Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43.557
Filtrar
1.
Anticancer Res ; 40(5): 2487-2495, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366393

RESUMEN

BACKGROUND/AIM: This study analyzed the gene expression of the "classic" KLK1 and "new" kallikreins KLK4-KLK15, in relation to the molecular characteristics and in vitro invasiveness of 21 breast cancer (BC) and three normal breast-derived cell lines (CLs). MATERIALS AND METHODS: Gene expression of KLKs was determined by using real-time polymerase chain reaction (PCR). The invasiveness of the CLs was examined using a fibroblast-collagen-based in vitro cell culture assay. RESULTS: KLK5 and KLK7-KLK11 were down-regulated in several BCCLs. In contrast, KLK4, KLK8, KLK12 and KLK15 demonstrated strikingly high expression in two BCCLs, UACC 812 and MDA-MB 330. The KLK expression differed frequently according to the presence of androgen receptor (KLK1 and KLK5-KLK9), and occasionally according to estrogen receptor (KLK9) and EGFR (KLK7). Two KLK clusters were detected (first: KLK1, 4, 12, 15; second: all other KLKs), with two subclasses within the second cluster (KLK5-9 and KLK10, 11, 13, and 14). The CLs that expressed at least six KLKs belonged predominantly to basal or HER2 intrinsic subtypes. No KLK predicted the in vitro invasiveness of CLs. CONCLUSION: Gene expression of KLKs was altered in BCCLs. This change was mostly down-regulation and often related to the presence of androgen receptor. The observed clusters point to a possible functional interplay of selected KLKs in BCCLs.


Asunto(s)
Expresión Génica , Calicreínas/genética , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Humanos , Calicreínas/metabolismo
2.
Medicine (Baltimore) ; 99(15): e19255, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32282693

RESUMEN

Identification of reliable predictive biomarkers for patients with breast cancer (BC).Univariate Cox proportional hazards regression model was conducted to identify genes correlated with the overall survival (OS) of patients in the TCGA-BRCA cohort. Functional enrichment analysis was conducted to investigate the biological meaning of these survival related genes. Then, patients in TCGA-BCRA were randomly divided into training set and test. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was performed and the risk score of BC patients in this model was used to build a prognostic signature. The prognostic performance of the signature was evaluated in the training set, test set, and an independent validation set GSE7390.2519 genes were demonstrated to be significantly associated with the OS of BC patients. Functional annotation of the 2519 genes suggested that these genes were associated with immune response and protein synthesis related gene ontology terms and pathways. 17 genes were identified in the LASSO Cox regression model and used to construct a 17-gene signature. Patients in the 17-gene signature low risk group have better OS and event-free survival compared with those in the 17-gene signature high risk group in the TCGA-BRCA cohort. The prognostic role of the 17-gene signature has been confirmed in the validation cohort. Multivariable Cox proportional hazards regression model suggested the 17-gene signature was an independent prognostic factor in BC.The 17-gene signature we developed could successfully classify patients into high- and low-risk groups, indicating that it might serve as candidate biomarker in BC.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Femenino , Perfilación de la Expresión Génica , Humanos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
3.
Anticancer Res ; 40(4): 2141-2150, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234907

RESUMEN

BACKGROUND/AIM: Patients with non-luminal breast cancer subtypes with high levels of tumor infiltrating lymphocytes (TILs) have better prognosis than those with luminal subtype. We evaluated the role of TILs according to the subtype. MATERIALS AND METHODS: An immunohistochemical analysis of 139 breast cancer cases was conducted to calculate the FOXP3+/CD8+ T cell ratios and their relationships with TILs and disease-free survival (DFS) were evaluated. RESULTS: FOXP3+/CD8+ T cell ratios were significantly associated with TIL levels only in luminal breast cancers (p=0.0001). Low FOXP3+/CD8+ T cell ratio was significantly associated with longer DFS (p=0.017). All luminal subtype patients with high TIL levels had high FOXP3+/CD8+ T cell ratios compared to only half of non-luminal subtype patients with high TIL levels. CONCLUSION: High FOXP3+/CD8+ T cell ratios in breast cancers may partly explain the worse prognosis of luminal breast cancers, but not that of non-luminal breast cancers with high TIL levels.


Asunto(s)
Neoplasias de la Mama/metabolismo , Linfocitos T CD8-positivos/metabolismo , Factores de Transcripción Forkhead/biosíntesis , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Anciano , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Recuento de Linfocitos , Persona de Mediana Edad , Pronóstico
4.
Anticancer Res ; 40(4): 2185-2190, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234913

RESUMEN

BACKGROUND/AIM: The study aimed at investigating the correlation between ductoscopic and histopathological findings and clarify whether the former allow for accurate prediction of malignancy. PATIENTS AND METHODS: The prospective national multi-center study covered a sample of 224 patients with pathologic nipple discharge. A total of 214 patients underwent ductoscopy with subsequent extirpation of the mammary duct. The ductoscopic findings were categorized according to shape, number, color and surface structure of lesions and vascularity and compared to the histological results and analyses. RESULTS: Ductoscopy revealed lesions in 134 of 214 patients (62.2%). The criteria "multiple versus solitary lesion" differed significantly between malignant and benign lesions. All other criteria were not statistically significant. Malignant tumors were more frequently presented as multiple lesions, benign lesions or masses as solitary lesions (80% vs. 24.8%; p=0.018). CONCLUSION: The ductoscopic criterion "solitary vs. multiple lesion" appears to have a low diagnostic prediction of malignancy or benignity.


Asunto(s)
Enfermedades de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , Endoscopía/métodos , Secreción del Pezón , Pezones/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Mama/metabolismo , Enfermedades de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Diagnóstico Diferencial , Femenino , Alemania , Humanos , Persona de Mediana Edad , Pezones/metabolismo , Estudios Prospectivos , Adulto Joven
5.
Anticancer Res ; 40(4): 2303-2309, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234930

RESUMEN

BACKGROUND/AIM: To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel. PATIENTS AND METHODS: We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen. RESULTS: Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes. CONCLUSION: Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Mama/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Antraciclinas/administración & dosificación , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/metabolismo , Docetaxel/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Inducción de Remisión , Trastuzumab/administración & dosificación , Carga Tumoral/efectos de los fármacos , Ultrasonografía
6.
Med Sci Monit ; 26: e921510, 2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32238796

RESUMEN

BACKGROUND SOX7 exerts a repressing effect against tumors and imposes vital influences on malignancies. Our research discussed the importance of SOX7 in breast cancer prognoses. MATERIAL AND METHODS SOX7 mRNA expression in breast cancer tissues samples and matched adjacent normal controls of breast cancer patients was measured by quantitative real-time-polymerase chain reaction (qRT-PCR). The relationship of SOX7 with clinicopathological characteristics were analyzed via chi-square test. The association of SOX7 levels with clinical outcomes was evaluated adopting the Kaplan-Meier method and multivariate Cox proportional hazards regression model. RESULTS SOX7 mRNA degree of expression exhibited a declining tendency in breast cancer tissue compared to paired bordering normal tissue specimens (P<0.001). In addition, the reduced SOX7 degree of expression had a strong correlation to larger cancer mass dimension (P=0.006) and lymph node metastasis (P=0.001). Survival analysis revealed that the overall survival (OS) time was much shorter among cases harboring low SOX7 degree of expression compared to high degree of expression (P=0.005). Moreover, SOX7 expression alone could predict OS among breast cancer patients (hazard ratio=3.956, 95% confidence interval=1.330-11.772, P=0.013). CONCLUSIONS SOX7 expression was downregulated in breast cancer tissues, and it could function as a useful prognostic marker in breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Factores de Transcripción SOXF/metabolismo , Biomarcadores de Tumor/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis Linfática , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Transcripción SOXF/genética , Análisis de Supervivencia
7.
Med Sci Monit ; 26: e921659, 2020 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-32248204

RESUMEN

BACKGROUND ZW10 binding factor (ZWINT) has been reported to be upregulated in various human cancers and predict worse survival. However, the expression profile, clinical significance, and biological role of ZWINT remains unclear in breast cancer. MATERIAL AND METHODS In this study, we investigated messenger RNA (mRNA) and protein expression levels of ZWINT in breast cancer tissues, and the prognostic value of ZWINT protein expression was validated in a cohort of breast cancer patients using immunohistochemistry analysis. Then, different bioinformatic analyses were combined to explore the potential cancer-related hallmark underlying ZWINT in breast cancer, and a series of experiments in vitro were performed to reveal the oncogenic role of ZWINT in breast cancer. RESULTS Significant upregulation of ZWINT was observed in breast cancer tissues compared to normal and para-tumor tissues and upregulation of ZWINT predicts poor prognosis in breast cancer patients. Additionally, ZWINT could promote breast cancer proliferation via cell cycle regulation, especially by influencing the expression of some critical cell cycle regulators involved in G1 phase and G1/S transition. Finally, miR-204 was identified as a tumor suppressor microRNA which directly targets a specific site in 3'-UTR of ZWINT. CONCLUSIONS Overall, our results indicated that miR-204/ZWINT/cell cycle process might play an important role in breast cancer progression.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Regiones no Traducidas 3' , Ciclo Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Inmunohistoquímica , MicroARNs , Proteínas Nucleares , Pronóstico , Análisis de Supervivencia , Regulación hacia Arriba
8.
Anticancer Res ; 40(3): 1387-1394, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132035

RESUMEN

BACKGROUND/AIM: Cancer cells are frequently exposed to microenvironmental stresses, including amino acid deprivation and hypoxia, which are often targeted for cancer therapy. Here, we examined the effect of hypoxia in cysteine-deprived breast cancer cells and the mechanism to counteract the hypoxia effect. MATERIALS AND METHODS: Cell death was determined by annexin V-FITC and propidium iodide staining. Expression of mRNAs and proteins was determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. RESULTS: Cysteine deprivation or sulfasalazine, a potent inhibitor of cysteine/glutamate transporter, induced cell death by activating transcription factor 4 (ATF4) up-regulation. Hypoxia significantly suppressed cell death and ATF4 up-regulation induced by cysteine deprived conditions. In addition, tumor necrosis factor-related apoptosis-inducing ligand reversed the effect of hypoxia on cysteine deprived conditions. CONCLUSION: Prevention of hypoxia may be a means for augmenting the effect of amino acid deprivation as a strategy for cancer therapy.


Asunto(s)
Factor de Transcripción Activador 4/metabolismo , Neoplasias de la Mama/metabolismo , Cisteína/deficiencia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Muerte Celular/fisiología , Hipoxia de la Célula/fisiología , Línea Celular Tumoral , Cisteína/antagonistas & inhibidores , Cisteína/metabolismo , Femenino , Humanos , Sulfasalazina/farmacología , Transfección , Regulación hacia Arriba
9.
Nat Cell Biol ; 22(3): 310-320, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32144411

RESUMEN

Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here, we establish a robust method for the identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA sequencing and patient-derived-xenograft models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity but micrometastases harbour a distinct transcriptome program conserved across patient-derived-xenograft models that is highly predictive of poor survival of patients. Pathway analysis revealed mitochondrial oxidative phosphorylation as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of oxidative phosphorylation dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of oxidative phosphorylation in metastasis and highlights its potential as a therapeutic target to prevent metastatic spread in patients with breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Transcriptoma , Animales , Neoplasias de la Mama/metabolismo , Metabolismo Energético , Femenino , Humanos , Ratones Endogámicos NOD , Ratones SCID , Mitocondrias/metabolismo , Metástasis de la Neoplasia , Fosforilación Oxidativa , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Transcripción Genética
10.
Biomed Khim ; 66(1): 89-94, 2020 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-32116231

RESUMEN

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.


Asunto(s)
Neoplasias de la Mama/metabolismo , Receptores Androgénicos/metabolismo , Receptores de Prolactina/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/clasificación , Femenino , Humanos , Receptor ErbB-2 , Receptores Estrogénicos , Receptores de Progesterona
11.
Bratisl Lek Listy ; 121(2): 111-116, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115962

RESUMEN

AIM: We aimed to determine the possible correlation between voltage­gated potassium channels and micro RNAs in breast cancer and metastatic breast cancer cells. METHOD: Kv1.3 and Kv10.1 channels were inhibited by specific siRNAs using a lipofectamine-based transfection in MCF-7 and MDA-MB-231 cells. After transfection, total RNA was isolated, and then miR-126 and miR-126* expressions were observed using RT-PCR. RESULTS: There was a negative correlation between Kv channels and miRNAs according to the characteristics of the breast cancer cells. The inhibition was observed not only in Kv1.3 but also in Kv10.1 in MCF-7 cells, and miR-126 and miR-126* expressions were downregulated compared to the control group (p < 0.001). The inhibition of these channels in MDA-MB-231 cells caused an upregulation of miR-126 and miR-126* expressions (p < 0.001). CONCLUSION: The miR-126 and miR-126* expressions differed according to benign and malign breast cancer cell lines. Furthermore, we found that miR-126/126* may interact with Kv1.3 and Kv10.1 voltage-gated potassium channels. Our study suggests and indicates the relationship between Kv channels and miRNAs in breast cancer cells (Tab. 1, Fig. 2, Ref. 51).


Asunto(s)
Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , MicroARNs , Canales de Potasio con Entrada de Voltaje , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Humanos , Células MCF-7 , MicroARNs/metabolismo
12.
Life Sci ; 250: 117579, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32209425

RESUMEN

Although extensive research progress has been made in breast cancer in recent years, yet the morbidity and mortality rates of breast cancer are rising, making it the major disease that endangers women's health. Energy metabolism reprogramming is featured by a state termed "aerobic glycolysis" or the Warburg effect that glycolysis is preferred even under aerobic conditions in neoplastic diseases. Widely acknowledged as an emerging hallmark in cancers, this metabolic switch shows a sophisticated role in the pathogenesis of breast cancer. The regulating effect of non-coding RNAs (ncRNAs) composed of microRNAs, long non-coding RNAs and circular RNAs is closely related to the glycolysis in breast cancer. Therefore, understand the mechanisms of ncRNAs of aerobic glycolysis in breast cancer may provide new strategy for the disease.


Asunto(s)
Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Glucólisis , ARN no Traducido/metabolismo , Aerobiosis , Línea Celular Tumoral , Femenino , Genes Supresores de Tumor , Glucosa/metabolismo , Humanos , MicroARNs/metabolismo , Neoplasias/metabolismo , Oncogenes , ARN Circular/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal
13.
Nat Commun ; 11(1): 735, 2020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-32024846

RESUMEN

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.


Asunto(s)
Biología Computacional/métodos , Redes y Vías Metabólicas/genética , Neoplasias/genética , Neoplasias/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Inmunoprecipitación de Cromatina , Bases de Datos Factuales , Femenino , Dosificación de Gen , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Genómica/métodos , Humanos , Mutación , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/genética , Análisis de Secuencia de ARN
14.
J Cancer Res Clin Oncol ; 146(5): 1299-1306, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32107626

RESUMEN

BACKGROUND: The aim of this study was to verify the predictors of recurrence and survival in lung adenocarcinoma patients with experiences of breast cancer therapies. METHODS: We retrospectively reviewed consecutive patients who were treated at our hospital for lung adenocarcinoma from 2004/01 to 2014/03. The patients were divided into groups of those with lung adenocarcinoma alone and those with lung and breast cancer. Kaplan-Meier plots and log-rank tests were used to estimate outcomes. RESULTS: 54 patients with lung adenocarcinoma and breast cancer were compared with 457 patients with single primary lung adenocarcinomas. After propensity score matching with control of age, operation type, smoking status and pathologic stage, tumor differentiation, recurrence rate and tumor size were significantly different between two groups. The significant predictors for recurrence included undergone chemotherapy (HR = 25, p < 0.001), moderate/poor differentiation (HR = 8.125, p = 0.012), tumor size ≧ 2 cm (HR = 15, p < 0.001), LVSI (HR = 13.67, p = 0.031) and GGO ratio < 50% (HR = 14.667, p = 0.014). The significant prognostic factors for survival were accepted chemotherapy (HR = 6.182, p = 0.021), LVSI (HR = 22, p = 0.012) and GGO ratio < 50% (HR = 9.143, p = 0.045). Kaplan-Meier analysis revealed that patients with lung adenocarcinoma and breast cancer had a better 5-year disease-free survival (p = 0.009), while the Her2-negative patients obtained a better overall survival (p = 0.038). CONCLUSIONS: In patients with breast cancer and lung adenocarcinoma, independent risk factors of recurrence were undergone chemotherapy, moderate/poor differentiation, tumor size ≧ 2 cm, LVSI and GGO ratio < 50%. Only undergone chemotherapy, LVSI and GGO ratio < 50% were significant poor predictors for survival. However, patients with metachronous lung adenocarcinoma and breast cancer had better disease-free survival and less tumor recurrence than patients with lung adenocarcinoma alone.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico , Neoplasias de la Mama/diagnóstico , Neoplasias Pulmonares/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Adenocarcinoma del Pulmón/epidemiología , Adenocarcinoma del Pulmón/metabolismo , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/metabolismo , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Primarias Secundarias/epidemiología , Pronóstico , Puntaje de Propensión , Receptor ErbB-2/metabolismo , Sistema de Registros , Estudios Retrospectivos , Riesgo , Taiwán/epidemiología
15.
Nat Cell Biol ; 22(2): 151-158, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32015439

RESUMEN

Under proteotoxic stress, some cells survive whereas others die. The mechanisms governing this heterogeneity in cell fate remain unknown. Here we report that condensation and phase transition of heat-shock factor 1 (HSF1), a transcriptional regulator of chaperones1,2, is integral to cell-fate decisions underlying survival or death. During stress, HSF1 drives chaperone expression but also accumulates separately in nuclear stress bodies called foci3-6. Foci formation has been regarded as a marker of cells actively upregulating chaperones3,6-10. Using multiplexed tissue imaging, we observed HSF1 foci in human tumours. Paradoxically, their presence inversely correlated with chaperone expression. By live-cell microscopy and single-cell analysis, we found that foci dissolution rather than formation promoted HSF1 activity and cell survival. During prolonged stress, the biophysical properties of HSF1 foci changed; small, fluid condensates enlarged into indissoluble gel-like arrangements with immobilized HSF1. Chaperone gene induction was reduced in such cells, which were prone to apoptosis. Quantitative analysis suggests that survival under stress results from competition between concurrent but opposing mechanisms. Foci may serve as sensors that tune cytoprotective responses, balancing rapid transient responses and irreversible outcomes.


Asunto(s)
Adaptación Fisiológica/genética , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción del Choque Térmico/genética , Proteínas de Choque Térmico/genética , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Diferenciación Celular , Línea Celular Tumoral , Supervivencia Celular/genética , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Femenino , Factores de Transcripción del Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Respuesta al Choque Térmico/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Transición de Fase , Transducción de Señal , Análisis de la Célula Individual , Transcripción Genética
16.
Biol Res ; 53(1): 5, 2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-32046779

RESUMEN

BACKGROUND: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. METHODS: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. RESULTS: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. CONCLUSION: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/patología , Células Endoteliales de la Vena Umbilical Humana/citología , Neuropilina-1/metabolismo , Receptores Notch/metabolismo , Factores de Transcripción/metabolismo , Microambiente Tumoral , Western Blotting , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal
17.
Gene ; 738: 144453, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32035242

RESUMEN

Breast cancer (BC) is the most common cancer among women that is responsible for the most of the cancer-related death in worldwide. Drug resistance is remaining as a significant clinical obstacle to treat BC patients effectively. Therefore, to help overcome this problem, it is necessary to understand the mechanisms of drug resistance. microRNAs classify as highly conserved non-coding RNAs (~22 nucleotides) and interact with mRNAs-coding genes for direct post-transcriptional repression. It has been reported that miR-21 is overexpressed and also acts as oncomiR in many human malignancies by targeting of several tumor suppressor genes-associated with apoptosis, proliferation and metastasis. Specifically, it has been reported that miR-21 is responsible for the drug resistance and its overexpression is related to the development of Multi Drug Resistance (MDR) in breast cancer. In this review, we discussed about the role of miR-21 on the drug resistance of breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , MicroARNs/genética , Apoptosis/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular/genética , Resistencia a Antineoplásicos/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor , Humanos , MicroARNs/metabolismo , Metástasis de la Neoplasia/genética , Oncogenes/genética , ARN Mensajero/genética , Transducción de Señal/genética
18.
J Photochem Photobiol B ; 204: 111811, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32028187

RESUMEN

The development of multidrug resistance is often associated with the over-expression of P-glycoprotein (P-gp). This protein prevents drug accumulation and extrudes them out of the cell before they reach the intended target. The aim of this study was to develop an in vitro MCF-7 cell line with increased expression of P-gp and test the phototoxicity of a novel photoactivated zinc phthalocyanine tetrasulfonic acid (ZnPcS4) on these cells. The over-expressed P-gp MCF-7 cells (MCF-7/DOX) were developed from wildtype (WT) MCF-7 cells by a stepwise continuous exposure of the WT cells to different concentrations of Doxorubicin (DOX) (0.1 - 1 µM) over a period of 4 months. The P-gp expression was measured using flow cytometry, immunofluorescence and enzyme immunoassay. To verify whether zinc phthalocyanine-mediated photodynamic therapy (ZnPcS4 - PDT) is effective in MCF-7/DOX, we studied the subcellular localization, phototoxicity and nuclear damage. The flow cytometry result showed two distinct peaks of P-gp positive and negative expression in MCF-7/DOX cell population, which correlates with the ELISA-based assay (p˂0.001). The ME16C (Normal breast cells) was used as control. The localization studies showed that ZnPcS4 have greater affinity for lysosome than mitochondria. Phototoxicity results indicated that photoactivated zinc phthalocyanine decreased the cell proliferation and viability as the drug and laser light dosages increased to 16 µM and 20 J/cm2 respectively. PDT-induced cytotoxicity using lactose dehydrogenase (LDH) enzyme leakage as measure did not increase likewise. The ZnPcS4-induced PDT was less effective for MCF-7/DOX cells which could be attributed to decreased retention of ZnPcS4 in major cellular organelles due to the presence of increased drug efflux P-gp. The current findings suggest that, increased P-gp expression, a characteristic of multidrug resistance together with other related intrinsic mechanisms might contribute to render MCF-7/DOX cells less sensitive to ZnPcS4-induced phototoxicity.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Proliferación Celular/efectos de los fármacos , Indoles/farmacología , Láseres de Semiconductores , Compuestos Organometálicos/farmacología , Adenosina Trifosfato/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de la radiación , Femenino , Humanos , Indoles/química , Células MCF-7 , Compuestos Organometálicos/química , Fotoquimioterapia , Rodamina 123/química , Rodamina 123/metabolismo
19.
J Cancer Res Clin Oncol ; 146(3): 605-619, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32036454

RESUMEN

PURPOSE: HER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient's live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies. METHODS: The CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2-/HSFs+). RESULTS: HER2-/HSFs+ breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+ and HER2- cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI = 17-32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2-/HSFs+ patient population. CONCLUSIONS: The CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+ population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20-25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal/fisiología , Animales , Antineoplásicos/farmacología , Impedancia Eléctrica , Femenino , Humanos , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Nat Commun ; 11(1): 785, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32034145

RESUMEN

Extracellular signals such as TGF-ß can induce epithelial-to-mesenchymal transition (EMT) in cancers of epithelial origin, promoting molecular and phenotypical changes resulting in pro-metastatic characteristics. We identified C/EBPα as one of the most TGF-ß-mediated downregulated transcription factors in human mammary epithelial cells. C/EBPα expression prevents TGF-ß-driven EMT by inhibiting expression of known EMT factors. Depletion of C/EBPα is sufficient to induce mesenchymal-like morphology and molecular features, while cells that had undergone TGF-ß-induced EMT reverted to an epithelial-like state upon C/EBPα re-expression. In vivo, mice injected with C/EBPα-expressing breast tumor organoids display a dramatic reduction of metastatic lesions. Collectively, our results show that C/EBPα is required for maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers, thereby preventing EMT-mediated tumorigenesis. These data suggest that C/EBPα is a master epithelial "gatekeeper" whose expression is required to prevent unwarranted mesenchymal transition, supporting an important role for EMT in mediating breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama/patología , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Glándulas Mamarias Humanas/patología , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Células Cultivadas , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Glándulas Mamarias Humanas/metabolismo , Ratones SCID , Proteína smad3/genética , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA