EMMANUEL DIAS NETO
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
59 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 59
- Da arte de fazer ciência e de comer jabuticabas – Uma homenagem ao Prof. Dr. Ricardo Renzo Brentani(2012) DIAS-NETO, Emmanuel; GATTAZ, Wagner E.
- Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling(2016) THOMAS, Andrew M.; JESUS, Eliane C.; LOPES, Ademar; AGUIAR JR., Samuel; BEGNAMI, Maria D.; ROCHA, Rafael M.; CARPINETTI, Paola Avelar; CAMARGO, Anamaria A.; HOFFMANN, Christian; FREITAS, Helano C.; SILVA, Israel T.; NUNES, Diana N.; SETUBAL, Joao C.; DIAS-NETO, EmmanuelSporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.
- 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.
- Mutational Signatures Driven by Epigenetic Determinants Enable the Stratification of Patients with Gastric Cancer for Therapeutic Intervention(2021) BUTTURA, Jaqueline Ramalho; SANTOS, Monize Nakamoto Provisor; VALIERIS, Renan; DRUMMOND, Rodrigo Duarte; DEFELICIBUS, Alexandre; LIMA, Joao Paulo; CALSAVARA, Vinicius Fernando; FREITAS, Helano Carioca; LIMA, Vladmir C. Cordeiro de; BARTELLI, Thais Fernanda; WIEDNER, Marc; ROSALES, Rafael; GOLLOB, Kenneth John; LOIZOU, Joanna; DIAS-NETO, Emmanuel; NUNES, Diana Noronha; SILVA, Israel Tojal daSimple Summary Mutational signatures due to DNA mismatch repair deficiency (dMMR) is common in many cancers. However, the prognostic value of dMMR-associated mutational signatures remains to be assessed. Here, we performed a de novo extraction of mutational signatures in a cohort of 787 patients with gastric cancer. We detected three dMMR-related signatures, one of which clearly discriminates tumors with MLH1 gene silencing through hypermethylation of its promoter. We showed evidence that classification based on mutational signature exposure can be used to identify groups of patients with common clinical, immunological, and mutational features related directly to better prognosis. DNA mismatch repair deficiency (dMMR) is associated with the microsatellite instability (MSI) phenotype and leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Various mutational signatures directly linked to dMMR have been described for primary cancers. To investigate which mutational signatures are associated with prognosis in gastric cancer, we performed a de novo extraction of mutational signatures in a cohort of 787 patients. We detected three dMMR-related signatures, one of which clearly discriminates tumors with MLH1 gene silencing caused by promoter hypermethylation (area under the curve = 98%). We then demonstrated that samples with the highest exposure of this signature share features related to better prognosis, encompassing clinical and molecular aspects and altered immune infiltrate composition. Overall, the assessment of the prognostic value and of the impact of modifications in MMR-related genes on shaping specific dMMR mutational signatures provides evidence that classification based on mutational signature exposure enables prognosis stratification.
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