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
6 resultados
Resultados de Busca
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- Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity(2019) COSTA, Pedro L. F.; FRANCA, Monica M.; KATAYAMA, Maria L.; CARNEIRO, Eduardo T.; MARTIN, Regina M.; FOLGUEIRA, Maria A. K.; LATRONICO, Ana C.; FERRAZ-DE-SOUZA, BrunoThe vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO). Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D. Novel VDR target genes identified in human fibroblasts included bone and cartilage factors CILP, EFNB2, and GALNT12. Vehicle-treated CO and MUT fibroblasts had strikingly different transcriptomes, suggesting basal VDR activity. Indeed, oppositional transcriptional effects in basal conditions versus after 1,25D activation were implied for a subset of target genes mostly involved with cell cycle. Cell proliferation assays corroborated this conjectured oppositional basal VDR activity, indicating that precise 1,25D dosage in target tissues might be essential for modulating vitamin D actions in human health.
- Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil(2019) GUINDALINI, Rodrigo Santa Cruz; CORMEDI, Marina Candido Visontai; MAISTRO, Simone; PASINI, Fatima Solange; BRANAS, Priscila Cristina Abduch Adas; SANTOS, Liliane dos; PEREIRA, Glaucia Fernanda de Lima; BOCK, Geertruida Hendrika de; SACCARO, Daniela Marques; KATAYAMA, Maria Lucia Hirata; FARAJ, Sheila Friedrich; SAFATLE-RIBEIRO, Adriana; RIBEIRO JUNIOR, Ulysses; DIZ, Maria Del Pilar Estevez; GOUVEA, Ana Carolina Ribeiro Chaves de; CHAMMAS, Roger; FOLGUEIRA, Maria Aparecida Azevedo KoikeIntroduction The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, <= 55 years old) patients. Methodology From 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled. All CDH1 exons and intronic boundaries were sequenced, and large genomic rearrangements were screened by MLPA. CDH1 transcription analysis was performed for variants that could potentially induce an effect on splicing. The diet and lifestyle habits of EOGC patients were compared to Brazilian population diet and lifestyle, obtained from governmental databases. Results Of 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. The majority of the tumors were diffuse (74%) and poorly differentiated (80%). In total, 4 novel missense variants of uncertain significance (VUS) were identified: c.313T>A, c.387G>T, c.1676G>A, and c.1806C>A. The MLPA results revealed no rearrangements and CDH1 transcription analysis for variants of interest were inconclusive. EOGC patients had a higher red (OR:2.6, 95%CI:1.4-4.9) and processed (OR:3.1, 95%CI:1.6-6.0) meat intake and higher fruit consumption (OR:0.4, 95%IC:0.3-0.7) compared to eating habits of the Brazilian population. Conclusions No unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Dietary habits may be associated with the EOGC development.
- 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
- 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 KoikeBreast 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.
- 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
- Somatic mutations in triple-negative breast carcinoma and high-grade serous ovarian carcinoma from young women.(2019) SERIO, Pedro Adolpho M. P.; PEREIRA, Glaucia Fernanda Lima; KATAYAMA, Maria Lucia Hirata; MAISTRO, Simone; LOPEZ, Rossana Veronica Mendoza; ROELA, Rosimeire Aparecida; RODRIGUES, Livia Munhoz; FOLGUEIRA, Maria A. A. Koike