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1.
Mol Genet Genomic Med ; 8(2): e1079, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31867841

RESUMO

BACKGROUND: One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. METHODS: Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2- BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. RESULTS: In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2-targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2- BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. CONCLUSIONS: In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2- BC patients, respectively.

2.
Cancer Med ; 8(12): 5544-5553, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385461

RESUMO

BACKGROUND: Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. METHODS: Refractory metastatic breast cancer patients who have received molecular screening using next-generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. RESULTS: A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48-8.81; P = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group (P = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively (P = .000). The incidence of grade 3-5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). CONCLUSIONS: Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off-label use in clinical practice.

3.
Clin Lab ; 65(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30775882

RESUMO

BACKGROUND: Recent studies have established non-coding RNAs, which include microRNAs and lncRNAs, are aberrantly expressed in breast cancer. In this study, we explore the expression profile of microRNAs and lncRNAs in ER positive (ER+) breast and paracancerous tissues and define their possible correlations. METHODS: We collected ER+ breast cancer patients' and paracancerous tissues from the specimen bank of Zhejiang Cancer Hospital to extract total RNA for obtaining the expression level of microRNAs and lncRNAs by qRT-PCR. RESULTS: The relative expression results indicated that microRNAs such as MIR-191, MIR-213, MIR-122A had significantly higher expression and MIR-125B-1, MIR-125B-2, MIR-145 had lower expression in ER positive breast cancer compared to normal breast. The interaction of microRNA and lncRNA results exhibited upregulated MIR382-5P and lncRNA 362 in ER+ breast cancer compared to non-cancerous breast. By contrast, MIR222 and NFIA-AS1 are down-regulated. Furthermore, MIR222 and NFIA-AS1 showed different expressions in different TNM stages. CONCLUSIONS: MicroRNAs and lncRNAs are aberrantly expressed in ER+ breast cancer. It is inferred that these microRNAs and lncRNAs may be promising biomarkers for ER positive breast cancer.


Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Receptores Estrogênicos/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação para Baixo , Feminino , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Longo não Codificante/metabolismo , Receptores Estrogênicos/metabolismo , Regulação para Cima
4.
Oncol Lett ; 14(5): 6156-6162, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29113261

RESUMO

It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the CYP19A1 rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of CYP19A1 rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for CYP19A1 rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment.

5.
Oncotarget ; 8(2): 2069-2075, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27906683

RESUMO

We examined the long-term clinical tolerance and cardiac safety of trastuzumab treatment in ninety-four female patients diagnosed with breast cancer with human epidermal growth factor receptor 2 (HER-2) overexpression. Electrocardiography (ECG) was monitored throughout trastuzumab treatment, and left ventricular ejection fractions (LVEFs) were estimated using echocardiography prior to treatment with trastuzumab and every 3 months after its first application. The duration of trastuzumab treatments ranged from 3 to 60 months. Declines in LVEF ≥ 15% were seen mainly after 3-15 months of trastuzumab treatment, and LVEF was lowest at 15 months, which coincided with the largest decline in LVEF from baseline. Spearman correlation coefficients indicated that accumulation of anthracycline, the use of cyto/cardioprotective drugs (CPD) and the duration of trastuzumab treatment were all associated with the change of LVEF, and there was a strong correlation between these factors and the change of LVEF (ρ=0.81, ρ=0.734 and ρ=0.777 respectively). These results indicate that significant decreases of LVEF may be seen after 3-15 months of trastuzumab treatment, but that there is a favorable benefit-risk ratio for patients undergoing long-term trastuzumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Coração/efeitos dos fármacos , Trastuzumab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/fisiopatologia , Cardiotoxicidade/epidemiologia , Monitoramento de Medicamentos/métodos , Ecocardiografia , Feminino , Seguimentos , Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Fatores de Tempo , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda/efeitos dos fármacos
6.
Mol Med Rep ; 13(5): 4046-50, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27035558

RESUMO

The aim of the present study was to establish the underlying regulatory mechanism of estrogen receptor (ER) in breast cancer cell gene expression. A gene expression profile (accession no. GSE11324) was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from an estrogen treatment group and a control group were identified. Chromatin immunoprecipitation with high­throughput sequencing data (series GSE25710) was obtained from the GEO for the ER binding sites, and binding and expression target analysis was performed. A total of 3,122 DEGs were obtained and ER was demonstrated to exhibit inhibition and activation roles during the regulation of its target gene expression. Motif analysis revealed that the upregulated target genes that demonstrated interactions with ER were meis homeobox 1 (MEIS1) and forkhead box P3 (FOXP3). The downregulated target genes, which demonstrated interactions with ER, were thyroid hormone receptor, ß (THRB) and grainyhead­like 1 (GRHL1). Thus, it was observed that ER stimulated gene expression by interacting with MEIS1 and FOXP3, and ER inhibited gene expression by interacting with THRB and GRHL1. However, additional experiments are required to provide further confirmation of these findings.


Assuntos
Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas de Neoplasias/genética , Receptores Estrogênicos/genética
7.
Oncoimmunology ; 5(1): e1063772, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26942079

RESUMO

Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune dysfunction is an important mechanism that leads to tumor immune escape and the inefficacy of cancer immunotherapy. Importantly, tumor-infiltrating MDSCs have much stronger ability compared to MDSCs in the periphery. However, the mechanisms that tumor microenvironment induces the accumulation and function of MDSCs are poorly understood. Here, we report that Interleukin-33 (IL-33) - a cytokine which can be abundantly released in tumor tissues both in 4T1-bearing mice and breast cancer patients, is crucial for facilitating the expansion of MDSCs. IL-33 in tumor microenvironment reduces the apoptosis and sustains the survival of MDSCs through induction of autocrine secretion of GM-CSF, which forms a positive amplifying loop for MDSC accumulation. This is in conjunction with IL-33-driven induction of arginase-1 expression and activation of NF-κB and MAPK signaling in MDSCs which augments their immunosuppressive ability, and histone modifications were involved in IL-33 signaling in MDSCs. In ST2-/- mice, the defect of IL-33 signaling in MDSCs attenuates the immunosuppressive and pro-tumoral capacity of MDSCs. Our results identify IL-33 as a critical mediator that contributes to the abnormal expansion and enhanced immunosuppressive function of MDSCs within tumor microenvironment, which can be potentially targeted to reverse MDSC-mediated tumor immune evasion.

8.
Oncol Rep ; 35(2): 683-90, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26572075

RESUMO

MicroRNAs are emerging as critical regulators of the initiation and progression of multiple types of human cancers, including breast cancer. In the present study, the expression of miR-181b in breast cancer patient serum and breast cancer cell lines was evaluated. It was demonstrated that the miR-181b level was significantly upregulated in patient serum and breast cancer cell lines compared with that in normal controls. The results of in vitro 3H thymidine incorporation and Transwell migration assay indicated that miR-181b overexpression markedly promoted the proliferation and metastasis of breast cancer cells. These data suggest that miR-181b is a tumor promoter in breast cancer. Furthermore, miR-181b expression was found to be upregulated in doxorubicin (DOX)-resistant T-47D cells (T-47D-R) compared with that in the parental T-47D cells, and upregulation of miR-181b expression decreased the anticancer effect of DOX in the T-47D cells. Mechanistic studies demonstrated that the Bim gene, an essential initiator of apoptosis, was inhibited by miR-181b overexpression. We observed that knockdown of miR-181b by its specific inhibitors significantly re-sensitized the T-47D-R cells to the cytotoxicity of DOX. Importantly, we demonstrated that miR-181b inhibitors increased the level of Bim in the T-47D-R cells, resulting in the loss of mitochondrial membrane potential (MMP) and the activation of caspases caused by DOX. In summary, the results of the present study suggest that miR-181b functions as an oncogene during breast cancer development, and the miR-181b/Bim pathway may be a novel target used to overcome the chemoresistance in breast cancer.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Membrana/biossíntese , MicroRNAs/genética , Proteínas Proto-Oncogênicas/biossíntese , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Western Blotting , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Membrana/genética , Oncogenes/genética , Proteínas Proto-Oncogênicas/genética , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
9.
Oncol Lett ; 10(2): 723-729, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26622560

RESUMO

The aim of the present study was to investigate the immunohistochemical expression of cluster of differentiation (CD) 34 and vascular endothelial growth factor (VEGF) in breast cancer tissue, and their prognostic significance. High CD34 expression levels (microvessel density, >15/HPF) were identified in 27.3% (12/44) of cases, exhibiting no significant correlation with the clinicopathological characteristics of the patients. However, Kaplan-Meier analysis demonstrated that the survival time of patients with high CD34 expression was significantly shorter than that of patients with low CD34 expression (50.0 vs. 90.6%; P=0.003). Samples with high VEGF expression levels (++ or +++) accounted for 63.6% (28/44) of the total number of cases. High VEGF expression was significantly prevalent in patients aged ≥50 years compared with patients aged <50 years (≤78.6 vs. 37.5%; P=0.006). Furthermore, all patients with vascular invasion exhibited high VEGF expression levels; thus, patients with vascular invasion presented with significantly higher VEGF expression rates compared with patients with no vascular invasion (100.0 vs. 55.6%; P=0.018). However, Kaplan-Meier analysis demonstrated that high VEGF expression was not correlated with the overall survival of the patients (P=0.366). By contrast, Cox multivariate analysis identified that clinical stage, triple-negative subtype and age were independent prognostic factors for patients with breast cancer (P=0.005, P=0.006 and P=0.032, respectively), and that CD34 expression was a potential independent prognostic factor (P=0.055). Therefore, the present study determined that for patients with breast cancer, a high level of CD34 expression may be a potential indicator of a poor prognosis.

10.
Int J Clin Exp Pathol ; 8(5): 5309-17, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26191232

RESUMO

PURPOSE: The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. METHODS: Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). RESULTS: Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P=0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P=0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P=0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P=0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P=0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P=0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P=0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P=0.013). CONCLUSIONS: The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Aromatase/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antineoplásicos Hormonais/farmacocinética , Aromatase/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Hormônio-Dependentes/enzimologia , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/mortalidade , Seleção de Pacientes , Farmacogenética , Fenótipo , Pós-Menopausa , Medicina de Precisão , Pré-Menopausa , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
PLoS One ; 10(3): e0121535, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25793413

RESUMO

PURPOSE: Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study. METHODS: Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I-II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS). RESULTS: In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002). CONCLUSIONS: The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer.


Assuntos
Aromatase/genética , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Pré-Menopausa/genética , Prognóstico , Adulto Jovem
12.
Int J Clin Exp Pathol ; 7(3): 1108-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24696727

RESUMO

BACKGROUND: HER-2 overexpression is an independent predictor for poor prognosis of breast cancer patients. Recently, extracellular domain of HER-2 (ECD) was found detectable in the serum of breast cancer patients. In this prospective study, we wonder whether ECD levels predict the clinical outcome of metastatic breast cancer patients. METHODS: ECD were measured in 190 women with metastatic breast cancer. Chi-square test was performed to determine the relationship between ECD status and clinical outcomes. Kaplan-Meier curves were applied for survival analysis. RESULTS: Elevated ECD levels were significantly associated with short-term response to Herceptin treatment. The median PFS was significantly longer in ECD-Low patients. The patients who remained low ECD levels or achieved low ECD levels after treatments have significantly longer PFS than those whose levels remained high or converted from low to high. CONCLUSIONS: Overall, our results support the clinical utility of measuring serum HER2 ECD levels in patients with advanced breast cancer. Baseline and serial measurements of serum ECD levels are reliably predictive of clinical outcome of breast cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estrutura Terciária de Proteína , Trastuzumab
13.
Anat Rec (Hoboken) ; 294(6): 941-4, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21548109

RESUMO

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to screen serum samples to identify protein markers for early breast cancer relapse. We collected 67 serum samples from patients with breast cancer (24 preoperative; 23 postoperative without breast cancer relapse; 20 postoperative with breast cancer relapse). Eight protein peaks varied between the presurgical group and the postsurgical group without breast cancer relapse; 4 protein peaks were differentially expressed between the postsurgical patients without relapse and patients with relapse. The peak at 3964 m/z dropped after surgery and rebounded after relapse (P < 0.01). These results indicate that there are differences in serum protein expression among the three different groups of patients. SELDI-TOF MS could be used to screen blood samples for the early detection of relapse in primary breast cancer patients. Specifically, protein peak at 3964 m/z is a potential biomarker for the detection of early breast cancer relapse.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Idoso , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade
14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(2): 189-94, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21488216

RESUMO

OBJECTIVE: To construct eukaryotic expression plasmids containing green fluorescent protein gene and CYP19 wild-type or its variants (W39R, R264C, W39R-R264C) and to observe its expression in MCF-7 and Bcap-37 cells. METHODS: The aromatase WT cDNA sequence was obtained by RT-PCR amplification and cloned into the eukaryotic expression vector pcDNA3.1(+). pcDNA3.1(+)-CYP19-GFP plasmid was then used as the template for site-directed mutation to create variant constructs (W39R, R264C, W39R-R264C). pcDNA3.1(+)-CYP19-GFP was transfected and expressed in MCF-7 and Bcap-37 cells. RESULT: The construction of pcDNA3.1(+)-CYP19-GFP plasmid was confirmed by enzyme digestion and DNA sequencing. pcDNA3.1(+)-CYP19(W39R)-GFP, pcDNA3.1(+)-CYP19(R264C)-GFP, pcDNA3.1(+)- CYP19(W39R-R264C)-GFP plasmids were confirmed by DNA sequencing. The MCF-7 and Bcap-37 cells transfected with the pcDNA3.1(+)-CYP19-GFP plasmid expressed reporter gene of GFP. CONCLUSION: The eukaryotic expression plasmids have been constructed and expressed in MCF-7 and Bcap-37 cells successfully, which lays the foundation for the research of biological activities of CYP19 variant allozymes.


Assuntos
Aromatase/genética , Vetores Genéticos , Plasmídeos/genética , Linhagem Celular Tumoral , Proteínas de Fluorescência Verde/genética , Humanos , Mutagênese Sítio-Dirigida , Proteínas Recombinantes de Fusão/genética , Transfecção
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