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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- 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 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.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.- Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma(2012) SOUZA, Paola da Costa; PARRA, Edwin Roger; ATANAZIO, Marcelo Junqueira; SILVA, Osmar Bianchi da; NOLETO, Gustavo Sousa; AB'SABER, Alexandre Muxfeldt; FERNEZLIAN, Sandra de Morais; TAKAGAKI, Tereza; CAPELOZZI, Vera LuizaAims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.
- Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy(2015) RANGEL, M.P.; DE SÁ, V.K.; MARTINS, V.; MARTINS, J.R.M.; PARRA, E.R.; MENDES, A.; ANDRADE, P.C.; REIS, R.M.; LONGATTO-FILHO, A.; OLIVEIRA, C.Z.; TAKAGAKI, T.; CARRARO, D.M.; NADER, H.B.; CAPELOZZI, V.L.Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.
- Hyaluronidase splice variants are associated with histology and outcome in adenocarcinoma and squamous cell carcinoma of the lung(2012) SA, Vanessa Karen de; OLIVIERI, Eloisa; PARRA, Edwin Roger; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa; SOARES, Fernando Augusto; CARRARO, Dirce; CARVALHO, Lina; CAPELOZZI, Vera LuizaHeterogeneity of hyaluronidase (HYAL) expression has been identified in tumors and shows promise as an indicator of disease progression. The expression profile of alternatively spliced forms of HYAL was evaluated in tumors and normal lung tissue from 69 resected tumors of patients with adenocarcinomas and squamous cell carcinomas. HYAL1-wild-type (wt) and variants 1 to 5, HYAL2-wt, and HYAL3-wt, and variants 1 to 3 were identified by polymerase chain reaction and direct sequencing. Different proportions of the 3 HYAL-wt and variants were expressed in tumor and normal lung tissues. HYAL1-wt was associated with a poorer prognosis and HYAL3-vl with a better prognosis. HYAL splice variants are associated with histology and outcome, suggesting that strategies aimed at modulating their levels may be effective for lung cancer treatment.
conferenceObject Hyaluronan: A novel sputum marker for the screening and diagnosis of lung cancer patients(2012) RANGEL, Maristela Peres; SA, Vanessa Karen de; MARTINS, Joao Roberto Maciel; CUENTAS, Edwin Roger Parra; REIS, Rui Vieira; LONGATTO FILHO, Adhemar; TAKAGAKI, Tereza; NADER, Helena; CAPELOZZI, Vera LuizaconferenceObject SPUTUM HYALURONAN ANALYSIS AS A NEW STRATEGY FOR THE SCREENING AND DIAGNOSIS OF LUNG CANCER(2012) RANGEL, Maristela P.; SA, Vanessa K. De; MARTINS, Joao Roberto M.; CUENTAS, Edwin Roger P.; TAKAGAKI, Tereza; FILHO, Adhemar L.; REIS, Rui; NADER, Helena; CAPELOZZI, Vera L.Background: Hyaluronic Acid (HA) concentration is elevated in several cancers, but there is no data regarding its concentration in the sputum of lung cancer patients.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. Methods: HA was examined in 45 paired tissues samples and sputum samples were collected from 90 lung cancer patients. Twenty five COPD patients were selected to compose a high risk group and 15 healthy volunteers were analysed as controls. All the patients and controls underwent a sputum induction. Sputum samples were incubated with urea 7M and tissue samples were dehydrated with acetone prior to analysis. Afterwards both were incubated with a proteolytic enzyme. The levels of HA were measured by a noncompetitive ELISA-like fluorometric assay. Results and Conclusion: A significant different concentration pattern of HA in the tissues 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 Fig1A). When comparing the groups separately, a difference was found between sputum HA from LC vs.healthy volunteers (p<0.001) and LC vs.COPD patients (p=0.002). ROC curve between LC and healthy volunteers furnished an area of 0.821. Assuming a cut off value of 31,44ng/mg, the specificity was 100% and the sensitivity was 51% (Fig1B). ROC curve to distinguish COPD patients from LC patients showed an area of 0.698 and the cut off value of 48.3ng/mg presented 100% of specificity and 33% of sensitivity.