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Biomedical subjects

A Arakelian

Publications and source records attributed to A Arakelian.

5 recordsLinked to original sources
PubMed2005

Regulation of parathyroid hormone-related peptide by estradiol: effect on tumor growth and metastasis in vitro and in vivo.

We evaluated the capacity of estradiol (E(2)) to regulate PTHrP production, cell growth, tumor growth, and metastasis to the skeleton in breast cancer. In estrogen receptor (ER)-negative human breast cancer cells, MDA-MB-231, and cells transfected with full-length cDNA encoding ER (S-30), E(2) caused a marked decrease in cell growth and PTHrP production, effects that were abrogated by anti-E(2) tamoxifen. E(2) also inhibited PTHrP promoter activity in S-30 cells. For in vivo studies, MDA-MB-231 and S-30 cells were inoculated into the mammary fat pad of female BALB/c nu.nu mice. Animals receiving S-30 cells developed tumors of significantly smaller volume compared with MDA-MB-231 tumor-bearing animals. This change in tumor volume was reversed when S-30 cells were inoculated into ovariectomized (OVX) hosts. Inoculation of MDA-MB-231 cells into the left ventricle resulted in the development of lesions in femora and tibia as determined by x-ray analysis. In contrast, these lesions were significantly smaller in volume and number in animals inoculated with S-30, and this lower incidence was reversed in OVX animals. Bone histological analysis showed that the tumor volume to tissue volume ratio was comparable with that seen by x-ray. Immunohistochemical analysis showed that PTHrP production was inhibited in S-30 group and restored to levels comparable to that seen in MDA-MB-231 tumor-bearing animals when S-30 cells were inoculated in OVX animals. Collectively these studies show that E(2) production is inversely correlated with PTHrP production and that the growth-promoting effect of PTHrP has a direct impact on tumor growth at both nonskeletal and skeletal sites.

Animals↗
PubMed2003

[Circulating immune complexes in ischemic and hemorrhagic strokes].

The study aimed at determination of circulating immune complexes (CIC) levels in a serum of patients with ischemic and hemorrhagic strokes, isolation of the complexes and their antigen composition identification. Spectrophotometric assay, polyethylene glycol precipitation and SDS PAG electrophoresis were used. Comparing to controls, significantly elevated levels of both small and big CIC were detected in the serum of the patients with ischemic stroke, while in the patients with hemorrhage stroke only the level of small CIC was elevated. The antigen CIC composition was specific for each stroke form and for control group either. Being compared to literature data, the results obtained revealed a specificity of the antigen CIC composition in ischemic and hemorrhagic strokes.

Adult↗
PubMed2000

A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.

Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and endothelial cell migration in a dose-dependent manner in vitro without altering cell doubling time. Intraperitoneal administration of A6 resulted in a significant inhibition of tumor growth and suppressed the development of lymph node metastases in several models of breast cancer cell growth and metastasis. Large areas of tumor necrosis and extensive positive staining by TUNEL were observed on histological and immunohistochemical analysis of experimental tumor sections from A6-treated animals. A6 treatment also resulted in a decrease in factor VIII-positive tumor microvessel hot-spots. These results identify a new epitope in uPA that is involved in the uPA-uPAR interaction and indicate that an antagonist based on this epitope is able to inhibit tumor progression by modulating the tumor microenvironment in the absence of direct cytotoxic effects in vivo.

Amino Acid Sequence↗
PubMed1999

Counting the costs of drug-related adverse events.

Adverse drug events occur frequently and lead to a significant number of fatalities each year. It has been estimated that fatalities directly attributable to adverse drug reactions are the fourth to sixth leading cause of death in US hospitals, exceeding deaths caused by pneumonia and diabetes. The economic burden resulting from drug-related morbidity and mortality is equally significant and has been conservatively estimated at $US30 billion dollars annually, and could exceed $US130 billion in a worst-case scenario. Since many adverse drug events are considered preventable, increased efforts should be made to avoid classes of drugs that are problem-prone and to initiate diligent monitoring of drugs with predictable toxicities. Programmes should also be implemented that improve medication use practices within institutions. Although nearly all drugs are capable of producing an injury, certain drugs are more likely to do so. Prevention of drug-related morbidity and mortality has become an increasingly important requirement for reducing healthcare expenditures. This article will review studies that examine the economic implications of drug-related adverse events.

Animals↗