In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We stud...

BACKGROUND The preferred immunosuppressive drug for long term treatment of myasthenia gravis (MG) is azathioprine (AZA). Mycophenolate mofetil (MMF) was suggested as an effective and safe second line alternative to AZA. METHODS In a prospective open-label study, 11 patients with acetylcholine receptor antibody (AChR-ab) positive MG (n=4 ocular MG, n=7 generalized MG) were treated with MMF whi...

Mesenchymal stem cell (MSC) transplantation has been demonstrated to be promising in the treatment of inflammatory bowel disease (IBD). Azathioprine (AZA) is widely used in IBD patients. Infliximab, as a representative of biological therapy for IBD, is important in the treatment regimen. In the present study we investigated the effects of AZA and infliximab on the cell proliferation, cell cycle...

5-azacytidine (5-aza) is a hypomethylating agent approved for the treatment of high-risk myelodysplastic syndrome (MDS). It is assumed to act by demethylating tumor suppressor genes and via direct cytotoxic effects on malignant cells. In vitro treatment with hypomethylating agents has profound effects on the expression of killer-cell immunoglobulin-like (KIR) receptors on natural killer (NK) ce...

Hyperhomocysteinemia (HHcy) is prevalent in patients with hypertension and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to the accumulation of collagen in the aorta and resulting in stiffness and development of hypertension. Although the exact mechan...

Immunosuppressive drugs are known to disturb bone remodeling. Azathioprine (AZA) is a potent immunosuppressive drug, but its effect on the skeletal system has not been reported so far. The aim of the present study was to investigate the effect of AZA on the rat bone remodeling, and the effect of alendronate on development of skeletal changes induced by AZA. The experiments were carried out on 3...

PURPOSE This study aims to investigate the possibility of using epigenetic inhibitors against lung cancer. METHODS The changes in the proliferation of human lung cancer cells, NCI-H1975 and NCI-H1299 cells, treated with various doses of inhibitors of DNA methyltransferase (azacitidine [5-AZA]) or histone deacetylase inhibitors (trichostatin A [TSA]) were determined by cell counting. The cell ...

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or ...

DNA methyltransferase inhibitors (DNMTIs) such as 5-azacytidine (5-AZA) have been used for treatment of acute myeloid leukemia (AML) and other malignancies. Although inhibiting global/gene-specific DNA methylation is widely accepted as a key mechanism behind DNMTI anti-tumor activity, other mechanisms are likely involved in DNMTI's action. Because telomerase reverse transcriptase (TERT) plays k...

We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2'-deoxyc...