free(5.3 mg g−1)than bound lipids(2.5 mg g−1)and a higher content of USFA in the *** antioxidant activity of Pavia rice extract was higher than that of both Sybaris ***:The two Sybaris varieties are richer in lipids than the Pavia rice,while exhibiting the same qualitative fatty acid profile with some differences in the content of individual fatty *** distribution of lipids(free or bound)was found to be significantly different in the Carnaroli varieties,highlighting the effects of different climatic and pedological areas.

关键词： free and bound lipids radical scavenging free and bound phenolics

Neuroendocrine tumors resistant to mammalian target of rapamycin inhibitors:A difficult conversion from biology to the clinic

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World Journal of Clinical Oncology 2015年第6期6卷 194-197页

作者： Nicola fazio Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology

deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.

关键词： Everolimus BEZ235 Mammalian target of rapamycin Phosphoinositide 3-kinase Mammalian target of rapamycin C Resistance Mammalian target of rapamycin inhibitor