DNA methylation at CpG motifs provides an epigenetic route to regulate gene expression. In general, inverse correlation between hypermethylation and expression is observed. Epstein Barr-virus (EBV) infects people the EBV genome resides in nucleus where either its replication cycle initiates or it enters a long-term latency state viral becomes hypermethylated motifs. Viral shows largely with hyp...

Purpose: By hypomethylating genes, decitabine may up-regulate factors required for chemotherapeutic cytotoxicity. Platinum-resistant cells may have reduced expression of the copper/platinum transporter CTR1. Experimental Design: Thirty-one patients with refractory malignancies received decitabine 2.5 to 10 mg/m on days 1 to 5, and 8 to 12 or 15 to 20 mg/m on days 1 to 5. Tumor was assessed for ...

Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We fo...

SECTION 1 A 69-year-old man was admitted to our hospital with left upper quadrant pain, splenomegaly, acute renal failure, hyperuricemia, thrombocytopenia (platelet count 32,000/mm), and leukocytosis (leukocyte count 88,000/mm). His medical history was significant for prior diagnosis of myelodysplastic syndrome (MDS) by bone marrow biopsy at an outside institution treated with the hypomethylati...

The cytosine analogues 5-azacytosine (azacytidine) and 2'-deoxy-5-azacytidine (decitabine) are the currently most advanced drugs for epigenetic cancer therapies. These compounds function as DNA methyltransferase inhibitors and have shown substantial potency in reactivating epigenetically silenced tumor suppressor genes in vitro. However, it has been difficult to define the mode of action of the...

PURPOSE Patients with Hodgkin lymphoma (HL) relapsing after hematopoietic stem cell transplant have limited options for long-term cure. We have shown that infused cytotoxic T cells (CTL) targeting Epstein Barr virus (EBV)-derived proteins induced complete remissions in EBV(+) HL patients. A limitation of this approach is that up to 70% of relapsed HL tumors are EBV-negative. For these patients,...

Multiple myeloma is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMC), primarily in the bone marrow. Novel compounds are currently tested in this disease, but partial or minor patients' responses are observed for most compounds used as a single agent. The design of predictors for drug efficacy could be most useful to better understand...

Life expectancy of patients affected by glioblastoma multiforme is extremely low. The therapeutic use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed to treat this disease based on its ability to kill glioma cell lines in vitro and in vivo. Here, we show that, differently from glioma cell lines, glioblastoma multiforme tumors were resistant to TRAIL stimulat...