MARIA LUCIA HIRATA KATAYAMA

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Departamento de Radiologia, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: ROSIMEIRE APARECIDA ROELA ×

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Agora exibindo 1 - 10 de 21
  • article 7 Citação(ões) na Scopus
    Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences
    (2021) SERIO, Pedro Adolpho de Menezes Pacheco; PEREIRA, Glaucia Fernanda de Lima; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; MAISTRO, Simone; FOLGUEIRA, Maria Aparecida Azevedo Koike
    Background: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y <= 40 years) and elderly (E >= 75 years) patients. Methods: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients. Potential driver genes were those that were present in the Cancer Gene Census-CGC, the Candidate Cancer Gene Database-CCGD, or OncoKB and those that were considered pathogenic in variant effect prediction tools. Results: Mutational signature 3 (homologous repair defects) was the only gene that was represented in all four subgroups. The median number of mutated CGCs per sample was similar in HGSOC (Y:3 vs. E:4), but it was higher in elderly TNBC than it was in young TNBC (Y:3 vs. E:6). At least 90% of the samples from TNBC and HGSOC from Y and E patients presented at least one known affected TSG. Besides TP53, which was mutated in 67-83% of the samples, the affected TSG in TP53 wild-type samples were NF1 (yHGSOC and yTNBC), PHF6 (eHGSOC and yTNBC), PTEN, PIK3R1 and ZHFX3 (yTNBC), KMT2C, ARID1B, TBX3, and ATM (eTNBC). A few samples only presented one affected oncogene (but no TSG): KRAS and TSHR in eHGSOC and RAC1 and PREX2 (a regulator of RAC1) in yTNBC. At least 2/3 of the tumors presented mutated oncogenes associated with tumor suppressor genes; the Ras and/or PIK3CA signaling pathways were altered in 15% HGSOC and 20-35% TNBC (Y vs. E); DNA repair genes were mutated in 19-33% of the HGSOC tumors but were more frequently mutated in E-TNBC (56%). However, in HGSOC, 9.5% and 3.3% of the young and elderly patients, respectively, did not present any tumors with an affected CGC nor did 4.65% and none of the young and elderly TNBC patients. Conclusion: Most HGSOC and TNBC from young and elderly patients present an affected TSG, mainly TP53, as well as mutational signature 3; however, a few tumors only present an affected oncogene or no affected cancer-causing genes.
  • conferenceObject
    Profile of somatic mutations in young adults with pancreatic cancer.
    (2019) RODRIGUES, Livia Munhoz; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; FOLGUEIRA, Maria A. A. Koike
  • article 24 Citação(ões) na Scopus
    Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
    (2019) KATAYAMA, Maria Lucia Hirata; VIEIRA, Rene Aloisio Costa; ANDRADE, Victor Piana; ROELA, Rosimeire Aparecida; LIMA, Luiz Guilherme Cernaglia Aureliano; KERR, Ligia Maria; CAMPOS, Adriano Polpo de; PEREIRA, Carlos Alberto de Braganca; SERIO, Pedro Adolpho de Menezes Pacheco; ENCINAS, Giselly; MAISTRO, Simone; PETRONI, Matheus de Almeida Leite; BRENTANI, Maria Mitzi; FOLGUEIRA, Maria Aparecida Azevedo Koike
    Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.
  • conferenceObject
    End-to-end training of convolutional network for breast cancer detection in two-view mammography.
    (2021) PETRINI, Daniel G.; SHIMIZU, Carlos; VALENTE, Gabriel V.; FOLGUEIRA, Guilherme; NOVAES, Guilherme A.; KATAYAMA, Maria L.; SERIO, Pedro; ROELA, Rosimeire A.; TUCUNDUVA, Tatiana C.; FOLGUEIRA, Maria Aparecida A.; KIM, Hae Y.
  • article 2 Citação(ões) na Scopus
    Survival analysis of young adults from a Brazilian cohort of non-small cell lung cancer patients
    (2021) NICOLAU, Jessica Silva; LOPEZ, Rossana Veronica Mendoza; LUIZAGA, Carolina Terra de Moraes; RIBEIRO, Karina Braga; ROELA, Rosimeire Aparecida; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; NATALINO, Renato Jose Mendonca; JR, Gilberto de Castro; NETO, Jose Eluf; FOLGUEIRA, Maria Aparecida Azevedo Koike
    Background: The influence of age at diagnosis in non-small cell lung cancer (NSCLC) prognosis is unclear. Objectives: To compare in a Brazilian cohort of NSCLC patients of different age groups: 1) The overall survival; 2) Clinical features and treatment options. Methods: This is a retrospective cohort study using a hospital-based registry, for NSCLC patients registered in years 2000-2009. Patients were grouped into three age groups: Young adults (YA: < 40 years), middle-aged (MA: 40-64 years) and elderly (E: >= 65 years). Kaplan-Meier was used to estimate overall survival and Cox regression for hazard ratios (HRs) and 95% confidence intervals. Results: 17,422 NSCLC patients were included: 370 YA (2.1%), 8,697 MA (49.9%) and 8,355 E (48.0%). Compared with older age groups, the YA group had a higher proportion of females, patients diagnosed with adenocarcinoma and metastatic disease (63.2%). Overall survival was longer in YA in the entire cohort and in all clinical stages (CSs) (p < 0.001). For YA, higher education level was a good prognosis factor (compared with illiterate and incomplete elementary); advanced or metastatic disease (compared with early-stage disease) and treatment based in radiotherapy or chemotherapy (CT) (without surgery), compared with treatment combinations with surgery, were poor prognostic factors. Young men (but not women) had lower HR of death compared with older groups; YA had lower HR of death in all CSs compared with patients from older groups. A higher percentage of YA were treated with surgery or CT in early-stage disease compared with older groups. Besides that, YA and MA patients treated with surgery or CT had a better prognosis than elderlies. Conclusions: In this Brazilian cohort of NSCLC patients, most young individuals were diagnosed with metastatic disease. YA presented longer survival than older age groups in all CSs, but mainly in CS I/II and III, where some patients may achieve long remissions or cure.
  • article 5 Citação(ões) na Scopus
    Gene Expression Profile in Response to Doxorubicin-Rapamycin Combined Treatment of HER-2-Overexpressing Human Mammary Epithelial Cell Lines
    (2012) TRAPE, Adriana Priscila; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; BRENTANI, Helena; RAVACCI, Graziela Rosa; LIMA, Leandro de Araujo; BRENTANI, Maria Mitzi
    HER-2-positive breast cancers frequently sustain elevated AKT/mTOR signaling, which has been associated with resistance to doxorubicin treatment. Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification. The epithelial mammary cell line HB4a was also analyzed. The combined treatment using 20 nmol/L of rapamycin and 30 nmol/L of doxorubicin arrested HB4a and C5.2 cells in S to G(2)-M, whereas SKBR3 cells showed an increase in the G(0)-G(1) phase. Rapamycin increased the sensitivity to doxorubicin in HER-2-overexpressing cells by approximately 2-fold, suggesting that the combination displayed a more effective antiproliferative action. Gene expression profiling showed that these results might reflect alterations in genes involved in canonical pathways related to purine metabolism, oxidative phosphorylation, protein ubiquitination, and mitochondrial dysfunction. A set of 122 genes modulated by the combined treatment and specifically related to HER-2 overexpression was determined by finding genes commonly regulated in both C5.2 and SKBR3 that were not affected in HB4a cells. Network analysis of this particular set showed a smaller subgroup of genes in which coexpression pattern in HB4a cells was disrupted in C5.2 and SKBR3. Altogether, our data showed a subset of genes that might be more robust than individual markers in predicting the response of HER-2-overexpressing breast cancers to doxorubicin and rapamycin combination.
  • article 18 Citação(ões) na Scopus
    Breast cancer tissue slices as a model for evaluation of response to rapamycin
    (2013) GROSSO, Stana Helena Giorgi; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; NONOGAKI, Suely; SOARES, Fernando Augusto; BRENTANI, Helena; LIMA, Leandro; FOLGUEIRA, Maria Aparecida Azevedo Koike; WAITZBERG, Angela Flavia Logullo; PASINI, Faima Solange; GOES, Joao Carlos Guedes Sampaio; BRENTANI, M. Mitzi
    Rapamycin is a selective inhibitor of the mammalian target of rapamycin (mTOR), a regulator kinase that integrates growth factors signaling via the phosphoinositide-3-kinase pathway and that has emerged as a novel therapeutic modality in breast cancer (BC). We propose a pre-clinical ""ex-vivo"" personalized organotypic culture of BC that preserves the microenvironment to evaluate rapamycin-mediated gene expression changes. Freshly excised ductal invasive BC slices, 400 mu m thick (n=30), were cultured in the presence or absence (control) of rapamycin (20 nM) for 24 h. Some slices were formalin-fixed for immunohistochemical determinations and some were processed for microarray analysis. Control slices in culture retained their tissue morphology and tissue viability (detected by BrdU uptake). The percentage of proliferating cells (assessed by Ki67) did not change up to 24 h of treatment. Immunohistochemical evaluation of p-AKT, p-mTOR, p-4EBP1 and p-S6K1 indicated that AKT/mTOR pathway activation was maintained during cultivation. For microarray analysis, slices were divided into two groups, according to the presence/absence of epidermal growth factor receptor-type 2 and analyzed separately. Limited overlap was seen among differentially expressed genes after treatment (P < 0.01) in both groups suggesting different responses to rapamycin between these BC subtypes. Ontology analysis indicated that genes involved in biosynthetic processes were commonly reduced by rapamycin. Our network analysis suggested that concerted expression of these genes might distinguish controls from treated slices. Thus, breast carcinoma slices constitute a suitable physiological tool to evaluate the short-term effects of rapamycin on the gene profile of individual BC samples.
  • article 19 Citação(ões) na Scopus
    Specific upregulation of RHOA and RAC1 in cancer-associated fibroblasts found at primary tumor and lymph node metastatic sites in breast cancer
    (2015) ROZENCHAN, Patricia Bortman; PASINI, Fatima Solange; ROELA, Rosimeire A.; KATAYAMA, Maria Lucia Hirata; MUNDIM, Fiorita Gonzales Lopes; BRENTANI, Helena; LYRA, Eduardo C.; BRENTANI, Maria Mitzi
    The importance of tumor-stromal cell interactions in breast tumor progression and invasion is well established. Here, an evaluation of differential genomic profiles of carcinoma-associated fibroblasts (CAFs) compared to fibroblasts derived from tissues adjacent to fibroadenomas (NAFs) revealed altered focal adhesion pathways. These data were validated through confocal assays. To verify the possible role of fibroblasts in lymph node invasion, we constructed a tissue microarray consisting of primary breast cancer samples and corresponding lymph node metastasis and compared the expression of adhesion markers RhoA and Rac1 in fibroblasts located at these different locations. Two distinct tissue microarrays were constructed from the stromal component of 43 primary tumors and matched lymph node samples, respectively. Fibroblasts were characterized for their expression of alpha-smooth muscle actin (alpha-SMA) and vimentin. Moreover, we verified the level of these proteins in the stromal compartment from normal adjacent tissue and in non-compromised lymph nodes. Our immunohistochemistry revealed that 59 % of fibroblasts associated with primary tumors and 41 % of the respective metastatic lymph nodes (p = 0.271) displayed positive staining for RhoA. In line with this, 57.1 % of fibroblasts associated with primary tumors presented Rac1-positive staining, and the frequency of co-positivity within the lymph nodes was 42.9 % (p = 0.16). Expression of RhoA and Rac1 was absent in fibroblasts of adjacent normal tissue and in compromised lymph nodes. Based on our findings that no significant changes were observed between primary and metastatic lymph nodes, we suggest that fibroblasts are active participants in the invasion of cancer cells to lymph nodes and support the hypothesis that metastatic tumor cells continue to depend on their microenvironment.
  • conferenceObject
    Cancer driver genes in prostate cancer from young men.
    (2019) MAISTRO, Simone; XAVIER, Camila dos Santos; SERIO, Pedro Adolpho M. P.; KATAYAMA, Maria Lucia Hirata; ROELA, Rosimeire Aparecida; FOLGUEIRA, Maria A. A. Koike
  • conferenceObject
    High-accuracy breast cancer detection in mammography using EfficientNet and end-to-end training.
    (2021) PETRINI, Daniel G.; SHIMIZU, Carlos; VALENTE, Gabriel V.; FOLGUEIRA, Guilherme; NOVAES, Guilherme A.; KATAYAMA, Maria L.; SERIO, Pedro; ROELA, Rosimeire A.; TUCUNDUVA, Tatiana C.; FOLGUEIRA, Maria Aparecida A.; KIM, Hae Y.