RESUMO
The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.
RESUMO
Objective:To evaluate the clinical efficacy of paclitaxel combined with epirubicin neoadjuvant chemotherapy in the treatment of triple negative breast cancer and the effect on the Ki-67,p53,P-glycoprotein (P-gp) and glutathione transferase (GST-π).Methods:84 patients with triple-negative breast cancer admitted in our hospital from June 2010 to June 2012 were selected and divided into the observation group and the control group according to the order of admission.The control group was treated with epirubicin,and cyclophosphamide.The observation group was given paclitaxel neoadjuvant chemotherapy combined with epirubicin.The clinical efficacy,expressions of Ki-67,p53,P-gp and GST-π were compared between the two groups.Results:After treatment,the total remission rate of observation group was significantly higher than that of the control group [76.19％(32/42) vs 45.24％(19/42)] (P ＜0.05).Before chemotherapy,the positive expression rates of Ki-67,p53,P-gp and GST-π in the two groups showed no statistical difference(P＞0.05).After chemotherapy,the positive expression rates of Ki-67,p53,P-gp and GST-π in the observation group were significantly lower than those of the control group (P＜0.05),but the positive expression rates of Ki-67,p53,P-gp and GST-π in the control group had no significant difference compared with those before chemotherapy (P＞0.05).The positive expression rates of Ki-67,p53,P-gp and GST-π in the observation group were significantly lower than those of the control group (P ＜0.05).There was no significant difference in the incidence of adverse reaction rate between the observation group and the control group (P＞ 0.05).Conclusion:Paclitaxel combined with Epirubicin neoadjuvant chemotherapy could effectively reduce the expression of Ki-67,p53,P-gp and GST-π in triple-negative breast cancer with exact clinical efficacy.
