Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

A phase II trial of docetaxel plus nedaplatin and 5-fluorouracil in treating advanced esophageal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Accumulating data indicate that docetaxel plus cisplatin and 5-fluorouracil has certain effect on advanced gastric or gastro-oesophageal junction adenocarcinoma. This study was to evaluate the efficacy and toxicity of docetaxel plus nedaplatin and 5-fluorouracil (DNF regimen) in treating advanced esophageal carcinoma.</p><p><b>METHODS</b>Forty-three patients with pathologically confirmed advanced esophageal carcinoma treated by DNF regimen: intravenous infusion of docetaxel (75 mg/m(2)) over 1 h, intravenous infusion of nedaplatin (100 mg/m(2)) over 3 h, intravenous infusion of leucovorin (CF, 200 mg/m(2)) over 2 h, intravenous injection of 5-fluorouracil (375 mg/m(2)) over 10 min, followed by a 46-hour infusion of 5-fluorouracil (2.6 g/m(2)). The cycle was repeated every three weeks. Treatment efficacy was evaluated every two weeks according to the WHO standards. All patients received at least two cycles of chemotherapy.</p><p><b>RESULTS</b>Patients received a total of 144 cycles of treatment, and all were evaluable for efficacy and toxicity. Of the 43 patients, 2 (4.65%) achieved complete response (CR), 25 (58.14%) achieved partial response (PR), 9 (20.93%) had stable disease (SD), and 7 (16.28%) had progressive disease (PD). The overall response rate was 62.8%. The median time-to-progression (TTP) was 201 days and the median survival time (MST) was 310 days. Grade III/IV adverse events mainly included neutropenia (20.93%), febrile neutropenia (4.65%), thrombocytopenia (6.98%) and vomiting (9.30%). One patient died of grade IV thrombocytopenia.</p><p><b>CONCLUSION</b>DNF regimen is effective for and well tolerated by patients with advanced esophageal carcinoma.</p>