MARIA LUCIA HIRATA KATAYAMA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, 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
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- Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis(2015) ENCINAS, Giselly; MAISTRO, Simone; PASINI, Fatima Solange; KATAYAMA, Maria Lucia Hirata; BRENTANI, Maria Mitzi; BOCK, Geertruida Hendrika de; FOLGUEIRA, Maria Aparecida Azevedo KoikeObjective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at <= 35 and <= 40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger) and 16 studies (598, 41 younger), were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER) status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.
- Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series(2013) FOLGUEIRA, Maria Aparecida Azevedo Koike; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; MUNDIM, Fiorita Gonzales Lopes; NANOGAKI, Suely; BOCK, Geertruida H. de; BRENTANI, M. MitziCAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: 'breast cancer' and 'lymph node' and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside-binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types.
- Abnormal collagen V deposition in dermis correlates with skin thickening and disease activity in systemic sclerosis(2012) MARTIN, Patricia; TEODORO, Walcy R.; VELOSA, Ana Paula P.; MORAIS, Jymenez de; CARRASCO, Solange; CHRISTMANN, Romy B.; GOLDENSTEIN-SCHAINBERG, Claudia; PARRA, Edwin R.; KATAYAMA, Maria Lucia; SOTTO, Mirian N.; CAPELOZZI, Vera L.; YOSHINARI, Natalino H.Objective: The physiological and mechanical properties of the skin, the primary tissue affected by systemic sclerosis, depend on the assembly of collagen types I, Ill and V, which form heterotypic fibers. Collagen V (COLV) regulates heterotypic fiber diameter, and the maintenance of its properties is important for maintaining normal tissue architecture and function. Based on a COLV-induced experimental SSc model, in which overexpression of abnormal COLV was a prominent feature, we assumed that this abnormality could be present in SSc patients and could be correlated to disease duration, skin thickening and disease activity. Methods: Skin biopsies from 18 patients (6 early-stage and 12 late-stage) and 10 healthy controls were studied. Skin thickening assessment was performed with the Modified Rodnan Skin Score (MRSS), and activity was calculated using the Valentini Disease Activity Index. Morphology, morphometry of COLV deposition in dermis, as well as, quantitative RT-PCR and 3D-reconstruction of the dermal fibroblast culture were performed. Results: Structurally abnormal COLV was overexpressed in SSc skin, mainly in the early stages of the disease, when compared to normal controls and late-stage. A positive correlation between COLV expression and MRSS and disease activity was observed. Collagen V alpha-1 and alpha-2 mRNA expression levels were higher in SSc. Tridimensional reconstruction of SSc dermal heterotypic fibers confirmed the presence of atypical COLV. Conclusion: Increased synthesis of abnormal COLV and its correlation with disease stage, activity and MRSS suggest that this collagen can be a possible trigger involved in the pathogenesis of SSc.
article 2 Citação(ões) na Scopus Transcriptional profile and response to neoadjuvant chemotherapy in breast cancer(2011) FOLGUEIRA, Maria Aparecida Azevedo Koike; SNITCOVSKY, Igor Moyses Longo; VALLE, Paulo Roberto Del; KATAYAMA, Maria Lucia Hirata; BRENTANI, Maria Mitzi; VIEIRA, Rene Aloisio da CostaObjective: To improve the accuracy predictive models of response to neoadjuvant chemotherapy in breast cancer, cDNA microarray technology was used to study tumor transcriptional profile. Gene signatures associated with predicting the response to neoadjuvant chemotherapy are the subject of this review. Methods: The data base http://www.ncbi.nlm.nih.gov/pubmed/ search was conducted by using the words ""breast cancer"" AND ""neoadjuvant/primary chemotherapy"" AND ""gene expression profile/microarray"". After excluding the repeats and selecting the publications considered most relevant by the authors to be presented, 279 publications were retrieved. Results: The number of publications regarding this subject has been increasing over the years, reaching over 50 in 2010, including the response to different chemotherapeutic drugs, such as anthracyclines and taxanes either alone or in combination. The first studies are from early last decade and used microarray platforms produced by the investigators. Recent studies have used commercial microarray platforms whose data have been stored in public databases, allowing for the analysis of a higher number of samples. Several transcriptional profiles associated with the complete pathological response were identified. Other authors used the clinical response to treatment as an endpoint, and, in this case, a predictive panel of resistance to the chemotherapeutic regimen at issue was determined. This is also a key issue, as it can contribute to individualize treatment, allowing patients resistant to a certain chemotherapeutic agent to be offered another therapeutic regimen. Conclusion: Identifying patients responsive to chemotherapy is of essential interest and despite major steps have been taken, the issue warrants further studies in view of its complexity.