Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
Life Sci ; 336: 122332, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070862

RESUMO

Breast cancer (BC), a heterogeneous group of diseases, is the most frequent type and the leading cause of cancer-related death among women worldwide. Tumor heterogeneity directly impacts cancer progression and treatment, as evidenced by the patients´ diverse prognosis and treatment responses across the distinct molecular subtypes. Triple-negative breast cancer (TNBC), which accounts for 10-20% of all diagnosed BC cases, is an aggressive BC subtype with a challenging prognosis. Current treatment options include systemic chemotherapy and/or target therapies based on PARP and PD-L1 inhibitors for eligible patients. MicroRNAs (miRNAs) are important regulatory non-coding RNAs (ncRNAs) in TNBC tumorigenesis. These molecules are present both intracellularly and released into biofluids, packaged into extracellular vesicles (EVs). Emerging evidence indicates that EVs-associated miRNAs (EVs-miRNAs), transferred from parental to recipient cells, are key mediators of cell-to-cell communication. Considering their stability and abundance in several biofluids, these molecules may reflect the epigenomic composition of their tumors of origin and contribute to mediate tumorigenesis, similar to their intracellular counterparts. This review provides the current knowledge on EVs-miRNAs in the TNBC subtype, focusing on their role in regulating mRNA targets involved in tumor phenotypes and their clinical relevance as promising biomarkers in liquid biopsies.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Relevância Clínica , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Carcinogênese , Biologia , Biomarcadores Tumorais/genética
2.
Arq. Asma, Alerg. Imunol ; 7(1): 96-102, 20230300. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-1509636

RESUMO

Introduction: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a systemic hyperinflammatory disease that occurs in a small number of children after being infected with SARS-CoV-2. Macrophage activation syndrome, an aggressive condition characterized by the excessive inflammation and activation of well-differentiated macrophages, has been shown to occur in patients infected by SARS-CoV-2. Considering the clinical and pathophysiological similarities between these diseases, our main objective was to determine whether gene polymorphisms associated with macrophage activation syndrome were also present in patients with PIMS-TS. Methods: DNA from 10 pediatric patients with PIMS-TS (case group) and ten COVID-19 patients without PIMS-TS (control group) were genotyped by Real-time PCR analysis (TaqMan®) for single nucleotide polymorphisms (SNP) in four genes associated with macrophage activation syndrome: perforin 1 (PRF1), granzyme B (GZMB), syntaxin 11 (STX11), and syntaxin binding protein 2 (STXBP2). The SNP analysis was performed using the additive, dominant, and recessive models. Results: A significantly higher frequency of an SNP (C wild allele in rs6573910) in the GZMB gene was observed in both the additive and dominant models in the PIMS-TS group than controls. A borderline significant difference was also observed for the G allele in rs7764017 of the STX11 gene in the PIMS-TS group in the additive model. Conclusions: This study indicated the presence of two polymorphisms in genes associated with macrophage activation syndrome (GZMB and STX11) in patients who developed PIMS-TS. If the presence of these SNPs is validated in a larger number of PIMS-TS cases, they can be used as potential biomarkers for early identification of pediatric patients with a higher probability of developing PIMS-TS associated with SARS-CoV-2 infection.


Introdução: A síndrome multissistêmica inflamatória pediátrica temporariamente associada ao SARS-CoV-2 (SIMP-TS) é uma doença hiperinflamatória sistêmica que ocorre em um pequeno número de crianças após serem infectadas pelo SARS-CoV-2. A síndrome de ativação de macrófagos (SAM), uma condição agressiva caracterizada pela inflamação excessiva e ativação de macrófagos bem diferenciados, demonstrou ocorrer em pacientes infectados por SARS-CoV-2. Considerando as semelhanças clínicas e fisiopatológicas entre essas doenças, neste estudo o nosso principal objetivo foi determinar se polimorfismos gênicos associados à SAM também estavam presentes em pacientes com SIMP-TS. Métodos: DNA de dez pacientes pediátricos com SIMP (grupo caso) e dez pacientes COVID-19 sem SIMP (grupo controle) foram genotipados por análise de PCR em tempo real (tecnologia TaqMan®) para polimorfismos de nucleotídeo único (SNPs) em quatro genes selecionados associados com SAM: perforina 1 (PRF1), granzima B (GZMB), sintaxina 11 (STX11) e proteína de ligação de sintaxina 2 (STXBP2). A análise dos SNPs foi realizada utilizando o modelo aditivo, dominante e recessivo. Resultados: Uma frequência significativamente maior de um SNP (alelo selvagem C em rs6573910) no gene GZMB foi observada pelos modelos aditivo e dominante no grupo SIMP quando comparado aos controles. Além disso, uma significância limítrofe foi observada para o alelo G em rs7764017 do gene STX11 no grupo SIMP pelo modelo aditivo. Conclusões: Nosso estudo indicou a presença de dois polimorfismos em genes associados à SAM (GZMB e STX11) em pacientes que desenvolveram SIMP-TS. Uma vez validada a presença desses SNPs em um número maior de casos de SIMP-TS, eles podem ser usados como potenciais biomarcadores para a identificação precoce de pacientes pediátricos com maior probabilidade de desenvolver SIMP-TS associado à infecção por SARS-CoV-2.


Assuntos
Humanos , Pré-Escolar , Criança
3.
Int J Mol Sci ; 23(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36430597

RESUMO

Fanconi Anemia (FA) is a disease characterized by genomic instability, increased sensitivity to DNA cross-linking agents, and the presence of clonal chromosomal abnormalities. This genomic instability can compromise the bone marrow (BM) and confer a high cancer risk to the patients, particularly in the development of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). The diagnosis of FA patients is complex and cannot be based only on clinical features at presentation. The gold standard diagnostic assay for these patients is cytogenetic analysis, revealing chromosomal breaks induced by DNA cross-linking agents. Clonal chromosome abnormalities, such as the ones involving chromosomes 1q, 3q, and 7, are also common features in FA patients and are associated with progressive BM failure and/or a pre-leukemia condition. In this review, we discuss the cytogenetic methods and their application in diagnosis, stratification of the patients into distinct prognostic groups, and the clinical follow-up of FA patients. These methods have been invaluable for the understanding of FA pathogenesis and identifying novel disease biomarkers. Additional evidence is required to determine the association of these biomarkers with prognosis and cancer risk, and their potential as druggable targets for FA therapy.


Assuntos
Anemia de Fanconi , Leucemia Mieloide Aguda , Humanos , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Seguimentos , Análise Citogenética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Instabilidade Genômica , Aberrações Cromossômicas , Biomarcadores
4.
Front Genet ; 13: 875939, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812732

RESUMO

Cancer development by the human papillomavirus (HPV) infection can occur through the canonical HPV/p53/RB1 pathway mediated by the E2/E6/E7 viral oncoproteins. During the transformation process, HPV inserts its genetic material into host Integration Sites (IS), affecting coding genes and miRNAs. In penile cancer (PeCa) there is limited data on the miRNAs that regulate mRNA targets associated with HPV, such as the TP53 and RB1 genes. Considering the high frequency of HPV infection in PeCa patients in Northeast Brazil, global miRNA expression profiling was performed in high-risk HPV-associated PeCa that presented with TP53 and RB1 mRNA downregulated expression. The miRNA expression profile of 22 PeCa tissue samples and five non-tumor penile tissues showed 507 differentially expressed miRNAs: 494 downregulated and 13 upregulated (let-7a-5p, miR-130a-3p, miR-142-3p, miR-15b-5p miR-16-5p, miR-200c-3p, miR-205-5p, miR-21-5p, miR-223-3p, miR-22-3p, miR-25-3p, miR-31-5p and miR-93-5p), of which 11 were identified to be in HPV16-IS and targeting TP53 and RB1 genes. One hundred and thirty-one and 490 miRNA binding sites were observed for TP53 and RB1, respectively, most of which were in seedless regions. These findings suggest that up-regulation of miRNA expression can directly repress TP53 and RB1 expression by their binding sites in the non-canonical seedless regions.

5.
Biomolecules ; 12(2)2022 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-35204688

RESUMO

Prostate cancer (PCa) is a clinically heterogeneous disease, where deregulation of epigenetic events, such as miRNA expression alterations, are determinants for its development and progression. MiR-182-5p, a member of the miR-183 family, when overexpressed has been associated with PCa tumor progression and decreased patients' survival rates. In this study, we determined the regulatory role of miR-182-5p in modulating aggressive tumor phenotypes in androgen-refractory PCa cell lines (PC3 and DU-145). The transient transfection of the cell lines with miR-182-5p inhibitor and mimic systems, significantly affected cell proliferation, adhesion, migration, and the viability of the cells to the chemotherapeutic agents, docetaxel, and abiraterone. It also affected the protein expression levels of the tumor progression marker pAKT. These changes, however, were differentially observed in the cell lines studied. A comprehensive biological and functional enrichment analysis and miRNA/mRNA interaction revealed its strong involvement in the epithelial-mesenchymal transition (EMT) process; expression analysis of EMT markers in the PCa transfected cells directly or indirectly modulated the analyzed tumor phenotypes. In conclusion, miR-182-5p differentially impacts tumorigenesis in androgen-refractory PCa cells, in a compatible oncomiR mode of action by targeting EMT-associated pathways.


Assuntos
MicroRNAs , Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , Neoplasias da Próstata/metabolismo
6.
Genet Mol Biol ; 44(1): e20190410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656060

RESUMO

Male breast cancer (MBC) is a rare malignancy that accounts for about 1.8% of all breast cancer cases. In contrast to the high number of the "omics" studies in breast cancer in women, only recently molecular approaches have been performed in MBC research. High-throughput proteomics based methodologies are promisor strategies to characterize the MBC proteomic signatures and their association with clinico-pathological parameters. In this study, the label-free quantification-mass spectrometry and bioinformatics approaches were applied to analyze the proteomic profiling of a MBC case using the primary breast tumor and the corresponding axillary metastatic lymph nodes and adjacent non-tumor breast tissues. The differentially expressed proteins were identified in the signaling pathways of granzyme B, sirtuins, eIF2, actin cytoskeleton, eNOS, acute phase response and calcium and were connected to the upstream regulators MYC, PI3K SMARCA4 and cancer-related chemical drugs. An additional proteomic comparative analysis was performed with a primary breast tumor of a female patient and revealed an interesting set of proteins, which were mainly involved in cancer biology. Together, our data provide a relevant data source for the MBC research that can help the therapeutic strategies for its management.

7.
Exp Biol Med (Maywood) ; 245(18): 1637-1647, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787463

RESUMO

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients' prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients' tumor specimens, in the direction toward personalized medicine.


Assuntos
Linhagem da Célula , Modelos Biológicos , Neuroblastoma/patologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Humanos , Neuroblastoma/genética , Fenótipo
8.
Data Brief ; 25: 104125, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31294064

RESUMO

Data present here describe a comparative proteomic analysis among the malignant [primary breast tumor (PT) and axillary metastatic lymph nodes (LN)], and the non-tumor [contralateral (NCT) and adjacent (ANT)] breast tissues. Protein identification and quantification were performed through label-free mass spectrometry using a nano-liquid chromatography coupled to an electrospray ionization-mass spectrometry (nLC-ESI-MS/MS). The mass spectrometry proteomic data have been deposited to the ProteomeXchange Consortium via PRIDE partner repository with the dataset identifier PXD012431. A total of 462 differentially expressed proteins was identified among these tissues and was analyzed in six groups' comparisons (named NCTxANT, PTxNCT, PTxANT, LNxNCT, LNxANT and PTxLN). Proteins at 1.5 log2 fold change were submitted to the Ingenuity® Pathway Analysis (IPA) software version 2.3 (QIAGEN Inc.) to identify biological pathways, disease and function annotation, and interaction networks related to cancer biology. The detailed data present here provides information about the proteome alterations and their role on breast tumorigenesis. This information can lead to novel biological insights on cancer research. For further interpretation of these data, please see our research article 'Quantitative label-free mass spectrometry using contralateral and adjacent breast tissues reveal differentially expressed proteins and their predicted impacts on pathways and cellular functions in breast cancer' [2].

9.
Epigenetics ; 14(8): 741-750, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31062660

RESUMO

Alternative protein-coding transcripts of the RASSF1 gene have been associated with dual functions in human cancer: while RASSF1C isoform has oncogenic properties, RASSF1A is a tumour suppressor frequently silenced by hypermethylation. Recently, the antisense long non-coding RNA RASSF1 (ANRASSF1) was implicated in a locus-specific mechanism for the RASSF1A epigenetic repression mediated by PRC2 (Polycomb Repressive Complex 2). Here, we evaluated the methylation patterns of the promoter regions of RASSF1A and RASSF1C and the expression levels of these RASSF1 transcripts in breast cancer and breast cancer cell lines. As expected, RASSF1C remained unmethylated and RASSF1A was hypermethylated at high frequencies in 75 primary breast cancers, and also in a panel of three mammary epithelial cells (MEC) and 10 breast cancer cell lines (BCC). Although RASSF1C was expressed in all cell lines, only two of them expressed the transcript RASSF1A. ANRASSF1 expression levels were increased in six BCCs. In vitro induced demethylation with 5-Aza-2'-deoxicytydine (5-Aza-dC) resulted in up-regulation of RASSF1A and an inverse correlation with ANRASSF1 relative abundance in BCCs. However, increased levels of both transcripts were observed in two MECs (184A1 and MCF10A) after treatment with 5-Aza-dC. Overall, these findings indicate that ANRASSF1 is differentially expressed in MECs and BCCs. The lncRNA ANRASSF1 provides new perspectives as a therapeutic target for locus-specific regulation of RASSF1A.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA , RNA Longo não Codificante/genética , Proteínas Supressoras de Tumor/genética , Processamento Alternativo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Carga Tumoral
10.
Genet Mol Biol ; 42(1): 26-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30816904

RESUMO

Copy number alterations (CNAs) are a frequent feature in human breast cancer, and one of the hallmarks of genomic instability. The FOSL1, GSTP1 and CCND1 genes are located at 11q13, a cytoband commonly affected by CNA in breast cancer, with relevant function in progression and invasion. Our main goal was to analyze CNAs of these genes and determine their association with breast cancer subtypes. Seventy-three cases of invasive breast tumors [52 Luminal, 7 HER2+ and 14 triple negative (TNBC) subtypes] were analyzed by TaqMan assays. CNAs were observed for all genes, with gains more frequently observed. Gains of the FOSL1 gene were observed in 71% of the cases. This gene was the only one with a statistically significant difference (p<0.001) among tumor subtypes, with increased copy number in TNBC compared to luminal and HER2+. No significant association of CNA and clinical and histopathological parameters from the patients was observed. Additional studies in larger breast cancer patient cohorts based on more refined molecular subtypes are necessary to confirm the observed association of FOSL1 gain with aggressive breast tumors phenotypes.

11.
J Proteomics ; 199: 1-14, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30772490

RESUMO

Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. A total of 462 proteins was observed as differentially expressed (DEPs) among the groups analyzed. A high level of similarity was observed in the proteome profile of both non-tumor breast tissues and DEPs (n = 12) were mainly predicted in the RNA metabolism. The DEPs among the malignant and non-tumor breast tissues [n = 396 (PTxNCT) and n = 410 (LNxNCT)] were related to pathways of the LXR/RXR, NO, eNOS, eIF2 and sirtuins, tumor-related functions, fatty acid metabolism and oxidative stress. Remarkable similarity was observed between both malignant tissues, which the DEPs were related to metastatic capabilities. Altogether, our findings revealed differential proteomic profiles that affected cancer associated and interconnected signaling processes. Validation studies are recommended to demonstrate the potential of individual proteins and/or pathways as biological markers in breast cancer. SIGNIFICANCE: The proteomic analysis of this study revealed high similarity in the proteomic profile of the contralateral and adjacent non-tumor breast tissues. Significant differences were identified among the proteome of the malignant and non-tumor tissue groups of the same patients, providing relevant insights into the hallmarks, signaling pathways, biological functions, and interactive protein networks that act during tumorigenesis and breast cancer progression. These proteins are suggested as targets of relevant interest to be explored as potential biological markers related to tumor development and metastatic progression in the breast cancer disease.


Assuntos
Neoplasias da Mama/química , Mama/citologia , Proteínas de Neoplasias/análise , Proteoma/análise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/química , Feminino , Humanos , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Regulação para Cima
12.
Breast Cancer Res Treat ; 172(3): 713-723, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30173296

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, is genetically heterogeneous which challenges the identification of clinically effective molecular makers. Extracellular vesicles (EVs) are key players in the intercellular signaling communication and have been shown to be involved in tumorigenesis. The main goal of this study was to evaluate the role and mechanisms of EVs derived from TNBC cells in modulating proliferation and cytotoxicity to chemotherapeutic agents in non-tumorigenic breast cells (MCF10A). METHODS: EVs were isolated from TNBC cell lines and characterized by nanoparticle tracking analysis, Western blot, and transmission electron microscopy. MCF10A cells were treated with the isolated EVs and evaluated for cell proliferation and cytotoxicity to Docetaxel and Doxorubicin by the MTT and MTS assays, respectively. Gene and miRNA expression profiling was performed in the treated cells to determine expression changes that may be caused by EVs treatment. RESULTS: MCF10A cells treated with HCC1806-EVs (MCF10A/HCC1806-EVs) showed a significant increase in cell proliferation and resistance to the therapeutic agents tested. No significant effects were observed in the MCF10A cells treated with EVs derived from MDA-MB-231 cells. Gene and miRNA expression profiling revealed 138 genes and 70 miRNAs significantly differentially expressed among the MCF10A/HCC1806-EVs and the untreated MCF10A cells, affecting mostly the PI3K/AKT, MAPK, and HIF1A pathways. CONCLUSION: EVs isolated from the HCC1806 TNBC cells are capable of inducing proliferation and drug resistance on the non-tumorigenic MCF10A breast cells, potentially mediated by changes in genes and miRNAs expression associated with cell proliferation, apoptosis, invasion, and migration.


Assuntos
Mama/patologia , Vesículas Extracelulares/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Feminino , Perfilação da Expressão Gênica , Humanos , MicroRNAs/análise , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
Hum Pathol ; 43(10): 1661-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22503535

RESUMO

The 2 main histologic types of infiltrating breast cancer, invasive lobular and invasive ductal carcinoma, are morphologically and clinically distinct. Studies revealed that different patterns of gene expression and loss of heterozygosity can also distinguish these 2 subtypes. A whole-genome study using single nucleotide polymorphism array found a significantly higher frequency of loss of heterozygosity on 3p in invasive ductal carcinoma when compared with invasive lobular carcinoma. In this study, we performed a loss of heterozygosity analysis of the 3p chromosome region in ductal and lobular breast tumors. Seven microsatellite markers were evaluated in a series of 136 sporadic breast cancer cases (118 invasive ductal carcinoma and 18 invasive lobular carcinoma) and correlated with clinical-histopathologic parameters from the patients. A significantly higher frequency of loss of heterozygosity was observed in invasive ductal carcinoma (65.3%) when compared with invasive lobular carcinoma (38.9%). When the markers were analyzed separately, loss of heterozygosity at 3 of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3, and D3S1300 in 3p14.2, were significantly more frequent in ductal than in lobular tumors. D3S1307 marker showed the highest frequency of loss of heterozygosity in invasive ductal carcinoma (46.2%), and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples. Our results confirm the observations that invasive ductal carcinoma has a higher frequency of loss of heterozygosity events across the 3p region than invasive lobular carcinoma and show that specific losses on 3p26.3, 3p24.3, and 3p14.2 regions are more frequent in ductal than in lobular tumors. We discuss our data in relation to the known tumor suppressor genes that are mapped at the 3p loci investigated and their present relevant roles in breast cancer.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Cromossomos Humanos Par 3/genética , Perda de Heterozigosidade/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Reação em Cadeia da Polimerase
14.
Epigenetics ; 6(12): 1413-24, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22139571

RESUMO

Epigenetic mechanisms are frequently deregulated in cancer cells and can lead to the silencing of genes with tumor suppressor activities. The isoform A of the Ras-association domain family member 1 (RASSF1A) gene is one of the most frequently silenced transcripts in human tumors, however, few studies have simultaneously investigated epigenetic abnormalities associated with the 3p21.3 tumor suppressor gene cluster flanking RASSF1 (i.e., SEMA3B, HYAL3, HYAL2, HYAL1, TUSC2, RASSF1, ZMYND10, NPRL2, TMEM115, and CACNA2D2). This study aimed to investigate the role of epigenetic changes to these genes in seventeen breast cancer cell lines and in three non-tumorigenic epithelial breast cell lines (184A1, 184B5, and MCF 10A) and to evaluate the effect on gene expression of treatment with the demethylating agent 5-Aza-2'-deoxycytidine and/or Trichostatin A (TSA), a histone deacetylase inhibitor. We report that, although the RASSF1A isoform was determined to be epigenetically silenced in 15 of the 17 breast cancer cell lines, all the cell lines expressed the RASSF1C isoform. Five breast cancer cell lines overexpressed RASSF1C, when compared to the normal epithelial cell line 184A1. Furthermore, the genes HYAL1 and CACNA2D2 were significantly overexpressed after the treatments. After the combinated treatment, RASSF1A re-expression was accompanied by an increase in expression levels of the flanking genes. The Spearman's correlation coefficient indicated a positive co-regulation of the following gene pairs: RASSF1 and TUSC2 (r=0.64, p=0.002), RASSF1 and ZMYND10 (r=0.58, p=0.07), RASSF1 and NPRL2 (r=0.48, p=0.03), ZMYND10 and NPRL2 (r=0.71; p=0,0004), and NPRL2 and TMEM115 (r=0.66, p=0.001). Interestingly, the genes TUSC2, NPRL2 and TMEM115 were found to be unmethylated in each of the untreated cell lines. Chromatin immunoprecipitation using antibodies against the acetylated and trimethylated lysine 9 of histone H3 demonstrated low levels of histone methylation in these genes, which are located closest to RASSF1. These results provide evidence that epigenetic repression is involved in the down-regulation of multiple genes at 3p21.3 in breast cancer cells.


Assuntos
Neoplasias da Mama/genética , Cromossomos Humanos Par 3/genética , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Família Multigênica , Acetilação , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Decitabina , Feminino , Inativação Gênica , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Lisina/metabolismo , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor
15.
Cancer Genet Cytogenet ; 199(1): 24-30, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20417865

RESUMO

Previous studies have shown loss of heterozygosity (LOH) at the BRCA1 and FHIT genes in sporadic primary breast cancer. The aim of this study was to evaluate concomitant LOH at the BRCA1 and FHIT genes in sporadic breast cancer and investigate its influence on patient survival. Loss of heterozygosity was determined using microsatellite markers. The analysis on the informative cases (n = 72) indicated LOH at both the BRCA1 and FHIT loci in 25 cases (35%), the absence of LOH at both loci in 23 cases (32%), and the presence of LOH at one of the loci in 24 cases (33%). The concomitant LOH was associated with poor prognostic factors, such as large tumors (P = 0.01), axillary nodal involvement (P < 0.01), histologic grade III (P < 0.01), vascular invasion (P = 0.01), and negative hormone receptor (P = 0.02). After a median follow-up period of 48 months, the concomitant LOH group had the shortest survival (P < 0.02 by log-rank test; P < 0.05 by Cox model; hazard ratio of 4.87), compared with patients without LOH. These data suggest that concomitant allelic losses of the BRCA1 and FHIT genes are associated with more aggressive breast tumors.


Assuntos
Hidrolases Anidrido Ácido/genética , Proteína BRCA1/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Perda de Heterozigosidade/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Loci Gênicos/genética , Humanos , Estimativa de Kaplan-Meier , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais
16.
Artigo em Português | Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES | ID: biblio-1060727

RESUMO

O câncer de mama é a segunda neoplasia mais frequente em mulheres brasileiras. Dados do Instituto Nacional do Câncer (Inca) estimaram a ocorrência de 49.400 novos casos para o ano de 2008, no Brasil, com taxa de incidência de 51 casos a cada 100.000 mulheres. O Sul do País apresenta uma das mais altas taxas de incidência, com uma estimativa de 56,16 novos casos a cada 100.000 mulheres. Neste estudo, avaliamos 142 pacientes portadoras de carcinoma mamário, provenientes dessa região, em relação às características epidemiológicas e a parâmetros clínicos e histopatológicos. A média de idade das pacientes com diagnóstico confirmado foi de 57,7 + 13,7 anos; 17,6% apresentaram menarca precoce (antes dos 12 anos de idade); 14,7% apresentaram menopausa tardia (após os 55 anos); 18,1% eram nulíparas e 13,9% tiveram a primeira gestação após os 30 anos. Aproximadamente 40% das pacientes declararam ter feito uso de contraceptivos orais durante mais de dez anos e 24% eram fumantes. Grau tumoral II ou III foi observado em 81,1% das pacientes, presença de metástase em linfonodos regionais em 48% e tumor maior que 2 cm em 86%, indicando que o diagnóstico foi realizado em um estádio já avançado da doença. Considerando-se que a detecção precoce do câncer de mama é fator decisivo na determinação do prognóstico, estudos epidemiológicos em diferentes regiões do Brasil são importantes para o desenvolvimento de melhores programas de prevenção e rastreamento.


Assuntos
Feminino , Humanos , Fatores de Risco , Mulheres , Neoplasias da Mama , Neoplasias da Mama/epidemiologia
17.
Cancer Genet Cytogenet ; 173(2): 114-21, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17321326

RESUMO

Genetic heterogeneity is high in breast cancer, and hence it is difficult to link a specific chromosome alteration to a specific clinicopathologic feature. We examined clonal chromosome alterations in 45 breast carcinomas and statistically correlated the findings with clinical-histopathological parameters of the patients. The most common abnormalities were losses of chromosomes 19, 22, 21, X, and 17 and gains of chromosomes 9 and 18. A statistically significant correlation was found between clonal aberrations in chromosomes 17, 20, and 21 and positive lymph node involvement (LN+) and between clonal aberrations in chromosomes X and 6 and negative involvement (LN-). The average number of chromosome abnormalities was the same for both LN- and LN+ groups, and numerical and structural alterations were equally distributed. The mean number of chromosome aberrations did not differ significantly among tumor grades, but when aberrations were analyzed as monosomies, trisomies, and structural aberrations, a heterogeneous distribution was observed. Further cytogenetic investigation of breast tumors and their variable pathological features is undoubtedly necessary. The recognition and ultimately the molecular understanding of these abnormalities may improve breast cancer taxonomy and provide important prognostic information for both the patient and clinician.


Assuntos
Neoplasias da Mama Masculina/genética , Neoplasias da Mama/genética , Aberrações Cromossômicas , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Feminino , Heterogeneidade Genética , Humanos , Cariotipagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade
18.
Leuk Res ; 28(10): 1033-8, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15289014

RESUMO

The presence of the t(12;21)(p13;q22) distinguishes a subset of children with acute lymphoblastic leukemia (ALL) that present a favorable prognosis. This is a cryptic translocation difficult to detect through conventional cytogenetics. In this study, bone marrow samples from 30 children with ALL from southern Brazil were evaluated by fluorescence in situ hybridization (FISH) for the t(12;21), using locus specific probes to detect the TEL/AML1 rearrangement. The selection criteria included: age (0-12 years old); FAB classification (L1 or L2), absence of specific clonal chromosomal aberrations; and adequate cellular integrity to perform FISH analysis. A frequency of 40% of the t(12;21) was observed, in addition to extra copies of the AML1 gene in 7.5% of patients. These findings were analyzed in relation to the patient's clinical parameters and compared with other pediatric populations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 21/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Medula Óssea/patologia , Brasil , Criança , Pré-Escolar , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Sensibilidade e Especificidade , Resultado do Tratamento
19.
Cancer Genet Cytogenet ; 134(2): 123-6, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-12034524

RESUMO

Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3 through pter, 11p14 through q12, and 17p11.2 through qter, and loss of 1q41 through qter and 4q33 through qter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2 through qter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer.


Assuntos
Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/patologia , Invasividade Neoplásica/genética , Adolescente , Adulto , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 8/genética , Análise Citogenética , Humanos , Masculino , Hibridização de Ácido Nucleico
20.
Cancer Genet Cytogenet ; 132(2): 165-8, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11850083

RESUMO

Mature ovarian teratomas are benign ovarian germ cell tumors that usually present with a normal karyotype. There are very few reports describing chromosomal abnormalities in these tumors, none of which are recurrent. In this study we report on a mature teratoma case with clonal chromosomal alterations which include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14 and 21; and deletions of Xq, 5p, 16p, and 17p. Comparative genomic hybridization evaluation of the sample revealed a normal profile. These findings are discussed together with the cytogenetic reports on other cases of ovarian teratomas described in the literature.


Assuntos
Aberrações Cromossômicas , Neoplasias Ovarianas/genética , Teratoma/genética , Adulto , Feminino , Humanos , Cariotipagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...