5 results on '"Braconi, C."'
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2. Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage
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Nicola Valeri, David Cunningham, Pietro Carotenuto, Somaieh Hedayat, Nigel B. Jamieson, Colin Rae, Albert Hallsworth, David Watkins, Anguraj Sadanandam, Matteo Fassan, Kyriakos Kouvelakis, Claudia Parisi, Sergio Xavier Azevedo, Francesco Amato, Vincenza Guzzardo, Ruwaida Begum, Ian Chau, Andrea Lanese, Kate Young, Vasiliki Michalarea, Maya Raj, Caterina Vicentini, Domenico Zito, Maria C. Previdi, Aldo Scarpa, Naureen Starling, Sheela Rao, Andrew Wotherspoon, Andrew V. Biankin, Ian Said-Huntingford, Andrea Lampis, David K. Chang, Paul Workman, Vladimir Kirkin, Francesco Sclafani, Jens C. Hahne, Rosie Upstill-Goddard, Chiara Braconi, Carotenuto, P., Amato, F., Lampis, A., Rae, C., Hedayat, S., Previdi, M. C., Zito, D., Raj, M., Guzzardo, V., Sclafani, F., Lanese, A., Parisi, C., Vicentini, C., Said-Huntingford, I., Hahne, J. C., Hallsworth, A., Kirkin, V., Young, K., Begum, R., Wotherspoon, A., Kouvelakis, K., Azevedo, S. X., Michalarea, V., Upstill-Goddard, R., Rao, S., Watkins, D., Starling, N., Sadanandam, A., Chang, D. K., Biankin, A. V., Jamieson, N. B., Scarpa, A., Cunningham, D., Chau, I., Workman, P., Fassan, M., Valeri, N., and Braconi, C.
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Outcome Assessment ,endocrine system diseases ,FOLFIRINOX ,medicine.medical_treatment ,Leucovorin ,PROTEIN ,General Physics and Astronomy ,Kaplan-Meier Estimate ,THERAPY ,Outcome Assessment, Health Care ,Antineoplastic Combined Chemotherapy Protocols ,TUMOR-SUPPRESSOR ,Multidisciplinary ,Pancreatic Neoplasm ,MicroRNA ,CLIC4 ,ASSOCIATION ,Neoadjuvant Therapy ,Gene Expression Regulation, Neoplastic ,Oxaliplatin ,Pancreatic Ductal ,miRNAs ,SURVIVAL ,GROWTH ,Fluorouracil ,Carcinoma, Pancreatic Ductal ,Humans ,Irinotecan ,MicroRNAs ,Pancreatic Neoplasms ,DNA Damage ,Human ,medicine.drug ,EXPRESSION ,DNA damage ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,In vivo ,microRNA ,medicine ,Neoplastic ,Chemotherapy ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Carcinoma ,Pancreatic cancer ,General Chemistry ,EFFICACY ,digestive system diseases ,Health Care ,GEMCITABINE ,Gene Expression Regulation ,Apoptosis ,Cancer research ,TUMOR-SUPPRESSOR, EXPRESSION, GEMCITABINE, SURVIVAL, PROTEIN, ASSOCIATION, EFFICACY, THERAPY, GROWTH, CLIC4 ,business - Abstract
FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome., Understanding which patients will respond to FOLFIRINOX therapy is important for clinical outcome. Here, the authors show that the MIR1307 is increased pancreatic cancer cell lines and inhibition of the microRNA sensitises cells to treatment.’ stratifying patients to achieve the best clinical outcome. Here, the authors show that the MIR1307 is increased in a subgroup of human pancreatic cancers and inhibition of the microRNA in in vitro and in vivo models of pancreatic cancer sensitises cells to treatment.
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- 2021
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3. Current and novel therapeutic opportunities for systemic therapy in biliary cancer
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Giovanni Brandi, Giulia Mentrasti, Vincenzo Cardinale, Jose J.G. Marin, Maite G. Fernandez-Barrena, John Bridgewater, Oreste Segatto, Angela Lamarca, Rocio I.R. Macias, Arndt Vogel, Jesus M. Banales, Patricia Munoz-Garrido, Pilar Acedo, Ana Landa-Magdalena, Cecília M. P. Rodrigues, Juan W. Valle, Marco Marzioni, Chiara Braconi, Adelaida La Casta, Pedro M. Rodrigues, Simona Tavolari, Joachim C. Mertens, Ana Da Silva Ruivo, Maria Giuseppina Prete, Marin J.J.G., Prete M.G., Lamarca A., Tavolari S., Landa-Magdalena A., Brandi G., Segatto O., Vogel A., Macias R.I.R., Rodrigues P.M., Casta A.L., Mertens J., Rodrigues C.M.P., Fernandez-Barrena M.G., Da Silva Ruivo A., Marzioni M., Mentrasti G., Acedo P., Munoz-Garrido P., Cardinale V., Banales J.M., Valle J.W., Bridgewater J., and Braconi C.
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Review Article ,biliary tract cancer, chemotherapy ,Systemic therapy ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Stroma ,Internal medicine ,Tumor Microenvironment ,Medicine ,Humans ,Molecular Targeted Therapy ,Precision Medicine ,Chemotherapy ,Clinical Trials as Topic ,Molecular medicine ,business.industry ,Liquid Biopsy ,Correction ,Biliary cancer ,Phenotype ,3. Good health ,Strategies for treating patients ,Biliary Tract Neoplasms ,Liver ,Biliary tract ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Molecular targets ,Biliary tract cancer ,Immunotherapy ,business ,Biliary tract cancers (BTCs) ,Adjuvant ,Aggressive malignancies - Abstract
Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.
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- 2020
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4. Cholangiocarcinoma 2020: the next horizon in mechanisms and management
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Sergio A. Gradilone, Mario Strazzabosco, Jesper B. Andersen, Cédric Coulouarn, Gregory J. Gores, Rocio I.R. Macias, John Bridgewater, Pedro M. Rodrigues, Vincenzo Cardinale, Lewis R. Roberts, Chiara Raggi, Chiara Braconi, Anja Moncsek, Jordi Bruix, Shahid A. Khan, Juan W. Valle, Marco Marzioni, Alejandro Forner, Angela Lamarca, Domenico Alvaro, Luca Fabris, Guido Carpino, Luke Boulter, Maria J. Perugorria, Joachim C. Mertens, Julie K. Heimbach, Sumera Rizvi, Eugenio Gaudio, Jesus M. Banales, Bas Groot Koerkamp, Jose J.G. Marin, Diego F. Calvisi, Pietro Invernizzi, Laura Fouassier, European Commission, Surgery, Basque Foundation for Science (Ikerbasque), Instituto de Salud Carlos III [Madrid] (ISC), Universidad de Salamanca, University of Manchester [Manchester], Imperial College London, Mayo Clinic, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Roma 'Foro Italico', University of Copenhagen = Københavns Universitet (KU), University of Glasgow, Universität Regensburg (UR), Yale University [New Haven], University of Edinburgh, University of Minnesota System, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Universität Zürich [Zürich] = University of Zurich (UZH), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Spanish Ministry of Economy and Competitiveness [FIS PI12/00380, FIS PI15/01132, FIS PI18/01075, CON14/00129, FIS PI14/00399, FIS PI17/00022, RYC-2015-17755], 'Fondo Europeo de Desarrollo Regional' (FEDER)European Union (EU), ISCIII CIBERehd, Diputacion Foral de Gipuzkoa [DFG15/010, DFG16/004], BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia) [BIO15/CA/016/BD], Department of Health of the Basque CountryBasque Government [2015111100, 2017111010], 'Fundacion Cientifica de la Asociacion Espanola Contra el Cancer' (AECC Scientific Foundation), European Commission Horizon 2020 programme (ESCALON project) [825510], Danish Medical Research CouncilDanish Medical Research Council, Danish Cancer SocietyDanish Cancer Society, Novo Nordisk FoundationNovo Nordisk Foundation, A.P. MOller Foundation, Carlos III Institute of Health, SpainInstituto de Salud Carlos III [PI16/00598, PI18/00428], European Regional Development FundEuropean Union (EU), Ministry of Science and Innovation, SpainSpanish Government [SAF2016-75197-R], 'Asociacion Espanola Contra el Cancer', Spain (AECC-2017), 'Centro Internacional sobre el Envejecimiento', Spain (OLD-HEPAMARKER) [0348-CIE-6-E], Christie Charity, Universita Politecnica delle Marche, Ancona, Italy [040020_R.SCIENT.A_2018_MARZIONI_M_STRATEGICO_2017], Yale Liver Center Clinical and Translational Core and the Cellular and Molecular Core (Silvio O. Conte Digestive Diseases Research Center) [DK034989], INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm), Universite de Rennes, INCaInstitut National du Cancer (INCA) France, ITMO Cancer AVIESAN dans le cadre du Plan Cancer (Non-coding RNA in Cancerology: Fundamental to Translational), Ligue Contre le CancerLigue nationale contre le cancer, Region BretagneRegion Bretagne, Instituto de Salud Carlos IIIInstituto de Salud Carlos III [PI18/00763], AECC [PI044031], WCR (AICR) [16-0026], ISCIIIInstituto de Salud Carlos III [PI13/01229, PI18/00542], Instituto de Salud Carlos IIIInstituto de Salud Carlos III, EASL Registry Award 2016 (European CCA Registry, ENS-CCA), EASL Registry Award 2019 (European CCA Registry, ENS-CCA), Ikerbasque - Basque Foundation for Science, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Banales, J, Marin, J, Lamarca, A, Rodrigues, P, Khan, S, Roberts, L, Cardinale, V, Carpino, G, Andersen, J, Braconi, C, Calvisi, D, Perugorria, M, Fabris, L, Boulter, L, Macias, R, Gaudio, E, Alvaro, D, Gradilone, S, Strazzabosco, M, Marzioni, M, Coulouarn, C, Fouassier, L, Raggi, C, Invernizzi, P, Mertens, J, Moncsek, A, Rizvi, S, Heimbach, J, Koerkamp, B, Bruix, J, Forner, A, Bridgewater, J, Valle, J, Gores, G, and HAL UR1, Admin
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medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Diagnostic tools ,Bioinformatics ,bile duct neoplasms ,cholangiocarcinoma ,humans ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Biomarker discovery ,030304 developmental biology ,Cancer ,0303 health sciences ,Biliary tract cancer ,Hepatology ,business.industry ,Extramural ,Gastroenterology ,Consensus Statement ,Expert consensus ,medicine.disease ,3. Good health ,[SDV] Life Sciences [q-bio] ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Hepatology, cholangiocarcinoma, therapy ,business - Abstract
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted., Cholangiocarcinoma (CCA) comprises heterogeneous biliary malignant tumours, and their incidence is increasing worldwide. This expert Consensus Statement, endorsed by the ENS-CCA, summarizes the latest advances in CCA, including classification, genetics and treatment, and provides recommendations for CCA management and priorities across basic, translational and clinical research.
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- 2020
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5. Modulation of mismatch repair and genomic stability by miR-155
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Pierluigi Gasparini, Manuela Ferracin, Francesca Fanini, Angelo Veronese, Stefano Volinia, Massimo Negrini, Muller Fabbri, Stefan Costinean, Roberta Gafà, Brett Adair, Michael A. McIlhatton, Sukhinder K. Sandhu, Francesca Lovat, Chiara Braconi, Federica Calore, Ivan Vannini, Arianna Bottoni, Giovanni Lanza, Richard Fishel, Nicola Valeri, Carlo M. Croce, Gerard J. Nuovo, Hansjuerg Alder, Dino Amadori, Valeri N., Gasparini P., Fabbri M., Braconi C., Veronese A., Lovat F., Adair B., Vannini I., Fanini F., Bottoni A., Costinean S., Sandhu S. K., Nuovo G. J., Alder H., Gafa R., Calore F., Ferracin M., Lanza G., Volinia S., Negrini M., McIlhatton M. A., Amadori D., Fishel R., and Croce C. M.
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Genome instability ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Repair ,Genotype ,DNA repair ,Down-Regulation ,colorectal cancer ,Biology ,MLH1 ,DNA Mismatch Repair ,Genomic Instability ,Cell Line, Tumor ,medicine ,Humans ,neoplasms ,Adaptor Proteins, Signal Transducing ,Multidisciplinary ,microRNA ,Nuclear Proteins ,nutritional and metabolic diseases ,Cancer ,Microsatellite instability ,Biological Sciences ,medicine.disease ,digestive system diseases ,Lynch syndrome ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,MutS Homolog 2 Protein ,Phenotype ,MSH2 ,Mutation ,Cancer research ,Colorectal cancer ,DNA mismatch repair ,Colorectal Neoplasms ,MutL Protein Homolog 1 - Abstract
Inactivation of mismatch repair (MMR) is the cause of the common cancer predisposition disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), as well as 10–40% of sporadic colorectal, endometrial, ovarian, gastric, and urothelial cancers. Elevated mutation rates (mutator phenotype), including simple repeat instability [microsatellite instability (MSI)] are a signature of MMR defects. MicroRNAs (miRs) have been implicated in the control of critical cellular pathways involved in development and cancer. Here we show that overexpression of miR-155 significantly down-regulates the core MMR proteins, hMSH2, hMSH6, and hMLH1, inducing a mutator phenotype and MSI. An inverse correlation between the expression of miR-155 and the expression of MLH1 or MSH2 proteins was found in human colorectal cancer. Finally, a number of MSI tumors with unknown cause of MMR inactivation displayed miR-155 overexpression. These data provide support for miR-155 modulation of MMR as a mechanism of cancer pathogenesis.
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- 2010
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