Lapatinib is an inhibitor of the tyrosine kinases of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor type 1, with clinical activity in HER2-positive metastatic breast cancer. ...Lapatinib is an inhibitor of the tyrosine kinases of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor type 1, with clinical activity in HER2-positive metastatic breast cancer. We present here a 60 year-old patient with metastatic breast cancer who presented with jaundice and increased serum aminotransferase levels and who had been treated with lapatinib for the previous 14 days. Laboratory tests excluded other causes of acute liver injury. Liver biopsy revealed lesions compatible with drug-induced hepatotoxicity. Bilirubin and liver enzymes returned to normal within three months of lapatinib discontinuation. Lapatinib should be included among the causes of druginduced hepatitis.展开更多
Objective: To investigate the effect of bone morphogenetic proteins (BMPs) on hematopoietic injury of acute radiation sickness in mice. Methods: Mice were subjected to whole-body 60Co γ ray irradiation, then bpBMP wa...Objective: To investigate the effect of bone morphogenetic proteins (BMPs) on hematopoietic injury of acute radiation sickness in mice. Methods: Mice were subjected to whole-body 60Co γ ray irradiation, then bpBMP was put into spatium intermusculare or rhBMP-2m, PBK/ hBMP-2 -NIH3T3 cells were injected into abdominal cavity. The effect of BMPs on hematopoiesis including some hematological parameters, the survival rate of 30 d and formation of bone marrow CFU-GM colony were detected at postradiation. Results: pbBMP (purified bovine bone morphogenetic protein) increased the formation of bone marrow CFU-GM colony (P<0. 05) on d 10 after irradiation. rhBMP-2m increased the survival rate of mice irradiated by 7. 5 Gys Mice in control group died in 30 days, while 10%, 15% and 35% mice survived when they were injected i. p. with 0. 5 mg, 1. 0 mg and 2. 0 mg of rhBMP-2m respectively. All hematological parameters of treated mice were significantly higher than those of control group (P<0. 01). PBK/ hBMP-2 -NIH3T3 cells were established and transplanted into mice irradiated by 7. 0 Gy γ ray with i. p. . The survival ratio of treated mice was higher than that of negative control group (P<0. 01), and all hematopoietic parameters were increased statistically significantly (P<0. 01). Conclusion: Results indicate that in adult mice, BMPs can recover or treat the hematopoietic injury of acute radiation sickness, the mechanism may be related with repairing of hematopoietic injury.展开更多
Objective： To assess the effects of penehyclidine hydrochloride on patients with acute lung injury （ALI）, to observe the expression of Toll-like receptor 4 （TLR4） on the peripheral monocytes of ALI patients and c...Objective： To assess the effects of penehyclidine hydrochloride on patients with acute lung injury （ALI）, to observe the expression of Toll-like receptor 4 （TLR4） on the peripheral monocytes of ALI patients and changes of inflammatory ＆ anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.Methods： Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group （P group, n=21） and conventional treatment group （control group, C group, n=24）. Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride （1 mg, im, q. 12 h） in addition.The TLR4 expression of 20 healthy volunteers were detected.The clinical effect, average length of stay in ICU and hospital,values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.Results： The general conditions of the two groups were improved gradually and PaO2 increased progressively.Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased （P＜0.05）. The improvement in P group was obviously greater than that in C group （P＜0.05）. The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU （t=3.485, P＜0.01）. The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers （P＜0.01）. It decreased significantly at 24 h （t=2.032, P＜0.05） and 48 h （t=3.620, P＜0.01）and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome （ARDS）. The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h.Until148 h, there were other two patients developing ARDS in control group. Serum IL-l, IL-8 and TNF-α expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group （P＜0.05）. IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups （t=1.028, P＞0.05）.Conclusions： Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.展开更多
文摘Lapatinib is an inhibitor of the tyrosine kinases of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor type 1, with clinical activity in HER2-positive metastatic breast cancer. We present here a 60 year-old patient with metastatic breast cancer who presented with jaundice and increased serum aminotransferase levels and who had been treated with lapatinib for the previous 14 days. Laboratory tests excluded other causes of acute liver injury. Liver biopsy revealed lesions compatible with drug-induced hepatotoxicity. Bilirubin and liver enzymes returned to normal within three months of lapatinib discontinuation. Lapatinib should be included among the causes of druginduced hepatitis.
文摘Objective: To investigate the effect of bone morphogenetic proteins (BMPs) on hematopoietic injury of acute radiation sickness in mice. Methods: Mice were subjected to whole-body 60Co γ ray irradiation, then bpBMP was put into spatium intermusculare or rhBMP-2m, PBK/ hBMP-2 -NIH3T3 cells were injected into abdominal cavity. The effect of BMPs on hematopoiesis including some hematological parameters, the survival rate of 30 d and formation of bone marrow CFU-GM colony were detected at postradiation. Results: pbBMP (purified bovine bone morphogenetic protein) increased the formation of bone marrow CFU-GM colony (P<0. 05) on d 10 after irradiation. rhBMP-2m increased the survival rate of mice irradiated by 7. 5 Gys Mice in control group died in 30 days, while 10%, 15% and 35% mice survived when they were injected i. p. with 0. 5 mg, 1. 0 mg and 2. 0 mg of rhBMP-2m respectively. All hematological parameters of treated mice were significantly higher than those of control group (P<0. 01). PBK/ hBMP-2 -NIH3T3 cells were established and transplanted into mice irradiated by 7. 0 Gy γ ray with i. p. . The survival ratio of treated mice was higher than that of negative control group (P<0. 01), and all hematopoietic parameters were increased statistically significantly (P<0. 01). Conclusion: Results indicate that in adult mice, BMPs can recover or treat the hematopoietic injury of acute radiation sickness, the mechanism may be related with repairing of hematopoietic injury.
文摘Objective： To assess the effects of penehyclidine hydrochloride on patients with acute lung injury （ALI）, to observe the expression of Toll-like receptor 4 （TLR4） on the peripheral monocytes of ALI patients and changes of inflammatory ＆ anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.Methods： Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group （P group, n=21） and conventional treatment group （control group, C group, n=24）. Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride （1 mg, im, q. 12 h） in addition.The TLR4 expression of 20 healthy volunteers were detected.The clinical effect, average length of stay in ICU and hospital,values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.Results： The general conditions of the two groups were improved gradually and PaO2 increased progressively.Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased （P＜0.05）. The improvement in P group was obviously greater than that in C group （P＜0.05）. The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU （t=3.485, P＜0.01）. The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers （P＜0.01）. It decreased significantly at 24 h （t=2.032, P＜0.05） and 48 h （t=3.620, P＜0.01）and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome （ARDS）. The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h.Until148 h, there were other two patients developing ARDS in control group. Serum IL-l, IL-8 and TNF-α expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group （P＜0.05）. IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups （t=1.028, P＞0.05）.Conclusions： Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.
