RESUMO
Breast cancer is one of the common tumors occurring in woman and despite treatment, the prognostic is poor. Genistein, a soy isoflavone, has been reported to have chemopreventive\chemotherapeutic potential in multiple tumor types. Here, we investigated the genistein antiproliferative effect in MCF-7 breast cancer, underlying the molecular mechanisms involved in this effect. MCF-7 cancer and CCD1059sK fibroblast cells were treated with estradiol (10 nM) or genistein (0.01-100 µM) for 24, 48, and 72 h and the cell proliferation was investigated by MTT; membrane cell permeability was evaluated by LDH and PI incorporation; apoptosis was investigated by externalization of phosphatidylserine by FACS; and presence of autophagy was detected by LC3A/B immunostaining. The expression of apoptotic proteins and antioxidant enzymes was evaluated by qPCR. The results demonstrate that genistein (100 µM) for 72 h of treatment selectively reduced MCF-7 cell proliferation independent of estrogen receptor activation, while no cytotoxicity was observed in fibroblast cells. Further experiments showed that genistein induced phosphatidylserine externalization and LC3A/B immunopositivity in MCF-7 cells, indicating apoptosis and autophagy cell death. Genistein increased in three times proapoptotic BAX/Bcl-2 ratio and promoted a parallel downregulation of 20 times of antiapoptotic survivin. In addition, genistein promoted a decrease of 5.5, 9.3, and 3.6 times of MnSOD, CuZnSOD, and TrxR mRNA expression, respectively, while the GPx expression was increased by 6.5 times. These results suggest that the antitumor effect of genistein involved the modulation of antioxidant enzyme and apoptotic signaling expression, which resulted in apoptosis and progression of autophagy.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias da Mama/genética , Genisteína/administração & dosagem , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Estresse Oxidativo/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
INTRODUCTION: End-stage renal disease (ESRD) is a prevalent, important cause of death. Transplantation increases survival and improves the quality of life of patients with ESRD while long-term dialysis is related to poor outcomes even among patients who undergo subsequent transplantations. OBJECTIVES: To compare the advantages of preemptive procedures with kidney transplants among patients on renal replacement therapy. METHODS: This retrospective study was performed in two Córdoba city transplantation centers. Patients were divided into three groups: preemptive kidney transplant (PKT), patients on hemodialysis who received living donor kidney transplants (LDT), and subjects who received grafts from deceased donors (DDT). Serum creatinine, delayed graft function (DGF), subclinical rejection, and interstitial fibrosis/tubular atrophy (IF/TA) were evaluated at 6 months. RESULTS: Eighty patients were included: PKT (n = 28), LDT (n = 27), DDT (n = 25) mean age 29, 30, and 35 years, respectively. Women predominated among PKT and men in the other groups. In all groups, cyclosporine was the calcineurin inhibitor mostly used. Creatinine at 6 months was lower in the living donor groups (1.26 mg/dL PKT and 1.32 mg/dL LDT; P = NS) in relation to the deceased donor group (1.96 mg/dL; P < .05). DDT had the highest rate of DGF: 44% DDT versus 11.5% LDT vs 0% PKT (P < .05). Subclinical rejection was significantly lower among preemptive transplantations: PKT 7.6% versus LDT 18.5% versus DDT 24% (P < .05). IF/TA was higher in transplants from deceased donors: PKT 11.1%; LDT 11.5%; DDT 32%. CONCLUSIONS: Preemptive kidney transplantation offered the advantages of a lower creatinine, no DGF, as well as a reduced incidence of subclinical rejection and chronic allograft nephropathy at 6 months posttransplantation.
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim/métodos , Adulto , Calcineurina/farmacologia , Ciclosporina/farmacologia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Doadores Vivos , Masculino , Diálise Renal , Terapia de Substituição Renal/métodos , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
An eastern woodrat (Neotoma floridana) collected in January 2001 near Bedias, Grimes County, Texas, had extensive lesions of both ears and swollen feet. Impression smears and histologic sections demonstrated the presence of Leishmania in both ears and the one foot that was screened. Polymerase chain reaction screening using species-specific primers detected parasites in both ears and all four feet and indicated the parasites were L. mexicana. The detection of L. mexicana in N. floridana represents a new host record in a new ecologic region and may help explain a human infection acquired outside the previously-known range of the disease. Given the geographic distribution of N. floridana and the two other species of Neotoma found naturally infected, enzootic foci of Leishmania could be present over much of the southern United States.
Assuntos
Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/veterinária , Doenças dos Roedores/diagnóstico , Animais , Primers do DNA , DNA de Protozoário/análise , Leishmania mexicana/genética , Leishmaniose Cutânea/diagnóstico , Masculino , Reação em Cadeia da Polimerase , Ratos , Doenças dos Roedores/patologia , TexasRESUMO
A urticária Ú uma enfermidade comum e multifatorial. Estima-se que 10 por cento a 20 por cento da populaçäo apresente um episódio de urticária em alguma fase de sua vida. As neoplasias estÒo entre as causas mais raras. Apresentamos um caso de urticária crônica cujo diagnóstico final foi de mieloma múltiplo (MM), alertando para a necessidade de uma investigaçäo sistemática e criteriosa destes pacientes.