ABSTRACT
Objective • To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods • The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results • Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models(P<0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion • ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
ABSTRACT
Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
ABSTRACT
The aim of study was to evaluate the clinical efficacy and toxicity of fludarabine combined with cytarabine (FA) regimen in the treatment of patients with refractory and/or relapsed acute myeloid leukemia (AML). Nineteen cases with refractory/relapsed AML were treated with FA regimen in which fludarabine phosphate 25 mg/(m(2) x d), d1-5; cytarabine (Ara-C) 2 g/(m(2) x d), d1-5. Another 20 cases were treated with salvage chemotherapy (MAE regimen: mitoxantrone, Ara-C and etoposide or DAE regimen: daunorubicin, Ara-C and etoposide). All patients received at least 2 cycles chemotherapy. The results showed that 9 patients (47%) in FA regimen group achieved complete remission (CR), 8 cases (42%) obtained partial remission (PR), the clinical efficacy was superior to that of the MAE or DAE regimens (p < 0.05). Major toxicity of FA regimen was myelosuppression. Grade IV hematologic toxicity occurred in all patients received FA regimen. Nonhematologic complications consisted of gastrointestinal side effects, mucositis, liver toxicity, which were mild to moderate and could be alleviated with supportive therapy. In conclusion, FA regimen is an effective regimen for treatment of refractory and relapsed AML.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cytarabine , Leukemia, Myeloid, Acute , Drug Therapy , Recurrence , VidarabineABSTRACT
In this research, the effect of novel retinoid SX-116 on acute promyelocytic leukemia cell line NB4 was studied in vitro. Cell proliferation, cell morphological characters, flow cytometry, DNA electrophoresis and RT-PCR were observational parameters. The results showed that treated with SX-116 at 10(-6) mol/L, the growth and survival of NB4 cells were markedly inhibited, morphological changes of apoptosis, including membrane blebbing, chromosome condensation and fragmentation of nuclei were observed in NB4 cells after 24 hours exposure of SX-116. Further studies showed "DNA ladder" in genomic DNA electrophoresis, as well as a typical apoptotic peak below G(1) phase presented in flow cytometry. The expression of apoptosis - related gene bcl-2 and p53 were examined. The level of bcl-2 mRNA was downregulated by 6-hour treatment of SX-116, while the gene restored to the normal level by following 12-, 24- and 48-hour exposure. However, p53 mRNA was unchanged during the treatment. The results demonstrated that SX-116 could induce apoptosis of NB4 cells while the mechanism remains to be studied.