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Shigeki Yagyu, Valentina Hoyos, Francesca Del Bufalo, Malcolm K Brenner
Expression of the inducible caspase-9 (iC9) suicide gene is one of the most appealing safety strategies for cell therapy and has been applied for human-induced pluripotent stem cells (hiPSC) to control the cell fate of hiPSC. iC9 can induce cell death of over 99% of iC9-transduced hiPSC (iC9-hiPSC) in less than 24 hours after exposure to chemical inducer of dimerization (CID). There is, however, a small number of resistant cells that subsequently outgrows. To ensure greater uniformity of the hiPSC response to iC9 activation, we purified a resistant population by culturing iC9-hiPSC with CID and analyzing the mechanisms by which the cells evade killing...
2016: Molecular Therapy. Methods & Clinical Development
Michela Massoud, Francesca Del Bufalo, Anna Maria Caterina Musolino, Paolo Maria Schingo, Stefania Gaspari, Mara Pisani, Cinzia Orazi, Antonino Reale, Umberto Raucci
BACKGROUND: Low back pain is a common symptom in the pediatric population; approximately half of all children present with at least one episode of low back pain. The majority of cases are due to nonspecific causes such as musculoskeletal trauma with spontaneous regression. On some occasions, however, life-threatening diseases have to be considered. CASE REPORT: A 15-year-old girl presented to the Pediatric Emergency Department for a history of continuous 2-day duration of low back pain and transient paresthesia of the right gluteal area...
September 2016: Journal of Emergency Medicine
Marta Di Martile, Donatella Del Bufalo, Daniela Trisciuoglio
Lysine acetylation is a post-translational modification that regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. Recently, several reports have demonstrated that numerous cytosolic proteins are also acetylated and that this modification, affecting protein activity, localization and stability has profound consequences on their cellular functions. Interestingly, most non-histone proteins targeted by acetylation are relevant for tumorigenesis. In this review, we will analyze the functional implications of lysine acetylation in different cellular compartments, and will examine our current understanding of lysine acetyltransferases family, highlighting the biological role and prognostic value of these enzymes and their substrates in cancer...
June 14, 2016: Oncotarget
Jennifer Búfalo, Tatiane Maria Rodrigues, Luiz Fernando Rolim de Almeida, Luiz Ricardo Dos Santos Tozin, Marcia Ortiz Mayo Marques, Carmen Silvia Fernandes Boaro
The present study investigated whether osmotic stress induced by the exposure of peppermint (Mentha x piperita L.) to moderate and severe stress for short periods of time changes the plant's physiological parameters, leaf anatomy and ultrastructure and essential oil. Plants were exposed to two levels of polyethyleneglycol (50 g L(-1) and 100 g L(-1) of PEG) in a hydroponic experiment. The plants exposed to 50 g L(-1) maintained metabolic functions similar to those of the control group (0 g L(-1)) without changes in gas exchange or structural characteristics...
August 2016: Plant Physiology and Biochemistry: PPB
Donatella Del Bufalo, Francesca Degrassi
[This corrects the article on p. 902 in vol. 2, PMID: 26697517.].
2016: Oncoscience
Giulio Conte, Maria Luce Caputo, François Regoli, Serena Marcon, Catherine Klersy, Boris Adjibodou, Alessandro Del Bufalo, Tiziano Moccetti, Angelo Auricchio
AIMS: Out-of-hospital cardiac arrest (OHCA) in the absence of evident structural heart disease is rare and can be due to subclinical cardiomyopathy and primary electrical disorders, including idiopathic ventricular fibrillation (IVF) with early repolarization (ER) pattern. Aim of this study was to investigate prevalence, clinical features, and long-term prognosis of IVF in OHCA survivors with otherwise normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with IVF in the absence of ER pattern or atrioventricular conduction abnormalities were considered eligible for this study...
February 17, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Luiz Fernando Rolim de Almeida, Roberto de Oliveira Portella, Jennifer Bufalo, Márcia Ortiz Mayo Marques, Roselaine Facanali, Fernando Frei
The present study aimed to evaluate the effect of seasonal and diurnal events on the chemical profile of the essential oil obtained from the leaves of Copaifera langsdorffii Desf. This study was performed in a Brazilian savanna named Cerrado. We identified the best harvesting period for obtaining the highest amount of compounds used for commercial and industrial purposes. The chemical profile of the essential oils was evaluated by GC-FID and GC-MS, and the results were assessed through multivariate analyses...
2016: PloS One
Marta Di Martile, Marianna Desideri, Teresa De Luca, Chiara Gabellini, Simonetta Buglioni, Adriana Eramo, Giovanni Sette, Michele Milella, Dante Rotili, Antonello Mai, Simone Carradori, Daniela Secci, Ruggero De Maria, Donatella Del Bufalo, Daniela Trisciuoglio
Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells...
March 8, 2016: Oncotarget
D Trisciuoglio, M Desideri, V Farini, T De Luca, M Di Martile, M G Tupone, A Urbani, S D'Aguanno, D Del Bufalo
Members of the bcl-2 protein family share regions of sequence similarity, the bcl-2 homology (BH) domains. Bcl-2, the most studied member of this family, has four BH domains, BH1-4, and has a critical role in resistance to antineoplastic drugs by regulating the mitochondrial apoptotic pathway. Moreover, it is also involved in other relevant cellular processes such as tumor progression, angiogenesis and autophagy. Deciphering the network of bcl-2-interacting factors should provide a critical advance in understanding the different functions of bcl-2...
2016: Cell Death & Disease
Sergio Valente, Paolo Mellini, Francesco Spallotta, Vincenzo Carafa, Angela Nebbioso, Lucia Polletta, Ilaria Carnevale, Serena Saladini, Daniela Trisciuoglio, Chiara Gabellini, Maria Tardugno, Clemens Zwergel, Chiara Cencioni, Sandra Atlante, Sébastien Moniot, Clemens Steegborn, Roberta Budriesi, Marco Tafani, Donatella Del Bufalo, Lucia Altucci, Carlo Gaetano, Antonello Mai
Modulators of sirtuins are considered promising therapeutic targets for the treatment of cancer, cardiovascular, metabolic, inflammatory, and neurodegenerative diseases. Here we prepared new 1,4-dihydropyridines (DHPs) bearing changes at the C2/C6, C3/C5, C4, or N1 position. Tested with the SIRTainty procedure, some of them displayed increased SIRT1 activation with respect to the prototype 3a, high NO release in HaCat cells, and ameliorated skin repair in a mouse model of wound healing. In C2C12 myoblasts, two of them improved mitochondrial density and functions...
February 25, 2016: Journal of Medicinal Chemistry
Patrizia Russo, Alessandra Del Bufalo, Massimo Fini
The deep-sea habitat is a source of very potent marine-derived agents that may inhibit the growth of human cancer cells "in vitro" and "in vivo". Salinosporamide-A, Marizomib, by Salinispora species is a proteasome inhibitor with promising anticancer activity (Phase I/II trials). Different deep-sea-derived drugs are under preclinical evaluation. Cancer is a complex disease that may be represented by network medicine. A simple consequence is the change of the concept of target entity from a single protein to a whole molecular pathway and or cellular network...
2015: EXCLI journal
Teresa De Luca, Andrea Pelosi, Daniela Trisciuoglio, Simona D'Aguanno, Marianna Desideri, Valentina Farini, Marta Di Martile, Barbara Bellei, Maria Grazia Tupone, Antonio Candiloro, Giulia Regazzo, Maria Giulia Rizzo, Donatella Del Bufalo
Melanoma, the most lethal form of skin cancer, is frequently associated with alterations in several genes, among which the Bcl-2 oncogene plays an important role in progression, chemosensitivity and angiogenesis. Also microRNA (miRNA) are emerging as modulators of melanoma development and progression, and among them, miR-211, located within the melastatin-1/TRPM1 (transient receptor potential cation channel, subfamily M, member 1 protein) gene, is prevalently expressed in the melanocyte lineage and acts as oncosuppressor...
November 24, 2015: Molecular Carcinogenesis
Carolina Panis, Luciana Pizzatti, Aedra Carla Bufalo, Ana Cristina Herrera, Vanessa Jacob Victorino, Rubens Cecchini, Eliana Abdelhay
Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
F A Batista, L S Ward, M A Marcello, M B Martins, K C Peres, C Torricelli, N E Bufalo, F A Soares, M J da Silva, L V M Assumpção
PURPOSE: The role of thyroid-specific transcription factors in thyroid malignancy is still poorly understood, so we investigate thyroid-specific transcription factors gene expression both in benign and in malignant thyroid nodules, aiming to study a possible clinical utility of these molecules. METHODS: We quantified TTF-1, FOXE1 and PAX8 mRNA levels, relating their expression to diagnostic and prognostic features of thyroid tumors. RNA was extracted from 4 normal thyroid tissues, 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesion tissues [49 goiter and 50 follicular adenomas (FA)]...
April 2016: Journal of Endocrinological Investigation
Romano Mauri, Roman Burkart, Claudio Benvenuti, Maria Luce Caputo, Tiziano Moccetti, Alessandro Del Bufalo, Augusto Gallino, Carlo Casso, Luciano Anselmi, Tiziano Cassina, Catherine Klersy, Angelo Auricchio
AIM: To determine the incidence of out-of-hospital cardiac arrest (OHCA) fulfilling Utstein criteria in the Canton Ticino, Switzerland, the survival rate of OHCA patients and their neurological outcome. METHODS AND RESULTS: All OHCAs treated in Canton Ticino between 1 January 2005 and 31 December 2014 were followed until either death or hospital discharge. The survival and neurological outcome of those OHCA fulfilling Utstein criteria are reported. A total of 3367 OHCAs occurred in the Canton Ticino over a 10-year period...
March 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Filippo Lococo, Alfredo Cesario, Alessandra Del Bufalo, Alessia Ciarrocchi, Giulia Prinzi, Marco Mina, Stefano Bonassi, Patrizia Russo
Respiratory diseases including chronic-obstructive-pulmonary-disease (COPD) are globally increasing, with COPD predicted to become the third leading cause of global mortality by 2020. COPD is a heterogeneous disease with COPD-patients displaying different phenotypes as a result of a complex interaction between various genetic, environmental and life-style factors. In recent years, several investigations have been performed to better define such interactions, but the identification of the resulting phenotypes is still somewhat difficult, and may lead to inadequate assessment and management of COPD (usually based solely on the severity of airflow limitation parameter FEV1)...
2015: Current Medicinal Chemistry
Jennifer Búfalo, Charles L Cantrell, Melissa R Jacob, Kevin K Schrader, Babu L Tekwani, Tatyana S Kustova, Abbas Ali, Carmen S F Boaro
Four diterpenes with biological activity were isolated from Salvia deserta roots. Taxodione was considered leishmanicidal with an IC50 value of 1.46 µM (0.46 mg/L) against Leishmania donovani and also exhibited antifungal and antimicrobial activities. Ferruginol displayed the greatest activity [24-h IC50 of 4.5 µM (1.29 mg/L)] against the fish pathogenic bacteria Streptococcus iniae. The crude extract fraction that contained the isolated compounds 7-O-acetylhorminone and horminone showed stronger in vitro antibacterial activity (1...
January 2016: Planta Medica
Mirta Milic, Alessandra Frustaci, Alessandra Del Bufalo, Juana Sánchez-Alarcón, Rafael Valencia-Quintana, Patrizia Russo, Stefano Bonassi
Non-communicable diseases (NCDs) are a leading cause of death and disability, representing 63% of the total death number worldwide. A characteristic phenotype of these diseases is the accelerated aging, which is the result of phenomena such as accumulated DNA damage, telomere capping loss and subcellular irreversible/nonrepaired oxidative damage. DNA damage, mostly oxidative, plays a key role in the development of most common NCDs. The present review will gather some of the most relevant knowledge concerning the presence of DNA damage in NCDs focusing on cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, and neurodegenerative disorders, and discussing a selection of papers from the most informative literature...
June 2015: Mutation Research
Valentina Hoyos, Francesca Del Bufalo, Shigeki Yagyu, Miki Ando, Gianpietro Dotti, Masataka Suzuki, Lisa Bouchier-Hayes, Ramon Alemany, Malcolm K Brenner
Oncolytic adenoviruses (OAdV) represent a promising strategy for cancer therapy. Despite their activity in preclinical models, to date the clinical efficacy remains confined to minor responses after intratumor injection. To overcome these limitations, we developed an alternative approach using the combination of the OAdv ICOVIR15 with a replication incompetent adenoviral vector carrying the suicide gene of inducible Caspase 9 (Ad.iC9), both of which are delivered by mesenchymal stromal cells (MSCs). We hypothesized that coinfection with ICOVIR15 and Ad...
September 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Shigeki Yagyu, Valentina Hoyos, Francesca Del Bufalo, Malcolm K Brenner
Human induced pluripotent stem cells (hiPSC) hold promise for regenerative therapies, though there are several safety concerns including the risk of oncogenic transformation or unwanted adverse effects associated with hiPSC or their differentiated progeny. Introduction of the inducible caspase-9 (iC9) suicide gene, which is activated by a specific chemical inducer of dimerization (CID), is one of the most appealing safety strategies for cell therapies and is currently being tested in multicenter clinical trials...
September 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
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