High-grade gliomas (HGG) are serious primary brain tumors that may prevent the patient from functioning normally in social, emotional and cognitive respect. Often the partner's role will convert to that of informal caregiver. Consequently, they may experience significant stress and reductions in caregiver mastery, negatively affecting their health-related quality of life (HRQOL). We aimed at (1) determining factors that impact HRQOL and mastery of caregivers of HGG patients, and (2) investigate if a structured intervention consisting of psychoeducation and cognitive behavioral therapy leads to improvements in the mental component of HRQOL and mastery of caregivers. Fifty-six patient-caregiver dyads were randomly assigned to the intervention group or the care as usual group. The intervention program consisted of six one-hour sessions with a psychologist. Participants completed questionnaires concerning their perceptions of the patients' HRQOL (SF-36), neurological functioning (BN20), and cognitive functioning (MOS), and concerning their own HRQOL (SF-36) and feelings of caregiver mastery (CMS) both at baseline (i.e. before randomization) and every 2 months thereafter until 8 months later, five times in total. Patients' HRQOL and neurological functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an 8 month period. Our findings suggest that informal caregivers can benefit from a psychological intervention as it is a helpful tool in maintaining a stable level of mental functioning and caregiver mastery.

Recent studies show that different aspects of smoking behavior are associated with the α-5 subunit of the nicotinic acetylcholine receptor (CHRNA5) gene and the gene coding for brain-derived neurotrophic factor (BDNF). This raises the question whether the amount of cigarettes smoked per day has a different genetic background than smoking initiation and what other smoking phenotypes may be relevant. The aim of this study was to replicate these associations in a large population-based sample. We investigated the association with smoking initiation and the number of cigarettes used per day and additional smoking phenotypes in a population-based sample of 2166 participants of Dutch origin. Rs6265 in BDNF was not associated with smoking initiation. This single nucleotide polymorphism was associated with smoking cessation. Rs16969968 in CHRNA5 was associated with the amount of nicotine used and in particular smoking 25 cigarettes or more per day. Overall, the results confirm the involvement of the CHRNA5 gene in the amount of nicotine use and further suggest involvement of the BDNF gene in smoking behavior.

INTRODUCTION: Recent trials have shown that the addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT) improves survival in anaplastic oligodendroglioma. With improved survival, the quality of survival becomes pivotal. Because data regarding longterm functioning in anaplastic glioma patients are lacking, we evaluated cognitive functioning and health-related quality of life (HRQOL) in a cohort of Dutch and French long-term survivors from the European Organisation for Research and Treatment of Cancer (EORTC) trial 26951 on adjuvant PCV for anaplastic glioma. METHODS: Of the 28 Dutch patients and 9 French patients, 25 (89%) and 7 (78%), respectively, included in EORTC trial 26951 who were still alive agreed to participate. Cognitive functioning (assessed using neuropsychological tests for six cognitive domains) was compared with matched healthy controls. Patients' HRQOL (assessed with the EORTC QLQ-C30 and BN20 questionnaires) was compared with that of healthy controls, with the patients' own HRQOL 2.5 years following initial RT, and with the patient by proxy. Tumor histology, location, and recurrence; treatment; and the presence of epilepsy in the last year were recorded. RESULTS: The median survival time was 147 months. A total of 41% of patients did not have cognitive impairment, and 34% had severe impairment (≥ 4 domains affected). A total of 31% of patients were employed, 78% were independent in the activities of daily living. Patients' HRQOL was worse than controls' but was similar to 2.5 years after initial treatment. Treatment (in 35% of patients RT only, in 65% RT/PCV), histology and location were not correlated with cognition or HRQOL. Current epilepsy was associated with slower speed and poorer memory. Recent recurrence (13%) was associated with worse HRQOL. CONCLUSIONS: Cognitive functioning in longterm anaplastic glioma survivors is variable. However, most patients function independently. HRQOL is relatively stable during the course of the disease but is affected by recent recurrence. No effect of the addition of PCV to RT on cognition or on quality of survival could be identified in this patient group.

lower than that for both of these agents added sequentially. Interestingly, when the sequence of addition of drugs was reversed using 5azaD/SAHA, the reduction in growth (66% vs. 85%, P , 0.05) and percentage of apoptotic cells were lower than in cultures treated with SAHA/5azaD. The greatest amount of glioma cell death induced by SAHA/5azaD corresponded with higher protein levels of the cyclin dependent kinase inhibitor, P 21 , and the minimum fraction of cells in active phases of cell cycle (19% in control vs. 11% in SAHA/5azaD). Furthermore, glioma cells treated with SAHA/ 5azaD or 5azaD/SAHA displayed the highest levels of acetylated histone H4 protein levels, indicating possible epigenetic changes. Our data indicating that the effects of SAHA/5azaD are likely mediated by epigenetic mechanisms is made evident by increases in P 21 and acetylated histone H4 protein levels. Whether such strategies are also effective in primary human glioma tumor cells will be tested, which may ultimately open untapped territories to search for curative therapies.