RESUMO
Resveratrol is a natural phytoestrogen with antiproliferative properties present in red wine, grapes, and berries. Published reports on the effects of resveratrol in human endometrial function are limited. The objective of this study was to investigate the expression of estrogen receptor α (ESR1), Ki-67 (a proliferative marker), aryl hydrocarbon receptor (AhR), and members of the cytochrome P450 superfamily of enzymes (CYP1A1 and CYP1B1) in an in vitro and vivo assay. Alkaline phosphatase assay of estrogenicity was used to compare estrogen activity of different concentrations of resveratrol to estradiol (E2) and diethylstilbestrol (DES), using Ishikawa cell culture. Immunohistochemical expression of ESR1 and Ki67, and reverse transcriptase polymerase chain reaction of AhR, CYP1A1, and CYP1B1 were analyzed from xenograft implants of human endometrial tissue in ovariectomized immunodeficient RAG-2-γ(c) mice, after 30 days of treatment with subcutaneous pellets of E2, E2 plus progesterone (P4), or E2 plus resveratrol (6, 30, or 60 mg) for 30 days. Compared to E2, resveratrol acted as an agonist and antagonist of estrogen in low and high concentrations, respectively, when combined with E2. Xenografts of human endometrial tissues in RAG-2 mice exhibited reduced expression of ESR1 and proliferative activity (Ki67) with 60 mg of resveratrol. This study suggests that resveratrol, at high doses, has the potential benefit to reduce proliferation of human endometrium through ESR1.
Assuntos
Endométrio/efeitos dos fármacos , Fitoestrógenos/farmacologia , Estilbenos/farmacologia , Vinho , Fosfatase Alcalina/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Dietilestilbestrol/farmacologia , Relação Dose-Resposta a Droga , Endométrio/transplante , Estradiol/farmacologia , Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Xenoenxertos , Humanos , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovariectomia , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Resveratrol , Fatores de TempoRESUMO
We have been pleased with our initial experience in an evolving program. As newer surgical and radiotherapy techniques have become available, the role of radiosurgery has been and will continue to be modified. As more commercially available systems have been marketed, the availability will become more widespread. A battery of residents in neurosurgery and radiation oncology trained in these technologies will provide leadership and future directions of this therapy.
Assuntos
Neoplasias Encefálicas/cirurgia , Radiocirurgia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Radiocirurgia/tendências , South CarolinaRESUMO
We describe a system for stereotactic radiosurgery with a linear accelerator. This technique allows treatment of small (less than 40 mm diameter) intracranial lesions, including vascular malformations, and primary and metastatic tumors that are deep within the brain or in areas not amenable to open surgery. A beam of ionizing radiation (1800 to 2500 cGy) is focused on the center of the lesion, which is determined by stereotactic localization. "Dynamic rotation" of the linac gantry and table continuously about this predetermined point ensures that only the lesion receives the full radiation dose, while the normal structures in the head receive minimal amounts of radiation. The system combines, for the first time in one place, elements of radiosurgical technique developed at various centers. Testing for accuracy compares favorably with results at other centers using linac-based systems as well as comparing favorably with the gamma knife.