Improved Therapeutic Effect against Leukemia by a Combination of the Histone Methyltransferase Inhibitor Chaetocin and the Histone Deacetylase Inhibitor Trichostatin A

SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia.

Prenatal diagnosis by FISH technique in fetal cystic hygromas

Background: Cystic hygromas is a common abnormal event in obstetrics ultrasound, which is induced by a chromosome disorder; it is also one of the major causes inducing fetus\u2019s congenital malformation. Objective: Determining chromosomal aberration in nuchal cystic hygromas by FISH technique and outcomes the value of factors in prognosis fetuses with cystic hygroma. Subject and methods: 53 fetuses with cystic hygroma, which are detected by ultrasound scan, are analyzed by FISH technique. Compare results of FISH, band G chromosomal analysis, ultrasonographic abnormalities, followed the fetuses. Results: Chromosomal and FISH analysis give the same detection: abnormal chromosomes: 75.46%, the highest rate is Turner syndrome: 50.94%, normal chromosome: 24.53%. Abnormal chromosomal fetuses: multi-malformation, grim prognosis. Cystic hygroma with other malformation in scan: high rate chromosomal aberrations and septated hygroma, Turner syndrome fetuses have large cystic hygroma, 4/6 fetuses with normal chromosome and without other abnormal result scan have resolutions of hygroma in the second trimester, normal birth. Conclusions: Abnormal chromosomes: 75.46%. Prognosis is grim: abnormal chromosomes, other malformations in scan, large cystic, septated hygroma. Prognosis is better: normal chromosomes, without other ultrasonographic abnormalities, small cystic, nonseptated hygroma, resolution of cystic hygroma.

Application of techniques of molecular biology in diagnosis of fragile X syndrome

Background: Fragile X Syndrome (FXS) is the second cause of Mental Retardation (MR) and the first cause of familiar MR. This syndrome affects up to 1/4000 men and 1/8000 women. X syndrome is often diagnosed by molecular biology technique such as RCR and Southern blot. Until now there is no study on FXS in Vietnam. Objectives: This study is aimed at: (1) Determine FXS among children with MR by technique of molecular biology. (2) Determine the mutation of FMR1 gen in families having children with FXS. Subject and Method: 214 children between 6 and 16 years of age (136 male and 78 female) with MR were analyzed FMR1 gen by PCR and Southern blot techniques. Families of children with FXS were also analyzed. Result and conclusion: This is the first study on FXS using the techniques of molecular biology in Vietnam. Identified 3 children with FXS, accounting for 1.4% of MR. Children with FXS and members with full mutation and premutation were found.

Prenatal diagnosis of turner syndrome

Background/Introduction:The proportion of TS \u2013 Q96 ranges from 1/1500 \u2013 1.300 female newborns and about 3% of fetuses. In most of the world, TS can be diagnosed and treated at the early stages of pregnancies. In Vietnam, TS patients are frequently detected at the later stages with serious syndromes. TS diagnosis mainly relies on chromosomal analysis of amnion cells. Thus, prenatal diagnosis of TS is the rationale of this study.\r\n', u'Objectives: Utilize chromosomal analysis and FISH methods to diagnose Turner syndrome from amnion cells. \r\n', u'Subject and method: 30 pregnancies (from week 14-22) with high risks of TS, which were detected by ultrasound scan and triple test, 15 mil amnio fluid is withdrawn for the FISH technique from interphase amniocytes and amnio cultures, chromosomal analysis from metaphase cultured cells. \r\n', u'Results/Outcomes: Chromosomal analysis and FISH analysis give the same results: - 12/30 fetus with TS, 5/30 fetus with normal female results, \u2013 4/30 fetus with normal male normal results, \u2013 4/30 fetus with Down syndrome, \u2013 5/30 fetus with Edward syndrome. 11/12 TS fetus have large cystic hygromas, 9/11 cystic hygromas are separated. 12/12 TS fetus have triple test (+) with the threshold: APF \u2264 0.7 MoM, HCG \u2265 2 MoM, uE3 \u2264 0.7 MoM.\r\n', u'Conclusion:Chromosonal analysis and FISH are standards for diagnosing TS fetus. FISH can provide a quick result (48-72h). \r\n', u'

Some ultrasound markers that association with down syndrome fetus

Background: Down syndrome is a developmental disorder caused by an extra copy of chromosome 21, is a condition in which extra genetic material causes delays in the way a child develops, both mentally and physically. It affects about 1 in every 700 babies. The fetus having high risk for Down syndrome (OS) can be detected early by ultrasound. Objectives: The aim of the study is to find out some ultrasound markers that relate to OS fetus. Subjects and method: A descriptive study was carried out on 612 pregnant women with fetus \ufffd?12 weeks by ultrasound to detect abnormal markers in fetus. The fetus were diagnosed Down syndrome by analysis chromosome from amniocyte and monitor up to the neonate. Then, finding out association between OS fetus and ultrasound markers. Results: Among 612 pregnant women,36/12 pregnant women had abnormal imaging in fetus, 11/12 pregnant women had OS fetus. There were 12 pregnant women detected OS fetus. 6/12 OS fetus associated with the maker of nuchal skin fold (cut off 2: 3mm at the first trimester and 2: 6 mm at the second trimester): Detection rate (DR) was 50%; false positive rate (FOR): 0,83%. 3/12 OS fetus associated with the marker of duodenal atresia. DR was 25%; FOR: 0%. Conclusions: The two common markers associated with OS fetus: \r\n', u'the first marker was nuchal skin fold (with cut off 2: 3mm at the first trimester and > 6 mm at the second trimester) and the second marker was duodenal atresia. \r\n', u' \r\n', u'

Screening for down syndrome fetus by alpha-fetoprotein and beta human chorionic gonadotropin in maternal serum \r\n', u'

Background: The fetus having risk for Down sydrome (DS) can be detected early by AFP, \u03b2hCG in maternal serum to detect the fetus having risk of Down sydrome. Objectives: Determining values of AFP, \u03b2hCG in maternal serum to detect the fetus having risk of DS. Subjects and method: Determining the concentration of AFP, \u03b2hCG in maternal serum of 591 pregnant with fetus \ufffd?12 weeks to detect the fetus having DS screening risk. The fetus are diagnosed DS by analysing chromosome from amniocyte and monitor up to the neonate. Then, finding out association between DS fetus and AFP, \u03b2hCG in maternal serum. Results: 75/591 of subjects screened were screen positive, 6/7 DS fetus associated withscreen positive, (cut off AFP \ufffd?0,75 MoM, \u03b2hCG \ufffd?2,2 MoM). Detection rate (DR) was 85,71%; false positive rate (FDR): 11,81%. Only base on AFP: DR was 71,43%; FDR: 11,81%. Only base on \u03b2hCG DR was 28,57%; FDR: 0,51%. Conclusion: DR base on AFP is higher than base on \u03b2hCG. If combining AFP and \u03b2hCG, DR is the highest. AFP is important role in screening DS fetus.

Prenatal diagnosis down syndrome, turner syndrome by using fluorescence in situ hybridization (FISH) technique with chromosome analysis from amniotic cell

Background: FISH can detect number and structural chromosome aberrations in DNA. FISH is new technique in Vietnam, we combine FISH with chromosome analysis to prenatal diagnosis Down syndrome and turner syndrome that are high rate in birth defect.Objectives: To detect Down syndrome and turner syndrome by using FISH technique with chromosome analysis from amniotic cell.Subjects and method: 14amniotic cells samples 15th - 20th week with high risk of birth defects. Advance using FISH and chromosome analysis from amniotic cell. Results: We obtained results as follow: - 14/14 samples: correspondence between FISH and chromosome analysis. \ufffd?Detected 2 Down syndrome (female. Trisomi 21) and 4 Turner syndrome (45, X). Conclusion: Detected Down syndrome and Turner syndrome by using FISH technique with chromosome analysis from amniotic cell.

Study of prevalence of mental retardation among children in some quarters and communes of Hue city

Background: Mental retardation is a common pathological state in children, accounting for about 1 - 3%. Children with mental retardation should have a life of integrity and proper support. The discovery and assessment the children will help us to orient the education, assistance and early intervention for them at each location. Objectives: This study aimed at determining the prevalence of mental retardation (MR) among children in some quarters and communes of Hue city and the degrees of mental retardation in these children. Subjects and method: Screening by WHO questionnaire \u201cTen Question screen for disability\ufffd?and learning results (if possible) of children from 6 to under 16 years old in 5 quarters (urban) and 2 communes (rural) randomly selected in Hue. Diagnostics and evaluations are based on the criteria of ICD \ufffd?10. Results: The prevalence of MR in this study was 0.94% (95%CI = 0.82 \ufffd?1.07), 1.18% in rural area and 0.84% in urban area; 1.16% among boys and 0.70% among girls. Mild MR accounts for 62.67% moderate: 19.36%, severe: 11.52% and profound: 6.45%. Conclusion: The prevalence was statistically significant higher in rural area than in urban area and in boys than in girls. There were predominant percentages of severe and profound MR.

Using G banding technique to determine karyotyp for patients with suspected genetic disorders

In 1997 (1/1997-10/1997) with lymphocytes culture technique, technique for preparing chromosome slides, and Barr body technique (giemsa + trypsin). We determined Karyotyp for 60 patients with suspected genetic disorders. The result showed determined sex for 40 patients (Karyotyp 46,XX or 46,XY). 2 interrex with Karyotyp 46,XX/46,XY. 2 intersex with Karyotyp 46,XX. Determining Karyotyp for 8 patients with suspected Turner Syndrome. One of them: 45,X/46, X, r(X). Determining Karyotyp for 2 patients with suspected Down Syndrome. (1 case: 46,XX; another: 47,XX, +21). Determining Karyotyp for another patients: suspected: panconi; 47,XYY; Sterility..

Study on situation of training methods at Hµ Néi Medical University

143 lecturers and 1360 students in basic, biomedical, clinical and community departments of Ha Noi Medical University were interviewed on the current situation of training methods. The results showed that 38.4% teachers applied active training methods and there is a dramatic change in comparison to prior 1995 in biomedical group (p<0.05), more than 70% lecturers had syllabus, gave questionnaires and assessment after lesson. 60% lecturers reported that traditional training methods made students become negative while active method made students more active. 54.2% of students read references that related to clinical subjects. 96.5% of students read the bulletin of basic medical departments. 61.2% students like the active methods in training