FLAVIA REGINA ROTEA MANGONE
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion(2013) FREITAS, Vanessa M.; AMARAL, Jonatas Bussador do; SILVA, Thaiomara A.; SANTOS, Emerson S.; MANGONE, Flavia R.; PINHEIRO, Joao de Jesus; JAEGER, Ruy G.; NAGAI, Maria A.; MACHADO-SANTELLI, Glaucia MariaBackground: ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results: In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions: ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.
- Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes(2022) PAVANELLI, Ana Carolina; MANGONE, Flavia Rotea; YOGANATHAN, Piriya; BESSA, Simone Aparecida; NONOGAKI, Suely; OSORIO, Cynthia A. B. de Toledo; ANDRADE, Victor Piana de; SOARES, Ibere Cauduro; MELLO, Evandro Sobrosa de; MULLIGAN, Lois M.; NAGAI, Maria AparecidaPurpose Breast cancer (BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance. Methods Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays (TMAs) containing a cohort of 361 Luminal subtype BC. Results Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015). Conclusion Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC.
- SMC6 down-regulation: marker of genetic instability and poor outcome in breast cancer(2023) MANGONE, Flavia R. Rotea; KREPISCHI, Ana Cristina V.; CARRARO, Dirce M.; NAGAI, Maria A.
- Gene expression profiling of triple-negative breast tumors with different expression of secreted protein acidic and cysteine rich (SPARC)(2018) ALCANTARA FILHO, Paulo R. de; MANGONE, Flavia R.; PAVANELLI, Ana C.; GARCIA, Simone A. de Bessa; NONOGAKI, Suely; OSORIO, Cynthia A. B. de Toledo; ANDRADE, Victor P. de; NAGAI, Maria A.Aim: To determine the expression signature of triple-negative breast cancer (TNBC) with differences of secreted protein acidic and rich in cysteine expression and clinical behavior. Patients, materials & methods: cDNA microarray analysis was performed to determine the expression profiling of TNBC, characterized regarding secreted protein acidic and rich in cysteine expression status. Immunohistochemistry analysis on tissue microarrays containing an independent cohort of TNBC was performed for validation. Results: Negative staining of SOHLH2 and positive staining of DNAJC12 and LIM1 was correlated with a poor outcome of the patients. Conclusion: Our findings provide new information on transcriptome changes associated with the clinical behavior of TNBC that may serve as a potential tool for the identification and characterization of new candidate biomarkers.
conferenceObject Prognostic impact of primary tumor sidedness in stage III colorectal cancer(2023) PROTASIO, Bruno Mendonca; CASTRIA, Tiago Biachi de; SARAGIOTTO, Daniel Fernandes; NATALINO, Renato Jose Mendonca; MANGONE, Flavia Regina Rotea; SABBAGA, Jorge; HOFF, Paulo M.; CHAMMAS, RogerconferenceObject Prostate apoptosis response-4 (PAR4) secretion in breast tumor and normal cell lines cultured in hypoxic conditions(2018) GARCIA, Simone Aparecida de Bessa; BROBOVNITCHAIA, Irina Gueroldovna; MANGONE, Flavia Rotea; NAGAI, Maria Aparecida- Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma(2012) PASINI, Fatima Solange; MAISTRO, Simone; SNITCOVSKY, Igor; BARBETA, Lilian P.; MANGONE, Flavia R. Rotea; LEHN, Carlos N.; WALDER, Fernando; CARVALHO, Marcos B.; BRENTANI, M. Mitzi; FEDERICO, Miriam H. H.Background. Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. Material and methods. We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. Results. Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN+) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN+ with an accuracy of 80.0% (p = 0.012). Conclusions. The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our ""Nodal Index"" model are predictive of lymph node metastasis in OSCC.
conferenceObject Potential role of SMC6 downregulation as an indicator of tumor genetic instability in breast cancer.(2018) MANGONE, Flavia Rotea; KREPISCHI, Ana Cristina Victorino; NONOGAKI, Suely; CARRARO, Dirce Maria; NAGAI, Maria Aparecida