TERESA YAE TAKAGAKI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort(2023) 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.; NAGAI, M. A.; CAPELOZZI, V. L.TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early -stage resected EGFR-mutated NSCLC.
conferenceObject Immune Profiling Data and Mutational Status Improves Prediction of Risk of Death in Non-Small Cell Lung Carcinoma(2019) PARRA, E.; JANG, M.; MACHADO-RUGOLO, J.; FARHAT, C.; NAGAI, M.; TAKAGAKI, T.; TERRA, R.; FABRO, A.; CAPELOZZI, V.conferenceObject Hyaluronan and its impact in the screening and diagnosis of lung cancer patients(2012) RANGEL, M. P.; SA, V. K. de; MARTINS, J. R. Maciel; PARRA, E. R.; TAKAGAKI, T.; LONGATTO FILHO, A.; REIS, R.; CARRARO, D. M.; CAPELOZZI, V. L.Introduction: Hyaluronic Acid (HA) concentration is elevated in several cancers, but there is no data regarding its concentration related to lung cancer. In this study, we examined the HA concentrations in the tissue and in the sputum of lung cancer patients and its impact on the screening and diagnosis of the disease. Materials and Methods: HA was examined in tissue samples of 45 patients and sputum samples of 90 lung cancer patients. The controls were 25 COPD patients and 15 healthy controls. All the patients and controls underwent a sputum induction. Tissue and sputum samples were incubated with a proteolytic enzyme. The levels of HA were measured by a noncompetitive ELISA-like fluorometric assay. Results: A significant different concentration pattern of HA in the tissue was found between tumoral and non-tumoral samples (P < 0.001). Equally significant was the difference found in the sputum among lung cancer, COPD and healthy individuals (P < 0.001). ROC curve between lung cancer and healthy volunteers furnished an area of 0.821. Assuming a cut-off value of 31.44 ng/mg, the specificity was 100% and the sensitivity was 51%. ROC curve to distinguish COPD patients from lung cancer patients showed an area of 0.698 and the cut-off value of 48.3 ng/mg presented 100% specificity and 33% sensitivity. Conclusion: The results presented suggest a possible role of HA on lung cancer development as well as a promising role as a novel screening and diagnostic marker in the sputum for differentiating normal from lung cancer patients.- Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor(2022) 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.; NAGAI, M. A.; CAPELOZZI, V. L.The common epidermal growth factor receptor (EGFR) mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-tyrosine kinase inhibitors (EGFR-TKI). However, the clinical outcome and response to treatment for many other rarer mutations are still unclear. In this study, we report the results of Brazilian patients in stage IB-IIIA non-small cell lung cancer (NSCLC) following complete resection with minimal residual disease and EGFR mutations treated with adjuvant chemotherapy and/or EGFR-TKIs. The frequency of EGFR mutations was investigated in 70 cases of early stage NSCLC. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, as well as in exons 3, 7, 14, 16, 22, 27, and 28, and/or the presence of different mutations in a single tumor (complex mutations) are considered rare. EGFR mutations were detected in 23 tumors (32.9%). Fourteen cases carried rare mutations and were treated with platinum-based chemotherapy and two cases were treated with erlotinib. The clinical outcome is described case by case with references to the literature. Notably, we found two rare EGFR mutations and one of them with an unknown response to chemotherapy and/or EGFR-TKIs. We have provided complementary information concerning the clinical outcome and treatment of patients with early stage NSCLC for several rare EGFR mutations not previously or only rarely reported. Description of cases harboring rare mutations can support the decision-making process in this subset of patients.
- A semi-automated microscopic image analysis method for scoring Ki-67 nuclear immunostaining(2023) FERNEZLIAN, S. M.; BALDAVIRA, C. M.; SOUZA, M. L. F. de; FARHAT, C.; VILHENA, A. F. de; PEREIRA, J. C. N.; CAMPOS, J. R. M. de; TAKAGAKI, T.; BALANCIN, M. L.; AB'SABER, A. M.; CAPELOZZI, V. L.Nuclear proliferation marker MIB-1 (Ki-67) immunohistochemistry (IHC) is used to examine tumor cell proliferation. However, the diagnostic or prognostic value of the Ki-67 nuclear staining intensity and location, defined as nuclear gradient (NG), has not been assessed. This study examined the potential association between Ki-67 NG and cell cycle phases and its effect on the prognosis of pulmonary typical carcinoid (PTC) tumors. We propose a method for classifying the NG of Ki-67 during the cell cycle and compare the results between PTC, pulmonary adenocarcinoma (PAD), and breast ductal carcinoma (BDC). A literature review and objective analysis of IHC-stained paraffin sections were used to determine the Ki-67 labeling index and composed a stratification of the NG into NG1, NG2, and NG3/4 categories. A semi-automated image analysis protocol was established to determine the Ki-67 NG in PTC, PAD, and BDC. High intraobserver consistency and moderate interobserver agreement were achieved in the determination of Ki-67 NG in tumor specimens. NG1 and NG2 were lower in PTC than in PAD and BDC. Cox multivariate analysis of PTC after adjusting for age and number of metastatic lymph nodes showed that Ki-67 NG1 and NG2 significantly predicted clinical outcomes. The semi-automated method for quantification of Ki-67 nuclear immunostaining proposed in this study could become a valuable diagnostic and prognostic tool in PTC.
conferenceObject Assessment of PDL1 and Immunoprofiling Using Multiplex Quantitative Immunofluorescence in Lung Cancer: Clinical Implications(2017) PRIETO, T.; FAHRAT, C.; TAKAGAKI, T.; RODRIGUEZ-CANALES, J.; WISTUBA, I.; CAPELOZZI, V.; CUENTAS, E. ParraconferenceObject DLL-3 and ASCL-1 Expression Emerge as Promising Therapeutic Targets in High-Grade Neuroendocrine Lung Tumors: A Preliminary Study(2021) PRIETO, T.; BALDAVIRA, C. Machado; ABSABER, A.; TAKAGAKI, T.; CAPELOZZI, V.- CNS Metastases of Pulmonary Adenocarcinoma Harboring EGFR-Activating Mutations: a Multidisciplinary Approach, Including EGFR-TKis(2017) HARADA, G.; BONADIO, R.; MARTA, G.; TAKAHASHI, T.; TAKAGAKI, T.; CASTRO JR., G. De
conferenceObject Mutation profile and protein expression for predictive testing in lung adenocarcinoma: A study of 200 patients from Brazil(2016) MACHADO, J. R.; FABRO, A. T.; ASCHERI, D.; LEAO, P. d. Santos; SANTOS, A. L. dos; SA, V. K. de; RAINHO, C. A.; CUENTAS, E. R. Para; TAKAGAKI, T.; CAPELOZZI, V. L.- Detection of sputum cofilin-1 as indicator of malignancy(2018) RANGEL, M.P.; ANTONANGELO, L.; ACENCIO, M.M.P.; FARIA, C.S.; DE SÁ, V.K.; LEÃO, P.S.; FARHAT, C.; FABRO, A.T.; LONGATTO FILHO, A.; REIS, R.M.; TAKAGAKI, T.; CAPELOZZI, V.L.Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.