results from a retrospective study of DA-EPOCH-R check details from another center to independently verify the outcomes.
The patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.
Therapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00001337.)”
oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is a retrograde neuronal messenger that participates in synaptic plasticity, including late-phase long-term potentiation (LTP) Fedratinib in vitro and long-term memory (LTM) formation. Our recent studies have shown that nNOS knockout (KO) mice have a severe deficit in contextual fear conditioning compared to wild type (WT) counterparts (Kelley et al. 2009).
Given the role of the nNOS gene in fear conditioning, we investigated whether systemic administration of modulators of NO signaling
affect the formation of contextual and cued fear memories and the effects of these modulators on cyclic 3’5′-guanosine monophosphate (cGMP) levels in the hippocampus and amygdala.
The preferential nNOS inhibitor S-methyl-l-thiocitrulline (SMTC; 10-200 mg/kg) was administered this website (IP) to WT mice, and the NO donor molsidomine (10 mg/kg) was administered (IP) to nNOS KO mice either 30 min pretraining or immediately posttraining.
Pretraining SMTC administration to WT mice impaired both short- and long-term memories of contextual (36% inhibition) but not cued fear conditioning. Pretraining molsidomine administration to nNOS KO mice improved their deficit in short- and long-term memories of contextual fear conditioning (46% increase). Posttraining drug administration had no effect on WT and nNOS KO mice. The systemic administration of SMTC dose-dependently decreased cGMP concentrations down to 25% of control, while molsidomine increased cGMP concentration (three- and five-fold) in amygdala and hippocampus, respectively.
These findings suggest that neuronal NO and its downstream second messenger cGMP are important for acquisition and subsequent consolidation of LTM of contextual fear conditioning.