Intercellular adhesion molecule 1 (ICAM-1) is a glycoprotein expressed on the surface of both hemopoietic and nonhemopoietic cells that mediates, in part, the emigration of leukocytes out of the vasculature. Expression of ICAM-1 on the surface of human umbilical vein endothelial cells and a human lung carcinoma cell line (A549) was increased by interleukin-1 beta, tumor necrosis factor alpha, a...

G-quadruplex-forming oligonucleotides containing modified nucleotide chemistries have demonstrated promising pharmaceutical potential. In this work, we systematically investigate the effects of sugar-modified guanosines on the structure and stability of a (4+0) parallel and a (3+1) hybrid G-quadruplex using over 60 modified sequences containing a single-position substitution of 2'-O-4'-C-methyl...

RATIONALE Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negative regulator of the reverse cholesterol transport factors, ATP-binding casse...

Systematic secondary structure simulation of a target mRNA sequence is shown to be effective for locating a good anti-sense target site. Multiple selected anti-sense sequences were placed in a single molecule. The anti-sense oligonucleotide (oligo) was covalently closed to avoid exonuclease activities and was designated CMAS (covalently closed multiple anti-sense)-oligo. CMAS-oligo was found to...

background: malignant melanoma is a highly metastatic cutaneous cancer and typically refractory to chemotherapy. deregulated apoptosis has been identified as a major cause of cancer drug resistance, and upregulated expression of the inhibitor of apoptosis protein melanom, an inhibitor of apoptosis (ml-iap) is frequent in melanoma. methods: based on the conclusion that ml-iap expression contribu...

To overcome the problem of multidrug resistance, we investigated the effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein (P-gp) was decre...

A normal cell cycle in most eukaryotic cells consists of a tightly regulated sequence of phases including DNA synthesis (S) followed by a gap (G2), mitosis (M), and a gap (G1). In the megakaryocytic lineage, the cells undergo endomitosis, which involves DNA synthesis in the absence of mitosis, thus giving rise to polyploid cells. We aimed at defining whether the megakaryocytic cell cycle consis...

Defining target sites for antisense oligonucleotides in highly structured RNA is a non-trivial exercise that has received much attention. Here we describe a novel and simple method to generate a library composed of all 20mer oligoribonucleotides that are sense- and antisense to any given sequence or genome and apply the method to the highly structured HIV-1 leader RNA. Oligoribonucleotides that...

The c-myc oncogene is one of the most commonly malfunctioning genes in human cancers, and is an attractive target for anti-gene therapy. Although synthetic oligonucleotides designed to silence c-myc expression via one of its major control elements function well in vitro, their mode of action has been indefinite. Here we show that the targeted control element adopts an intrastrand fold-back DNA ...