RESUMEN
As is known, hepatic stellate cells (HSCs) activation contributes to liver cirrhosis. This study aims to find out the acting mechanisms of miR-454 inhibiting the activation and proliferation of hepatic stellate cells. The expression of Col1A1, α-smooth muscle actin (α-SMA) and Wnt10a were determined by western blot, and the miR-454 level was determined by quantitative real-time PCR in this study. We took two objects as experiment subjects, one was liver cirrhosis rats, and the other was transforming growth factor (TGF)-ß1-stimulated HSC-T6 cells. After activated with TGF-ß1 and transfected with microRNA-454 mimic, separately or successively, the changes on the Col1A1 and α-SMA expression, HSC proliferation, miR-454 level and Wnt10a expression were examined in HSC-T6 cells, respectively. Interaction between miR-454 and Wnt10a was evaluated with dual luciferase reporter assay. MiR-454 expression was down-regulated in tissues of liver cirrhosis rats. TGF-ß1 caused the down-regulation of the miR-454 in HSC-T6 cells. MiR-454 inhibited the activation and proliferation of HSC-T6 cells. Wnt10a had a targeting relationship with miR-454. TGF-ß1 promoted HSC-T6 activation and proliferation via down-regulating miR-454 expression, which further up-regulated Wnt10a expression. MiR-454 mimic inhibited cirrhosis progression in liver cirrhosis rats. MiR-454 can inhibit the activation and proliferation of HSCs via suppressing the expression of Wnt10a, to restrain liver cirrhosis.
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Proliferación Celular , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/metabolismo , MicroARNs/metabolismo , Proteínas Wnt/metabolismo , Animales , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Células Estrelladas Hepáticas/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Ratas , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Juvenile papillomatosis (JP), also termed Swiss cheese disease, is a rare and benign type of proliferative breast tumor that is specifically observed in children and adolescents. The majority of JP patients are Caucasian and exhibit a single breast mass. The current report presents an unusual case of bifocal JP in an 11-year-old Chinese female. The patient presented with a slow-growing palpable mass in the upper outer quadrant of the left breast. Ultrasonography identified a further impalpable lesion in the lower outer quadrant of the ipsilateral breast. The preoperative clinical diagnosis of the two masses was fibroadenoma, however, following complete excision of the two tumors, histopathology revealed JP. Furthermore, the patient had a family history of breast cancer. The current report describes a review of the literature regarding the presentation, pathology, diagnosis, and treatment of JP and its association with breast carcinoma. In the current case, JP was associated with an increased risk of breast cancer in the patient, as well as the patient's elder female relatives; therefore, a more thorough medical follow-up may prove prudent for those individuals with a high risk of developing breast cancer.
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OBJECTIVE: Trastuzmab combined therapy has been recommended as standard therapy for HER-2-positive breast cancer. However, more than 70% HER-2-positive cases do not recur and might thus be with overtreatment risk. The aim of this study was to explore the significance of TIMP-1 and nm-23 expression in identifying the good prognosis subtype in HER-2-positive breast cancer. METHODS: One hundred and sixty-five cases of HER-2-positive breast cancer treated in Tianjin Medical University Cancer Hospital from Jan. 1987 to Dec. 1988 were studied. Expressions of TIMP-1 and nm-23 were detected by immunohistochemistry and the correlation with clinicopathologic characteristics and long-term outcome was analyzed. RESULTS: 53.3% (88/165) of TIMP-1 and 72.7% (120/165) of nm-23 expression were detected in the patients. The TIMP-1-negative patients classified as good prognosis group had a 10-year metastasis free survival (MFS) of 58.4% and 10-year overall survival (OS) of 68.8%, compared with the 10-year MFS of 43.2% (P = 0.041) and 10-year OS of 52.0% in the positive group (P = 0.020). The nm-23-positive patients classified as good prognosis group had a 10-year MFS of 54.2% and 10-year OS of 65.7%, compared with the 10-year MFS of 40.0% (P = 0.049) and 44.1% (P = 0.015) in the negative group. The multivariate analysis showed that expressions of TIMP-1 and nm-23, tumor size and lymph node involvement were independent prognostic factors. CONCLUSIONS: In HER-2-positive breast cancer, TIMP-1 and nm-23 can be used to further distinguish between low-risk and high-risk subgroups, and they are independent factors in prognosis.
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Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Nucleósido Difosfato Quinasas NM23/metabolismo , Receptor ErbB-2/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Mastectomía Radical Modificada , Persona de Mediana Edad , Tasa de Supervivencia , Carga Tumoral , Adulto JovenRESUMEN
OBJECTIVE: To study the clinicopathologic features and prognosis of primary lymphoma of breast. METHODS: Forty cases of primary breast lymphoma, diagnosed according to the 2008 World Health Organization classification of hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemistry was performed by SP method. The follow-up data were analyzed. RESULTS: (1) All the patients were females and the median age was 47 years. Unilateral and bilateral breast involvement were noted in 36 and 4 patients, respectively. The number of tumor were 31 cases (77.5%, 31/40) less than 3, and 9 cases (22.5%, 9/40) were 3 and more than 3. According to Ann Arbor staging system, 33 cases (82.5%) were in stage I to II and 7 cases (17.5%) in stage III to IV. The level of LDH in 9 cases (24.3%, 9/37) went up. For ECOG scores, 34 cases (85.0%) were 0 to 1 score and 6 cases (15.0%) were more than 2 scores. With respect to international prognostic index, 83.8% (31/37) were of score 0 to 2 and 16.2% (6/37) were of score 3 and more than 3. The axillary lymph nodes of 21 patients (53.8%, 21/39) were involved by the malignancy. (2) Histologically, 38 cases (95.0%, 38/40) were classified as B-cell lymphoma [including 27 cases (67.5%) of diffuse large B-cell lymphoma, 8 cases (20.0%) of mucosa-associated lymphoid tissue lymphoma, 2 cases of follicular lymphoma and 1 case of lymphoplasmacytic lymphoma]. The remaining cases included one case of peripheral T-cell lymphoma and one case of lymphoblastic lymphoma. Immunohistochemically, expression of CD20+/- CD79a were demonstrated in the 38 cases (95.0%) of B-cell lymphoma. The staining for CK was negative in all cases. In 33 cases, the positive rates of MUM-1, bcl-6 and bcl-2 were 57.6% (19/33), 30.3% (10/33) and 72.7% (24/33), respectively. Three cases were germinal center B cell phenotype and 21 cases were non-germinal center B cell phenotype. (3) Follow-up information was available in 37 patients (92.5%, 37/40). Twenty-three patients (62.2%, 23/37) were still alive and fourteen ones (37.8%, 14/37) died. For the 27 cases with diffuse large B-cell lymphoma, the five-year and disease-free survival rates were 48.0% and 36.0%, respectively. CONCLUSIONS: Primary breast lymphoma is a rare disease entity. Diffuse large B-cell lymphoma is the commonest histologic type and the majority show a non-germinal center B cell phenotype. The level of LDH, number of tumor and international prognostic index are of prognostic significance.
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Neoplasias de la Mama/patología , Linfoma de Células B Grandes Difuso/patología , Linfoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/cirugía , Antígenos CD79/metabolismo , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Factores Reguladores del Interferón/metabolismo , L-Lactato Deshidrogenasa/sangre , Metástasis Linfática , Linfoma/tratamiento farmacológico , Linfoma/metabolismo , Linfoma/cirugía , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/cirugía , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Linfoma Folicular/cirugía , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/cirugía , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/cirugía , Mastectomía/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Although cytological methods for breast oncology have been used in recent decades, intra-operative frozen section has been playing a vital role in making therapeutic decisions. We analyzed a large series of frozen section diagnoses for Chinese cases of breast lesion within the last 15 years. The experience was expected to increase the diagnostic accuracy of cases with breast lesions. METHODS: The data from consecutive 13243 cases of breast lesions diagnosed with intra-operative frozen sections between 1988 to 2002 were compared with paraffin sections in a case by case manner. The causes of false negative and positive diagnoses as well as delayed diagnoses were analyzed. RESULTS: One hundred and seventeen cases (0.9%) were falsely diagnosed, with one false positive case and 116 false negative cases. The diagnosis of 47 cases (0.4%) was delayed. The proportion of several lesions had the features of the patients' ages. Six types (false invasion, peri-papilloma, adenoma of nipple duct, florid adenosis, sclerosing adenosis, and granulose cell tumor) of lesions may lead to false positive, and four types (morphological changes responding chemotherapy, well differentiated papillary carcinoma, invasive lobular carcinoma, and tubular carcinoma) to a false negative. Gross and microscopic findings may be inconsistent in two types of lesions (radial scar and florid adenosis) microscopic and clinical findings in three types (ganulomatous mastitis mammary, duct ectasia, and fat necrosis), and three types (abundant fat or sclerous tissues; borderline lesions and changes of post-chemotherapy) were likely wrongly classified. CONCLUSIONS: Intra-operative frozen section can accurately identify breast lesions in many instances, leading to fewer errors on account of more diagnostic experience and understanding of diagnostic limitations.
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Enfermedades de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico , Secciones por Congelación/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Biopsia/métodos , Mama/patología , Enfermedades de la Mama/patología , Neoplasias de la Mama/patología , Niño , China , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Persona de Mediana Edad , Adhesión en Parafina/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To study the clinical and pathologic characteristics of primary angiosarcoma of breast. METHODS: Five cases of primary angiosarcoma of breast were reviewed. Immunohistochemical study (SP method) for factor VIII-related antigen, CD31, CD34, estrogen receptor, progesterone receptor and c-erbB-2 was performed. The clinical data were also analyzed. RESULTS: All of the 5 patients had a history of a painless breast lump. Ultrasound examination and mammogram did not reveal any specific findings. Histologically, various degree of cellular pleomorphism was noted. Immunohistochemical study showed a positive expression of endothelial associated antigens of the tumors cells in all the 5 cases. The staining result for estrogen receptor, progesterone receptor and c-erbB-2 was negative. CONCLUSIONS: Primary angiosarcoma of breast is a rare entity. The diagnosis is rather difficult owing to the lack of specific clinical findings and histological heterogeneity. Application of Positive expression of endothelial associated antigens of the tumors cells is helpful in making a pathological diagnosis morphologically.
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Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama/patología , Hemangiosarcoma/patología , Adulto , Antígenos CD34/metabolismo , Mama/metabolismo , Mama/patología , Mama/cirugía , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/cirugía , Neoplasias de la Mama Masculina/metabolismo , Neoplasias de la Mama Masculina/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Hemangiosarcoma/metabolismo , Hemangiosarcoma/cirugía , Humanos , Inmunohistoquímica , Masculino , Mastectomía/métodos , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
OBJECTIVE: E2F-1 and Rb are involved in cell cycle regulation. This study was to illustrate the mechanism of transformation from benign papillomatosis to ductal carcinoma in situ (DCIS) of the breast in relation to E2F-1 and Rb expression. METHODS: In situ hybridization (ISH) was used to determinate the expression of E2F-1 and Rb mRNA of mild papillomatosis (MP, n = 40), severe papillomatosis (SP, n = 40) and DCIS (n = 40). Immunohistochemistry (IHC) was used to examine the expression of E2F-1 and Rb protein. RESULTS: The positive rate of E2F-1 mRNA expression in MP, SP and DCIS was 17.5%, 45.0% and 80.0%, and that of E2F-1 protein expression was 20.0%, 47.5% and 77.5%, respectively. There were significant differences among the three groups (P < 0.01), and between any two groups (P < 0.01). The positive rate of Rb mRNA expression in MP, SP and DCIS was 90.0%, 50.5% and 20.0%, and that of Rb protein expression was 85.0%, 52.5% and 22.5%, respectively, with statistically significant difference similar with that of E2F-1. With the progression of papillomatosis to DCIS, the expression of E2F-1 mRNA and protein increased, while that of Rb decreased. The protein expression by IHC was positively correlated with the mRNA expression by ISH. However, that of E2F-1 was negatively correlated with Rb. CONCLUSION: E2F-1 and Rb might provide a valuable basis for screening high risk papillomatosis and new target of gene therapy for pre-cancerous lesions of the breast.
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Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Papiloma/metabolismo , Proteína de Retinoblastoma/biosíntesis , Factores de Transcripción/biosíntesis , Neoplasias de la Mama/genética , Carcinoma Intraductal no Infiltrante/genética , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción E2F , Factor de Transcripción E2F1 , Femenino , Regulación Neoplásica de la Expresión Génica , Genes de Retinoblastoma , Humanos , Inmunohistoquímica , Hibridación in Situ , Papiloma/genética , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteína de Retinoblastoma/genética , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: To investigate the clinical significance of the protein expression of 4 cell cycle regulators in papillomatosis of the breast. METHODS: Immunohistochemistry was used to examine the protein expression of CyclinD1, p16, E2F-1 and Rb in 4 groups (196 cases) with mild papillomatosis (MP), moderate papillomatosis (MoP), serious papillomatosis (SP) and ductal carcinoma in situ (DCIS). RESULTS: There were significant difference of the positive rate and the intensity of CyclinD1, p16, E2F-1 and Rb expression among the groups, respectively (chi(2) were 16.702, 20.742, 40.335, 42.317; 19.120, 29.469, 45.080, 46.920, P < 0.01. Meaning time there were significant difference in the expression of these 4 factors between MoP and SP (P < 0.05). There was significance of E2F-1 or Rb expression between SP and DCIS (P < 0.01), but there was no significance to be found in the expression of CyclinD1 or p16 between the two groups (P > 0.05). Rb was screened as the highest risk factor by Odd Risk Logistic Analysis. CONCLUSION: CyclinD1, p16, E2F-1 and Rb played the important roles from MP into SP and then DCIS. E2F-1 and Rb can be used as the assistant indicators on the differentiation of SP and DCIS. Rb may be helpful in screening high risk cases from SP or MoP.