We previously reported that upregulation of SMYD3, a histone H3 lysine-4-specific methyltransferase, plays a key role in the proliferation of colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC). In the present study, we reveal that SMYD3 expression is also elevated in the great majority of breast cancer tissues. Similarly to CRC and HCC, silencing of SMYD3 by small interfering RNA to this gene resulted in the inhibited growth of breast cancer cells, suggesting that increased SMYD3 expression is also essential for the proliferation of breast cancer cells. Moreover, we show here that SMYD3 could promote breast carcinogenesis by directly regulating expression of the proto-oncogene WNT10B. These data imply that augmented SMYD3 expression plays a crucial role in breast carcinogenesis, and that inhibition of SMYD3 should be a novel therapeutic strategy for treatment of breast cancer. (Cancer Sci 2006; 97: 113-118) R ecent molecular studies have disclosed that breast carcinogenesis involves not only genetic alterations in oncogenes and tumor suppressor genes, but also epigenetic dysregulation of a number of genes associated with growth, survival, cell motility and differentiation.(1-3) For example, several oncogenes have been described as being amplified in breast cancer, including HER2, EGFR, MYC, CCND1, Although expression profile analysis using cDNA microarray or DNA chip technology has facilitated the identification of genes with altered expression in cancer, the mechanisms of deregulated expression need to be further investigated. A multistep model of mammary carcinogenesis has been proposed; transformation of normal cells leads to atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and eventually invasive ductal carcinoma (IDC). However, precise molecular mechanisms underlying breast cancer remain unresolved.Chromatin is composed of genomic DNA and nuclear proteins including histones, and serves as the template for processing genetic information. The dynamic DNA-protein structure of chromatin is influenced by epigenetic modifications on both the DNA and nucleosomal histones. Under the euchromatin state where chromatin forms a relaxed state, the underlying DNA is accesible to transcription factors. In contrast, DNA in the heterochromatin state, where chromatin forms a condensed state, is transcriptionally restricted and thus untranscribed. Recent advances have shown that covalent histone modifications play critical roles in chromatin structure.One of the best-characterized modifications is acetylation, which is controlled by both histone acetyltransferases and deacetylases. Additionally, histone methylation has emerged as another modification that significantly impacts chromatin structure. We reported previously that SMYD3 shows histone H3-K4-specific methyltransferase activity, leading to transcriptional activation of downstream genes including Nkx2.8, and that elevated SMYD3 expression is involved in the growth of human colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC) cells. (14)...

H epatitis B virus (HBV) is a small enveloped DNA virus and causes chronic infection of the liver that often leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. [1][2][3][4] The lack of a practical small animal model has impeded the study of the biology of this virus and the development of effective antiviral therapies. Chimpanzee is the only natural host that allows active replication of HBV. [5][6][7] Although this animal is a valuable model for the study of hepatitis viruses, 8 the practical use of chimpanzees is severely limited both ethically and economically.Several small animal models of HBV infection have been reported. The HBV transgenic mouse is a very useful model for the study of virology and evaluation of antiviral drugs. [9][10][11][12] However, the liver cells of this model are not permissive for HBV infection; therefore, studying virus-cell interactions such as receptor binding and entry is not possible. The HBVtrimera mouse is another useful mouse model. 13 In this model, ex vivo HBV-infected human liver fragments are implanted into lethally irradiated mice after SCID mouse bone marrow transplantation. Approximately 80% of the mice develop viremia 2 to 3 weeks after infection. However, the rate of positivity subsequently decreases to less than 20% 6 weeks after infection. The level viremia is approximately 10 5 copies/mL. More recently, HBV-containing human serum samples were used to infect human hepatocyte repopulated mice. 14 A high-level viremia (4.5 and 10 ϫ 10 8 copy/ mL) and HBs antigenemia are observed 8 weeks after injection. This mouse model is promising because HBV replicates in natural host cells, human hepatocytes. However,

These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.

Aim:To compare the efficacy and safety of edoxaban and warfarin for treatment of portal vein thrombosis (PVT) following danaparoid sodium in patients with liver cirrhosis.Methods: Fifty cirrhotic patients with PVT treated initially for 2 weeks with danaparoid sodium were enrolled in this retrospective cohort study. Treatment was later switched to either edoxaban (n = 20) or warfarin (n = 30). We compared the efficacy and safety of edoxaban and warfarin for up to 6 months. The PVT volume was measured by dynamic computed tomography before treatment, at 2 weeks, and at 1, 3, and 6 months.