Sensitivity and mechanisms of taxol-resistant prostate adenocarcinoma cells to Vernonia amygdalina extract

Prostate cancer (PC) patients once Paclitaxel (TAX) treatment responsive later develop hormone refractory PC, thus becoming TAX-insensitive. This underscores the urgent need to develop novel anti-PC therapies. Vernonia amygdalina (VA) could be one such candidate agent. We have shown that androgen-independent PC-3 cells are sensitive to VA treatment in vitro. VA extract (0.01, 0.1 and 1 mg/ml) inhibited DNA synthesis by 12%, 45% (p < 0.05), and 73% (p < 0.01) respectively. In contrast, TAX (0.01, 0.1, and 1 μM) failed to significantly affect cell growth, suggesting TAX resistance. We tested molecular mechanisms which may lend to the observed PC-3 cell VA sensitivity/TAX resistance. Though both VA and TAX stimulated MAPK activity, VA's induction was more intense, but transient, compared to TAX's sustained action. NF-κB activation was inhibited on average by 50% by either 1 mg/ml VA or 1 μM TAX. VA extract caused 35% and 45% increases in c-Myc activity at 10 and 60 min intervals respectively, with the highest stimulation attained 1 h after treatment. In contrast, similar levels were attained by TAX rapidly (within 5 min) and were sustained compared to the slow/multi-phasic action of VA. VA extract treatments had no effect on AKT gene expression, while TAX treatments yielded a four-fold (P < 0.01) increase; and P-glycoprotein (P-gp) activity was inhibited by VA and stimulated by TAX, compared to control (basal ATPase activity). This study shows that TAX-resistant PC-3 cells are sensitive to VA, perhaps explained by differential regulatory patterns of MAPK, c-Myc, AKT, and Pgp activities/expressions.     

Promoting Father Involvement for Child and Family Health

Paternal involvement in children's lives is associated with a variety of child outcomes, including improved cognition, improved mental health, reduced obesity rates, and asthma exacerbation. Given this evidence, the American Academy of Pediatrics has promoted actions by pediatricians to engage fathers in pediatric care. Despite these recommendations, the mother–child dyad, rather than the mother–father–child triad, remains a frequent focus of care. Furthermore, pediatric care is often leveraged to improve maternal health, such as screening for maternal depression, but paternal health is infrequently addressed even as men tend to exhibit riskier behaviors, poorer primary care utilization, and lower life expectancy. Therefore, increasing efforts by pediatric clinicians to engage fathers may affect the health of both father and child. These efforts to engage fathers are informed by currently used definitions and measures of father involvement, which are discussed here. Factors described in the literature that affect father involvement are also summarized, including culture and context; interpersonal factors; logistics; knowledge and self-efficacy; and attitudes, beliefs, and incentives. Innovative ways to reach fathers both in the clinic and in other settings are currently under investigation, including use of behavior change models, motivational interviewing, mobile technologies, peer support groups, and policy advocacy efforts. These modalities show promise in effectively engaging fathers and improving family health.