RESUMEN
BACKGROUND: Cells within breast cancer stem cell populations have been confirmed to have a CD44(+)CD24(-) phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells. METHODS: In this study, we reduced CD44 expression in CD44(+)CD24(-) breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44(+)CD24(-) breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug. RESULTS: The proliferation of CD44 downregulated CD44(+)CD24(-) breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups. CONCLUSIONS: It would appear that expression of CD44 is integral among the CD44(+)CD24(-) cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.
RESUMEN
Type 1 diabetes occurs when pancreatic islet ß-cells are damaged and are thus unable to secrete insulin. Pancreas- or islet-grafting therapy offers highly efficient treatment but is limited by inadequate donor islets or pancreases for transplantation. Stem-cell therapy holds tremendous potential and promises to enhance treatment efficiency by overcoming the limitations of traditional therapies. In this study, we evaluated the efficiency of preclinical diabetic treatment. Diabetes was induced in mice by injections of streptozotocin. Mesenchymal stem cells (MSCs) were derived from mouse bone marrow or human umbilical cord blood and subsequently differentiated into insulin-producing cells. These insulin-producing cells were encapsulated in an alginate membrane to form capsules. Finally, these capsules were grafted into diabetic mice by intraperitoneal injection. Treatment efficiency was evaluated by monitoring body weight and blood glucose levels. Immune reactions after transplantation were monitored by counting total white blood cells. Allografting or xenografting of encapsulated insulin-producing cells (IPCs) reduced blood glucose levels and increased body weight following transplantation. Encapsulation with alginate conferred immune isolation and prevented graft rejection. These results provide further evidence supporting the use of allogeneic or xenogeneic MSCs obtained from bone marrow or umbilical cord blood for treating type 1 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Insulina/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Alginatos , Animales , Células de la Médula Ósea/citología , Diferenciación Celular , Separación Celular/métodos , Células Cultivadas , Modelos Animales de Enfermedad , Sangre Fetal/citología , Ácido Glucurónico , Ácidos Hexurónicos , Humanos , Secreción de Insulina , Masculino , Ratones , Trasplante Heterólogo , Trasplante HomólogoRESUMEN
The screening of the HIV-1 protease (PR) inhibitory activity (IC-50) of various substituted 3-phenyl-4-hydroxycoumarins, 3-benzyl-4-hydroxycoumarins, 3-phenoxy-4-hydroxy-coumarins, 3-benzenesulfonyl-4-hydroxycoumarins and 3-(7-coumarinyloxy)-4-hydroxycoumarins was performed. The data indicate the importance of substituents at positions 5 and 7 of the coumarin ring on the inhibitory potency of the HIV-1-PR.