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INCT 2014: on Oncogenomics and Therapeutic Inovations

Abstract

INCiTO-INOTE will continue to support the scientific program previously created by the INCiTO, exploring bench-to-bedside-to-bench concepts, in order to face the challenges that are still limiting cancer prevention, diagnosis and treatment. The Institute will explore its large experience in genetics, epigenetics “comics”, bioinformatics and biomarkers to focus in areas where it can be worldwide competitive and add relevant contribution 10 science and innovation in oncology. Hereditary Cancer Syndromes were one of the major areas studied in the previously project. The present proposal will continue to boost efforts to investigate the clinical, epidemiological and molecular aspects of these syndromes, and also to identify new cancer susceptibility genes. This strategy will allow to proper follow the large percentage of patients; particularly women that are negative for the most frequent mutations but are certainly carriers of genetic alterations that lead to increased cancer risk. INCiTO-INOTE will also address rare tumors, which together represent 22-25% of all cancers and restrict information about their biological and genetic aspects are available. These tumors present worse prognosis when compared to more prevalent tumors, mainly due to the limited knowledge of their biology and the lack of clinical studies that can improve treatment efficiency. Furthermore, the lack of epidemiological studies on this topic results in a blurred picture of the impact of these diseases in our society. Indeed, INCiTO-INOTE will establish the Brazilian Initiative in Rate Tumors (BIRT) and support the Latin American Renal Cancer Group (LARCG) with the aim to organize what could be one of the largest cohorts of rare tumors in the world. The first xenograft bank from rare tumors in South America will be established. Allowing conduct pre-clinical trials and the development of more effective treatments. The study of these tumors offers a unique opportunity in bringing improvements in patient care and produce cutting-edge knowledge. Resistance to cancer treatment is one of the main challenges in current oncology. The absence of predictor biomarkers to access drug resistance hampers efficient treatment and exposes patients to ineffective toxic agents, decreasing their quality of life and increasing the costs of cancer treatment. The INCiTO-INOTE will focus on identifying biomarkers in liquid biopsies obtained from patients receiving chemotherapy or target drugs. These information will be gathered and integrated to generate a very important tool for identification and validation of potential biomarkers for drug resistance. The INCiTO-INOTE established a partnership with the INCT for Diagnostics in Public Health to promote technology transfer, and nationalization of the main genetic diagnostic tests, aiming to reduce costs and the dependence of imported products. In addition, this collaboration will improve patient’s access to personalized medicine. INCT-Open Access Medical Chemistry and The National Institute of Structural Biology and Bioimaging (INBEB) will work with INCiTO-INOTE to perform functional characterization of mutated gene products associated with HCS and rare tumors. A platform that allowed the evaluation of the importance of the microbiome for the effects caused by alcohol and tobacco in the oral mucosa and the disbiosis in rectal carcinomas was developed by INCiTO-INOTE Now, in partnership with the biotechnology company NEOPROSPECTA, the studies on the microbiome of rare tumors will be complemented, by the analysis of protozoa, fungi and viruses and their possible roles in rare tumors, including the possible identification of new etiological entities associated to tumor development. A start-up company at Federal University of Paraná “Imunova Análises Biológicas Ltda.” will be engaged in the generation of immunobiological reagents, including monoclonal antibodies to be employed both in conventional diagnostic routines (immunohistochemistry and flow cytometry) and coupled bioelectrodes to detect tumoral antigens by electrochemical devices (collaborative project with SENAl Institute for Electrochemistry, Curitiba, Paraná). Immunohistochemistry and FISH tests for new biomarkers will be developed in association with Roche-Ventana. INCiTO-INOTE will partner with the INCT in Basic and Applied Optics For Life Science 10 conduct clinical tests for validation of photonic-based devices that will improve cancer diagnosis and treatment with lower cost solutions. The INCiTO-INOTE will expand the contribution in Education for graduate, undergraduate students, professionals, teachers and students from public schools and for the general public. A number of dissemination actions aimed at having an impact both on publicizing scientific excellence and on increasing the public awareness on cancer risk and prevention strategies is in our plans. Our proposal is to use the technological potential in understanding and adoption of concepts of medical needs and products for the benefit of cancer patients and society. (AU)

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Scientific publications (21)
(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)
TORRES, JACQUELINE APARECIDA; BRITO, ANGELO BORSARELLI CARVALHO; SILVA, VIRGILIO SOUZA E; MESSIAS, IARA MONIQUE; BRAUN, ALEXCIA CAMILA; RUANO, ANNA PAULA CARRETA; BUIM, MARCILEI E. C.; CARRARO, DIRCE MARIA; CHINEN, LUDMILLA THOME DOMINGOS. CD47 Expression in Circulating Tumor Cells and Circulating Tumor Microemboli from Non-Small Cell Lung Cancer Patients Is a Poor Prognosis Factor. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 15, p. 16-pg., . (13/23277-8, 14/50943-1, 21/04920-3, 19/18100-8)
SILVA, VIRGILIO SOUZA E; ABDALLAH, EMNE ALI; FLORES, BIANCA DE CASSIA TRONCARELLI; BRAUN, ALEXCIA CAMILA; COSTA, DANIELA DE JESUS FERREIRA; RUANO, ANNA PAULA CARRETA; GASPARINI, VANESSA ALVES; SILVA, MARIA LETICIA GOBO; MENDES, GUSTAVO GOMES; CLARO, LAURA CAROLINA LOPEZ; et al. Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer. CELLS, v. 10, n. 6, . (14/50943-1)
STAMBONI, MERIN BARBARA; DE MELLO GOMES, AGATHA NAGLI; DE SOUZA, MILENA MONTEIRO; OLIVEIRA, KATIA KLUG; JOCA ARRUDA, CLAUDIA FABIANA; DE PAULA, FERNANDA; BETTIM, BARBARA BELTRAME; MARQUES, MARCIA MARTINS; KOWALSKI, LUIZ PAULO; LOPES PINTO, CLOVIS ANTONIO; et al. Aquaporin 1, 3, and 5 Patterns in Salivary Gland Mucoepidermoid Carcinoma: Expression in Surgical Specimens and an In Vitro Pilot Study. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 4, . (11/02051-6, 14/50943-1)
BESERRA, ADRIANO O.; ESTEVAN, ETHIENE C.; BEZERRA, STEPHANIA M.; TORREZAN, GIOVANA T.; IKEGAMI, AMANDA; DELLE, HUMBERTO; CUNHA, ISABELA W.; MEIRA, ISABELLA T.; CARRARO, DIRCE M.; LARA, PRIMO N., JR.; et al. Patient-Derived Renal Cell Carcinoma Xenografts Capture Tumor Genetic Profiles and Aggressive Behaviors. KIDNEY CANCER, v. 6, n. 1, p. 12-pg., . (14/50943-1, 15/50428-2)
PAIXAO, DANIELE; TORREZAN, GIOVANA TARDIN; SANTIAGO, KARINA MIRANDA; FORMIGA, MARIA NIRVANA; AHUNO, SAMUEL TERKPER; DIAS-NETO, EMMANUEL; TOJAL DA SILVA, ISRAEL; FOULKES, WILLIAM D.; POLAK, PAZ; CARRARO, DIRCE MARIA. Characterization of genetic predisposition to molecular subtypes of breast cancer in Brazilian patients. FRONTIERS IN ONCOLOGY, v. 12, p. 14-pg., . (14/50943-1)
DE CARVALHO, NATHALIA DE ANGELIS; NIITSUMA, BIANCA NAOMI; KOZAK, VANESSA NASCIMENTO; COSTA, FELIPE D'ALMEIDA; DE MACEDO, MARIANA PETACCIA; CATIN KUPPER, BRUNA ELISA; GOBO SILVA, MARIA LETICIA; FORMIGA, MARIA NIRVANA; VOLC, SAHLUA MIGUEL; AGUIAR JUNIOR, JR., SAMUEL; et al. Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association withMSH2Germline Pathogenic Variants. CANCERS, v. 12, n. 7, . (18/06269-5, 14/50943-1)
SIMOES, MARIA FERNANDA EVANGELISTA; DA COSTA, ALEXANDRE ANDRE BALIEIRO ANASTACIO; SILVA, TULLIO NOVAES; FERNANDES, LIZIEUX; BOVOLIM, GRAZIELE; TORREZAN, GIOVANA TARDIN; CARRARO, DIRCE MARIA; BAIOCCHI, GLAUCO; MENEZES, ADEMIR NARCIZO OLIVEIRA; SANTANA DOS SANTOS, ELIZABETH; et al. Case Report of Small Cell Carcinoma of the Ovary, Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition. CURRENT ONCOLOGY, v. 29, n. 2, p. 12-pg., . (14/50943-1, 18/06269-5)
DE CAMPOS, NAJLA SANTOS PACHECO; DE OLIVEIRA BESERRA, ADRIANO; PEREIRA, PEDRO HENRIQUE BARBOSA; CHAVES, ALEXANDRE SILVA; FONSECA, FERNANDO LUIZ AFFONSO; DA SILVA MEDINA, TIAGO; DOS SANTOS, TIAGO GOSS; WANG, YUFEI; MARASCO, WAYNE ANTHONY; SUAREZ, ELOAH RABELLO. Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 10, p. 17-pg., . (14/50943-1, 18/14034-8, 18/17656-0, 18/25541-8)
PORTO, ANA CAROLINA; BLUMETTI, TATIANA PINTO; CALSAVARA, VINICIUS FERNANDO; TORREZAN, GIOVANA TARDIN; ANDRADE DE PAULA, CLAUDIA ALESSANDRA; LELLIS, RUTE; DUPRAT NETO, JOAO PEDREIRA; CARRARO, DIRCE MARIA; TAVOLONI BRAGA, J. CASAGRANDE. A cross-sectional study of clinical, dermoscopic, histopathological, and molecular patterns of scalp melanoma in patients with or without androgenetic alopecia. SCIENTIFIC REPORTS, v. 12, n. 1, p. 10-pg., . (19/05098-5, 14/50943-1)
MORENO, MARCELO; OLIVEIRA, JULIA SALLES; BRIANESE, RAFAEL CANFIELD; DE CASTRO, DOUGLAS GUEDES; SANCHES, SOLANGE MORAES; TORREZAN, GIOVANA TARDIN; SANTIAGO, KARINA MIRANDA; DE BROT, MARINA; CORDEIRO DE LIMA, VLADMIR CLAUDIO; ALVES MAKDISSI, FABIANA BARONI; et al. Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer. CANCER MEDICINE, v. N/A, p. 13-pg., . (13/23277-8, 14/50943-1)
MELLO, CELSO ABDON; BATISTA CAMPOS, FERNANDO AUGUSTO; SANTOS, TIAGO GOSS; GOBO SILVA, MARIA LETICIA; TORREZAN, GIOVANA TARDIN; COSTA, FELIPE D'ALMEIDA; FORMIGA, MARIA NIRVANA; NICOLAU, ULISSES; NASCIMENTO, ANTONIO GERALDO; SILVA, CASSIA; et al. Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy. CANCERS, v. 13, n. 3, . (14/50943-1, 18/06269-5, 18/25541-8)
KINKER, G. S.; OSTROWSKI, L. H.; RIBEIRO, P. A. C.; CHANOCH, R.; MUXEL, S. M.; TIROSH, I.; SPADONI, G.; RIVARA, S.; MARTINS, V. R.; SANTOS, T. G.; et al. MT1 and MT2 melatonin receptors play opposite roles in brain cancer progression. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 99, n. 2, . (14/23830-1, 14/27287-0, 13/13691-1, 17/24287-8, 14/50943-1, 15/23348-8)
PINERO, TAMARA ALEJANDRA; SOUKARIEH, OMAR; ROLAIN, MARION; ALVAREZ, KARIN; LOPEZ-KOSTNER, FRANCISCO; TORREZAN, GIOVANA TARDIN; CARRARO, DIRCE MARIA; DE OLIVEIRA NASCIMENTO, IVANA LUCIA; BOMFIM, THAIS FERREIRA; MACHADO-LOPES, TAISA MANUELA BONFIM; et al. MLH1 intronic variants mapping to+5 position of splice donor sites lead to deleterious effects on RNA splicing. FAMILIAL CANCER, v. 19, n. 4, . (14/50943-1)
TAKENAKA, ISABELLA KUNIKO T. M.; BARTELLI, THAIS F.; DEFELICIBUS, ALEXANDRE; SENDOYA, JUAN M.; GOLUBICKI, MARIANO; ROBBIO, JUAN; SERPA, MARIANNA S.; BRANCO, GABRIELA P.; SANTOS, LUANA B. C.; CLARO, LAURA C. L.; et al. Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer. FRONTIERS IN ONCOLOGY, v. 12, p. 16-pg., . (14/50943-1, 13/23277-8)
KINKER, GABRIELA SARTI; VITIELLO, GLAUCO AKELINGHTON FREIRE; FERREIRA, WALLAX AUGUSTO SILVA; CHAVES, ALEXANDRE SILVA; CORDEIRO DE LIMA, VLADMIR CLAUDIO; MEDINA, TIAGO DA SILVA. B Cell Orchestration of Anti-tumor Immune Responses: A Matter of Cell Localization and Communication. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, . (18/14034-8, 19/25129-2, 14/50943-1)
ALVES DE CASTRO, JOAO VICTOR; D'ALMEIDA COSTA, FELIPE; TORREZAN, GIOVANA TARDIN; CARRARO, DIRCE MARIA; NICOLAU, ULISSES RIBALDO; DO NASCIMENTO, ANTONIO GERALDO. TRK-rearranged mesenchymal tumour with epithelioid features: expanding the morphological spectrum of NTRK-fused neoplasm. Histopathology, v. 80, n. 4, . (14/50943-1)
FIDALGO, FELIPE; TORREZAN, GIOVANA TARDIN; SOARES DE SA, BIANCA COSTA; DE FIGUEIREDO BARROS, BRUNA DURAES; MOREDO, LUCIANA FACURE; VALIERIS, RENAN; DE SOUZA, SANDRO J.; DUPRAT, JOAO PEREIRA; VICTORINO KREPISCHI, ANA CRISTINA; CARRARO, DIRCE MARIA. Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families. PLoS One, v. 17, n. 1, p. 16-pg., . (14/50943-1)
RIECHELMANN, RACHEL P.; SOARES, DIOGO C.; DIAS, CARLA; CARRARO, DIRCE M.; TORREZAN, GIOVANA. Li-Fraumeni-associated pancreatic neuroendocrine tumour and XAF1 p.Glu134Ter risk modifier variant. ECANCERMEDICALSCIENCE, v. 16, p. 5-pg., . (14/50943-1, 18/06269-5)
BATISTA CAMPOS, FERNANDO AUGUSTO; ROULEAU, ETIENNE; TORREZAN, GIOVANA TARDIN; CARRARO, DIRCE MARIA; CASALI DA ROCHA, JOSE CLAUDIO; MANTOVANI, HIGOR KASSOUF; DA SILVA, LEONARDO ROBERTO; BUENO DE TOLEDO OSORIO, CYNTHIA APARECIDA; SANCHES, SOLANGE MORAES; CAPUTO, SANDRINE M.; et al. Genetic Landscape of Male Breast Cancer. CANCERS, v. 13, n. 14, . (14/50943-1)
VITIELLO, GLAUCO AKELINGHTON FREIRE; FERREIRA, WALLAX AUGUSTO SILVA; CORDEIRO DE LIMA, VLADMIR CLAUDIO; MEDINA, TIAGO DA SILVA. Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment. FRONTIERS IN IMMUNOLOGY, v. 12, . (20/10299-7, 14/50943-1, 18/14034-8)
TRONCARELLI FLORES, BIANCA C.; SOUZA E SILVA, VIRGILIO; ABDALLAH, EMNE ALI; MELLO, CELSO A. L.; GOBO SILVA, MARIA LETICIA; MENDES, GUSTAVO GOMES; BRAUN, ALEXCIA CAMILA; AGUIAR JUNIOR, SAMUEL; DOMINGOS CHINEN, LUDMILLA THOME. Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients. CELLS, v. 8, n. 7, . (14/50943-1)

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