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PURPOSE We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month(More)
Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not(More)
OBJECTIVE To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. METHODS This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months(More)
ATR is an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. Cancer-specific defects in the DNA damage response (DDR) may render cancer cells vulnerable to ATR inhibition alone. We determined the cytotoxicity of the ATR inhibitor VE-821 in isogenically matched cells with DDR(More)
Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We(More)
BACKGROUND Most solid tumours contain regions of sub-optimal oxygen concentration (hypoxia). Hypoxic cancer cells are more resistant to radiotherapy and represent the most aggressive fraction of a tumour. It is therefore essential that strategies continue to be developed to target hypoxic cancer cells. Inhibition of the DNA damage response (DDR) might be an(More)
When neuroimaging reveals a brain lesion, drug-resistant epilepsy patients show better outcomes after resective surgery than do the one-third of drug-resistant epilepsy patients who have normal brain magnetic resonance imaging (MRI). We applied a glutamate imaging method, GluCEST (glutamate chemical exchange saturation transfer), to patients with(More)
UCB SA was developing the high-affinity synaptic vesicle glycoprotein 2A ligand, seletracetam, an analog of levetiracetam, for the potential oral treatment of epilepsy. Phase II epilepsy trials were underway, but in July 2007, the company stated that development of seletracetam had been put on hold and it is unknown whether planned phase IIb/III trials will(More)