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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

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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

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DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor

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World Journal of Gastroenterology 2005年第42期11卷 6694-6700页

作者： Paola Mazzarelli Paola Parrella Davide Seripa Emanuela Signori Giuseppe Perrone Carla Rabitti Domenico Borzomati Armando Gabbrielli Maria Giovanna Matera Carolina Gravina Marco Caricato Maria Luana Poeta Monica Rinaldi Sergio Valeri Roberto Coppola vito michele fazio Laboratory of Molecular Medicine and Biotechnology Interdisciplinary Center for Biomedical Research Università Campus Bio-Medico Rome 00155 Italy Laboratory of Gene Therapy and Oncology IRCCS "Casa Sollievo della Sofferenza" Hospital San Giovanni Rotondo (FG) 71013 Italy Service of Histopathology Università Campus Bio-Medico Rome 00155 Italy Department of General Surgery Università Campus Bio-Medico Rome 00155 Italy Department of Digestive Disease Università Campus Bio-Medico Rome 00155 Italy CNR Gene-Medicine Division Section of Molecular Medicine Institute of Neurobiology and Molecular Medicine Rome 00133 Italy Laboratory of Gene Therapy and Oncology IRCCS "Casa Sollievo della Sofferenza" Hospital San Giovanni Rotondo (FG) 71013 Italy CNR Gene-Medicine Division Section of Molecular Medicine Institute of Neurobiology and Molecular Medicine Rome 00133 Italy

AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal ***: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot ***: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P＜0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the ***, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P＜0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy ***: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

关键词： DNA Ku70/80 异质二聚体基因表达结肠癌直肠癌

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Sphincteroplasty for fecal incontinence in the era of sacral nerve modulation

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World Journal of Gastroenterology 2010年第42期16卷 5267-5271页

作者： Donato F Altomare michele De fazio Ramona Tiziana Giuliani Giorgio Catalano Filippa Cuccia General Surgery and Liver Transplantation Units Department of Emergency and Organ TransplantationUniversity of Bari "Aldo Moro"11-70124 BariItaly

The role of sphincteroplasty in the treatment of patients with fecal incontinence due to anal sphincter defects has been questioned because the success rate declines in the long-term.A new emerging treatment for fecal incontinence,sacral nerve stimulation,has been shown to be effective in these ***,the success rate of sphincteroplasty may depend of several patient-related and surgical-related factors and the outcome from sphincteroplasty has been evaluated differently(with qualitative data) from that after sacral nerve stimulation(quantitative data using scoring systems and quality of life).Furthermore,the data available so far on the longterm success rate after sacral nerve modulation do not differ substantially from those after *** actual data do not support the replacement of sphincteroplasty with sacral nerve stimulation in patients with fecal incontinence secondary to sphincter defects.

关键词： Fecal incontinence Sacral nerve stimulation Sphincteroplasty

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Apple whole genome sequences:recent advances and new prospects

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Horticulture Research 2019年第1期6卷 1247-1270页

作者： Cameron P.Peace Luca Bianco Michela Troggio Eric van de Weg Nicholas P.Howard Amandine Cornille Charles-Eric Durel Sean Myles ZoëMigicovsky Robert J.Schaffer Evelyne Costes Gennaro fazio Hisayo Yamane Steve van Nocker Chris Gottschalk Fabrizio Costa David Chagné Xinzhong Zhang Andrea Patocchi Susan E.Gardiner Craig Hardner Satish Kumar Francois Laurens Etienne Bucher Dorrie Main Sook Jung Stijn Vanderzande Department of Horticulture Washington State UniversityPullmanWA 99164USA Computational Biology Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Department of Genomics and Biology of Fruit Crops Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Plant Breeding Wageningen University and ResearchWageningen 6708PBThe Netherlands Department of Horticultural Science University of MinnesotaSt.PaulMN 55108USA Institut für Biologie und Umweltwissenschaften Carl von Ossietzky Universität26129 OldenburgGermany GQE-Le Moulon Institut National de la Recherche AgronomiqueUniversity of Paris-SudCNRSAgroParisTechUniversitéParis-Saclay91190 Gif-sur-YvetteFrance Institut National de la Recherche Agronomique Institut de Recherche en Horticulture et SemencesUMR 134549071 BeaucouzéFrance Department of Plant Food and Environmental SciencesFaculty of AgricultureDalhousie UniversityTruroNS B2N 5E3Canada The New Zealand Institute for Plant and Food Research Ltd Motueka 7198New Zealand School of Biological Sciences University of AucklandAuckland 1142New Zealand AGAP INRACIRADMontpellier SupAgroUniversity of MontpellierMontpellierFrance Plant Genetic Resources Unit USDA ARSGenevaNY 14456USA Laboratory of Pomology Graduate School of AgricultureKyoto UniversityKyoto 606-8502Japan Department of Horticulture Michigan State UniversityEast LansingMI 48824USA The New Zealand Institute for Plant and Food Research Ltd(Plant&Food Research) Palmerston North Research CentrePalmerston North 4474New Zealand College of Horticulture China Agricultural University100193 BeijingChina Agroscope 8820 WädenswilSwitzerland Queensland Alliance of Agriculture and Food Innovation University of QueenslandSt Lucia 4072Australia New Cultivar Innovation Plant and Food ResearchHavelock North 4130New Zealand Agroscope 1260 ChanginsSwitzerland

In 2010,a major scientific milestone was achieved for tree fruit crops:publication of the first draft whole genome sequence(WGS)for apple(Malus domestica).This WGS,v1.0,was valuable as the initial reference for sequence information,fine mapping,gene discovery,variant discovery,and tool development.A new,high quality apple WGS,GDDH13 v1.1,was released in 2017 and now serves as the reference genome for *** the past decade,these apple WGSs have had an enormous impact on our understanding of apple biological functioning,trait physiology and inheritance,leading to practical applications for improving this highly valued *** gene identities for phenotypes of fundamental and practical interest can today be discovered much more ***-wide polymorphisms at high genetic resolution are screened efficiently over hundreds to thousands of individuals with new insights into genetic relationships and ***-density genetic maps are constructed efficiently and quantitative trait loci for valuable traits are readily associated with positional candidate genes and/or converted into diagnostic tests for *** understand the species,geographical,and genomic origins of domesticated apple more precisely,as well as its relationship to wild *** WGS has turbo-charged application of these classical research steps to crop improvement and drives innovative methods to achieve more durable,environmentally sound,productive,and consumer-desirable apple *** review includes examples of basic and practical breakthroughs and challenges in using the apple *** for“what’s next”focus on necessary upgrades to the genome sequence data pool,as well as for use of the data,to reach new frontiers in genomics-based scientific understanding of apple.

关键词： breakthrough hundreds frontier

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