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Cancer Prev Res (Phila) ; 6(12): 1283-92, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24136864


Epidemiologic, laboratory, and animal evidence suggests that progestins and vitamin D may be potent ovarian cancer preventives. Our objectives were to evaluate progestins as reproductive tract cancer chemopreventives in the chicken, determine whether restricted ovulation affected the incidence of reproductive tract tumors, and assess whether vitamin D would confer cancer protection either alone or in addition to progestin. A total of 2,400 two-year-old Single Comb White Leghorns were randomized into six groups (400 each) with hormonal and dietary manipulation for 2 years as follows: (i) no intervention, regular feed/caloric intake, (ii) control, (iii) vitamin D, (iv) the progestin levonorgestrel, (v) vitamin D plus levonorgestrel, and (vi) the progestin Provera (medroxyprogesterone acetate). Groups 2 to 6 were caloric restricted to inhibit ovulation. Our results indicated that caloric restriction decreased egg production by more than 60%, and was associated with a greater than 70% decrease in reproductive tract cancers. Ovulatory events did not differ among the caloric-restricted groups (groups 2-6), except for the group receiving levonorgestrel, which had fewer ovulatory events than controls (P = 0.046). After correcting for egg production, birds receiving progestins had significantly fewer reproductive tract cancers [OR, 0.61; confidence interval (CI), 0.39-0.95; P = 0.03], with similar proportionate reductions in tumors arising in either the ovary or oviduct. Vitamin D did not significantly affect cancer incidence overall, or add to the cancer preventive effect of progestins. This study suggests a protective effect of progestins against ovarian and oviductal cancers. These data support the concept that progestins provide a chemopreventive effect unrelated to ovulation.

Adenocarcinoma/prevención & control , Neoplasias Ováricas/prevención & control , Oviposición/efectos de los fármacos , Ovulación/efectos de los fármacos , Progestinas/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Pollos , Suplementos Dietéticos , Huevos , Femenino , Vitamina D/administración & dosificación
Mol Cancer Res ; 7(2): 210-20, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19208743


Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein, we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary serous epithelial ovarian cancer and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using small interfering RNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in ovarian cancer and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule-stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA cross-linking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility, and proliferation but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.

Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Paclitaxel/uso terapéutico , Factor de Transcripción YY1/genética , Sitios de Unión , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/uso terapéutico , Hibridación Genómica Comparativa , Docetaxel , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Epigénesis Genética , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/mortalidad , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/mortalidad , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Taxoides/uso terapéutico , Cicatrización de Heridas , Factor de Transcripción YY1/antagonistas & inhibidores