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Articles by T Chen
Total Records ( 4 ) for T Chen
  A Boquoi , T Chen and G. H. Enders
 

Despite advances in screening and treatment, colorectal cancer remains the second leading cause of cancer-related death in the United States. Cyclin-dependent kinases (Cdk) are deregulated in colorectal cancer by silencing of the Cdk inhibitor p16Ink4a and other mechanisms. We tested whether the small molecule Cdk inhibitor SNS-032 (formerly BMS-387032), which targets Cdk2, Cdk7, and Cdk9, can prevent intestinal tumorigenesis in mouse models. We generated mice with high intestinal tumor loads by combining the multiple intestinal neoplasia (Min) mutation with Ink4a/Arf mutations and inducing colitis with dextran sulfate sodium. p16-null Min mice (n = 17) began dextran sulfate sodium treatment at week 5 and i.p. injection of carrier or SNS-032 at week 6. Mice were sacrificed at week 12. SNS-032 was well tolerated and reduced colon tumor burden to 36% of that in carrier-treated mice (P < 0.001). We then extended the study to Ink4/Arf-null Min mice (n = 14) and increased the drug dose frequency. SNS-032 treatment reduced the intestinal tumor number to 25% and intestinal tumor burden to 16% of carrier-treated mice (P < 0.0001). DNA synthesis in non-neoplastic and tumor epithelial cells, detected by bromodeoxyuridine incorporation, was modestly reduced by acute SNS-032 treatment. The mitotic index, detected by histone H3 phosphorylation, was distinctly decreased (P < 0.03), and apoptosis, detected by caspase 3 activation, was increased (P < 0.005). These results show the chemoprevention of intestinal tumorigenesis by SNS-032. Our findings support further study of Cdk inhibitors for chemoprevention and therapy of colon cancer.

  T Chen , Z Huang , L Wang , Y Wang , F Wu , S Meng and C. Wang
  Aims

The inflammatory responses of monocytes/macrophages and the stimulation of lipid uptake into these cells by oxidized low density lipoprotein (oxLDL) are critical to the initiation and development of atherosclerosis. Increasing evidence has demonstrated that many microRNAs play important roles in the cell proliferation, apoptosis, and differentiation that accompany inflammatory responses. However, whether microRNAs are associated with monocyte/macrophage inflammatory responses or oxLDL stimulation is not yet known. The aim of the present study is to investigate microRNAs in monocytes/macrophages and their potential role in oxLDL-stimulation of lipid uptake and other atherosclerotic responses.

Methods and results

Microarrays were used to analyse the global expression of microRNAs in oxLDL-stimulated human primary peripheral blood monocytes. Expression profiles of the microRNAs were verified using TaqMan real-time PCR. Five microRNAs (microRNA-125a-5p, microRNA-9, microRNA-146a, microRNA-146b-5p, and microRNA-155) were aberrantly expressed after oxLDL treatment of human primary monocytes. Bioinformatics analysis suggested that microRNA-125a-5p is related to a protein similar to ORP9 (oxysterol binding protein-like 9) and this was confirmed by a luciferase reporter assay. MicroRNA-125a-5p was found to mediate lipid uptake and to decrease the secretion of some inflammatory cytokines (interleukin-2, interleukin-6, tumour necrosis factor-, transforming growth factor-beta) in oxLDL-stimulated monocyte-derived macrophages.

Conclusion

MicroRNA-125a-5p may partly provide post-transcriptional regulation of the proinflammatory response, lipid uptake, and expression of ORP9 in oxLDL-stimulated monocyte/macrophages.

  F. Q Huo , T Chen , B. C Lv , J Wang , T Zhang , C. L Qu , Y. Q Li and J. S. Tang
 

The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system, consisting of the spinal cord–thalamic nucleus submedius–VLO periaqueductal gray (PAG)–spinal cord loop. The present study examined morphological connections of GABAergic (-aminobutyric acidergic) neurons and serotonergic projection terminals from the dorsal raphe nucleus (DR), as well as the relationship between GABAergic terminals and VLO neurons projecting to the PAG, by using anterograde and retrograde tracing combined with immunofluorescence, immunohistochemistry, and electron microscopy methods. Results indicate that the majority (93%) of GABAergic neurons in the VLO also express the 5-HT1A (5-hydroxytryptamine 1A) receptor, and serotonergic terminals originating from the DR nucleus made symmetrical synapses with GABAergic neuronal cell bodies and dendrites within the VLO. GABAergic terminals also made symmetrical synapses with neurons expressing GABAA receptors and projecting to the PAG. These results suggest that a local neuronal circuit, consisting of 5-HTergic terminals, GABAergic interneurons, and projection neurons, exists in the VLO, and provides morphological evidence for the hypothesis that GABAergic modulation is involved in 5-HT1A receptor activation-evoked antinociception.

  H. L Huang , F. L Chen , C. C Hsu , Y. Y Yen , T Chen , C. M Huang , H. Y Shi , C. Y Hu and C. H. Lee
 

The aim was to comprehensively examine school-based tobacco policy status, implementation and students’ perceived smoking at school in regard to gender-specific differences in smoking behavior. We conducted a multilevel-based study to assess two-level effects for smoking among 2350 grades three to six students in 26 randomly selected elementary schools in southern Taiwan. A series of multilevel models were analyzed separately for male and female students. The school-level variables appear to be related to smoking behavior in male students. Among males, the risk of ever-smoking was significantly associated with those schools without antitobacco health education activities or curricula [adjusted odds ratio (aOR) = 6.23, 95% confidence interval (CI): 2.55–15.24], with a high perceived smoking rate (aOR = 3.08, 95% CI: 1.41–6.72) and located in a mountainous region (aOR = 2.53, 95% CI: 1.15–5.58). The risk of ever-smoking among females was significantly associated with those schools without antitobacco activities or curricula (aOR = 3.10, 95% CI: 1.27–7.55). As compared with female counterparts, the specific school that the male students attended had a positive significant effect on the risk of being ever-smokers. The findings suggest that effective tobacco policy implementation should be considered in elementary schools that are currently putting children at the greatest risk for cigarette smoking, especially in regard to male students.

 
 
 
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