Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.

PURPOSE: The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. METHODS: The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. RESULTS: Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-kappaB, and autophagy (programmed cell death type II). CONCLUSION: A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.     

The conventional versus automated measurement of blood pressure in the office (CAMBO) trial: masked hypertension sub-study

OBJECTIVES:: To determine the prevalence of masked hypertension [normal office blood pressure (BP) with high awake ambulatory BP] using automated office BP (AOBP) or conventional manual office BP (MOBP) measurement in routine clinical practice. METHODS:: The prevalence of masked hypertension was evaluated on three consecutive visits during a median 6 months period in patients with systolic hypertension randomized to management with AOBP (n?=?140) or continued conventional MOBP (n?=?112) in routine primary care practice. AOBP was recorded using the automated BpTRU device with the patient resting alone in a quiet examining room. All patients underwent 24-h ambulatory BP monitoring. RESULTS:: The prevalence of masked hypertension on any one of three visits calculated using only SBP varied between 12 and 17% in the AOBP group compared with 19 and 22 % in the MOBP group. Masked hypertension was present on both of the first two visits in 7 and 12% and on all three visits in 6 and 7% of AOBP and MOBP patients, respectively. The prevalence for masked hypertension based upon both SBP and DBP was similar being 11-15% for AOBP and 19-20% for MOBP patients on single visits, but decreased to 6 and 10% when readings from the first two visits were used and to 4 and 6% when all three visits were used for the AOBP and MOBP groups, respectively. CONCLUSION:: The prevalence of masked hypertension is lower with AOBP compared with MOBP. The number of patients with masked hypertension decreases if the criteria for having this condition need to be met on multiple visits.