Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.     

PLENARY LECTURES-PL1 Toxicity of perfluorooctane sulfonate and perfluorooctanoate

Persistent perfluorinated organic compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are used in a variety of industrial applications. They are very stable in the environment, distribute widely in the global environment and in wild life, and are detected in human sera.     

Bioactive asterosaponins from the starfish Culcita novaeguineae

Two new sulfated steroidal pentaglycosides（asterosaponins）,novaeguinosides Ⅰ（2） and （Ⅱ）2,along with the known regularoside B（1）were isolated from the starfish Culcita novaeguineae.Their structures were elucidated by extensive NMR techniques as well as chemical evidence.     

CDDO-Imidazolide inhibits growth and survival of c-Myc-induced mouse B cell and plasma cell neoplasms

Background  

Gene-targeted iMyc^Eμ mice that carry a His₆-tagged mouse Myc(c-myc)cDNA, Myc ^His, just 5' of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell neoplasms, such as lymphoblastic B-cell lymphoma (LBL) and plasmacytoma (PCT). Cell lines derived from Myc-induced neoplasms of this sort may provide a good model system for the design and testing of new approaches to prevent and treat MYC-driven B cell and plasma cell neoplasms in human beings. To test this hypothesis, we used the LBL-derived cell line, iMyc^Eμ-1, and the newly established PCT-derived cell line, iMyc^Eμ-2, to evaluate the growth inhibitory and death inducing potency of the cancer drug candidate, CDDO-imidazolide (CDDO-Im).     

间硝苯地平对血管紧张素Ⅱ促进血管平滑肌细胞增殖和蛋白质合成的影响

以培养血管平滑肌细胞(vascularsmcothmusclecell,VSMC)为模型,观察了间硝苯地平(m-nifedipine,m-Nif)对血管紧张素Ⅱ(angiotensinⅡ,ANGⅡ)促进VSMC增殖和蛋白质合成的影响。结果表明,m-Nif抑制ANGⅡ(100nmol·L^-1)引起VSMC[³H]thymidine和[³H]leucine参入,并呈剂量依赖性。m-Nif(2×10^-6mol·L^-1)可抑制ANGⅡ对VSMC的刺激、DNA及蛋白质合成速率,分别降低了46%,58%,53%。提示m-Nif可抑制ANGⅡ对VSMC增殖和蛋白合成的促进作用。     

Molecular and cytological features of the mouse B-cell lymphoma line iMycEμ-1

Background

Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMyc^Eμ mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMyc^Eμ mice that carry a His₆-tagged mouse Myc cDNA, Myc ^His, just 5' of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell tumors. The predominant tumor (~50%) that arose in the iMyc^Eμ mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMyc^Eμ-1, for the in-depth evaluation of LBL in vitro.

Methods

The morphological features and the surface marker expression profile of the iMyc^Eμ-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMyc^Eμ-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted Myc ^His gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMyc^Eμ-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip^© and Superarray^© cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR.

Results

Consistent with their derivation from LBL, the iMyc^Eμ-1 cells were found to be neoplastic IgM^highIgD^low lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMyc^Eμ-1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed Myc ^His at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip^© microarrays that were consistent with Myc ^His-driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray^© cDNA macroarrays, the iMyc^Eμ-1 cells showed the highest number of changes on the NFκB array.

Conclusion

The iMyc^Eμ-1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc-driven mouse LBL in vitro.     

Prevalence of alcohol use disorder in a South Korean community

Abstract Background This study investigated the prevalence of alcohol use disorder in a Korean community and compared the results with 1984 epidemiological data. Method A sample of 1,059 residents aged 18–64 years was interviewed using the Korean version of the Composite International Diagnostic Interview (K-CIDI). The results obtained were compared with those of a 1984 epidemiological study. Results Lifetime prevalence of alcohol use disorder was 15.6% (abuse 6.8%, dependence 8.8 %) and 1-year prevalence 7.5% (abuse 2.5%,dependence 5 %).The male-to-female ratio of life-time prevalence was 5.8,which markedly decreased with decreasing age. A cohort effect, i. e. increases of lifetime prevalence in younger cohorts, was observed, with the exception of the 60- to 64-year-old cohort. The mean age of onset was 27.7 years (male 28.2 years, female 24.2 years). When the results of the present study were compared with those of the 1984 study, it was found that, during the past 15 years, lifetime prevalence has decreased, prevalence ratios of abuse and dependence have become reversed, and the male-to-female ratio has decreased. Conclusion Remarkable changes in the pattern of prevalence, which have occurred between 1984 and 1999, may be attributed to significant sociocultural changes and to a decrease in the proportion of a high-risk cohort in the populations.     

Intellect declines in healthy elderly subjects and cerebellum

Scores of the performance scale of the Wechsler Adult Intelligence Scale (WAIS) declined linearly with age from the 6th decade, whereas those of the verbal scale did not. This decrease in performance intelligence was thought to be related to an age-related frontal atrophy. The relationship between scores of the WAIS and changes in regional cortical gray matter density were examined in healthy elderly subjects using voxel-based morphometry. Thirty healthy non-demented individuals >50 years of age were tested with the WAIS and scanned with brain magnetic resonance imaging (MRI). The right neocerebellum was significantly associated with scores of the performance intelligence scale while frontal lobes were not. The current study suggests that the cerebellum may play an important role in changes of intellectual capacity in old age.     

Liver regeneration in living-donor liver transplantation

Liver regeneration in living-donor liver transplantation is summarized from the authors' data. In donors, liver function tests recovered to within the normal range 2 weeks after surgery regardless of graft type. At 2 weeks, the volumetric recovery of the remnant liver was 65% and 80% of the original volume in right and left lobe donors, respectively. These results suggest that functional recovery occurs earlier than morphologic restoration in donors. In recipients, the factor that affected the regeneration rate in size 4 weeks after transplantation was only implanted graft size; the rate was greater in patients in whom smaller grafts were implanted. In recipients with a rate of two or more, however, high portal vein pressure and flow were observed. Further, persistent low platelet counts and hyperbilirubinemia were seen in those patients. These results indicate that size enlargement may be caused by engorgement, and functional recovery is not achieved concurrently with morphologic restoration, especially in patients with smaller grafts. In patients with fulminant hepatic failure who receive auxiliary partial orthotopic liver transplantation, sequential histopathologic observations of the diseased liver revealed that liver regeneration initiates from cytokeratin 17-positive ductules and at least 1 year is necessary for complete recovery.