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1.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462019

RESUMO

Male breast cancer is rare and has been frequently associated with cancer predisposing variants, particularly in BRCA 1 and BRCA 2 genes. ATM pathogenic variants may also increase risk for breast and other cancers. However, less than 10 cases relating ATM mutations and male breast cancer have been previously reported. Therefore, risk estimates and surveillance recommendations are not well established. We report a case of a male patient with breast cancer found to be heterozygous for a pathogenic ATM variant after multigene testing. We also review the literature regarding increased cancer risk associated with ATM germline variants, with emphasis on potential recommendations for surveillance and follow-up.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama Masculina/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/genética , Mutação em Linhagem Germinativa , Neoplasias da Mama Masculina/genética , Humanos , Masculino , Pessoa de Meia-Idade
2.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370954

RESUMO

Type 1 multiple endocrine neoplasia (MEN-1) syndrome is an autosomal dominant disease, associated with germline mutations in the MEN-1 tumour suppressor gene (encoding the menin protein). Recent studies, through a better characterisation of the functions of the menin protein, have started to demonstrate how changes in this protein may be related to breast cancer. We present the case of a patient whose diagnosis of MEN-1 syndrome was made during treatment for a breast tumour-this diagnosis was obtained after finding multiple neoplastic lesions that fitted the MEN-1 syndrome spectrum, during the initial staging and subsequent follow-up of a breast tumour. In line with the growing evidence that links MEN-1 syndrome to breast cancer tumorigenesis, this case report highlights the following question: should we start screening this subset of patients earlier for breast cancer?


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Proteínas Proto-Oncogênicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Tumor Carcinoide/sangue , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Feminino , Aconselhamento Genético , Mutação em Linhagem Germinativa , Humanos , Achados Incidentais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imagem por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/terapia , Mutação , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Glândulas Paratireoides/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/terapia , Paratireoidectomia , Pneumonectomia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X , Ultrassonografia Mamária
3.
Medicine (Baltimore) ; 99(40): e22203, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019395

RESUMO

Breast cancer (BC) is a disease of high mortality rate because of high malignant, while early diagnosis and personal management may make a better prognosis possible. This study aimed to establish and validate lncRNAs signatures to improve the prognostic prediction for BC.RNA sequencing data along with the corresponding clinical information of patients with BC were gained from The Cancer Genome Atlas (TCGA). Prognostic differentially expressed lncRNAs were obtained using differentially expressed lncRNAs analysis (P value <.01 and |fold change| > 2) and univariate cox regression (P value <.05). By applying least absolute shrinkage and selection operation (LASSO) Cox regression analysis along with 10-fold cross-validation, 2 lncRNA-based signatures were constructed in the training, test and whole set.A 14-lncRNAs signature and a 10-lncRNAs signature were built for overall survival (OS) and relapse-free survival (RFS) respectively in the 3 sets. BC patients were divided into high-risk groups and low-risk groups depended on median risk score value. Significant differences were found for OS and RFS between 2 groups in the 3 sets. The time-dependent receiver operating characteristic (ROC) curves analysis demonstrated that our lncRNAs signatures had better predictive capacities of survival and recurrence for BC patients as well as enhancing the predictive ability of the tumor node metastasis (TNM) stage system.These results indicate that the 2 lncRNAs signatures with the potential to be biomarkers to predict the prognosis of BC for OS and RFS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC
4.
Anticancer Res ; 40(10): 5649-5657, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988889

RESUMO

BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67. MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of ≥5% nüclear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive. RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger. CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.


Assuntos
Carcinoma Ductal de Mama/genética , Fator de Transcrição GATA3/genética , Antígeno Ki-67/genética , Recidiva Local de Neoplasia/genética , Adulto , Biomarcadores Tumorais , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Intervalo Livre de Doença , Estrogênios/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Progesterona/genética , Prognóstico , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética
5.
PLoS One ; 15(9): e0238262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886682

RESUMO

Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal de Mama/etnologia , Carcinoma Ductal de Mama/genética , Hispano-Americanos/estatística & dados numéricos , Mutação , Neoplasias de Mama Triplo Negativas/etnologia , Neoplasias de Mama Triplo Negativas/genética , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/patologia
6.
Br J Radiol ; 93(1115): 20200135, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32816520

RESUMO

For many individuals, the term 'cancer' equates to a disease that if untreated will progress, spread from the area initially affected and ultimately cause death. 'Breast cancer', however, is a diverse of range of pathological entities, incorporating indolent to fast-growing and aggressive lesions, with varying histological patterns, clinical presentations, treatment responses and outcomes. Screening for malignancy is based on the assumption that cancer has a gradual, orderly progression and that detecting lesions earlier in their natural history, and intervening, will reduce mortality. The natural history of epithelial atypia, ductal carcinoma in situ and even invasive breast cancer is poorly understood, but widely variable. We believe that population breast screening methodology needs to change to focus on diagnosis of lesions of greatest clinical relevance.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Programas de Rastreamento/métodos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/genética , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Perfilação da Expressão Gênica , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Programas de Rastreamento/efeitos adversos
7.
PLoS One ; 15(6): e0234012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544183

RESUMO

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.


Assuntos
Carcinoma Ductal de Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral , Antígeno CD24/metabolismo , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Microfluídica/métodos , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/genética
8.
Breast Cancer Res ; 22(1): 68, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576280

RESUMO

BACKGROUND: Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. Here we describe six breast cancer cell lines derived from patient-derived xenografts (PDX) and their general characteristics. METHODS: Established breast cancer PDX were processed into cell suspensions and placed into standard 2D cell culture; six emerged into long-term passageable cell lines. Cell lines were assessed for protein expression of common luminal, basal, and mesenchymal markers, growth assessed in response to estrogens and endocrine therapies, and RNA-seq and oncogenomics testing performed to compare relative transcript levels and identify putative oncogenic drivers. RESULTS: Three cell lines express ER and two are also progesterone receptor (PR) positive; PAM50 subtyping identified one line as luminal A. One of the ER+PR+ lines harbors a D538G mutation in the gene for ER (ESR1), providing a natural model that contains this endocrine-resistant genotype. The third ER+PR-/low cell line has mucinous features, a rare histologic type of breast cancer. The three other lines are ER- and represent two basal-like and a mixed ductal/lobular breast cancer. The cell lines show varied responses to tamoxifen and fulvestrant, and three were demonstrated to regrow tumors in vivo. RNA sequencing confirms all cell lines are human and epithelial. Targeted oncogenomics testing confirmed the noted ESR1 mutation in addition to other mutations (i.e., PIK3CA, BRCA2, CCND1, NF1, TP53, MYC) and amplifications (i.e., FGFR1, FGFR3) frequently found in breast cancers. CONCLUSIONS: These new generation breast cancer cell lines add to the existing repository of breast cancer models, increase the number of ER+ lines, and provide a resource that can be genetically modified for studying several important clinical breast cancer features.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linhagem Celular Tumoral , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Técnicas de Cultura de Células , Feminino , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
10.
Nat Commun ; 11(1): 1723, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265444

RESUMO

Metaplastic breast carcinoma (MBC) is a highly aggressive form of triple-negative cancer (TNBC), defined by the presence of metaplastic components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantify 5798 proteins in MBC, TNBC, and normal breast from 27 patients. Comparing MBC and TNBC protein profiles we show MBC-specific increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. MBC subtypes exhibit distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous, and extracellular matrix proteins in sarcomatoid subtypes. Comparison of the proteomes of human spindle MBC with mouse spindle (CCN6 knockout) MBC tumors reveals a shared spindle-specific signature of 17 upregulated proteins involved in translation and 19 downregulated proteins with roles in cell metabolism. These data identify potential subtype specific MBC biomarkers and therapeutic targets.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteoma/metabolismo , Sarcoma/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Transição Epitelial-Mesenquimal/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Redes e Vias Metabólicas/genética , Metaplasia/genética , Metaplasia/metabolismo , Camundongos , Pessoa de Meia-Idade , Mutação , Biossíntese de Proteínas/genética , Proteoma/genética , Proteômica , Sarcoma/genética , Sarcoma/secundário , Fuso Acromático/genética , Fuso Acromático/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
11.
Oncol Rep ; 43(6): 1819-1830, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236595

RESUMO

Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para­carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Dano ao DNA , Histonas/metabolismo , Lisina/química , Proteômica/métodos , Acetilação , Adulto , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Ácido Succínico/química , Regulação para Cima
12.
Sci Rep ; 10(1): 4113, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139710

RESUMO

Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.


Assuntos
Neoplasias da Mama/classificação , Carcinoma Ductal de Mama/classificação , Aprendizado de Máquina Supervisionado , Transcriptoma , Algoritmos , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Detecção Precoce de Câncer , Feminino , Ontologia Genética , Humanos , Aprendizado de Máquina , Análise em Microsséries , Modelos Biológicos , Estadiamento de Neoplasias , Mapas de Interação de Proteínas , RNA Neoplásico , RNA-Seq , Reprodutibilidade dos Testes
13.
Chem Biol Interact ; 323: 109057, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32198086

RESUMO

Runx2 (Runt-related transcription factor 2) is a key transcription factor which is associated with osteoblast differentiation and expressed in ER+ (estrogen receptor positive) human breast cancer cell lines. Runx2 also participates in mammary gland development. Deregulation of RNA Pol III genes (polymerase III-dependent genes) is tightly linked to tumor development, while Brf1 (TFIIB-related factor 1) specifically regulates these gene transcription. However, nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription. Expression of Runx2, Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT-qPCR, immunoblot, luciferase reporter activity, immunohistochemistry, chromatin immunoprecipitation and Immunofluorescence. High expression of Runx2 is observed in the cases of breast cancer. The patients of high Runx2 expression at early stages display longer survival period, whereas the cases of high Runx2 at advanced stages reveal faster recurrence. The identification of signaling pathway indicates that JNK1 and c-Jun mediate Runx2 transcription. Repression of Runx2 reduces Brf1 expression and Pol III gene transcription. Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue. Both Runx2 and Brf1 synergistically modulate Pol III gene transcription. These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer, while high Runx2 expression indicates long survival period and faster recurrence. Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , RNA Polimerase III/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Transcrição Genética/efeitos dos fármacos , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Transdução de Sinais , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/genética , Adulto Jovem
14.
Sci Rep ; 10(1): 3242, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094468

RESUMO

Most gene-environmental studies have focused on breast cancers generally, the preponderance of which occur after age 50. Young-onset breast cancers (YOBC) tend to be aggressive and may be etiologically different. The goal of this analysis was to assess interactions between an established 77-SNP polygenic risk score (PRS) and non-genetic risk factors for YOBC. We constructed the PRS using a family-based study of 1,291 women diagnosed with breast cancer before age 50 and their parents and unaffected sisters. We used conditional logistic regression to analyze interactions between the PRS and 14 established risk factors. In further analyses we assessed the same interactions, but for invasive cancer, estrogen receptor (ER) positive cancer and with broader inclusion of racial/ethnic groups. Results showed a decreased association between the PRS and YOBC risk for women who had ever used hormonal birth control (odds ratio [OR] = 2.20 versus 3.89) and a stronger association between the PRS and YOBC risk in pre-menopausal women (OR = 2.46 versus 1.23). Restricting the analysis to ER+ cancers or invasive cancers or using samples from all ethnic groups produced similar results. In conclusion, the PRS may interact with hormonal birth control use and with menopausal status on risk of YOBC.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Herança Multifatorial/genética , Idade de Início , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Grupo com Ancestrais do Continente Europeu , Família , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Fatores de Risco
15.
Arch Med Res ; 51(1): 41-53, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32086108

RESUMO

BACKGROUND AND AIMS: HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis. METHODS: TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured. RESULTS: Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells. CONCLUSION: Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Proteínas do Citoesqueleto/genética , Metabolismo Energético/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Antígenos CD/genética , Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Caderinas/genética , Anidrase Carbônica IX/genética , Carcinoma Ductal de Mama/genética , Proliferação de Células/genética , Proteínas do Citoesqueleto/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células MCF-7 , Metástase Neoplásica , Regulação para Cima/genética
16.
BMC Cancer ; 20(1): 119, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050925

RESUMO

BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk. METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies. RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis. CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Biologia Computacional , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transcriptoma
17.
Indian J Pathol Microbiol ; 63(1): 19-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32031117

RESUMO

Background: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated. Methods: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated. Results: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF. Conclusion: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Transativadores/genética , Adulto , Biomarcadores Tumorais , Carcinoma Ductal de Mama/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética
19.
Eur J Cancer ; 127: 240-250, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31956037

RESUMO

BACKGROUND: The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy. PATIENTS AND METHODS: Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization. RESULTS: TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71-0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68-0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy. CONCLUSION: In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Linfócitos do Interstício Tumoral/imunologia , Mutação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carboplatina/administração & dosagem , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/imunologia , Carcinoma Lobular/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Tiotepa/administração & dosagem , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia
20.
Asian Pac J Cancer Prev ; 21(1): 255-258, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983193

RESUMO

BACKGROUND: Paraoxonase 1 (PON1), a multifactorial antioxidant enzyme, has a defensive role against oxidative stress, which is believed to contribute to cancer development. This study aimed to investigate the association of PON1-L55M functional polymorphism with breast cancer risk. MATERIAL AND METHODS: In the experimental study, blood samples were collected from 150 healthy women controls and 150 breast cancer subjects. The L55M genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Our analysis showed that the genotypes distribution is in Hardy-Weinberg equilibrium for both case and control groups. Our data revealed that there are significant associations between PON1-L55M polymorphism and breast cancer risk in homozygote (OR= 2.13, 95%CI= 1.14-4.00, p= 0.018), dominant (OR= 1.72, 95%CI= 1.07-2.76, p= 0.024), and allelic (OR= 1.55, 95%CI= 1.12-2.15, p= 0.008) models. CONCLUSIONS: Our results suggest that the PON1-L55M genetic variation could be a genetic risk factor for breast cancer risk and it could be considered as a molecular biomarker for screening of susceptible women.
.


Assuntos
Arildialquilfosfatase/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Predisposição Genética para Doença , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Polimorfismo Genético , Prognóstico , Fatores de Risco
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