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Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients.
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Apoptosis , Neoplasias de la Mama , Proliferación Celular , Janus Quinasa 2 , Simulación del Acoplamiento Molecular , Farmacología en Red , Factor de Transcripción STAT3 , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Janus Quinasa 2/metabolismo , Proteoglicanos/farmacología , Células MCF-7 , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.
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Neoplasias de la Mama , Mama , Sensibilidad y Especificidad , Ultrasonografía Mamaria , Humanos , Femenino , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Anciano , Adulto , Mama/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
Abnormal expression or activity of proteins that regulate cell polarity can contribute to tumour progression. Discs large homolog (DLG) proteins play crucial roles in the maintenance of cell polarity and tissue morphogenesis. Previous studies of breast cancer patients showed that DLG3 had greater expression in the cancerous tissues than non-cancerous tissues, but the relationship between DLG3 expression and breast cancer progression and prognosis is not clear. Here, we investigated the association of DLG3 expression with breast cancer progression and prognosis using data on clinicopathological parameters from The Cancer Genome Atlas (TCGA) database, with different clinicopathological parameters using ualcan and LinkedOmics, and with different stages and subtypes using immunohistochemical staining. The results indicated greater DLG3 expression in cancerous breast tissues than normal breast tissues and in luminal and Her2+ subtypes than in the triple-negative subtype. DLG3 expression also had a positive correlation with pathologic stage and decreased survival rate. Our data suggest that DLG3 should be considered as a new diagnostic and prognostic biomarker for breast cancer.
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Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/genética , Factores de Transcripción/genética , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer. RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR. The effect of CNTN1 overexpression on proliferation, migration and invasion of Hs578T breast cancer cells was assessed in vitro and in vivo. Our results showed that CNTN1 overexpression promoted Hs578T cell proliferation, cell cycle progression, colony formation, invasion and migration. Notably, overexpression of CNTN1 in Hs578T cells enhanced the growth of mouse xenograft tumors. CONCLUSIONS: CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. Thus, therapies targeting CNTN1 may prove efficacious for breast cancer. However, further investigation is required to understand the mechanism by which CNTN1 influences proliferation, metastasis and invasion in breast cancer.
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Neoplasias de la Mama/patología , Movimiento Celular , Contactina 1/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Masculino , Ratones Desnudos , Invasividad Neoplásica , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: This study aimed to (1) identify distinct patterns of unmet needs in Chinese cancer patients; (2) examine whether sociodemographic and medical characteristics distinguished these patterns; and (3) examine whether people with distinct patterns reported differential quality of life (QoL). METHODS: This cross-sectional study recruited 301 cancer patients from 2 hospitals in China. The 34-item Supportive Care Needs Survey Short-Form was used to measure unmet needs across 5 domains: physical and daily living, psychological, patient care and support, health systems and information, and sexuality. Latent class analysis was performed to identify patterns of unmet needs across these domains. RESULTS: Four patterns of unmet needs were identified, differing in levels and nature of unmet needs. Participants in class 1 (47%) reported few unmet needs. Patients in class 2 (15%) had moderate levels of unmet needs, displaying similar levels across 5 domains. People in class 3 (25%) and class 4 (13%) reported similarly high levels on "psychological," "health care system and information," "physical and daily living," and "patient care," but differing in "sexuality," with class 3 reporting low levels while class 4 high on "sexuality." None of sociodemographic and medical characteristics distinguished these patterns significantly. Compared to other classes, people in class 1 reported highest levels of QoL. CONCLUSIONS: This study demonstrates the existence of 4 patterns of unmet supportive needs in Chinese cancer patients. Patients with few unmet needs reported the best QoL.
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Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Evaluación de Necesidades/estadística & datos numéricos , Neoplasias/psicología , Calidad de Vida/psicología , Adulto , Anciano , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Apoyo SocialRESUMEN
BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mamografía/métodos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , China , Femenino , Humanos , Estilo de Vida , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Sphingosine kinase 1 (SphK1) expression is elevated in various cancers and is associated with shorter survival times for patients. However, the molecular mechanism of SphK1 up-regulation in triple-negative breast cancer (TNBC) remains unclear. In this study, we assayed the expression level of SphK1 in TNBC tissues by qRT-PCR and immunohistochemistry. The level of S1P was quantified by ELISA in the serum of TNBC patients. Our results found that the levels of SphK1 and S1P were significantly increased in TNBC patients compared with normal control. Furthermore, knockdown of SphK1 with siRNA decreased TNBC cell proliferation and inhibited cell migration/invasion. These data suggest that SphK1 has an important role in TNBC and presents an attractive therapeutic target for the treatment for TNBC.
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Proteínas Adaptadoras Transductoras de Señales/fisiología , Proteínas de Neoplasias/fisiología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de Señal , Neoplasias de la Mama Triple Negativas/patología , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis , División Celular , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Lisofosfolípidos/metabolismo , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , ARN/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Ensayo de Tumor de Célula MadreRESUMEN
Metastasis is one of the main causes of breast cancer (BCa)-related deaths in female. It has been reported that cancer stem cell played an important role in metastasis. Here we first revealed a specific role of pyruvate kinase isozymes M2 (PKM2) in the stemness of breast cancer cells. Breast cancer tissue analysis confirmed the upregulation of PKM2 in breast cancer, and high PKM2 levels were associated with poor prognosis of breast cancer patients. Holoclone assay and colony formation assay significantly elucidated the role of PKM2 in the self-renewal of breast cancer cells. Moreover, PKM2 elevated the proportion of stem cell and the ability of sphere formation in breast cancer cells. PKM2 played its functional role in stemness by regulating ß-catenin. Collectively, we identified critical roles of PKM2 in the stemness of breast cancer cells which may elevate the therapeutic effect on breast cancer patients.
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Neoplasias de la Mama/enzimología , Células Madre Neoplásicas/enzimología , Piruvato Quinasa/fisiología , Vía de Señalización Wnt , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Autorrenovación de las Células , Femenino , Expresión Génica , Humanos , Isoenzimas/fisiología , Metástasis de la Neoplasia , Pronóstico , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
BACKGROUND: Energy metabolism has a complex intersection with pathogenesis and development of breast cancer (BC). This allows for the possibility of identifying energy-metabolism-related genes (EMRGs) as novel prognostic biomarkers for BC. 7-dehydrocholesterol reductase (DHCR7) is a key enzyme of cholesterol biosynthesis involved in many cancers, and in this paper, we investigate the effects of DHCR7 on the proliferation and mitochondrial function of BC. METHODS: EMRGs were identified from the Gene Expression Omnibus (GEO) and MSigDB databases using bioinformatics methods. Key EMRGs of BC were then identified and validated by functional enrichment analysis, interaction analysis, weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Cox analysis, and immune infiltration. Western blot, qRT-PCR, immunohistochemistry (IHC), MTT assay, colony formation assay and flow cytometry assay were then used to analyze DHCR7 expression and its biological effects on BC cells. RESULTS: We identified 31 EMRGs in BC. These 31 EMRGs and related transcription factors (TFs), miRNAs, and drugs were enriched in glycerophospholipid metabolism, glycoprotein metabolic process, breast cancer, and cell cycle. Crucially, DHCR7 was a key EMRG in BC identified and validated by WGCNA, LASSO regression and receiver operating characteristic (ROC) curve analysis. High DHCR7 expression was significantly associated with tumor immune infiltration level, pathological M, and poor prognosis in BC. In addition, DHCR7 knockdown inhibited cell proliferation, induced apoptosis and affected mitochondrial function in BC cells. CONCLUSIONS: DHCR7 was found to be a key EMRG up-regulated in BC cells. This study is the first to our knowledge to report that DHCR7 acts as an oncogene in BC, which might become a novel therapeutic target for BC patients.
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Biomarcadores de Tumor , Neoplasias de la Mama , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Mitocondrias , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Femenino , Proliferación Celular/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Mitocondrias/metabolismo , Mitocondrias/genética , Línea Celular Tumoral , Metabolismo Energético/genética , Pronóstico , Células MCF-7RESUMEN
Background: Triple-positive breast cancer (TPBC) is a specific type of breast cancer characterized by the positive expression of estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER-2). In recent years, the research on breast cancer has been increasing year by year, but there are few studies on TPBC, especially the lack of analysis with large sample size. In this study, sufficient samples were provided through the SEER database, explore the factors affecting the prognosis of TPBC, and construct a prediction model, in order to assess the individual survival of patients, and help clinicians accurately identify high-risk patients and develop personalized treatment plans. Methods: Patients pathologically diagnosed with TPBC were recruited from Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation groups (7:3 ratio). Univariate analysis was used to analyze the related factors affecting the prognosis of TPBC patients in the modeling group, and then multivariate Cox proportional hazards model was used to analyze the significant factors to screen out the independent risk factors affecting the 3- and 5-year overall survival (OS) rate and construct the prediction model. Using the concordance index (C-index) and calibration curve were performed to evaluate the predictive ability of the model. Results: The results of the Cox risk-scale model showed that race, age, marital status, tumor grade, tumor, node, metastasis stage, surgical treatment, chemotherapy, and radiotherapy affected the prognosis of TPBC patients (P<0.05) in the training group, and the factors were used to construct a nomogram. The internal and external validation of the nomogram chart indicated that the C-index of the training group was 0.85 [95% confidence interval (CI): 0.836, 0.863] and that of the verification group was 0.833 (95% CI: 0.807, 0.858). The calibration curves of the 2 groups showed that the OS predicted by the model was consistent with the actual survival of the patients. Conclusions: The prediction model accurately predicted the prognosis of and identified high-risk TPBC patients.
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BACKGROUND: Triple Negative Breast cancer (TNBC) is incurable cancer with higher rates of relapse and shorter overall survival compared with other subtypes of breast cancer. Cellular retinoic acid binding protein 2 (CRABP2) belongs to fatty acid binding protein (FABP) family which binds with all-trans retinoic acid (RA). Previous studies from the database have reported the patients with high expression of CRABP2 showed different prognosis in ER+ and ER- breast cancer. However, its biological role and exact mechanism in breast cancer remain unknown. This aim of this study was to explore how CRABP2 regulated invasion and metastasis based on the estrogen receptor-α (herein called ER) status in breast cancer. METHODS: Immunohistochemical staining method was used to analyze the expression of CRABP2 in human breast cancer tissues. Lentivirus vector-based shRNA technique was used to test the functional relevance of CRABP2 knockdown in breast tumors. Tail vein injection model was used to examine the lung metastasis. Co-immunoprecipitation, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to investigate the underlying mechanism that influenced the ER to the regulation of CRABP2 to Lats1. RESULTS: We observed that knockdown of CRABP2 promotes EMT, invasion and metastasis of ER+ breast cancer cells in vitro and in vivo, whereas overexpression of CRABP2 yields the reverse results. In ER+ mammary cancer cells, the interaction of CRABP2 and Lats1 suppress the ubiquitination of Lats1 to activate Hippo pathway to inhibit the invasion and metastasis of ER+ mammary cancer. However, in ER- mammary cancer cells, the interaction of CRABP2 and Lats1 promote the ubiquitination of Lats1 to inactivate Hippo pathway to promote the invasion and metastasis of ER- mammary cancer. CONCLUSIONS: Our findings indicate that CRABP2 can suppress invasion and metastasis of ER+ breast cancer and promote invasion and metastasis of ER- breast cancer by regulating the stability of Lats1 in vitro and in vivo, and it provides new ideas for breast cancer therapy.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Receptor alfa de Estrógeno/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Ácido Retinoico/metabolismo , Transducción de Señal , Animales , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Movimiento Celular , Proliferación Celular , Receptor alfa de Estrógeno/genética , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , Humanos , Ratones , Ratones SCID , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Receptores de Ácido Retinoico/genética , Células Tumorales Cultivadas , Ubiquitinación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2â¯cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.
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ROS1 fusion is a common genetic alteration in non-small-cell lung cancer. Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation. We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature. After crizotinib administration, overall recovery was good in this patient; the primary lesion was successfully treated, the lymph node metastases had disappeared, and the metabolism was normal.
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Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the presence of intrinsic or acquired resistance to the drug. Altered expression and functions of microRNAs (miRNAs) have been reportedly associated with tamoxifen resistance. In this study, we investigated the role of miR-27b-3p in resistance of breast cancer to tamoxifen. MiR-27b-3p levels were remarkably reduced in the tamoxifen-resistant breast cancer cells compared with their parental cells. In addition, miR-27b-3p was also significantly downregulated in breast tumor tissues relative to adjacent non-tumor tissues. Moreover, the expression levels of miR-27b-3p were lower in the breast cancer tissues from tamoxifen-resistant patients compared with that from untreated-tamoxifen patients. Notably, tamoxifen repressed miR-27b-3p expression, whereas estrogen induced miR-27b-3p expression in breast cancer cells. Besides, we provided experimental evidences that miR-27b-3p enhances the sensitivity of breast cancer cells to tamoxifen in vitro and in vivo models. More importantly, we validated that miR-27b-3p directly targeted and inhibited the expression of nuclear receptor subfamily 5 group A member 2 (NR5A2) and cAMP-response element binding protein 1 (CREB1) and therefore augmented tamoxifen-induced cytotoxicity in breast cancer. Lastly, miR-27b-3p levels were found to be significantly negatively correlated with both NR5A2 and CREB1 levels in breast cancer tissues. Our findings provided further evidence that miR-27b-3p might be considered as a novel and potential target for the diagnosis and treatment of tamoxifen-resistant breast cancer.
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Neoplasias de la Mama/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Regulación hacia Abajo/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Receptores Citoplasmáticos y Nucleares/genética , Tamoxifeno/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/patología , Supervivencia Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación hacia Abajo/genética , Resistencia a Antineoplásicos/genética , Estrógenos/farmacología , Femenino , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Modelos Biológicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
An approach to segment macular layer thicknesses from spectral domain optical coherence tomography has been proposed. The main contribution is to decrease computational costs while maintaining high accuracy via exploring Kalman filtering, customized active contour, and curve smoothing. Validation on 21 normal volumes shows that 8 layer boundaries could be segmented within 5.8 s with an average layer boundary error <2.35 µm. It has been compared with state-of-the-art methods for both normal and age-related macular degeneration cases to yield similar or significantly better accuracy and is 37 times faster. The proposed method could be a potential tool to clinically quantify the retinal layer boundaries.
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Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Mácula Lútea/patología , Degeneración Macular/patología , Reconocimiento de Normas Patrones Automatizadas/métodos , Tomografía de Coherencia Óptica/métodos , Sistemas de Computación , Humanos , Imagenología Tridimensional/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: To evaluate the relationship between the five common polymorphisms in miRNAs (miR-146a rs2910164 G>C, miR-149 rs2292832 C>T, miR-196a2 rs11614913 C>T, miR-499 rs3746444 A>G and miR-27a rs895819 A>G), and breast cancer (BC) risk. METHODS: Meta-analyses were performed on 15 published studies involving 8, 361 BC patients and 8, 504 cancer-free controls. There were 8 studies with 4, 314 cases and 4, 485 controls for rs2910164, 3 studies with 1, 439 cases and 1, 508 controls for rs2292832, 10 studies with 4, 618 cases and 5, 590 controls for rs11614913, 5 studies with 2, 924 cases and 3, 563 controls for rs3746444, and 5 studies with 2, 912 cases and 3, 697 controls for rs895819. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the BC risk. RESULTS: Meta-analyses showed that rs2910164 (miR-146a) was associated with BC risk in Caucasian population (homozygote comparison: OR = 1.29, 95%CI = 1.02-1.63, P=0.03; dominant model: OR = 1.31, 95% CI = 1.05-1.65, P=0.02), whereas negative results were obtained for Asians in all genetic models. rs11614913 (miR-196a2) was associated with BC risk in the overall population based on the recessive model (OR = 0.89, 95% CI = 0.80-0.99, P=0.03). Association of rs3746444 (miR-499) with BC risk was detected under three genetic models (allele contrast genetic model: OR = 1.13, 95%CI = 1.03-1.23, P=0.007; homozygote comparison: OR = 1.36, 95 %CI = 1.10-1.69, P=0.005 and recessive model: OR = 1.38, 95% CI = 1.12-1.70, P=0.003). When stratified by ethnicity, the effects remained in Asians. rs895819 (miR-27a) was associated with BC risk in the overall population based on the allele contrast genetic model (OR = 0.91, 95%CI = 0.85-0.98, P=0.02); heterozygote comparison (OR = 0.89, 95 %CI = 0.80-0.99, P=0.03) and the dominant model (OR = 0.89, 95% CI = 0.80-0.98, P=0.02). However, there was no association between rs2292832 (miR-149) polymorphism and BC susceptibility. CONCLUSION: Our meta-analysis results suggested that the rs2910164 and rs3746444 polymorphisms are associated with increased BC risk, while the rs11614913 and rs895819 polymorphisms correlate with reduced BC risk.
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Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Pueblo Asiatico/genética , Femenino , Humanos , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Riesgo , Población Blanca/genéticaRESUMEN
Since the electrochemical oxidation peaks of both DNA and anti-tumor drug tamoxifen (TAM) overlapped with each other, the known electrochemical methods were limited in the study of the interactions between DNA and TAM. In this paper, zero current potentiometry, a new electrochemical method, was used to study the interaction of calf thymus dsDNA with TAM. The dsDNA was immobilized on the surface of carbon paste (dsDNA/CP). The dsDNA/CP connected in series between the clips of working and counter electrodes of a potentiostat and a reference electrode were immersed in aqueous solution containing TAM, the interaction of dsDNA with TAM produced a change in interfacial potential at the dsDNA/CP/solution interface. When linear sweep potential was applied to the dsDNA/CP and the corresponding I-E curve was recorded, interfacial potential offset applied potential partially, making the I-E curve displace along potential axis. Zero current potential where circuit current I was equal to zero in the I-E curve was measured to check the displacement of the I-E curve. Based on the displacement, the thermodynamic constants of the interaction between dsDNA and TAM were determined. The binding ratio of dsDNA with TAM was found to be 1:1 and the apparent binding constant was (6.85±0.20)×10(6) M(-1). As zero current potentiometry was independent of the changes in redox potential or current of both dsDNA and TAM themselves, the interaction was studied in their natural forms without damage. Moreover, TAM can be determined. The detection limit was 1.1×10(-7) M.
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Técnicas Biosensibles/métodos , ADN/efectos de los fármacos , Potenciometría/métodos , Tamoxifeno/farmacología , Animales , Antineoplásicos Hormonales/química , Antineoplásicos Hormonales/farmacología , Técnicas Biosensibles/instrumentación , Carbono , Bovinos , ADN/química , Interacciones Farmacológicas , Electrodos , Moduladores de los Receptores de Estrógeno/química , Moduladores de los Receptores de Estrógeno/farmacología , Técnicas In Vitro , Compuestos de Mercurio , Tamoxifeno/química , TermodinámicaRESUMEN
BACKGROUND: The further application of conventional ultrasound (US) image-guided microwave (MW) ablation of liver cancer is often limited by two-dimensional (2D) imaging, inaccurate needle placement and the resulting skill requirement. The three-dimensional (3D) image-guided robotic-assisted system provides an appealing alternative option, enabling the physician to perform consistent, accurate therapy with improved treatment effectiveness. METHODS: Our robotic system is constructed by integrating an imaging module, a needle-driven robot, a MW thermal field simulation module, and surgical navigation software in a practical and user-friendly manner. The robot executes precise needle placement based on the 3D model reconstructed from freehand-tracked 2D B-scans. A qualitative slice guidance method for fine registration is introduced to reduce the placement error caused by target motion. By incorporating the 3D MW specific absorption rate (SAR) model into the heat transfer equation, the MW thermal field simulation module determines the MW power level and the coagulation time for improved ablation therapy. Two types of wrists are developed for the robot: a 'remote centre of motion' (RCM) wrist and a non-RCM wrist, which is preferred in real applications. RESULTS: The needle placement accuracies were < 3 mm for both wrists in the mechanical phantom experiment. The target accuracy for the robot with the RCM wrist was improved to 1.6 +/- 1.0 mm when real-time 2D US feedback was used in the artificial-tissue phantom experiment. By using the slice guidance method, the robot with the non-RCM wrist achieved accuracy of 1.8 +/- 0.9 mm in the ex vivo experiment; even target motion was introduced. In the thermal field experiment, a 5.6% relative mean error was observed between the experimental coagulated neurosis volume and the simulation result. CONCLUSION: The proposed robotic system holds promise to enhance the clinical performance of percutaneous MW ablation of malignant liver tumours.