Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting

Mifepristone 2.5 mg versus 5 mg daily in the treatment of leiomyoma before surgery

Josep L Carbonell Esteve1, Ana M Riverón2, Mariela Cano2, Alma I Ortiz3, Aleta Valle2, Carlos S Texidó2, Giuseppe Tomasi41Mediterránea Médica Clinic, Valencia, Spain; 2Eusebio Hernández Obstetrics Teaching Hospital, Havana, Cuba; 3Alemán Hospital, Managua, Nicaragua; 4Chemistry Department, University of the Basque Country, San Sebastian, SpainObjectives: To evaluate the efficacy and safety of 2.5 mg and 5 mg mifepristone during 3 months for the treatment of uterine fibroids before surgery.Design: Multicenter randomized clinical trial.Locations: Eusebio Hernández Hospital, Havana, Cuba and the Alemán Hospital, Managua, Nicaragua.Subjects: Included in the study were 146 women with symptomatic uterine fibroids.Treatment: Group I: half a tablet of 5 mg (2.5 mg) mifepristone taken orally every 24 hours, and Group II: one tablet of 5 mg mifepristone taken orally every 24 hours over a period of 3 months in both groups. Two endometrial biopsies were performed.Variables to evaluate efficacy: Increase in average hemoglobin, changes in fibroid and uterine volume, and symptomatic improvement.Results: The average hemoglobin at the end of treatment was 0.6 g/dL greater in the 5 mg mifepristone group (P = 0.033). In both groups there were similar reductions in fibroid volumes. Clinical improvement was more significant in the 5 mg group.Conclusion: The dose to be used should be 5 mg.Keywords: mifepristone, leiomyoma, fibroid , antiprogestin