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1.
Cancer Sci ; 105(10): 1369-76, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25155055

RESUMEN

The breast cancer susceptibility gene 1 (BRCA1) and glutathione S-transferase P1 (GSTP1) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study, BRCA1 and GSTP1 promoter methylation was examined by methylation-specific PCR assay. Patients with BRCA1-methylated (n = 15) or BRCA1-unmethylated (n = 15) tumors and those with GSTP1-methylated (n = 9) or GSTP1-unmethylated (n = 11) tumors were included in the present study. Methylation status of manually micro-dissected normal epithelial cells from the formalin-fixed paraffin-embedded sections of normal breast tissues adjacent to and distant from the tumors was examined at multiple sites (n = 1-5). Of the 15 patients with BRCA1-methylated tumors, 9 harbored BRCA1 promoter methylation in at least one site of the normal breast tissues. However, no BRCA1 promoter methylation was observed at any site of the normal tissues of the 15 patients with BRCA1-unmethylated tumors. No GSTP1 promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of BRCA1 promoter methylation in the normal tissues was confirmed in the epithelial cells enriched with the magnetic-activated cell sorting method. Our findings suggest that a small proportion of normal breast epithelial cells with BRCA1 promoter methylation can be precursor cells from which BRCA1-methylated breast tumors may originate. This does not apply to GSTP1 promoter methylation.


Asunto(s)
Proteína BRCA1/genética , Neoplasias de la Mama/genética , Mama/metabolismo , Metilación de ADN , Regiones Promotoras Genéticas , Adulto , Anciano , Proteína BRCA1/análisis , Células Epiteliales/metabolismo , Femenino , Gutatión-S-Transferasa pi/análisis , Gutatión-S-Transferasa pi/genética , Humanos , Separación Inmunomagnética , Persona de Mediana Edad
2.
Cancer Sci ; 103(5): 913-20, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22320227

RESUMEN

The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Gutatión-S-Transferasa pi/metabolismo , Receptores de Estrógenos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Ciclofosfamida/uso terapéutico , Metilación de ADN , Farmacorresistencia Microbiana , Resistencia a Antineoplásicos , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Gutatión-S-Transferasa pi/genética , Humanos , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Regiones Promotoras Genéticas
3.
Immunotherapy ; 13(3): 189-194, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33225795

RESUMEN

Rechallenge of immune checkpoint inhibitors has been reported for neoplasms other than breast cancer. Reported here is a case of a 55-year old woman diagnosed as having triple-negative right breast cancer with multiple metastases including lung. Atezolizumab and nab-paclitaxel were administered followed by epirubicin-cyclophosphamide. With subsequent eribulin, the overall best response was progressive disease, and curative surgical resection was performed. Three months after surgery (1.5 years after initial response of lung metastasis), right lung metastasis emerged at a site different from baseline. Based on the microsatellite instability-high status, pembrolizumab was administered and showed a good response. The patient has been treated with pembrolizumab, maintaining partial response, for over 9 months, which suggests the benefit of immune checkpoint inhibitors rechallenge in breast cancer.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Albúminas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Resistencia a Antineoplásicos , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Inestabilidad de Microsatélites , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Retratamiento , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/cirugía
4.
Microbes Environ ; 32(4): 376-385, 2017 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-29187707

RESUMEN

Biocontrol agents (BCA) effectively suppress soil-borne disease symptoms using natural antagonistic prokaryotes or eukaryotes. The main issue associated with the application of BCA is that disease reduction effects are unstable under different field conditions. In order to identify potentially effective BCA among several fields, we compared prokaryotic and eukaryotic communities in soil with and without tomato bacterial wilt from three different fields, each of which had the same field management and similar soil characteristics. Soil samples were collected from three fields and two depths because bacterial wilt pathogens were present in soil at a depth greater than 40 cm. We classified soil samples based on the presence or absence of the bacterial phcA gene, a key gene for bacterial wilt pathogenicity and tomato disease symptoms. Pyrosequencing of the prokaryotic 16S rRNA gene and eukaryotic internal transcribed spacer region sequences showed that the diversity and richness of the communities mostly did not correlate with disease symptoms. Prokaryotic and eukaryotic community structures were affected more by regional differences than the appearance of disease. Several prokaryotes and eukaryotes were more abundant in soil that lacked disease symptoms, and eight prokaryotes and one eukaryote of this group were commonly detected among the three fields. Some of these taxa were not previously found in disease-suppressive soil. Our results suggest that several prokaryotes and eukaryotes control plant disease symptoms.


Asunto(s)
Bacterias/clasificación , Agentes de Control Biológico/aislamiento & purificación , Eucariontes/clasificación , Enfermedades de las Plantas/microbiología , Ralstonia solanacearum/patogenicidad , Solanum lycopersicum/microbiología , Bacterias/genética , Eucariontes/genética , Microbiota/genética , ARN Ribosómico 16S/genética , Ralstonia solanacearum/aislamiento & purificación , Microbiología del Suelo , Factores de Transcripción/genética
5.
Hum Pathol ; 64: 145-155, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28434924

RESUMEN

Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/química , Carcinoma Intraductal no Infiltrante/cirugía , Distribución de Chi-Cuadrado , Técnicas de Apoyo para la Decisión , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Modelos Logísticos , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Curva ROC , Receptor ErbB-2/análisis , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
6.
Anticancer Res ; 33(12): 5617-23, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24324107

RESUMEN

AIM: We investigated the association of glutathione S-transferase P1 (GSTP1) expression and methylation status with clinicopathological characteristics of estrogen receptor (ER)-positive breast cancers. MATERIALS AND METHODS: Primary ER-positive breast cancer patients (n=177, stage I-III) were retrospectively analyzed. A quantitative GSTP1 methylation assay was performed using DNA micro-dissected from formalin-fixed and paraffin-embedded (FFPE) breast surgical specimens and GSTP1 expression was examined immunohistochemically. RESULTS: GSTP1 methylation index (MI) was higher for the following patient subsets: Large-size (p=0.029), high-grade (p=0.010), human epidermal growth factor receptor-2 (HER2)-positive (p=0.024) and Ki67-positive (p=0.001) patients. In addition, GSTP1 hyper-methylation was more frequently observed in the luminal-B than the luminal-A subtype (p<0.001) and there was no significant difference in GSTP1 positivity between the two subtypes (p=0.150). CONCLUSION: GSTP1 methylation may well be associated with the pathogenesis of the biologically-aggressive phenotype in ER-positive breast cancer.


Asunto(s)
Neoplasias de la Mama/enzimología , Metilación de ADN , Gutatión-S-Transferasa pi/genética , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Fenotipo , Regiones Promotoras Genéticas
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