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Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets

Grant number: 18/20403-6
Support Opportunities:Research Projects - Thematic Grants
Duration: June 01, 2019 - May 31, 2025
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Vera Luiza Capelozzi
Grantee:Vera Luiza Capelozzi
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Edwin Roger Parra Cuentas ; Lisete Ribeiro Teixeira ; Patricia Rieken Macedo Rocco ; Pedro Leme Silva
Associated grant(s):23/01158-9 - Modeling of the extracellular matrix and the epithelial-mesenchymal transition by histomolecular gradient in pulmonary neuroendocrine neoplasia for clinical decisions, AP.R
Associated scholarship(s):23/08136-0 - Quantitative study of glycosaminoglycans and proteoglycans in the extracellular matrix of surgical specimens of malignant pleural mesothelioma., BP.IC
23/02755-0 - Evaluation of epithelial-mesenchymal transition protein expression as a new perspective in biomarkers for determining prognosis, response and resistance to targeted therapy in non-small cell lung carcinomas, BP.PD
23/01978-6 - Quantification and evaluation of matrix fibrillar structures in lung carcinoma, BP.IC
+ associated scholarships 22/06510-0 - Study of immunocellular and immunobiological profiles as emerging predictive and prognostic markers for malignant mesothelioma, BP.IC
21/05917-6 - QuaMN-Ki study: quatitification with morphometry in neuroendocrine neoplasms and Ki-67 evaluation, BP.IC
20/01758-8 - Study of cellular, subcellular (especially mitochondria) and matrix components of bronchioles, alveoli and diaphragms by electron microscopy in pre-clinical models of gene and drug therapy and ventilatory strategies in asthma and COPD, BP.TT
19/12151-0 - Evaluation of the protein expression of DLL-3 and ASCL-1 as a new perspective in biomarkers for the early diagnosis of small cell lung carcinomas, BP.PD - associated scholarships

Abstract

The prevalence and social cost of respiratory diseases such as lung cancer, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease, asthma, silicosis, and pulmonary arterial hypertension are high and some of them have few therapeutic alternatives. The therapy of most of these diseases is based on symptomatic control and not on effective cure. The present proposal has as main objective the understanding of the activation and regulation pathways of the cellular responses to insults and also the development of the underlying mechanisms in the repair and remodeling of the lesions. There is a consensus that the elucidation of the pathways and factors involved in these responses will increase the ability to identify and develop more effective treatments for disease control as proposed in this project. The project will have the participation of researchers linked to 7 different institutions: (1) University of São Paulo: Pathology Department of FMUSP-SP, (2) University of São Paulo: Rheumatology Department of FMUSP-SP, São Paulo: Department of Pathology of FMUSP-RP, (4) Federal University of Rio de Janeiro: Carlos Chagas Filho Institute of Biophysics, (5) Universidade Estadual Paulista: Department of Genetics of IBB / UNESP, (6) Hospital AC Camargo Cancer Center and (7) Hospital de Cancer de Barretos. It is worth emphasizing the active participation of emerging researchers included in the group that maintains a work association and co-authorship of different degrees and extensions, as a result of post-doctoral or postdoctoral orientation histories. Post-doctoral students, graduate students and scientific initiation, as well as laboratory technicians, will participate in different subprojects generated from this proposal already in progress. This project will also count on the collaboration of professors and researchers outside Brazil: Dr. Ignacio Wistuba and Dr. Edwin Roger Parra - The University of Texas, M.D. Anderson Cancer Center, Department of Translational Molecular Pathology, USA. Postdoctoral student (Brazil) - The University of Texas, M.D. Anderson Cancer Center, Department of Translational Molecular Pathology, USA; Prof. Dr. Sem H. Phan, University of Michigan, Ann Arbor-MI, USA. The researchers associated with this proposal propose, with knowledge and experience - in several cases jointly acquired - to advance in the investigation of biomarkers that may contribute to the development of new therapeutic strategies in respiratory diseases. (AU)

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Scientific publications (28)
(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)
BALANCIN, MARCELO LUIZ; TEODORO, WALCY ROSOLIA; BALDAVIRA, CAMILA MACHADO; PRIETO, TABATHA GUTIERREZ; FARHAT, CECILIA; VELOSA, ANA PAULA; SOUZA, PAOLA DA COSTA; YAEGASHI, LYGIA BERTALHA; AB'SABER, ALEXANDRE MUXFELDT; TAKAGAKI, TERESA YAE; et al. Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value. PATHOLOGY RESEARCH AND PRACTICE, v. 216, n. 12, . (18/20403-6)
MARTINS, VANESSA; DA SILVA, ADRIANA LOPES; TEODORO, WALCY ROSOLIA; PEREIRA VELOSA, ANA PAULA; BALANCIN, MARCELO LUIZ; CRUZ, FERNANDA FERREIRA; SILVA, PEDRO LEME; MACEDO ROCCO, PATRICIA RIEKEN; CAPELOZZI, VERA LUIZA. In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice. PATHOLOGY RESEARCH AND PRACTICE, v. 216, n. 9, . (16/21429-3, 18/20403-6)
BALANCIN, MARCELO LUIZ; TEODORO, WALCY ROSOLIA; FARHAT, CECILIA; DE MIRANDA, TOMAS JURANDIR; ASSATO, ALINE KAWASSAKI; DE SOUZA SILVA, NEILA APARECIDA; VELOSA, ANA PAULA; FALZONI, ROBERTO; AB'SABER, ALEXANDRE MUXFELDT; RODEN, ANJA C.; et al. An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma. CANCER MEDICINE, v. 9, n. 13, . (18/20403-6)
FABRO, ALEXANDRE TODOROVIC; MACHADO-RUGOLO, JULIANA; BALDAVIRA, CAMILA MACHADO; PRIETO, TABATHA GUTIERREZ; FARHAT, CECILIA; ROTEA MANGONE, FLAVIA REGINA; BATAH, SABRINA SETEMBRE; CRUVINEL, HELOISA RESENDE; ALDA, MAIARA ALMEIDA; MONTEIRO, JHONATAS SIRINO; et al. Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension. FRONTIERS IN PHARMACOLOGY, v. 12, . (15/06387-0, 18/20403-6, 15/06708-0)
PRIETO, TABATHA GUTIERREZ; BALDAVIRA, CAMILA MACHADO; MACHADO-RUGOLO, JULIANA; FARHAT, CECILIA; RIBEIRO OLIVIERI, ELOISA HELENA; DE SA, VANESSA KAREN; ABILIO DA SILVA, EDUARDO CAETANO; BALANCIN, MARCELO LUIZ; AB SABER, ALEXANDRE MUXFELDT; TAKAGAKI, TERESA YAE; et al. Pulmonary Neuroendocrine Neoplasms Overexpressing Epithelial-Mesenchymal Transition Mechanical Barriers Genes Lack Immune-Suppressive Response and Present an Increased Risk of Metastasis. FRONTIERS IN ONCOLOGY, v. 11, . (18/20403-6, 19/12151-0)
PEREIRA VELOSA, ANA PAULA; BRITO, LAIS; DE JESUS QUEIROZ, ZELITA APARECIDA; CARRASCO, SOLANGE; DE MIRANDA, JURANDIR TOMAZ; FARHAT, CECILIA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; PARRA, EDWIN ROGER; OLIVEIRA DE ANDRADE, DANIELI CASTRO; SILVA, PEDRO LEME; et al. Identification of Autoimmunity to Peptides of Collagen V alpha 1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis. FRONTIERS IN IMMUNOLOGY, v. 11, . (16/05617-4, 17/11865-3, 18/20403-6)
MARANGONI, ROBERTA GONCALVES; KORMAN, BENJAMIN D.; PARRA, EDWIN R.; VELOSA, ANA PAULA P.; BARBEIRO, V, HERMES; MARTINS, VANESSA; DOS SANTOS, ANGELA B. G.; SORIANO, FRANCISCO; TEODORO, WALCY R.; SILVA, PEDRO LEME; et al. Pathological pulmonary vascular remodeling is induced by type V collagen in a model of scleroderma. PATHOLOGY RESEARCH AND PRACTICE, v. 220, . (18/20403-6)
BRINDO DA CRUZ, ISABELE CAMARGO; VELOSA, ANA PAULA PEREIRA; CARRASCO, SOLANGE; DOS SANTOS FILHO, ANTONIO; TOMAZ DE MIRANDA, JURANDIR; POMPEU, EDUARDO; FERNANDES, TIAGO LAZZARETTI; BUENO, DANIELA FRANCO; FANELLI, CAMILA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; et al. Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, . (18/20403-6, 14/11419-5)
BALDAVIRA, CAMILA M.; MACHADO-RUGOLO, JULIANA; PRIETO, TABATHA G.; BASTOS, DANIEL R.; BALANCIN, MARCELO; AB'SABER, ALEXANDRE M.; YAEGASHI, LYGIA B.; SOUZA, PAOLA C.; FARHAT, CECILIA; TAKAGAKI, TERESA Y.; et al. The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma. JOURNAL OF THORACIC DISEASE, v. 13, n. 2, . (18/20403-6)
CHINOCA, J.; ANDRADE, D. S.; MENDES, A.; DE MARCHI, P.; PRIETO, T. G.; BALDAVIRA, C. M.; FARHAT, C.; MARTINS, J. R. M.; NADER, H. B.; CARRARO, D. M.; et al. Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, p. 9-pg., . (15/26642-4, 18/20403-6)
SILVA, CARLA M.; ORNELLAS, DEBORA S.; ORNELLAS, FELIPE M.; SANTOS, RAQUEL S.; V. MARTINI, SABRINA; FERREIRA, DEBORA; MUILER, CAROLINE; CRUZ, FERNANDA F.; TAKIYA, CHRISTINA M.; ROCCO, PATRICIA R. M.; et al. Early effects of bone marrow-derived mononuclear cells on lung and kidney in experimental sepsis. Respiratory Physiology & Neurobiology, v. 309, p. 10-pg., . (18/20403-6)
FELIX, NATHANE S.; MAIA, LIGIA A.; ROCHA, NAZARETH N.; RODRIGUES, GISELE C.; MEDEIROS, MAYCK; DA SILVA, LETICIA A.; BALDAVIRA, CAMILA M.; FERNEZLIAN, SANDRA DE M.; EHER, ESMERALDA M.; CAPELOZZI, VERA L.; et al. Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome. FRONTIERS IN PHYSIOLOGY, v. 13, p. 13-pg., . (18/20403-6)
XAVIER, PAULO HENRIQUE; FONSECA, ANA CAROLINA FERNANDES; GONCALVES, LEONARDO ALVES; DE SOUSA, GISELLE CAVALHO; DA SILVA, MARIANA COELHO; SACRAMENTO, RAQUEL FERREIRA DE MAGALHAES; SAMARY, CYNTHIA DOS SANTOS; MEDEIROS, MAYCK; CRUZ, FERNANDA FERREIRA; CAPELOZZI, VERA LUIZA; et al. Lung Injury Is Induced by Abrupt Increase in Respiratory Rate but Prevented by Recruitment Maneuver in Mild Acute Respiratory Distress Syndrome in Rats. ANESTHESIOLOGY, v. 138, n. 4, p. 16-pg., . (18/20403-6)
C.M. BALDAVIRA; L.F. GOMES; L.T. DE LA CRUZ; D.A. MARIA; V.L. CAPELOZZI. In vivo evidence of angiogenesis inhibition by β2-glycoprotein I subfractions in the chorioallantoic membrane of chicken embryos. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, . (18/20403-6)
J. CHINOCA; D.S. ANDRADE; A. MENDES; P. DE MARCHI; T.G. PRIETO; C.M. BALDAVIRA; C. FARHAT; J.R.M. MARTINS; H.B. NADER; D.M. CARRARO; et al. Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum. Brazilian Journal of Medical and Biological Research, v. 55, . (18/20403-6, 15/26642-4)
DE MIRANDA, JURANDIR TOMAZ; BRINGEL, FABIANA DE ANDRADE; VELOSA, ANA PAULA PEREIRA; PROTOCEVICH, VERONICA; FERNEZLIAN, SANDRA DE MORAIS; SILVA, PEDRO LEME; CAPELOZZI, VERA LUIZA; MATHOR, MONICA BEATRIZ; TEODORO, WALCY ROSOLIA. Sterilized human skin graft with a dose of 25 kGy provides a privileged immune and collagen microenvironment in the adhesion of Nude mice wounds. PLoS One, v. 17, n. 1, p. 15-pg., . (18/20403-6)
BALDAVIRA, CAMILA MACHADO; PRIETO, TABATHA GUTIERREZ; MACHADO-RUGOLO, JULIANA; DE MIRANDA, JURANDIR TOMAZ; DE OLIVEIRA, LIZANDRE KEREN RAMOS; VELOSA, ANA PAULA PEREIRA; TEODORO, WALCY ROSOLIA; AB'SABER, ALEXANDRE; TAKAGAKI, TERESA; CAPELOZZI, VERA LUIZA. Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions. FRONTIERS IN ONCOLOGY, v. 12, p. 25-pg., . (18/20403-6)
DE MORAIS, JYMENEZ; VELOSA, ANA PAULA P.; ANDRADE, PRISCILA C.; FREDIANI, DENISE; CARRASCO, SOLANGE; QUEIROZ, ZELITA A. DE JESUS; MARTIN, PATRICIA; SAITO, RENATA F.; ELIAS, VITORIA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; et al. Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 20, p. 14-pg., . (18/20403-6, 18/00415-0, 21/13220-5)
PRIETO, TABATHA GUTIERREZ; MACHADO-RUGOLO, JULIANA; BALDAVIRA, CAMILA MACHADO; VELOSA, ANA PAULA PEREIRA; TEODORO, WALCY ROSOLIA; AB SABE, ALEXANDRE MUXFELDT; CAPELOZZI, VERA LUIZA. The Fibrosis-Targeted Collagen/Integrins Gene Profile Predicts Risk of Metastasis in Pulmonary Neuroendocrine Neoplasms. FRONTIERS IN ONCOLOGY, v. 11, . (18/20403-6, 19/12151-0)
FELIX, RENATO GONCALVES; CARVALHO BOVOLATO, ANA LIVIA; COTRIM, ONDINA SILVIA; LEAO, PATRICIA DOS SANTOS; BATAH, SABRINA SETEMBRE; GOLIM, MARJORIE DE ASSIS; VELOSA, ANA PAULA; TEODORO, WALCY; MARTINS, VANESSA; CRUZ, FERNANDA FERREIRA; et al. Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I-and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis. HISTOLOGY AND HISTOPATHOLOGY, v. 35, n. 3, p. 289-301, . (11/09181-2, 18/20403-6, 13/14277-4, 12/03543-2, 12/07040-5)
BALDAVIRA, C. M.; GOMES, L. F.; DE LA CRUZ, L. T.; MARIA, D. A.; CAPELOZZI, V. L.. In vivo evidence of angiogenesis inhibition by beta(2)-glycoprotein I subfractions in the chorioallantoic membrane of chicken embryos. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, . (18/20403-6)
VASWANI, CHIRAG M.; VARKOUHI, AMIR K.; GUPTA, SAHIL; EKTESABI, AMIN M.; TSOPORIS, JAMES N.; YOUSEF, SADIYA; PLANT, PAMELA J.; DA SILVA, ADRIANA L.; CEN, YUCHEN; TSENG, YI-CHIEH; et al. Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury. MOLECULAR THERAPY, v. 31, n. 9, p. 21-pg., . (18/20403-6)
MACHADO-RUGOLO, J.; BALDAVIRA, C. M.; PRIETO, T. G.; OLIVIERI, E. H. R.; FABRO, A. T.; RAINHO, C. A.; CASTELLI, E. C.; RIBOLLA, P. E. M.; AB'SABER, A. M.; TAKAGAKI, T.; et al. Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort. Brazilian Journal of Medical and Biological Research, v. 56, p. 11-pg., . (18/20403-6, 19/12151-0)
MACHADO-RUGOLO, J.; BALDAVIRA, C. M.; PRIETO, T. G.; OLIVIERI, E. H. R.; FABRO, A. T.; RAINHO, C. A.; CASTELLI, E. C.; RIBOLLA, P. E. M.; AB'SABER, A. M.; TAKAGAKI, T.; et al. Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, p. 10-pg., . (19/12151-0, 18/20403-6)
MACHADO-RUGOLO, JULIANA; PRIETO, TABATHA GUTIERREZ; FABRO, ALEXANDRE TODOROVIC; PARRA CUENTAS, EDWIN ROGER; SA, VANESSA KAREN; BALDAVIRA, CAMILA MACHADO; RAINHO, CLAUDIA APARECIDA; CASTELLI, ERICK C.; FARHAT, CECILIA; TAKAGAKI, TERESA YAE; et al. Relevance of PD-L1 Non-Coding Polymorphisms on the Prognosis of a Genetically Admixed NSCLC Cohort. PHARMACOGENOMICS & PERSONALIZED MEDICINE, v. 14, p. 239-252, . (18/20403-6, 13/14277-4)
TEODORO, WALCY ROSOLIA; DE JESUS QUEIROZ, ZELITA APARECIDA; DOS SANTOS, LAIS ARAUJO; CATANOZI, SERGIO; DOS SANTOS FILHO, ANTONIO; BUENO, CLEONICE; VENDRAMINI, MARGARETE B. G.; FERNEZLIAN, SANDRA DE MORAIS; EHER, ESMERALDA M.; SAMPAIO-BARROS, PERCIVAL D.; et al. Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity. ARTHRITIS RESEARCH & THERAPY, v. 21, n. 1, . (18/24210-8, 18/20403-6, 16/05617-4, 18/00415-0)
S.M. FERNEZLIAN; C.M. BALDAVIRA; M.L.F. DE SOUZA; C. FARHAT; A.F. DE VILHENA; J.C.N. PEREIRA; J.R.M. DE CAMPOS; T. TAKAGAKI; M.L. BALANCIN; A.M. AB'SABER; et al. A semi-automated microscopic image analysis method for scoring Ki-67 nuclear immunostaining. Brazilian Journal of Medical and Biological Research, v. 56, . (23/02755-0, 18/20403-6)
T.G. PRIETO; C.M. BALDAVIRA; J. MACHADO-RUGOLO; E.H.R. OLIVIERI; E.C.A. DA SILVA; V.G. SILVA; A.M. AB'SABER; T.Y. TAKAGAKI; V.L. CAPELOZZI. Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins. Brazilian Journal of Medical and Biological Research, v. 56, . (19/12151-0, 18/20403-6)

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