Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization.

We investigated the effects of propofol and propofol-ketamine on hemodynamics, sedation level, and recovery period in pediatric patients undergoing cardiac catheterization. We performed a prospective, randomized, double-blind study. The study included 60 American Society of Anesthesiologists physical status II or III (age range, 1 month-13 years) undergoing cardiac catheterization for evaluation of congenital heart disease. Propofol and ketamine were prepared in 5% glucose solution to a final concentration of 5 and 1 mg/ml, respectively; similar injectors containing 5% glucose solution only were prepared. Fentanyl (1 pg/kg) and propofol (1.5 mg/kg) were given to both groups. Then, group I received 0.5 ml/ kg, of 5% glucose and group 2 0.5 ml/kg of ketamine solution by an anesthesiologist who was unaware of the groups of patients. Local anesthesia with 1% lidocane was administered before intervention in all patients. The noninvasively measured mean arterial pressure, heart rate, respiratory rate, and peripheral oxygen saturation were recorded at the baseline, following drug administration, at 3, 5, 10, 15, 20, and 30 minutes and then at 15-minute intervals until the end of the procedure. Additional drug and fentanyl requirements to maintain a sedation level of 4 or 5 were recorded. After the procedure, the time to a Steward recovery score of 6 and adverse effects in the first 24 hours were recorded. The number of patients with more than a 20% decrease in mean arterial pressure was 11 in group 1 and 3 in group 2(p < 0.05). The number of patients who experienced more than a 20% decrease in heart rate was 12 in group I and 5 in group 2) = 0.054). Ten patients in group I and 3 patients in group 2 required additional fentanyl doses (p = 0.057). The number of additional propofol doses was lower in group 2) < 0.05). Propofol combined with low-dose ketamine preserves mean arterial pressure better without affecting the recovery and thus is a good option in pediatric patients undergoing cardiac catheterization