OBJECTIVETo investigate the relationship between DNA homologous recombination (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia (AML) with recurrent chromosome translocation.

METHODSGenomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFβ-MYH11 fusion gene was detected by TaqMan real-time PCR.

RESULTSThe XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv(16)/t(16;16)/CBFβ-MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P = 0.001) respectively increase in the risk of this subtype AML. In the irradiated group, the CBFβ-MYH11 mRNA level in HL-60 cells was 59.49 times increased than that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t(15;17)/PML-RARα(+)AML, t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes.

CONCLUSIONThe XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv(16)/t(16;16)/CBFβ-MYH11.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Child, Preschool ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Leukemia, Myeloid, Acute ; etiology ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Polymorphism, Single Nucleotide ; Rad51 Recombinase ; genetics ; Translocation, Genetic ; Young Adult

OBJECTIVETo investigate the impact of polymorphisms of DNA homologous recombination (HR) repair genes RAD51-G135C and XRCC3-C241T on the prognosis of acute myeloid leukemia (AML) with inv(16)/t(16;16)(CBFbeta-MYH1).

METHODSOne hundred and three de novo inv(16)/t(16;16) (CBFbeta-MYH11) AML patients were followed-up and retrospectively analyzed. Polymorphisms of RAD51-G135C and XRCC3-C241T were detected by PCR-RFLP. The prognostic factors,including sex, age, white blood cell count, platelet count, hemoglobin level, karyotype, KIT mutation, RAD51-G135C and XRCC3-C241T polymorphisms at diagnosis, for complete remission (CR) achievement, overall survival (OS) and relapse-free survival (RFS) were analyzed by univariate and multivariate analyses.

RESULTSThe median follow-up of all patients was 28 (1 - 106) months. The overall CR rate was 92.2%. The estimated 5-year OS and RFS rates were 43.6% (95% CI 37.7% - 49.5%) and 26.4% (95% CI 21.1% - 31.7%), and the median OS and RFS were 53 (95% CI 133.4 - 72.7) and 27 (95% CI 22.9 - 31.1) months, respectively. In multivariate analysis, higher WBC (P = 0.004) and older than 30 years of age (P = 0.035) were independent poor factors for CR achievement, the XRCC3-241T variant (P = 0.007) and higher WBC (P = 0.009) were independent poor factors for 5-year RFS, and higher WBC (P = 0.002) and trisomy 8 (P = 0.035) were independent poor factors for 5-year survival. Polymorphism of RAD51-G135C had no significant impact on the prognosis.

CONCLUSIONThe XRCC3-241T variant is an independent poor prognostic factor for AML with inv(16)/t(16;16)/CBFbeta-MYH11.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Polymorphism, Single Nucleotide ; Prognosis ; Rad51 Recombinase ; genetics ; Young Adult

OBJECTIVETo study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice.

METHODSThirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section.

RESULTSThe amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group.

CONCLUSIONRosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.

Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; physiology ; Atherosclerosis ; blood ; pathology ; prevention & control ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Hypoglycemic Agents ; therapeutic use ; Macrophages ; pathology ; Male ; Mice ; Mice, Knockout ; Thiazolidinediones ; therapeutic use ; Tumor Necrosis Factor-alpha ; biosynthesis

A fluorescence polarization immunoassay (FPIA) was developed for the analysis ofaflatoxins (AFs) using an anti-aflatoxin B1 (AFB1) monoclonal antibody and a novel fluorescein-labeled AFB1 tracer. The FPIA showed an IC50 value of 23.33 ng/mL with a limit of detection of 13.12 ng/mL for AFB1. The cross-reactivities of AFB1, AFB2, AFG1, AFG2, AFM1, and AFM2 with the antibody were 100%, 65.7%, 143%, 23.5%, 111.4%, and 2%, respectively. The group-specificity of anti-AFB1mAb indicated that the FPIA could potentially be used in a screening method for the detection of total AFs, albeit not AFG2 and AFM2. The total time required for analyzing 96 samples in one microplate was less than 5 min. This study demonstrates the potential usefulness of the FPIA as a rapid and simple technique for monitoring AFs.
Aflatoxins ; analysis ; Fluorescence Polarization Immunoassay