Cobra venom P-III class metalloproteinase atrase A induces inflammatory response and cell apoptosis in endothelial cells via its metalloproteinase domain.

Snake venom metalloproteinases (SVMPs), which are a critical component of viperid and crotalid venoms, play various important roles in the pathogenesis of snakebite envenomation. The SVMPs from elapid venoms are not well elucidated, as compared with those from viperid and crotalid venoms. Atrase A is a nonhemorrhagic P-III SVMP purified from Naja atra venom that possesses only weak fibrinogenolytic activity. In our prior study, we found that atrase A detached adherent cells from the substrate. In this work, we investigated further the effect and mechanism of atrase A on endothelial cells. Oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and MAPK signaling pathways were measured after HMEC-1 cells were exposed to atrase A. The results showed that HMEC-1 cells released inflammatory mediators, exihibited oxidative damage and apoptosis after exposure to atrase A. The Western blot analysis results revealed that atrase A increased Bax/Bcl-2 and caspase-3 levels and activated the NF-κB and MAPK signaling pathways in endothelial cells. The effects on endothelial cells were nearly completely abolished after atrase A was treated with ethylenediamine tetraacetic acid. These results showed that atrase A led to an inflammatory response, cellular injury and apoptosis in endothelial cells, and this effect was due to its metalloproteinase domain. The study contributes to a better understanding of the structures and functions of cobra venom P-III class metalloproteinases.

[Treatment results of stage IA Hodgkin lymphoma: a report of 97 cases].

BACKGROUND & OBJECTIVE: The treatment strategies of Hodgkin's lymphoma (HL) are different according to clinical stage and risk factors, yet the optimal treatment strategy remains unclear. This study was to analyze the treatment results and prognostic factors of stage IA HL. METHODS: According to prognosis, 97 patients with stage IA HL were divided into 3 groups: 7 (7.2%) in very favorable (VF) group, 72 (74.2%) in favorable (F) group, and 18 (18.6%) in unfavorable (UF) group. Short-term treatment outcome and long-term survival were analyzed. The prognosis was analyzed with Cox regression model. RESULTS: Median follow-up time was 65 months. After radiotherapy or radiochemotherapy, 90 patients (92.8%) achieved complete remission (CR). The 5-and 10-year overall survival (OS) rates were 87.7% and 76.3%; the 5-and 10-year disease-free survival (DFS) rates were 79.4% and 74.5%. The 5-and 10-year OS rates were 100% and 100% in VF group, 88.9% and 88.4% in F group, 78.1% and 39.1% in UF group (P=0.292). The 5-and 10-year DFS rates were 100% and 87.2% in VF group, 86.3% and 71.8% in F group, 73.6% and 34.5% in UF group (P=0.032). Cox analysis showed that pathologic type (P=0.056) and tumor relapse (P=0.011) influenced OS, and the response to primary treatment (P=0.024) influenced DFS. The relapse rate was 18.6%û there was no significant difference between the patients received radiotherapy alone and those received radiochemotherapy (Chi(2)=0.072, P=0.788). The occurrence rate of secondary malignancies was 5.2%, including 2 cases of non-Hodgkin's lymphoma. All the 12 patients who died had received radiotherapy alone. CONCLUSIONS: More than 90% of stage IA HL patients can achieve CR with radiotherapy alone or chemoradiotherapy. The long-term OS and DFS of the patients who received radiochemotherapy are better than those of the patients who received radiotherapy alone. The pathologic type, response to primary treatment and tumor relapse may be independent prognostic factors of stage IA HL.