TABATHA GUTIERREZ PRIETO MARTINS ROCHA

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LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina

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Assunto: Pathology ×

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Agora exibindo 1 - 6 de 6
  • article 7 Citação(ões) na Scopus
    Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology
    (2018) SOUZA, Paola da Costa; DONDO, Patricia Suemi; SOUZA, Gabriela; LOPES, Deborah; MOSCARDI, Marcel; MARTINHO, Vinicius de Miranda; LOURENCO, Rodolfo Daniel de Mattos; PRIETO, Tabatha; BALANCIN, Marcelo Luiz; ASSATO, Aline Kawassaki; TEODORO, Walcy Rosolia; RODRIGUES, Silvia; LIMA, Mariana; CASTELLANO, Maria Vera; COLETTA, Ester; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza
    This study analyzed the type 1 and type 2 T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-beta. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-beta might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
  • article 10 Citação(ões) na Scopus
    Variants in Epithelial-Mesenchymal Transition and Immune Checkpoint Genes Are Associated With Immune Cell Profiles and Predict Survival in Non-Small Cell Lung Cancer
    (2020) PARRA, Edwin Roger; JIANG, Mei; MACHADO-RUGOLO, Juliana; YAEGASHI, Lygia Bertalha; PRIETO, Tabatha; FARHAT, Cecilia; SA, Vanessa Karen de; NAGAI, Maria Aparecida; LIMA, Vladmir Claudio Cordeiro de; TAKAGAKI, Tereza; TERRA, Ricardo; FABRO, Alexandre Todorovic; CAPELOZZI, Vera Luiza
    Context.-Identification of gene mutations that are indicative of epithelial-mesenchymal transition and a noninflammatory immune phenotype may be important for predicting response to immune checkpoint inhibitors. Objective.-To evaluate the utility of multiplex immunofluorescence for immune profiling and to determine the relationships among tumor immune checkpoint and epithelial-mesenchymal transition genomic profiles and the clinical outcomes of patients with nonmetastatic non-small cell lung cancer. Design.-Tissue microarrays containing 164 primary tumor specimens from patients with stages I to IIIA non-small cell lung carcinoma were examined by multiplex immunofluorescence and image analysis to determine the expression of programmed death ligand-1 (PD-L1) on malignant cells, CD68; macrophages, and cells expressing the immune markers CD3, CD8, CD57, CD45RO, FOXP3, PD-1, and CD20. Immune phenotype data were tested for correlations with clinicopathologic characteristics, somatic and germline genetic variants, and outcome. Results.-A high percentage of PD-L1(+) malignant cells was associated with clinicopathologic characteristics, and high density of CD3+PD-1(+) T cells was associated with metastasis, suggesting that these phenotypes may be clinically useful to identify patients who will likely benefit from immunotherapy. We also found that ZEB2 mutations were a proxy for immunologic ignorance and immune tolerance microenvironments and may predict response to checkpoint inhibitors. A multivariate Cox regression model predicted a lower risk of death for patients with a high density of CD3(+)CD45RO(+) memory T cells, carriers of allele G of CTLA4 variant rs231775, and those whose tumors do not have ZEB2 mutations. Conclusions.-Genetic variants in epithelial mesenchymal transition and immune checkpoint genes are associated with immune cell profiles and may predict patient outcomes and response to immune checkpoint blockade.
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    T Cell Profiling to Predict ""Hot"" Immunophenotype Correlates with Mutational Drivers, Epithelial Mesenchymal Transition and Outcome in Non-Small-Cell Lung Cancer
    (2018) CAPELOZZI, Vera Luiza; MACHADO, Juliana; PRIETO, Tabatha; MARTINS, Vanessa; FAHRAT, Cecilia; FABRO, Alexandre; PARRA, Edwin R.
  • article 11 Citação(ões) na Scopus
    Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value
    (2020) 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; CAPELOZZI, Vera Luiza
    Previous studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V <= 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.
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