Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evide...Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.展开更多
Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL receive...Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL received treatment of merely 1.5 mg/m2 daily HHT for induction remission and long-term maintenance treatment. The apoptosis rate of bone marrow CD34+ cells induced by HHT was assayed with flow cytometer. Results: 86.8% patients achieved CHR, 13.2% patients PHR and 31.8% patients got cytogenetic response in HHT treatment group, which was longer than 31 (8-54) months in hydroxyurea (HU) group (P<0.05). The effect of apoptosis induction HHT was stronger on CGL-CP patients bone marrow CD34+ cells than on normal person bone marrow CD34+ cells. Conclusion: HHT is a very effective drug for remission induction and long-term maintenance treatment in early chronic phase CGL patients.展开更多
Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia(AML) patients. Methods · Forty-one pa...Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia(AML) patients. Methods · Forty-one patients with AML(aged 55-71 years) were randomly divided into two groups(Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival(RFS). Results · A total of 29 patients(70.7%) achieved complete remission(CR). The estimated 2-year overall survival(OS) was 66.8% in Group HCAG and 75.4% in Group IA(P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA(P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.展开更多
Induction of c-myc gene amplification in L1210 cells by hydroxyurea and its inhibition by homohar-ringtonine were investigated using the DNA-DNA molecular hybridization technique. When the cells were treated with hydr...Induction of c-myc gene amplification in L1210 cells by hydroxyurea and its inhibition by homohar-ringtonine were investigated using the DNA-DNA molecular hybridization technique. When the cells were treated with hydroxyurea 1.0 mM for 16 hours, and incubated a further 16 hours in a drug-free medium, the c-myc gene amplified 23.5-fold. If homohar-ringtonine 50 μM was used at the same time as hydroxyurea, gene amplification did not occur. Cycloheximide, an inhibitor of protein biosynthesis, produced a similar effect. Our results indicated that a (or some) protein factor(s) might be involved in gene amplification. Detailed analysis showed that the synthesis of this protein factor(s) started 4 hours before the initiation of the S phase but did not continue in the S phase. It was also found that this protein factor(s) was very labile and began to degrade 2 hours after its appearance.展开更多
To evaluate the inhibiting effect of Homoharringtonine （HHT） on the corneal haze after excimer laser photorefractive keratectomy （PRK） in rabbits. 18 healthy rabbits which underwent PRK were randomly divided into ...To evaluate the inhibiting effect of Homoharringtonine （HHT） on the corneal haze after excimer laser photorefractive keratectomy （PRK） in rabbits. 18 healthy rabbits which underwent PRK were randomly divided into three groups （A, B and C）. The refractive degree of ablation was - 10.0DS in each group. Group A was locally treated with a piece of filter paper soaked with 1 mg/ mL HHT for 5 min, and then the entire cornea was repeatedly irrigated with balance solution; Group B was dropped with 0.1 mg/mL HHT after PRK for 3 months; Group C was the control group, Corneal haze, histopathology, response, ect. were investigated. The corneal haze was significantly less in group A, while the difference between group B and group C was insignificant. Keratocytes and fibrocytes in corneal stroma were more active up to 3 months in group B and group C, Intraoperative use of topical HHT can reduce corneal haze after PRK in rabbits.展开更多
文摘Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.
文摘Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL received treatment of merely 1.5 mg/m2 daily HHT for induction remission and long-term maintenance treatment. The apoptosis rate of bone marrow CD34+ cells induced by HHT was assayed with flow cytometer. Results: 86.8% patients achieved CHR, 13.2% patients PHR and 31.8% patients got cytogenetic response in HHT treatment group, which was longer than 31 (8-54) months in hydroxyurea (HU) group (P<0.05). The effect of apoptosis induction HHT was stronger on CGL-CP patients bone marrow CD34+ cells than on normal person bone marrow CD34+ cells. Conclusion: HHT is a very effective drug for remission induction and long-term maintenance treatment in early chronic phase CGL patients.
基金National Natural Science Foundation of China(81270621,81300451)National Public Health Grand Research Foundation(201202003)+1 种基金Shanghai Health System Advanced and Appropriate Technology Promotion Projects(2013SY001)Multiple Clinical Research Center Program of Shanghai Jiao Tong University School of Medicine(DLY201513)
文摘Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia(AML) patients. Methods · Forty-one patients with AML(aged 55-71 years) were randomly divided into two groups(Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival(RFS). Results · A total of 29 patients(70.7%) achieved complete remission(CR). The estimated 2-year overall survival(OS) was 66.8% in Group HCAG and 75.4% in Group IA(P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA(P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.
文摘Induction of c-myc gene amplification in L1210 cells by hydroxyurea and its inhibition by homohar-ringtonine were investigated using the DNA-DNA molecular hybridization technique. When the cells were treated with hydroxyurea 1.0 mM for 16 hours, and incubated a further 16 hours in a drug-free medium, the c-myc gene amplified 23.5-fold. If homohar-ringtonine 50 μM was used at the same time as hydroxyurea, gene amplification did not occur. Cycloheximide, an inhibitor of protein biosynthesis, produced a similar effect. Our results indicated that a (or some) protein factor(s) might be involved in gene amplification. Detailed analysis showed that the synthesis of this protein factor(s) started 4 hours before the initiation of the S phase but did not continue in the S phase. It was also found that this protein factor(s) was very labile and began to degrade 2 hours after its appearance.
文摘To evaluate the inhibiting effect of Homoharringtonine （HHT） on the corneal haze after excimer laser photorefractive keratectomy （PRK） in rabbits. 18 healthy rabbits which underwent PRK were randomly divided into three groups （A, B and C）. The refractive degree of ablation was - 10.0DS in each group. Group A was locally treated with a piece of filter paper soaked with 1 mg/ mL HHT for 5 min, and then the entire cornea was repeatedly irrigated with balance solution; Group B was dropped with 0.1 mg/mL HHT after PRK for 3 months; Group C was the control group, Corneal haze, histopathology, response, ect. were investigated. The corneal haze was significantly less in group A, while the difference between group B and group C was insignificant. Keratocytes and fibrocytes in corneal stroma were more active up to 3 months in group B and group C, Intraoperative use of topical HHT can reduce corneal haze after PRK in rabbits.
