• Title/Summary/Keyword: DACT3

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Relationships among MTHFR a1298c Gene Polymorphisms and Methylation Status of Dact1 Gene in Transitional Cell Carcinomas

  • Cheng, Huan;Lu, Meng;Mao, Li-Jun;Wang, Jun-Qi;Li, Wang;Wen, Ru-Min;Chen, Jia-Cun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5069-5074
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    • 2012
  • Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy

  • Kim, Soo Jin;Kim, Suntae;Choi, Yong June;Kim, U Ji;Kang, Keon Wook
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.435-446
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    • 2022
  • The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

Effects of ${\beta}-amylase$ and Transglucosidase on the Qualities of Red Ginseng Extract (${\beta}-amylase$와 transglucosidase의 처리가 홍삼 extract의 품질에 미치는 영향)

  • Kim Na-Mi;Lee Jong-Soo;Lee Byung H.
    • Journal of Ginseng Research
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    • v.23 no.2 s.54
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    • pp.93-98
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    • 1999
  • In order to evalulate the qualities of red ginseng extract and decrease precipitate fonnation in ginseng drink, red ginseng extract was hydrolized with ${\beta}-amylase$ and transglucosidase. $5.2\%$ isomaltose was produced as isomaltooligosaccharides and glucose content was increased in the enzyme treated ginseng extract. Contents of ginsenoside $R-b_1\;and\;R-b_2$ were decreased, whereas ginsenoside-Rd was increased by the enzyme treatments. The growth of 3 strains of bifidus spp. and 4 strains of lactobacillus spp., beneficial intestinal bacteria, were enhanced by adding of the enzymatically hydrolized ginseng extract. Sweetness and sourness were increased, however, bitterness and astringency were decreased in the hydrolized ginseng extract. The fonnation of precipitates in hydrolized red ginseng extract of $pH\;3.0\~4.5$ were significantly decreased in the storage condition of $40^{\circ}C$ for 1 month compared to that of control.

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