Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB Inhibitors in Ovarian Cancer Therapy

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer

The Effect of Intervention Based on Pender's Model of Health-Promoting Self-Care Behaviors in Women who are the Head of their Household

Background: A number of studies have reported that women as the head of the household suffer from poor physical health. Yet, a few studies are available on the effects of health-promoting interventions for this vulnerable group. Objectives: The present study was conducted to determine the effect of an intervention based on Pender’s model on health-promoting behaviors in women who were the head of their household. Methods: A quasi-experimental study was conducted on 66 women, who were the heads of households with inappropriate physical health-promoting behaviors, selected by the consensus method and allocated to intervention and control groups using the randomized permuted block method. The intervention group received supportive-educational intervention according to Pender’s model. Posttest was carried out for both intervention and control groups two months after the end of the intervention. Data were analyzed using descriptive statistics and inferential tests, including independent samples t, paired t, Chi-square, Mantel-Haenszel tests and logistic regression analysis. Results: The subjects’ mean age was 39.58 ± 6.69 years, of whom, 47% were widowed; they were mostly housewives with a mean schooling of 7.97 ± 4.31 years, and 74.2% had insufficient income. Prior to the intervention, women who were the head of the household and had poor level of health-promoting behaviors were selected. There was no significant difference between the two groups in mean score of the components of the health-promoting model (P < 0.05). The intervention group had significantly better performance in physical health-promoting behaviors, two months after the intervention (P < 0.001). Conclusions: The supportive-educational intervention was effective on the physical health-promoting behaviors of women who were the head of the household. Thus, this model can be used as a framework for planning interventions to promote the physical health of such women