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
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bookPart Hemoptise(2013) SANTANA, Alfredo Nicodemos da Cruz; MARTINS, Herlon Saraiva; FEITOSA, Paulo H. R.; TAKAGAKI, Teresa YaeconferenceObject 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.- Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy(2016) ANTONANGELO, Leila; TUMA, Taila; FABRO, Alexandre; ACENCIO, Milena; TERRA, Ricardo; PARRA, Edwin; VARGAS, Francisco; TAKAGAKI, Teresa; CAPELOZZI, VeraInhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.
conferenceObject Radiation Pneumonitis in Patients with Interstitial Lung Disease and Lung Cancer: Report of 6 Cases(2020) FREITAS, L. V. de; SERRA, J. P.; NAJAS, G. F.; PRADO, G. F.; KAWASSAKI, A. M.; TAKAGAKI, T. Y.; GABRIELLI, F.; JUNIOR, G. C.; OLIVEIRA, M. R.; KAIRALLA, R. A.; BALDI, B. G.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.- Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non-small cell lung cancer(2019) MACHADO-RUGOLO, Juliana; FABRO, Alexandre Todorovic; ASCHERI, Daniel; FARHAT, Cecilia; AB'SABER, Alexandre Muxfeldt; SA, Vanessa Karen de; NAGAI, Maria Aparecida; TAKAGAKI, Teresa; TERRA, Ricardo; PARRA, Edwin Roger; CAPELOZZI, Vera LuizaTo demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-LI protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEBI. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCDILG2, or ZEBI complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis.
conferenceObject Efficacy and safety of adjuvant chemotherapy in lung cancer: Real-world evidence(2019) ROITBERG, F. S. R.; NEFFA, M. F. B. V.; BONADIO, R. R. C. C.; HARADA, G.; MENDOZA, E. Z.; MAK, M. P.; TAKAHASHI, T. K.; MARTINS, R. E.; MESQUITA, C.; SANTINI, F. C.; ARAUJO, P. H. X. N. de; LAURICELLA, L. L.; PRADO, G. F.; TAKAGAKI, T. Y.; MELLO, E. S. de; GABRIELLI, F.; CARVALHO, H. D. A. de Andrade; TERRA, R. M.; CASTRO JR., G. deconferenceObject ERCC1 AND BETA-TUBULIN III IN ADVANCED NSCLC PATIENTS TREATED WITH CISPLATIN-VINORELBINE(2012) CASTRO JR., G. de; VICTOR, C. R.; BIGATON, F. J.; TAKAHASHI, T. K.; FEHER, O.; SABER, A. M. Ab'; TAKAGAKI, T. Y.; SIQUEIRA, S. A. C.; CHAMMAS, R.; HOFF, P. M. G.Background: Platinum-containing chemotherapy remains as the standard treatment in advanced/metastatic non-small-cell lung cancer (NSC LC) patients (pts). Increased ERCC 1 expression has been associated with resistance to platinum-based therapies, and beta-tubulin III (TUBB 3) was shown to be involved in resistance to antimicrotubule agents. Here we studied these tumor markers in NSC LC pts treated with cisplatin-vinorelbine and correlated their expression with survival. Methods: It is a retrospective study on pts diagnosed with advanced/metastatic NSC LC (TNM 6th ed), consecutively identified. All pts were treated with cisplatin 80 mg/m2 d1 and vinorelbine 30 mg/m2 d1, d8, d15, every 21 days, 4–6 cycles, in our Institution, between Sep/2002 and Oct/2008. ERCC 1 (clone 8F1) and TUBB 3 (clone TUJ1) expression were evaluated by immunohistochemistry, and biomarker expression was considered as high when more than 10% of tumor cells presented moderate to strong staining, nuclear or cytoplasmic, respectively. Overall survival (OS) was estimated by the Kaplan-Meier method and curves were compared with log-rank. Results: 142 pts were studied; median age 63 y (34-87), 67% male and 86% current smokers. Adenocarcinoma (ADC, 58 pts, 43%), followed by squamous cell carcinoma (SCC , 50 pts, 37%) were the most frequent histologic types. 100 pts (71%) were staged as IV and 34 pts (24%) as IIIB. The median number of cycles was 4 (1-7). Median OS was 7.9 mo. Overall, high ERCC 1 expression was observed in 61/104 pts (59%) and high TUBB 3 expression in 55/109 pts (51%). According to histologic types, low ERCC 1 expression was observed in 7/42 SCC pts (16%) and in 35/63 ADC pts (56%) (p=0.0004). Among ADC pts, 1-y OS rate was 28% and 47% in pts which tumors presented with high and low ERCC 1 expression, respectively (HR 1.57, 95% CI 0.9-2.7, p=0.08). TUBB 3 expression neither presented any difference between SCC and ADC types, nor any prognostic impact in terms of OS. Conclusions: Low ERCC 1 expression was observed more frequently in pts with advanced lung ADC and it was a favorable prognostic factor in ADC pts treated with cisplatin-vinorelbine.- Biomolecular analysis of matrix proteoglycans as biomarkers in non small cell lung cancer(2018) RANGEL, Maristela P.; SA, Vanessa K. de; PRIETO, Tabatha; MARTINS, Joo Roberto M.; OLIVIERI, Eloisa R.; CARRARO, Dirce; TAKAGAKI, Teresa; CAPELOZZI, Vera LuizaMatrix proteoglycans (PGs) have shown promise as biomarker in malignancies. We employed agarose gel eletrophoresis, quantitative real- time reverse transcription-polymerase chain reaction and immunohistochemistry to evaluate the content of sulfated glicosaminoglycans (chondroitin sulfate and heparan sulfate) and expression of PG (biglycan, glypican, perlecan, syndecan e versican) in patient-matched normal and tumor tissues obtained from resected specimens of lung cancer. A significant increase of heparan sulfate (HS) and chondroitin sulfate (CS) concentrations was found in tumor tissue samples when compared to normal lung tissue samples. HS was also significantly increased in adenocarcinomas compared to squamous cell carcinomas. PG gene expression, with exception of syndecan, were significantly decreased in tumor tissue compared to normal lung, coinciding with significant decrease of PG protein levels in tumor cells and stroma compared to normal lung tissue (Kappa coefficient 0.41, 0.42 and 0,28, respectively). Women patients (p = 0.02), non smokers (p = 0.05), T stage (p = 0.009), N stage (p = 0.03) and adenocarcinoma (p = 0.05) were associated with improved overall survival (OS). Patients presenting tumors with low concentration of sulfated GAG and high PGs levels presented better OS compared to patients with high concentration of sulfated GAG and low expression of PGs. Cox regression model controlled by gender, tobacco history and histological type, showed that patients with high perlecan and versican expression in tumor presented respectively high probability of life (beta risk 11.64; 1.27 to 15.90) and low risk of death (beta risk 0.11; 0.02-0.51). The combined approach suggest matrix (PGs) as biomarkers in lung cancer.
bookPart Tosse(2015) ANDRADE, Marcelo Jorge de Souza Leão; DANTAS, Thiago Costa de Araújo; TAKAGAKI, Teresa Yae