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1.
Medicine (Baltimore) ; 100(22): e25878, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087829

RESUMO

ABSTRACT: The study aimed to explore the value of ultrasound (US) texture analysis in the differential diagnosis of triple-negative breast cancer (TNBC) and non-TNBC.Retrospective analysis was done on 93 patients with breast cancer (35 patients with TNBC and 38 patients with non-TNBC) who were admitted to Taizhou people's hospital from July 2015 to June 2019. All lesions were pathologically proven at surgery. US images of all patients were collected. Texture analysis of US images was performed using MaZda software package. The differences between textural features in TNBC and non-TNBC were assessed. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of textural parameters showing significant difference.Five optimal texture feature parameters were extracted from gray level run-length matrix, including gray level non-uniformity (GLNU) in horizontal direction, vertical gray level non-uniformity, GLNU in the 45 degree direction, run length non-uniformity in 135 degree direction, GLNU in the 135 degree direction. All these texture parameters were statistically higher in TNBC than in non-TNBC (P <.05). Receiver operating characteristic curve analysis indicated that at a threshold of 268.9068, GLNU in horizontal direction exhibited best diagnostic performance for differentiating TNBC from non-TNBC. Logistic regression model established based on all these parameters showed a sensitivity of 69.3%, specificity of 91.4% and area under the curve of 0.834.US texture features were significantly different between TNBC and non-TNBC, US texture analysis can be used for preliminary differentiation of TNBC from non-TNBC.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia
2.
Medicine (Baltimore) ; 100(22): e25889, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087833

RESUMO

BACKGROUND: With the attention paid to the heritability of breast cancer, the search for the genetic susceptibility gene of breast cancer has become a hot spot. At present, a number of studies have explored the relationship between rs13347 polymorphism of cluster of differentiation 44 (CD44) gene and breast cancer, but the research conclusions are inconsistent. Therefore, we will use this meta-analysis to explore the role of this gene polymorphism in breast cancer susceptibility. METHODS: The search time is set from the establishment of the database in March 2021 in this study. The search database include China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and China Biology Medicine disc, PubMed, EMBASE, Web of Science and the Cochrane Library. The subjects are observational studies on the relationship between rs13347 polymorphism of CD44 gene and breast cancer (including case-control study, cross-sectional study and a cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by two researchers independently. The data are statistically analyzed by Stata 16.0 software. RESULTS: Based on the existing studies, this study will systematically evaluate the relationship between CD44 gene rs13347 polymorphism and breast cancer. CONCLUSION: This study will provide evidence-based medical evidence to clarify the role of CD44 gene polymorphism in breast cancer, and provide help for the early detection and preventive intervention of breast cancer. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WBC7F.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores de Hialuronatos/genética , Humanos , Recidiva Local de Neoplasia , Polimorfismo de Nucleotídeo Único , Projetos de Pesquisa
3.
Medicine (Baltimore) ; 100(22): e25964, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087839

RESUMO

BACKGROUND: The latest global cancer data from 2020 shows that breast cancer has replaced lung cancer as the number one cancer in the world. Searching for new biomarkers of breast cancer has important clinical significance for early diagnosis, prediction of prognosis, and targeted therapy. MicroRNA-21 (miRNA-21) can be used as a new molecular marker for early diagnosis, prognosis, and treatment of tumors. However, the expression of miRNA-21 in breast cancer and its prognosis are not clear. Therefore, this study conducted a meta-analysis to further clarify the relationship between the expression of miRNA-21 in breast cancer and prognosis. At the same time, we carried out bioinformatics analysis to further analyze the possible molecular mechanism of miRNA-21, so as to provide potential clinical indicators for the diagnosis, treatment, and prognosis of patients. METHODS: PubMed, Medline, Embase, Web of Science, Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and other databases were used to retrieve the published relevant literatures. Include the eligible research, extract the survival data hazard ratios and 95% confidence intervals and other information. STATA16.0 software was used for meta-analysis. Download the miRNA data of breast cancer through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The data extracted for independent sample t test and ROC curve was drawn. OncomiR plotted the survival curve of miRNA-21 on the prognosis of breast cancer. The target genes of miRNA-21 were predicted, and the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed. STRING database and Cytoscape construct protein-protein interaction (PPI) network to obtain Hub gene. The correlation between the expression level of Hub gene in breast cancer and the abundance of immune cell infiltration was analyzed by TIMER database and verified by Kaplan-Meien plotter database. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: In this study, meta-analysis and bioinformatics analysis were used to further explore the prognosis, mechanism, and related pathways of miRNA-21 in breast cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/R32A9.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/biossíntese , Biomarcadores Tumorais , Biologia Computacional , Ontologia Genética , Humanos , Prognóstico , Mapas de Interação de Proteínas , Projetos de Pesquisa
4.
Medicine (Baltimore) ; 100(22): e26103, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087856

RESUMO

ABSTRACT: Breast cancer (BC) is a malignant tumor originating from cells of the breast. Notably, microRNAs have been recognized as biomarkers of BC metastasis. The present study is designed to evaluate the association between microRNA (miR)-367 expression and BC with the variance of clinicopathologic features and prognosis.Initially, 63 BC patients were allocated in the BC group, while the other 40 healthy volunteers were recruited as the control group. miR-367 expression in the serum of patients and healthy controls was detected using real-time polymerase chain reaction. Furthermore, the relation between miR-367 in serum and clinicopathologic features and prognosis of BC patients was accessed.miR-367 expression in serum of the BC group was evidently lower than that in the control group (all P < .001). Besides, miR-367 underexpression in the BC group was closely associated with the variance in tumor nodes metastasis advanced stage, tumor diameter, and lymph node metastasis of BC (all P < .001). In addition, compared with the control group, poorly expressed miR-367 BC group had short period of disease-free survival and overall survival (all P < .001).Our study demonstrated that miR-367 expression is associated with BC clinicopathologic features and prognosis. This investigation may offer new insight for BC treatment.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/biossíntese , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Carga Tumoral
5.
Nat Commun ; 12(1): 3444, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103528

RESUMO

AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.


Assuntos
Arginina/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antineoplásicos/farmacologia , Biocatálise/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Metilação/efeitos dos fármacos , Camundongos Nus , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína-Arginina N-Metiltransferases/deficiência , Proteínas Proto-Oncogênicas c-akt/química , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Pan Afr Med J ; 38: 245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104293

RESUMO

Pulmonary lesions on imaging are presumed to be metastatic lesions in patients with breast cancer. Here, we report an interesting case of a 63-year-old lady with breast carcinoma showing pulmonary lesions on imaging suggestive of pulmonary metastases. Detailed evaluation of pulmonary lesions confirmed the presence of co-existing pulmonary sarcoidosis. Modern diagnostic methods like 18-flurodeoxyglucose positron emission tomography (18-FDG PET) are unable to clearly differentiate metastatic disease from granulomatous diseases like sarcoidosis. Thus, histological confirmation is needed for accurate staging and determining response to treatment and rarely, in non-responders, detecting any co-existing disease. This case emphasizes the need for detailed histopathological examination of lymph nodes in patients with non-responsive disease or recurrent disease despite adequate chemotherapy.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias Pulmonares/diagnóstico , Sarcoidose Pulmonar/diagnóstico , Neoplasias da Mama/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Sarcoidose Pulmonar/patologia
7.
Pan Afr Med J ; 38: 255, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34104303

RESUMO

The management of breast cancer during pregnancy is a challenge for physicians due to mother´s desire to carry the pregnancy to term despite the need for chemotherapy. This study reports the case of a 37-year-old multiparous woman at 20 weeks and 4 days of amenorrhea (WA). She was hospitalized for dyspnoea (stage IV according to New York Heart Association (NYHA) classification). The patient had a syndrome of heavy left pleural effusion and bilateral mastitis. The diagnosis of metastatic breast cancer was retained based on cytological examination of pleural fluid and breast cytoponction revealing galactophoric carcinoma. The patient underwent pleural drainage with improvement of dyspnea but pleural fluid continued. After multidisciplinary consultation (MC), specific treatment of cancer was necessary. Five cycles of epirubicin- cyclophosphamide-5-FU-based chemotherapy was performed after the couple provided consent. Pleural fluid diminished significantly after the second cycle of treatment. After consultation with the obstetrician, chemotherapy was interrupted one month before the 37th week of amenorrhea. Pregnancy evolved favorable, vaginal birth was managed following rupture of membranes at term with good neonatal adaptation. After one-year follow-up, the mother was still on chemotherapy and the baby was in good health. Several parameters should be considered before the administration of antineoplastic agents, hence the role of early fetal and maternal monitoring. Multidisciplinary approach is recommended to support therapeutic decision and follow-up.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Derrame Pleural/diagnóstico , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/patologia
8.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065952

RESUMO

White adipose tissue (WAT) is a heterogeneous tissue that is composed of adipocytes and several non-adipocyte cell populations, including adipose progenitors, fibroblasts, endothelial and infiltrating immune cells [...].


Assuntos
Tecido Adiposo Branco/metabolismo , Neoplasias da Mama/patologia , Adipogenia , Animais , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos
9.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068438

RESUMO

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Interações Medicamentosas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Receptor Notch1/metabolismo , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Células MCF-7 , Receptor Notch1/genética
10.
Nat Commun ; 12(1): 2699, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976188

RESUMO

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 in the tumors of breast cancer patients with poor response to Herceptin-containing regimens. Collectively, we demonstrate that the IGF2/IGF-1R/IRS1 signaling is aberrantly activated in Herceptin-resistant breast cancer via disruption of the FOXO3a-miRNA negative feedback inhibition. Such insights provide avenues to identify predictive biomarkers and effective strategies overcoming Herceptin resistance.


Assuntos
Neoplasias da Mama/genética , Proteína Forkhead Box O3/genética , Proteínas Substratos do Receptor de Insulina/genética , Fator de Crescimento Insulin-Like II/genética , MicroRNAs/genética , Receptor ErbB-2/genética , Receptor IGF Tipo 1/genética , Animais , Antineoplásicos Imunológicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Calcineurina/genética , Calcineurina/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Retroalimentação Fisiológica , Feminino , Proteína Forkhead Box O3/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Fosforilação , Receptor ErbB-2/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Análise de Sobrevida , Trastuzumab/farmacologia , Carga Tumoral/efeitos dos fármacos
11.
Nat Commun ; 12(1): 2954, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34012010

RESUMO

How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.


Assuntos
Neoplasias da Mama/metabolismo , Replicação do DNA/fisiologia , Endonucleases Flap/metabolismo , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , DNA/química , DNA/metabolismo , Dano ao DNA , DNA Polimerase III/genética , DNA Polimerase III/metabolismo , Replicação do DNA/genética , Feminino , Endonucleases Flap/deficiência , Endonucleases Flap/genética , Técnicas de Inativação de Genes , Instabilidade Genômica , Células HCT116 , Humanos , Oxirredutases Intramoleculares/deficiência , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/deficiência , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Conformação de Ácido Nucleico , Poli(ADP-Ribose) Polimerase-1/metabolismo , Fase S , Especificidade por Substrato
12.
Anticancer Res ; 41(5): 2383-2395, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952463

RESUMO

BACKGROUND/AIM: This study aimed to investigate the effect of the new ciprofloxacin chalcone [7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl)] on the proliferation, migration, and metastasis of MCF-7 and MDA-MB-231 breast cancer cell lines. MATERIALS AND METHODS: Cell viability, colony formation and cell migration abilities were analysed. Cell cycle distribution and apoptosis were examined by flow cytometry. The molecular mechanism underlying chalcone's activity was investigated using qRT-PCR and western blotting. RESULTS: This new ciprofloxacin chalcone significantly inhibited proliferation, colony formation, and cell migration abilities of both cancer cell lines. Furthermore, it initiated apoptosis and caused cell cycle arrest at G2/M and S phase in MCF-7 and MDA-MB-231 cell lines, respectively. In addition, it up-regulated the expression of pro-apoptotic factors, p53, PUMA and NOXA, and down-regulated the expression of anti-apoptotic factors, MDM2 and MDM4. At the same time, it inhibited epithelial-mesenchymal transition by increasing the expression of E-cadherin and decreasing the expression of TGF-ß1, SNAI1, TWIST1, MMP2, and MMP9. CONCLUSION: This new ciprofloxacin chalcone exhibited promising apoptotic and anti-metastatic activities against MCF-7 and MDA-MB-231 breast cancer cell lines, and, therefore, is an attractive molecule for drug development in the treatment of breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Chalcona/farmacologia , Ciprofloxacina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/genética , Caderinas/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Chalcona/química , Ciprofloxacina/química , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Molecular , Proteínas/genética , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
13.
Medicine (Baltimore) ; 100(18): e25880, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33951002

RESUMO

ABSTRACT: Whether breast-conserving therapy (BCT) should be chosen as a local treatment for young women with early-stage breast cancer is controversial. This study compared the survival benefits of BCT or mastectomy in young women under 40 with early-stage breast cancer and further explored age-stratified outcomes. This study investigated whether there is a survival benefit when young women undergo BCT compared with mastectomy.The characteristics and prognosis of white women under 40 with stage I-II breast cancer from 1988 to 2016 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. These women were either treated with BCT or mastectomy. The log-rank test of the Kaplan-Meier survival curve and Cox proportional risk regression model were used to analyze the data and survival. The analysis was stratified by age (18-35 and 36-40 years).A total of 23,810 breast cancer patients were included, of whom 44.9% received BCT and 55.1% underwent mastectomy, with a median follow-up of 116 months. Patients undergoing mastectomy had a higher tumor burden and younger age. By the end of the 20th century, the proportion of BCT had grown from nearly 35% to approximately 60%, and then gradually fell to 35% into the 21st century. Compared with the mastectomy group, the BCT group had improved breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.917; 95% CI, 0.846-0.995, P = .037) and overall survival (OS) (HR 0.925; 95% CI, 0.859-0.997, P = .041). In stratified analysis according to the different ages, the survival benefit of BCT was more pronounced in the slightly older (36-40 years) group while there was no significant survival difference in the younger group (18-35 years).In young women with early-stage breast cancer, BCT showed survival benefits that were at least no worse than mastectomy, and these benefits were even better in the 36 to 40 years age group. Young age may not be a contraindication for BCT.


Assuntos
Neoplasias da Mama/cirurgia , Tomada de Decisão Clínica , Mastectomia Segmentar/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Contraindicações de Procedimentos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mastectomia Segmentar/efeitos adversos , Estadiamento de Neoplasias , Prognóstico , Medição de Risco/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
14.
Science ; 372(6543)2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33986153

RESUMO

Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report a systematic effort to decipher the RNA structural code that shapes pathological splicing during breast cancer metastasis. We discovered a previously unknown structural splicing enhancer that is enriched near cassette exons with increased inclusion in highly metastatic cells. We show that the spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts with these enhancers to promote cassette exon inclusion. This interaction enhances metastatic lung colonization and cancer cell invasion, in part through SNRPA1-mediated regulation of PLEC alternative splicing, which can be counteracted by splicing modulating morpholinos. Our findings establish a noncanonical regulatory role for SNRPA1 as a prometastatic splicing enhancer in breast cancer.


Assuntos
Processamento Alternativo , Neoplasias da Mama/patologia , Metástase Neoplásica/genética , RNA/genética , RNA/metabolismo , Ribonucleoproteína Nuclear Pequena U2/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Algoritmos , Animais , Sítios de Ligação , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Progressão da Doença , Éxons , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Transplante de Neoplasias , Conformação de Ácido Nucleico , Plectina/genética , Ligação Proteica , Interferência de RNA , RNA Nuclear Pequeno/química , RNA Nuclear Pequeno/metabolismo , RNA-Seq , Ribonucleoproteína Nuclear Pequena U2/genética , Software , Spliceossomos/metabolismo , Proteínas Supressoras de Tumor/genética
15.
Medicine (Baltimore) ; 100(21): e26146, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032767

RESUMO

RATIONALE: Hormone therapies, particularly those targeting estrogen and its receptors, are a key treatment modality for patients with estrogen receptor (ER)-positive breast or ovarian cancer. Some gastric cancers (GCs) express ERs, and preclinical studies suggest the potential of estrogen-targeting hormone therapy on GC; however, the clinical relevance of this hormone therapy on GC treatment has not been well elucidated. PATIENT CONCERNS: An 80-year-old female was admitted to our department with hypogastric pain and vomiting. Computed tomography demonstrated small bowel obstruction, and laparotomy after bowel decompression revealed peritoneal dissemination consisting of a poorly-differentiated adenocarcinoma. Intestinal bypass between the ileum and transverse colon was performed. DIAGNOSES: The tumor was ER- and mammaglobin-positive, indicating that it originated from a breast cancer. Diagnostic imaging revealed no evidence of breast cancer; however, right axillary ER- and mammaglobin-positive lymphadenopathy was found. INTERVENTIONS: The patient received hormone therapy using letrozole based on a clinical diagnosis of occult breast cancer with peritoneal dissemination and right axillary lymph node metastasis. OUTCOMES: The patient remained disease free until 37 months but deceased at 53 months from the onset of disease. An autopsy revealed no tumor cells in the right breast tissue; however, there was a massive invasion of cancer cells in the stomach. LESSONS: A patient with ER positive GC with peritoneal dissemination and right axillary lymph node metastasis presented remarkable response to letrozole. The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Letrozol/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Evolução Fatal , Feminino , Humanos , Metástase Linfática , Receptores de Estrogênio/análise , Neoplasias Gástricas/secundário
16.
Int J Nanomedicine ; 16: 3059-3071, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953555

RESUMO

Purpose: This study aimed to explain the influence of zein nanosphere (ZN NS) formulation on the pharmacotherapeutic profile of PTS in MCF7 cells. Methods: Liquid-liquid phase separation was used to formulate PTS-ZN NSs. The formulations developed were evaluated for particle-size analysis, encapsulation efficiency, and in vitro diffusion. Also, assays of cytotoxicity, uptake, cell-cycle progression, annexin V, apoptotic gene mRNA expression and biochemical assays were carried out. Results: The PTS-ZN NS formulation selected showed 104.5±6.2 nm, 33.4±1.8 mV, 95.1%±3.6%, and 89.1%±2.65% average particle size, zeta-potential, encapsulation efficiency and in vitro diffusion, respectively. With MCF7 cells, IC50 was reduced approximately 15-fold, with increased cellular uptake, accumulation in the G2/M phase, increased percentage of cells in the pre-G1 phase, amelioration of early and late apoptosis, raised mRNA expression of CASP3 and CASP7, lower expression of cyclin-CDK1, and enhanced oxidant potential through decreased glutathione reductase (GR) activity, and enhanced reactive oxygen-species generation and lipid-peroxidation products. Conclusion: PTS-ZN NSs indicated enhanced antiproliferative, proapoptotic, and oxidant potential toward MCF7 cells compared to free PTS. Ameliorated results of nanosized carriers, cellular uptake, and sustained diffusion may contribute to these outcomes.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Nanocompostos/química , Estilbenos/química , Estilbenos/farmacologia , Zeína/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Células MCF-7 , Oxidantes/química , Oxidantes/farmacologia , Oxirredução , Tamanho da Partícula
17.
Medicine (Baltimore) ; 100(18): e25545, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950928

RESUMO

BACKGROUND: Breast cancer is a common malignant tumor in women. In recent years, its incidence is increasing year by year, and its morbidity and mortality rank the first place among female malignant tumors. Some key enzymes and intermediates in glycolysis are closely related to tumor development. Pyruvate kinase M2 (PKM2) is an important rate-limiting enzyme in glycolysis pathway. Meanwhile, it is highly expressed in proliferative cells, especially in tumor cells, and plays an important role in the formation of Warburg effect and tumorigenesis. Previous studies have explored the effects of PKM2 expression on the prognosis and clinical significance of breast cancer patients, while the results are contradictory and uncertain. This study uses controversial data for meta-analysis to accurately evaluate the problem. We collected relevant Oncomine and The Cancer Genome Atlas (TCGA) data to further verify the results. Through bioinformatics analysis, the mechanism and related pathways of PKM2 in breast cancer are explored. METHODS: We searched Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases from inception to March 2021. The language restrictions are Chinese and English. The published literatures on PKM2 expression and prognosis or clinicopathological characteristics of breast cancer patients were statistically analyzed. Combined hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs) were used to evaluate the effects of PKM2 on the prognosis and clinicopathological features of breast cancer. Stata 14.0 software was applied for meta-analysis. Oncomine and TCGA databases were used to meta-analyze the differences of PKM2 mRNA expression between breast cancer and normal breast tissues. The expression of PKM2 protein was verified by Human Protein Atlas (HPA) database. The relationship between the gene and the survival of breast cancer patients was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between PKM2 gene and clinicopathological characteristics was analyzed by using LinkedOmics, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was performed by using Metascape. Protein-protein interaction (PPI) network was constructed by String website. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study provides high-quality medical evidence for the correlation between the expression of PKM2 and the prognosis and clinicopathological features of breast cancer. Through bioinformatics analysis, this study further deepens the understanding of the mechanism and related pathways of PKM2 in breast cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W52HB.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Mama/patologia , Carcinogênese/patologia , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Proteínas de Transporte/análise , Biologia Computacional , Intervalo Livre de Doença , Feminino , Humanos , Proteínas de Membrana/análise , Metanálise como Assunto , Prognóstico , Medição de Risco/métodos , Hormônios Tireóideos/análise
18.
Medicine (Baltimore) ; 100(18): e25835, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950995

RESUMO

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.


Assuntos
Antineoplásicos Hormonais/farmacologia , Produtos Biológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Antineoplásicos Hormonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Klebsiella pneumoniae/citologia , Klebsiella pneumoniae/metabolismo , Células MCF-7 , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Urina/citologia
19.
Anticancer Res ; 41(5): 2473-2476, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952473

RESUMO

BACKGROUND/AIM: During surgery for patients with known, diffuse metastatic bone disease (MBD), lesional tissue is routinely sent for pathological evaluation. However, there are limited data to assess whether there is a role for histopathology for MBD despite time and cost of interpretation, as well as whether a positive sample changes the subsequent treatment course. PATIENTS AND METHODS: Sixty-six cases from 2017 to 2020 were reviewed retrospectively. The median age at surgery was 63.5 years (range of 23 to 84 years), and the primary tumor was most frequently breast (24.2%, n=16), renal (21.2%, n=14) or lung (15.2%, n=10). The most common location of MBD was the femur (60.6%, n=40). RESULTS: The overall yield of a positive tissue sample of MBD was 77.3% (n=51). The positive rate from sending intramedullary reamings was 65.4% (n=17 of 26). Among the 66 cases (63 patients), a change in the subsequent clinical management was recorded in 9.1% (n=6). The most common change was related to the medication regimen (n=5), with one change related to recognition of the carcinoma origin via histology, which was previously unknown. CONCLUSION: Despite the routine practice of sending tissue for histology during surgery for known and diffuse MBD, a change in the subsequent clinical management is uncommon. Prior to sending tissue, surgeons should discuss this practice with the multidisciplinary care team on a per-patient basis.


Assuntos
Doenças Ósseas/cirurgia , Neoplasias da Mama/cirurgia , Fêmur/cirurgia , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
20.
Anticancer Res ; 41(5): 2489-2494, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952476

RESUMO

BACKGROUND/AIM: Most patients with breast cancer are assigned to radiotherapy, which may cause fears leading to sleep disorders. Very few data are available regarding the prevalence of sleep disorders and corresponding risk factors. PATIENTS AND METHODS: Data of 175 patients with breast cancer presenting for adjuvant radiotherapy were retrospectively analyzed. Twenty-three patient and tumor characteristics were investigated for associations with pre-radiotherapy sleep disorders. RESULTS: Seventy-eight patients (44.6%) stated sleep disorders prior to radiotherapy. These were significantly associated with higher distress score (p<0.0001); greater number of emotional (p<0.0001), physical (p<0.0001) or practical problems (p<0.001); and request for psycho-oncological support (p<0.001). Trends were found for worse performance status (p=0.062) and higher comorbidity index (p=0.059). CONCLUSION: Sleep disorders prior to radiotherapy for breast cancer are common. This applies particularly to patients with risk factors including distress due to emotional, physical or practical problems. These patients should be offered psycho-oncological support as soon as possible.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia Adjuvante/efeitos adversos , Transtornos do Sono-Vigília/radioterapia , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/patologia
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