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1.
Cancer Sci ; 111(1): 209-218, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31724785

RESUMO

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease-free survival (DFS) of patients with high CCL5 levels (cut-off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10-0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Quimiocina CCL5/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo
3.
Zhonghua Zhong Liu Za Zhi ; 41(12): 918-922, 2019 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-31874549

RESUMO

Objective: To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I). Methods: The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results: The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity. Conclusions: GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.


Assuntos
Neoplasias da Mama/sangue , Proteínas Musculares/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Fatores de Transcrição TFII/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Musculares/genética , Proteínas Nucleares/genética , Reação em Cadeia da Polimerase em Tempo Real , Transativadores/genética , Fatores de Transcrição TFII/metabolismo
4.
Anticancer Res ; 39(11): 6317-6324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704862

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate N-acetylgalactosamine-6-sulfatase (GALNS) as a new biomarker candidate for detecting lung cancer. Glycodelin or PAEP, the serum levels of which are known to be elevated in lung and other cancers, served as a benchmark for comparison. PATIENTS AND METHODS: A total of 170 serum samples from healthy controls and patients with pneumonia, lung cancer, breast cancer, colon cancer, liver cancer, and head and neck cancer were analyzed for the levels of GALNS and PAEP by ELISA. RESULTS: The median serum levels of GALNS and PAEP in all cancer types as well as pneumonia patients were significantly higher than those of the healthy controls. CONCLUSION: In addition to previously known cancers, the median serum levels of PAEP were also found to be higher in liver and head and neck cancer patients. GALNS and PAEP are promising general biomarkers for multiple cancers and deserve further evaluation.


Assuntos
Biomarcadores Tumorais/sangue , Condroitina Sulfatases/sangue , Glicodelina/sangue , Neoplasias Pulmonares/sangue , Área Sob a Curva , Benchmarking , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias do Colo/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Neoplasias Hepáticas/sangue , Pulmão/metabolismo , Neoplasias Pulmonares/diagnóstico , Masculino , Pneumonia/sangue
5.
Rev Assoc Med Bras (1992) ; 65(10): 1275-1282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721959

RESUMO

OBJECTIVE: The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older. METHODS: This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables. RESULTS: The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%. CONCLUSIONS: our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias dos Genitais Femininos/sangue , Neoplasias dos Genitais Femininos/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Brasil , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Menopausa Precoce , Estudos Retrospectivos
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 708-713, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762242

RESUMO

OBJECTIVE: To explore the relationships between plasma adiponectin levels and risk of breast cancer by molecular subtype. METHODS: A case-control study including 437 histopathologic confirmed primary breast cancer cases and 469 healthy female controls was conducted between April 2014 and May 2015. Basic information of the participants were collected using a structured questionnaire. Blood samples were collected and the plasma adiponectin levels were measured by enzyme-linked immunosorbent assay (ELASA). Analysis of variance (ANOVA) was used to compare the differences of plasma adiponectin levels among the control group and the breast cancer groups with different molecular subtypes. Multinomial logistic regression was used to investigate the association between plasma adiponectin levels and risk of breast cancer by molecular subtypes. All the statistical analyses were stratified by menopausal status. RESULTS: Among the 437 breast cancer cases, there were 310 Luminal breast cancer cases, 83 HER-2-enriched breast cancer cases and 44 basal-like breast cancer cases. The median (P25, P75) of plasma adiponectin level of the controls was 14.85 (9.69, 21.35) µg/mL. The medians (P25, P75) of plasma adiponectin levels of the cases were 11.74 (8.15, 16.14) µg/mL, 12.02(8.43, 16.96) µg/mL and 12.67(8.25, 17.27) µg/mL for Luminal, HER-2-enriched and basal-like subtype respectively, which were statistically different from the controls (P < 0.001). Multinomial logistic regression showed that, after adjustment for the confounders, the higher levels of plasma adiponectin were associated with the lower risks of pre-menopausal Luminal breast cancer (ORpre-menopausal Luminal=0.50, 95%CI: 0.27-0.92, Ptrend=0.001), post-menopausal Luminal breast cancer (ORpost-menopausal Luminal=0.06, 95%CI: 0.02-0.23, Ptrend < 0.001) and post-menopausal HER-2-enriched breast cancer (ORpost-menopausal HER-2-enriched=0.06, 95%CI: 0.01-0.62, Ptrend=0.001). CONCLUSION: Lower levels of plasma adiponectin may increase the risk of pre-menopausal and post-menopausal Luminal breast cancer and post-menopausal HER-2-enriched breast cancer.


Assuntos
Adiponectina/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/sangue , Neoplasias da Mama/classificação , Estudos de Casos e Controles , Feminino , Humanos , Fatores de Risco
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 738-743, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638571

RESUMO

Objective To investigate the value of serum interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels of breast cancer patients in evaluating immune function after radiotherapy. Methods We randomly selected 55 cases of breast cancer patients who had received radiotherapy as an observation group, and 55 cases of normal healthy adults as a control group. ELISA was used to detect serum IL-6 and sIL-6R levels. Flow cytometry was used to detect CD45+CD19+ B lymphocytes, CD45+CD3+CD4+ T lymphocytes, CD45+CD3+CD8+ T lymphocytes and CD45+CD16+CD56+ NK cells in peripheral blood. The correlation of lymphocyte subsets with IL-6 or sIL-6R levels was analyzed. Results Serum IL-6 and sIL-6R levels of the observation group patients after radiotherapy were significantly higher than those before radiotherapy and in the control group, and the IL-6 and sIL-6R levels of patients of III or IV stage breast cancer increased significantly. Flow cytometry showed that the ratios of total T lymphocytes and NK cells in the observation group after radiotherapy were significantly reduced, while the ratio of B lymphocytes was significantly elevated. In addition, the levels of IL-6 and sIL-6R were positively correlated with the ratio of NK cells and negatively correlated with the ratio of B lymphocytes. Conclusion Serum IL-6 and sIL-6R levels in patients with breast cancer can be used as references for assessing the course of breast cancer and immune function after radiotherapy.


Assuntos
Neoplasias da Mama , Interleucina-6 , Células Matadoras Naturais , Subpopulações de Linfócitos , Receptores de Interleucina-6 , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-6/sangue , Células Matadoras Naturais/citologia , Subpopulações de Linfócitos/citologia
8.
Anticancer Res ; 39(10): 5345-5352, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570428

RESUMO

BACKGROUND/AIM: Accurate and timely assessment of the human epidermal growth factor receptor 2 (HER2/neu) overexpression is pivotal for the identification of breast cancer (BC) patients that could benefit from HER2-targeted therapy. Currently approved tissue-based HER2 assays (tHER2) are limited to testing HER2 status on tumor samples obtained at a few points in time during the course of the disease. Herein, we assessed serum HER2 (sHER2) status longitudinally in 81 serial samples prospectively collected from 43 consenting patients pre- and post-therapy to revisit the idea of serum testing in the follow-up of BC patients. PATIENTS AND METHODS: The cohort included 11 patients with early BC (EBC), 17 with locally advanced BC (LABC), and 15 with metastatic BC (MBC). sHER2 concentrations were measured using a quantitative ELISA-based technique, using 15 ng/ml as the cut-off for positivity. RESULTS: At baseline, sHER2 was negative in all EBC patients while positive in 1 LABC and 5 MBC patients. Sixteen BC patients (10 LABC, 1 EBC, and 5 MBC) were tHER2 positive. sHER2 and tHER2 results were discordant in 14 patients. Among the 16 tHER2 positive patients, 9 LABC, 1 EBC and 2 MBC patients were sHER2 negative. Conversely, 2 MBC patients were sHER2 positive, despite being tHER2 negative. A rise or drop of sHER2 by >20% correlated with disease progression or pathological response to therapy, respectively. CONCLUSION: The study demonstrated the technical validity and feasibility of the sHER2 assay. Findings suggest that post initial tissue diagnosis (tHER2), sHER2 assay may supplement subsequent tissue tests to monitor disease status and response to therapy. Further studies to assess the role of HER2 targeted therapies in sHER-positive/tHER2-negative cases upon disease progression are warranted.


Assuntos
Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Oncogenes/genética , Projetos Piloto
9.
Anticancer Res ; 39(9): 5009-5018, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519608

RESUMO

BACKGROUND/AIM: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer. PATIENTS AND METHODS: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated. RESULTS: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs. CONCLUSION: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Interleucina-18/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Valores de Referência , Estudos Retrospectivos , Carga Tumoral
10.
BMC Med ; 17(1): 178, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31547832

RESUMO

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Metabolômica/métodos , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
11.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 64-72, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472049

RESUMO

Breast cancer is a malignant tumor that occurs in the glandular epithelial tissues of the breast. It is one of the most common malignant tumors in women. This study was aimed at investigating the role of cell-free DNA (cfDNA) as a potential biomarker for breast cancer diagnosis. Patients with primary breast cancer (n =110) were enrolled in the experimental group, 95 patients with benign breast tumors were in control group 1, while 90 healthy volunteers were in control group 2. Quantitative PCR was used to determine cfDNA concentration and integrity in each group. The cfDNA levels in different groups and their relationship with clinical features of breast cancer patients were analyzed. Receiver operational curves were established to analyze sensitivity and specificity of cfDNA concentration, cfDNA integrity, CEA, CA125 and CA15-3. The cfDNA concentration and cfDNA integrity of the experimental group were significantly higher than those of control groups 1 and 2. The cfDNA concentration and integrity in plasma of experimental group after chemotherapy were significantly lower than those before chemotherapy. While CEA and CA15-3 expressions were significantly correlated with cfDNA concentration, CA125 expression was significantly correlated with cfDNA integrity. Results from ROC curve analysis showed that the sensitivity and specificity of cfDNA concentration and integrity were higher than those of traditional tumor biomarkers. These results indicate that cfDNA concentration and integrity are significantly higher in primary breast cancer patients than in benign breast tumor patients and healthy people. Thus, cfDNA may serve as a potential biomarker of breast cancer.


Assuntos
Neoplasias da Mama/sangue , Ácidos Nucleicos Livres/sangue , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ácidos Nucleicos Livres/genética , DNA de Neoplasias/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Adulto Jovem
12.
Nat Commun ; 10(1): 3840, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477698

RESUMO

Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare subpopulation of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Antineoplásicos Hormonais/uso terapêutico , Mama/citologia , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Plasticidade Celular/efeitos dos fármacos , Plasticidade Celular/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Microscopia Intravital , Células MCF-7 , Aprendizado de Máquina , Mutação , Células Neoplásicas Circulantes/efeitos dos fármacos , Análise de Célula Única , Esferoides Celulares
13.
Anal Bioanal Chem ; 411(26): 6889-6897, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401668

RESUMO

Photoelectrochemical (PEC) sensor for sensitive detection of breast cancer biomarker human epidermal growth factor receptor 2 (HER2) utilizing hexagonal carbon nitride tubes (HCNT) as photoactive material is reported. The detection is based on suppression of the PEC current intensity of the sensor. HCNT were synthesized via a facile hydrothermal method with large specific surface area and low electron-hole recombination. Au nanoparticles (AuNPs) were deposited onto the surface of the HCNT, which enhanced the photocurrent intensity of the HCNT by one time. For HER2 detection, peptide specific to HER2 was immobilized on the AuNPs surface for capturing HER2 molecules. The following binding of HER2 with HER2 aptamer and the reaction of phosphate groups on aptamer with molybdate can form molybdophosphate precipitate, which sticks to the surface of HCNT and impedes electron transport. Thus, photocurrent intensity of the sensor was suppressed. Under optimal conditions, the linear relationship between the PEC intensity and the logarithm of HER2 concentration was from 0.5 to 1 ng mL-1 with low limit of detection (LOD) of 0.08 pg mL-1. Furthermore, the PEC sensor also displayed capability for detecting HER2 in human serum samples. This PEC sensor signal detection strategy can be easily adapted to other PEC sensors involving DNA and find wide applications. Graphical abstract.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/sangue , Nitrilos/química , Receptor ErbB-2/sangue , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Técnicas Eletroquímicas/métodos , Feminino , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Peptídeos/química , Receptor ErbB-2/análise
14.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414748

RESUMO

BACKGROUND: The current study aims to investigate the expression of HOXA transcript induced by transforming growth factor-ß (TGF-ß) (HIT) in plasma of women with breast cancer and its potential diagnostic value for breast cancer. METHODS: qRT-PCR was used to detect the expression of HIT in breast cancer tissues and the plasma of patients with breast cancer. The correlation between the expression of HIT in plasma and clinicopathological parameters of breast cancer was analyzed. The levels of CAl53 and CEA in plasma were also detected. Operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of plasma HIT for breast cancer. RESULTS: Compared with the adjacent tissues, the expression of HIT in breast cancer tissues was significantly increased. Meanwhile, the level of plasma HIT in the breast cancer group was significantly higher than that in the benign lesion group and healthy control group. The level of plasma HIT expression in breast cancer patients was correlated with estrogen receptor (ER) erbB-2 and lymph node metastasis (p < 0.05); the area under ROC curve (AUC) of plasma HIT in diagnosis of breast cancer alone was 0.827 with the sensitivity and specificity of 57.7% and 86.4%. The diagnostic efficacy of HIT, was significantly higher than that of CAl53 and CEA, and the combined diagnostic value of HIT, CAl53 and CEA was also higher than that of any single detection. CONCLUSIONS: High expression of HIT in plasma may be a potential biomarker for the diagnosis of breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , RNA Longo não Codificante/genética , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , RNA Longo não Codificante/sangue , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Sensibilidade e Especificidade
15.
Anal Bioanal Chem ; 411(25): 6667-6676, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31384983

RESUMO

Human epidermal growth factor receptor-2 (HER2) is an important biomarker in the diagnosis and prognosis of breast cancer. This work aimed to develop an aptasensor to detect HER2 in human serum. HER2 aptamer was immobilized by electrostatic adsorption on the surface of a homemade screen-printed electrode modified with poly-L-lysine. Measurements were made by differential pulse voltammetry using methylene blue as a redox indicator. A calibration curve was constructed (R2 = 0.997) using different concentrations of HER2 protein (10-60 ng/mL) in PBS buffer (pH 7.4), with a detection limit of 3.0 ng/mL. The aptasensor showed good reproducibility with relative standard deviations (RSDs) of 3% and remained stable for 3 days with an RSD around 2%. When the tests were performed with serum from a healthy woman, a peak of 6.72 µA was found without the addition of the protein. When we tested the serum of a woman with HER2+ breast cancer, we obtained a signal of 2.65 µA; the same pattern was found when adding to protein in serum control, i.e., the higher the concentration of protein, the lower the signal. The aptasensor was characterized by scanning electron microscopy and isothermal titration calorimetry (ITC), showing excellent interaction between aptamer and target protein. The results revealed a promising and sensitive tool capable of detecting HER2 protein in human serum with albumin depletion, aiding in the molecular diagnosis of breast cancer. Graphical abstract.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Desenho de Equipamento , Feminino , Humanos , Limite de Detecção , Receptor ErbB-2/análise , Reprodutibilidade dos Testes
16.
Nat Rev Cancer ; 19(10): 553-567, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31455893

RESUMO

Single-cell technologies have contributed to unravelling tumour heterogeneity, now considered a hallmark of cancer and one of the main causes of tumour resistance to cancer therapies. Liquid biopsy (LB), defined as the detection and analysis of cells or cell products released by tumours into the blood, offers an appealing minimally invasive approach that allows the characterization and monitoring of tumour heterogeneity in individual patients. Here, we will review and discuss how circulating tumour cell (CTC) analysis at single-cell resolution provides unique insights into tumour heterogeneity that are not revealed by analysis of circulating tumour DNA (ctDNA) derived from LBs. The molecular analysis of CTCs provides complementary information to that of genomic aberrations determined using ctDNA to fully describe many different cellular components (for example, DNA, RNA, proteins and metabolites) that can influence tumour heterogeneity.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Genômica , Neoplasias/sangue , Células Neoplásicas Circulantes/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Biópsia/métodos , Neoplasias da Mama/metabolismo , Aberrações Cromossômicas , Transição Epitelial-Mesenquimal , Feminino , Genótipo , Humanos , Masculino , Camundongos , Neoplasias/metabolismo , Fenótipo , Medicina de Precisão/métodos , Microambiente Tumoral
17.
Int J Nanomedicine ; 14: 6165-6178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447558

RESUMO

Purpose: Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. Patients and methods: Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis-linear discriminant analysis (PCA-LDA). Results: The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. Conclusion: SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.


Assuntos
Neoplasias/diagnóstico , Análise Espectral Raman/métodos , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Diagnóstico Diferencial , Análise Discriminante , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Análise de Componente Principal , Prata/química
18.
Biosens Bioelectron ; 142: 111503, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376716

RESUMO

Exosomes, lipid bilayer membrane vesicles, can guide various pathological and physiological processes. However, reliable, convenient and sensitive methods for exosome determination for early cancer diagnosis are still technically challenging. Herein, an electrochemical aptasensor based on click chemistry and the DNA hybridization chain reaction (HCR) for signal amplification has been developed for the ultrasensitive detection of tumor exosomes. CD63 aptamer was first immobilized on a glassy carbon electrode for capturing exosomes, and 4-oxo-2-nonenal alkyne (alkynyl-4-ONE) molecules, functionalized lipid electrophiles, were conjugated to the exosomes via the reaction of amino and aldehyde groups. Azide-labeled DNA probe as an anchor was then connected to the exosomes by copper (I)-catalyzed click chemistry. Signal amplification was achieved by HCR, and the numerous linked horseradish peroxidase (HRP) molecules could catalyze the reaction of o-phenylenediamine (OPD) and H2O2. The concentration of exosomes could be quantified by monitoring the electrochemical reduction current of 2,3-diaminophenazine (DAP). Under the optimal conditions, this method allowed the sensitive detection of exosomes in the range of 1.12 × 102 to 1.12 × 108 particles/µL with a limit of detection (LOD) of 96 particles/µL. Furthermore, the present assay enabled sensitive and accurate quantification of exosomes in human serum, and it has high potential for exosome analysis in clinical samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Neoplasias da Mama/patologia , Exossomos/patologia , Alquinos/química , Azidas/química , Neoplasias da Mama/sangue , Neoplasias da Mama/química , Química Click/métodos , Sondas de DNA/química , Técnicas Eletroquímicas/métodos , Exossomos/química , Feminino , Humanos , Células MCF-7 , Hibridização de Ácido Nucleico , Tetraspanina 30/análise
19.
BMC Cancer ; 19(1): 738, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351450

RESUMO

BACKGROUND: Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. METHODS: qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan-Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial-mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. RESULTS: Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. CONCLUSIONS: These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21-LZTFL1-EMT axis might be a promising strategy in breast cancer therapy. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/secundário , MicroRNAs/antagonistas & inibidores , MicroRNAs/fisiologia , Fatores de Transcrição/metabolismo , Animais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/cirurgia , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Células HEK293 , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Transcrição/genética , Transfecção , Carga Tumoral , beta Catenina/metabolismo
20.
Breast Cancer Res ; 21(1): 81, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337427

RESUMO

BACKGROUND: Mammographic density (MD) is a strong breast cancer risk factor that reflects fibroglandular and adipose tissue composition, but its biologic underpinnings are poorly understood. Insulin-like growth factor binding proteins (IGFBPs) are markers that may be associated with MD given their hypothesized role in breast carcinogenesis. IGFBPs sequester IGF-I, limiting its bioavailability. Prior studies have found positive associations between circulating IGF-I and the IGF-I:IGFBP-3 ratio and breast cancer risk. We evaluated the associations of IGF-I, IGFBP-3, and six other IGFBPs with MD. METHODS: Serum IGF measures were quantified in 296 women, ages 40-65, undergoing diagnostic image-guided breast biopsy. Volumetric density measures (MD-V) were assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Area density measures (MD-A) were estimated by computer-assisted thresholding software. Age, body mass index (BMI), and BMI2-adjusted linear regression models were used to examine associations of serum IGF measures with MD. Effect modification by BMI was also assessed. RESULTS: IGF-I and IGFBP-3 were not strongly associated with MD after BMI adjustment. In multivariable analyses among premenopausal women, IGFBP-2 was positively associated with both percent MD-V (ß = 1.49, p value = 0.02) and MD-A (ß = 1.55, p value = 0.05). Among postmenopausal women, positive relationships between IGFBP-2 and percent MD-V (ß = 2.04, p = 0.003) were observed; the positive associations between IGFBP-2 and percent MD-V were stronger among lean women (BMI < 25 kg/m2) (ß = 5.32, p = 0.0002; p interaction = 0.0003). CONCLUSIONS: In this comprehensive study of IGFBPs and MD, we observed a novel positive association between IGFBP-2 and MD, particularly among women with lower BMI. In concert with in vitro studies suggesting a dual role of IGFBP-2 on breast tissue, promoting cell proliferation as well as inhibiting tumorigenesis, our findings suggest that further studies assessing the role of IGFBP-2 in breast tissue composition, in addition to IGF-1 and IGFBP-3, are warranted.


Assuntos
Densidade da Mama , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Biópsia Guiada por Imagem , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Biomarcadores , Estudos Transversais , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Fatores de Risco
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