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Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system

Abstract

The main objective of the present project is to detect genes differentially expressed in central nervous system tumors to be useful as diagnostic markers, and as predictive factors of prognosis, in order to improve the therapeutical approaches, and to find future targets for gene therapy. As specific goals, this project was designed to pick up differentially expressed among astrocytomas of different grade of malignancy, medulloblastomas/PNET of child and adult, and oligodendrogliomas with and without LOH, by SAGE and microarray analysis. The gene expression will be validated by real time PCR, and its product will be analyzed on tissue samples by immunohistochemistry. Poli and/or monoclonal antibodies will be produced whenever it will not be available commercially. Functional studies will be carried out in vitro and in vivo in immunossupressed animal. The process of methylation of the promoter region will be analyzed on hypoexpressed genes with unknown function. The question of radio and chemoresistency will be addressed on animal models. Case-control study of polymorphisms will be performed using the samples of the DNA bank organized during the Clinical Genomics Project, over the last two years. The search of genes will the emphasized on the aspect of tumoral invisibility and angiogenesis, on which a common mechanism of extracellular matrix degradation is observed, allowing the infiltration of these tumors. Therefore, a complete resection is difficult, and it explains the inefficacy of the actual surgical, radio and chemotherapeutical approaches. It is relevant to search for clues on those pathways to improve the therapeutical results. (AU)

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Scientific publications (33)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BIANCO, ANDRE MACEDO; UNO, MIYUKI; OBA-SHINJO, SUELI MIEKO; CLARA, CARLOS AFONSO; DE ALMEIDA GALATRO, THAIS FERNANDA; ROSEMBERG, SERGIO; TEIXEIRA, MANOEL JACOBSEN; NAGAHASHI MARIE, SUELY KAZUE. CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1 alpha Expression and IDH1 Mutation. Pathology & Oncology Research, v. 21, n. 2, p. 229-240, . (04/12133-6)
NAGAHASHI MARIE, SUELY KAZUE; OBA-SHINJO, SUELI MIEKO; DA SILVA, ROSELI; GIMENEZ, MARCELA; REIS, GISELE NUNES; TASSAN, JEAN-PIERRE; ROSA, JOSE CESAR; UNO, MIYUKI. Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma. PROTEOME SCIENCE, v. 14, . (04/12133-6, 12/15896-7)
CORREIA, R. L.; OBA-SHINJO, S. M.; UNO, M.; HUANG, N.; MARIE, S. K. N.. Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas. MITOCHONDRION, v. 11, n. 1, p. 48-53, . (04/12133-6)
VULCANI-FREITAS, TANIA M.; SABA-SILVA, NAJSLA; CAPPELLANO, ANDREA; CAVALHEIRO, SERGIO; MARIE, SUELI K. N.; OBA-SHINJO, SUELI M.; MALHEIROS, SUZANA M. F.; CAMINADA DE TOLEDO, SILVIA REGINA. ASPM gene expression in medulloblastoma. CHILD'S NERVOUS SYSTEM, v. 27, n. 1, p. 71-74, . (04/12133-6)
CLARA, CARLOS AFONSO; MARIE, SUELY K. N.; WALTHER DE ALMEIDA, JOSE REYNALDO; WAKAMATSU, ALDA; OBA-SHINJO, SUELI MIEKO; UNO, MIYUKI; NEVILLE, MUNRO; ROSEMBERG, SERGIO. Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1 alpha in human glioblastoma. NEUROPATHOLOGY, v. 34, n. 4, p. 343-352, . (04/12133-6)
RAMAO, ANELISA; GIMENEZ, MARCELA; LAURE, HELEN JULIE; IZUMI, CLARICE; DOS SANTOS VIDA, RODRIGO CESAR; OBA-SHINJO, SUELI; NAGAHASHI MARIE, SUELY KAZUE; ROSA, JOSE CESAR. Changes in the expression of proteins associated with aerobic glycolysis and cell migration are involved in tumorigenic ability of two glioma cell lines. PROTEOME SCIENCE, v. 10, . (98/14247-6, 04/12133-6)
DA SILVA, ROSELI; MARIE, SUELY K. N.; UNO, MIYUKI; MATUSHITA, HAMILTON; WAKAMATSU, ALDA; ROSEMBERG, SERGIO; OBA-SHINJO, SUELI M.. CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants. Clinics, v. 68, n. 2, p. 167-172, . (04/12133-6)
GIMENEZ, MARCELA; MARIE, SUELY K. N.; OBA-SHINJO, SUELI M.; UNO, MIYUKI; DA SILVA, ROSELI; LAURE, HELEN JULIE; IZUMI, CLARICE; OTAKE, ANDREIA; CHAMMAS, ROGER; ROSA, JOSE CESAR. Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA. PROTEOMICS, v. 12, n. 17, SI, p. 2632-2640, . (04/12133-6, 11/07568-7)
DA SILVA, ROSELI; UNO, MIYUKI; NAGAHASHI MARIE, SUELY K.; OBA-SHINJO, SUELI M.. LOX Expression and Functional Analysis in Astrocytomas and Impact of IDH1 Mutation. PLoS One, v. 10, n. 3, . (04/12133-6)
ARAUJO PEREIRA, BENEDITO JAMILSON; DE SANTANA JUNIOR, PEDRO AUGUSTTO; DE ALMEIDA, ANTONIO NOGUEIRA; CAVALCANTE, STELLA GONCALVES; MARTINS DE MELO, KEYDE CRISTINA; PIRES DE AGUIAR, PAULO HENRIQUE; PAIVA, WELLINGSON DA SILVA; OBA-SHINJO, SUELI MIEKO; NAGAHASHI MARIE, SUELY KAZUE. Cyclin E1 expression and malignancy in meningiomas. CLINICAL NEUROLOGY AND NEUROSURGERY, v. 190, . (04/12133-6, 13/02162-8)
FIGUEIRA MUOIO, VALERIA MARQUES; UNO, MIYUKI; OBA-SHINJO, SUELI; DA SILVA, ROSELI; ARAUJO PEREIRA, BENEDITO JAMILSON; CLARA, CARLOS; MATUSHITA, HAMILTON; MARIE, SUELY N. K.. OTX1 and OTX2 Genes in Medulloblastoma. WORLD NEUROSURGERY, v. 127, p. E58-E64, . (04/12133-6)
ISABELE FATTORI MORETTI; ROSELI SILVA; SUELI MIEKO OBA-SHINJO; PRISCILA OLIVEIRA DE CARVALHO; LAIS CAVALCA CARDOSO; ISAC DE CASTRO; SUELY KAZUE NAGAHASHI MARIE. O IMPACTO DA EXPRESSÃO DOS RECEPTORES DE INTERLEUCINA-13 NA MIGRAÇÃO CELULAR EM ASTROCITOMAS. MedicalExpress (São Paulo, online), v. 2, n. 5, . (04/12133-6, 13/06315-3, 13/02162-8)
GIMENEZ, MARCELA; NAGAHASHI MARIE, SUELY KAZUE; OBA-SHINJO, SUELI; UNO, MIYUKI; IZUMI, CLARICE; OLIVEIRA, JOAO BOSCO; ROSA, JOSE CESAR. Quantitative proteomic analysis shows differentially expressed HSPB1 in glioblastoma as a discriminating short from long survival factor and NOVA1 as a differentiation factor between low-grade astrocytoma and oligodendroglioma. BMC CANCER, v. 15, . (13/02162-8, 11/07568-7, 04/12133-6, 13/06315-3)
CARVALHO, PRISCILA O.; UNO, MIYUKI; OBA-SHINJO, SUELI M.; ROSEMBERG, SERGIO; WAKAMATSU, ALDA; DA SILVA, CLEMAR C.; TEIXEIRA, MANOEL J.; MARIE, SUELY K. N.. Activation of EGFR signaling from pilocytic astrocytomas to glioblastomas. International Journal of Biological Markers, v. 29, n. 2, p. E120-E128, . (04/12133-6)
VALENTE, VALERIA; TEIXEIRA, SILVIA A.; NEDER, LUCIANO; OKAMOTO, OSWALDO K.; OBA-SHINJO, SUELI M.; MARIE, SUELY K. N.; SCRIDELI, CARLOS A.; PACO-LARSON, MARIA L.; CARLOTTI, JR., CARLOS G.. Selection of suitable housekeeping genes for expression analysis in glioblastoma using quantitative RT-PCR. BMC MOLECULAR BIOLOGY, v. 10, . (04/12133-6)
MORETTI, ISABELE F.; LERARIO, ANTONIO M.; TROMBETTA-LIMA, MARINA; SOLA, PAULA R.; SOARES, ROSELI DA SILVA; OBA-SHINJO, SUELI M.; MARIE, SUELY K. N.. Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. SCIENTIFIC REPORTS, v. 11, n. 1, . (13/02162-8, 16/14695-9, 15/26328-8, 04/12133-6)
MOREIRA FRANCO, YOLLANDA E.; ALVES, MARIA JOSE; UNO, MIYUKI; MORETTI, ISABELE FATTORI; TROMBETTA-LIMA, MARINA; DE SIQUEIRA SANTOS, SUZANA; DOS SANTOS, ANCELY FERREIRA; ARINI, GABRIEL SANTOS; BAPTISTA, MAURICIO S.; LERARIO, ANTONIO MARCONDES; et al. Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness. CANCER & METABOLISM, v. 9, n. 1, . (13/02162-8, 20/02988-7, 15/26328-8, 13/07937-8, 04/12133-6)
MARIA JOSÉ FERREIRA ALVES; MIYUKI UNO; ROSELI DA SILVA; SUELI MIEKO OBA-SHINJO; SUELY KAZUE NAGAHASHI MARIE. EXPRESSÃO DOS TRANSPORTADORES DE AMINOÁCIDOS ASCT2 (SLC1A5) E LAT1 (SLC7A5) EM ASTROCITOMAS. MedicalExpress (São Paulo, online), v. 3, n. 6, . (04/12133-6)
CARDOSO, LAIS C.; SOARES, ROSELI DA S.; LAURENTINO, TALITA DE S.; LERARIO, ANTONIO M.; MARIE, SUELY K. N.; OBA-SHINJO, SUELI MIEKO. CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 5, . (15/03614-5, 15/03995-9, 04/12133-6, 13/02162-8)
VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; SALOMAO, KARINA BEZERRA; OLIVEIRA DE BIAGI, JR., CARLOS ALBERTO; BAUMGARTNER, MARTIN; STURM, DOMINIK; PEIXOTO LIRA, REGIA CAROLINE; MAGALHAES, TACIANI DE ALMEIDA; MILAN, MIRELLA BARONI; SILVEIRA, VANESSA DA SILVA; SAGGIORO, FABIANO PINTO; et al. A simplified approach using Taqman low-density array for medulloblastoma subgrouping. ACTA NEUROPATHOLOGICA COMMUNICATIONS, v. 7, . (13/12006-3, 14/20341-0, 14/19976-0, 04/12133-6, 13/02162-8)
LOPES, M. H.; SANTOS, T. G.; RODRIGUES, B. R.; QUEIROZ-HAZARBASSANOV, N.; CUNHA, I. W.; WASILEWSKA-SAMPAIO, A. P.; COSTA-SILVA, B.; MARCHI, F. A.; BLEGGI-TORRES, L. F.; SANEMATSU, P. I.; et al. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. Oncogene, v. 34, n. 25, p. 3305-3314, . (07/08410-2, 12/19019-0, 09/14027-2, 04/12133-6, 10/20796-6)
URIAS, URSULA; MARIE, SUELY K. N.; UNO, MIYUKI; DA SILVA, ROSELI; EVAGELINELLIS, MARIA M.; CABALLERO, OTAVIA L.; STEVENSON, BRIAN J.; SILVA, JR., WILSON A.; SIMPSON, ANDREW J.; OBA-SHINJO, SUELI M.. CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage. JOURNAL OF NEURO-ONCOLOGY, v. 119, n. 1, p. 59-70, . (04/12133-6)
FRANCO, DAIANE G.; MORETTI, ISABELE F.; MARIE, SUELY K. N.. Mitochondria Transcription Factor A: A Putative Target for the Effect of Melatonin on U87MG Malignant Glioma Cell Line. Molecules, v. 23, n. 5, . (13/02162-8, 14/17220-6, 04/12133-6)
TROMBETTA-LIMA, MARINA; BROCHADO WINNISCHOFER, SHEILA MARIA; ALMEIDA DEMASI, MARCOS ANGELO; ASTORINO FILHO, RENATO; OLIVEIRA CARREIRA, ANA CLAUDIA; WEI, BEIYANG; RIBAS, THAIS DE ASSIS; KONIG, MICHELLE SILBERSPITZ; BOWMAN-COLIN, CHRISTIAN; OBA-SHINJO, SUELI MIEKO; et al. Isolation and characterization of novel RECK tumor suppressor gene splice variants. ONCOTARGET, v. 6, n. 32, p. 33120-33133, . (04/12133-6, 01/10707-7)
VULCANI-FREITAS, TANIA MARIA; SABA-SILVA, NASJLA; CAPPELLANO, ANDREA; CAVALHEIRO, SERGIO; CAMINADA DE TOLEDO, SILVIA REGINA. Perfil de expressão do gene PRAME em meduloblastoma. Arquivos de Neuro-Psiquiatria, v. 69, n. 1, p. 9-12, . (04/12133-6)
GIMENEZ, MARCELA; DE OLIVEIRA SOUZA, VANESSA CRISTINA; IZUMI, CLARICE; BARBIERI, MANUELA R.; CHAMMAS, ROGER; OBA-SHINJO, SUELI MIEKO; UNO, MIYUKI; NAGAHASHI MARIE, SUELY KAZUE; ROSA, JOSE CESAR. Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin. PROTEOMICS, v. 10, n. 15, p. 2812-2821, . (04/12133-6)
BARBOSA, K. C.; OBA-SHINJO, S. M.; UNO, M.; CARVALHO, PO.; ROSEMBERG, S.; AGUIAR, PH. P.; CARLOTTI, C. G.; MALHEIROS, S. M. F.; TOLEDOS, S.; LOTUFO, P.; et al. Association of EGFR c.2073A > T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study. International Journal of Biological Markers, v. 23, n. 3, p. 140-146, . (04/12133-6)
MIURA, FLAVIO KEY; FERREIRA ALVES, MARIA JOSE; ROCHA, MUSSYA CISOTTO; DA SILVA, ROSELI; OBA-SHINJO, SUELI MIEKO; NAGAHASHI MARIE, SUELY KAZUE. Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma. Clinics, v. 65, n. 3, p. 305-309, . (04/12133-6)
VALENTE, VALERIA; SERAFIM, RODOLFO BORTOLOZO; DE OLIVEIRA, LEONARDO CESAR; ADORNI, FERNANDO SOARES; TORRIERI, RAUL; DA CUNHA TIRAPELLI, DANIELA PRETTI; ESPREAFICO, ENILZA MARIA; OBA-SHINJO, SUELI MIEKO; NAGAHASHI MARIE, SUELY KAZUE; PACO-LARSON, MARIA LUISA; et al. Modulation of HJURP (Holliday Junction-Recognizing Protein) Levels Is Correlated with Glioblastoma Cells Survival. PLoS One, v. 8, n. 4, . (11/05674-4, 04/12133-6)
DE ALMEIDA GALATRO, THAIS FERNANDA; UNO, MIYUKI; OBA-SHINJO, SUELI MIEKO; ALMEIDA, ANTONIO NOGUEIRA; TEIXEIRA, MANOEL J.; ROSEMBERG, SERGIO; MARIE, SUELY KAZUE N.. Differential Expression of ID4 and Its Association with TP53 Mutation, SOX2, SOX4 and OCT-4 Expression Levels. PLoS One, v. 8, n. 4, . (04/12133-6)
BETTEGOWDA, CHETAN; AGRAWAL, NISHANT; JIAO, YUCHEN; WANG, YUXUAN; WOOD, LAURA D.; RODRIGUEZ, FAUSTO J.; HRUBAN, RALPH H.; GALLIA, GARY L.; BINDER, ZEV A.; RIGGINS, CALLEN J.; et al. Exomic Sequencing of Four Rare Central Nervous System Tumor Types. ONCOTARGET, v. 4, n. 4, p. 572-583, . (04/12133-6)
UNO, MIYUKI; OBA-SHINJO, SUELI MIEKO; CAMARGO, ANAMARIA ARANHA; MOURA, RICARDO PEREIRA; DE AGUIAR, PAULO HENRIQUE; CABRERA, HECTOR NAVARRO; BEGNAMI, MARCOS; ROSEMBERG, SERGIO; TEIXEIRA, MANOEL JACOBSEN; NAGAHASHI MARIE, SUELY KAZUE. Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma. Clinics, v. 66, n. 10, p. 1747-1755, . (04/12133-6)
UNO, MIYUKI; OBA-SHINJO, SUELI MIEKO; DA SILVA, ROSELI; MIURA, FLAVIO; CLARA, CARLOS AFONSO; WALTHER DE ALMEIDA, JOSE REYNALDO; MALHEIROS, SUZANA M. F.; BIANCO, ANDRE MACEDO; BRANDT, REYNALDO; RIBAS, GUILHERME CARVALHAL; et al. IDH1 mutations in a Brazilian series of Glioblastoma. Clinics, v. 66, n. 1, p. 163-165, . (04/12133-6)

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