EMMANUEL DIAS NETO
Projetos de Pesquisa
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LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
37 resultados
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Agora exibindo 1 - 10 de 37
- Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow-up(2019) PIZZI, Melissa Pool; BARTELLI, Thais Fernanda; PELOSOF, Adriane Graicer; FREITAS, Helano Carioca; BEGNAMI, Maria Dirlei; ABRANTES, Lais Lie Senda de; SZTOKFISZ, Claudia; VALIERIS, Renan; KNEBEL, Franciele Hinterholz; COELHO, Luiz Gonzaga Vaz; COSTA, Wilson Luiz da; COIMBRA, Felipe J. F.; SILVA, Israel Tojal da; AMORIM, Maria Galli de; NUNES, Diana Noronha; DIAS-NETO, EmmanuelWhereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53-a highly mutated and informative gene in GAC-to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash-GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000x. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW- (15.2%) and 6/46 PL-samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW-exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene-panel designed for this malignancy.
conferenceObject DETECTION OF SCHISTOSOMA MANSONI SPOROCYST STAGE IN BIOMPHALARIA GLABRATA MOLLUSK IN EXPERIMENTAL CONDITIONS(2018) CASOTTI, Marcia; TUAN, Roseli; GOMES, Michele; LUNA, Expedito Albuquerque; DIAS-NETO, Emmanuel; PAULA, Fabiana; PINHO, Joao Rebello; CARRILHO, Flair; GRYSCHEK, Ronaldo Borges; ESPIRITO-SANTO, MariaconferenceObject MOLECULAR CHARACTERIZATION OF THE LARVAL PHASE OF SCHISTOSOMA MANSONI IN BIOMPHALARIA GLABRATA MOLLUSKS UNDER EXPERIMENTAL CONDITIONS(2017) CASOTTI, Marcia Oliveira; TUAN, Roseli Tuan; GOMES, Michele; DIAS-NETO, Emmanuel; PINHO, Joao Renato Rebello; PAULA, Fabiana Martins; CARRILHO, Flair Jose Carrilho Jose; LUNA, Expedito Jose Albuquerque; GRYSCHEK, Ronaldo Cesar Borges Borges; ESPIRITO-SANTO, Maria Cristina- Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes(2016) DOBROFF, Andrey S.; D'ANGELO, Sara; ECKHARDT, Bedrich L.; FERRARA, Fortunato; STAQUICINI, Daniela I.; CARDO-VILA, Marina; STAQUICINI, Fernanda I.; NUNES, Diana N.; KIM, Kisu; DRIESSEN, Wouter H. P.; HAJITOU, Amin; LOMO, Lesley C.; BARRY, Marc; KRISHNAMURTHY, Savitri; SAHIN, Aysegul; WOODWARD, Wendy A.; PROSSNITZ, Eric R.; ANDERSON, Robin L.; DIAS-NETO, Emmanuel; BROWN-GLABERMAN, Ursa A.; ROYCE, Melanie E.; UENO, Naoto T.; CRISTOFANILLI, Massimo; HORTOBAGYI, Gabriel N.; MARCHIO, Serena; GELOVANI, Juri G.; SIDMAN, Richard L.; ARAP, Wadih; PASQUALINI, RenataInflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.
- Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch(2015) NUNES, Diana N.; DIAS-NETO, Emmanuel; CARDO-VILA, Marina; EDWARDS, Julianna K.; DOBROFF, Andrey S.; GIORDANO, Ricardo J.; MANDELIN, Jami; BRENTANI, Helena P.; HASSELGREN, Catrin; YAO, Virginia J.; MARCHIO, Serena; PEREIRA, Carlos A. B.; PASSETTI, Fabio; CALIN, George A.; SIDMAN, Richard L.; ARAP, Wadih; PASQUALINI, RenataSix members of the microRNA-17 (miR-17) family were mapped to three different chromosomes, although they share the same seed sequence and are predicted to target common genes, among which are those encoding hypoxia-inducible factor-1 alpha (HIF1A) and VEGFA. Here, we evaluated the in vivo expression profile of the miR-17 family in the murine retinopathy of prematurity (ROP) model, whereby Vegfa expression is highly enhanced at the early stage of retinal neovascularization, and we found simultaneous reduction of all miR-17 family members at this stage. Using gene reporter assays, we observed binding of these miRs to specific sites in the 3' UTRs of Hif1a and Vegfa. Furthermore, overexpression of these miRs decreased HIF1A and VEGFA expression in vitro. Our data indicate that this miR-17 family elicits a regulatory synergistic down-regulation of Hif1a and Vegfa expression in this biological model. We propose the existence of a coordinated regulatory network, in which diverse miRs are synchronously regulated to target the Hif1a transcription factor, which in turn, potentiates and reinforces the regulatory effects of the miRs on Vegfa to trigger and sustain a significant physiological response.
- PRUNE2 and PCA3 expression in paired non-malignant and tumor specimens from radical prostatectomy patients with gleason score 7 prostate cancer.(2017) LAUER, Richard C.; BARRY, Marc; WU, Jin; LEE, Ji-Hyun; MCCANCE, Dennis J.; DU, Ruofei; RAO, Arpit; DOBROFF, Andrey S.; DIAS-NETO, Emmanuel; CHEN, Isan; PASQUALINI, Renata; ARAP, Wadih
- PCA3 upregulation in prostate cancer: Analysis in a cohort of 497 subjects from TCGA.(2017) DIAS-NETO, Emmanuel; NUNES, Diana N.; THOMAS, Andrew M.; SMITH, Tracey L.; RAO, Arpit; LAUER, Richard C.; CHEN, Isan; ARAP, Wadih; PASQUALINI, Renata
- Survival of gastric cancer (GC) patients is not determined by the predominant genomic ancestry (PGA): Results from an ethnically admixed Brazilian cohort of GC patients.(2019) FREITAS, Helano C.; ARAUJO, Luiza Ferreira; NUNES, Diana Noronha; BEGNAMI, Maria D.; BARTELLI, Thais Fernanda; AMORIM, Maria Galli de; SILVA, Israel Toial da; VALIERIS, Renan; DEFELICIBUS, Alexandre; XERFAN, Mariana Pinheiro; COSTA JR., Wilson L.; JESUS, Victor Hugo Fonseca; PIZZI, Melissa; DIAS-NETO, Emmanuel
conferenceObject Clinical outcomes of patients with gastric cancer according to pre and post-neoadjuvant chemotherapy PD-L1 immunohistochemistry (IHC) expression.(2020) RIBEIRO, Heber Salvador de Castro; COSTA, Wilson Luiz da; BEGNAMI, Maria Dirlei de Souza; MELLO, Celso Abdon Lopes; NEOTTI, Tatiane; DINIZ, Alessandro Landskron; GODOY, Andre Luis; FARIAS, Igor Correa; TORRES, Silvio Melo; SILVA, Diego Greatti Vaz Vaz da; JESUS, Victor Hugo Fonseca; RIECHELMANN, Rachel Pimenta; DIAS-NETO, Emmanuel; COIMBRA, Felipe Jose Fernandez- A non-functional galanin receptor-2 in a multiple sclerosis patient(2019) GARCIA-ROSA, Sheila; TRIVELLA, Daniela B. B.; MARQUES, Vanessa D.; SERAFIM, Rodolfo B.; PEREIRA, Jose G. C.; LORENZI, Julio C. C.; MOLFETTA, Greice A.; CHRISTO, Paulo P.; OLIVAL, Guilherme S.; MARCHITTO, Vania B. T.; BRUM, Doralina G.; SABEDOT, Thais S.; NOUSHMEHR, Houtan; FARIAS, Alessandro S.; SANTOS, Leonilda M. B.; NOGUEIRA-MACHADO, Jose A.; SOUZA, Jorge E. S.; ROMANO, Camila M.; CONDE, Rodrigo M.; SANTOS, Antonio C.; GUERREIRO, Carlos T.; SCHREUDER, Willem H.; GLEBER-NETTO, Frederico O.; AMORIM, Maria; VALIERIS, Renan; SILVA, Israel Tojal da; SILVA JR., Wilson A.; NUNES, Diana N.; OLIVEIRA, Paulo S. L.; VALENTE, Valeria; ARRUDA, Maria Augusta; HILL, Stephen J.; BARREIRA, Amilton A.; DIAS-NETO, EmmanuelMultiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.