Biomedical subjects

Angela Wong

Publications and source records attributed to Angela Wong.

5 recordsLinked to original sources

PubMed2005

Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists.

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

Acetates↗

PubMed2005

Functional annotation and network reconstruction through cross-platform integration of microarray data.

The rapid accumulation of microarray data translates into a need for methods to effectively integrate data generated with different platforms. Here we introduce an approach, 2(nd)-order expression analysis, that addresses this challenge by first extracting expression patterns as meta-information from each data set (1(st)-order expression analysis) and then analyzing them across multiple data sets. Using yeast as a model system, we demonstrate two distinct advantages of our approach: we can identify genes of the same function yet without coexpression patterns and we can elucidate the cooperativities between transcription factors for regulatory network reconstruction by overcoming a key obstacle, namely the quantification of activities of transcription factors. Experiments reported in the literature and performed in our lab support a significant number of our predictions.

Algorithms↗

PubMed2005

Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist.

An investigation into the structure-activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC(50) values. A representative compound morpholinyl-4-piperidinylacetic acid derivative (13d: IC(50)=4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.

Administration, Oral↗

PubMed2005

Epidemiologic risk factors for Barrett's esophagus and associated adenocarcinoma.

The incidence of esophageal adenocarcinoma (AC) has increased dramatically in the Western world over the past 20 years and the majority of these cancers arise on the background of the preinvasive lesion Barrett's esophagus. The epidemiologic factors that contribute to an individual's susceptibility for Barrett's esophagus and associated cancer are likely to be multifactorial. However, the short time frame over which the incidence of adenocarcinoma has increased, and the increase across populations, provides a strong argument for environmental factors as etiologic agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. In this review we discuss the epidemiologic evidence for the proposed demographic and environmental risk factors for the development of both Barrett's esophagus and AC. The current evidence suggests that significant risk factors include male sex, Caucasian race, and the presence of duodenogastroesophageal reflux disease. The susceptibility for reflux disease may in turn be influenced by factors such as obesity, the use of drugs that lower the lower-esophageal sphincter tone, and a protective effect of Helicobacter pylori colonization. There appears to be a weak association between smoking and AC. The role of dietary factors has not been studied adequately and deserves further attention. An understanding of the factors that predispose to the development and progression of Barrett's esophagus is crucial to the implementation of effective screening and prevention programs.

Adenocarcinoma↗

PubMed2004

Progressive changes in regulation of apolipoproteins E and J in glial cultures during postnatal development and aging.

Apolipoprotein (Apo) E and ApoJ are lipid- and cholesterol-carriers in the central nervous system and are implicated in age-related neurodegenerative diseases. The primary source of secreted ApoE and ApoJ (clusterin) in the brain is glia. Regulation of these apolipoproteins in mixed glial cultures from rat cerebral cortex differed most strongly between neonatal- and adult-derived glia. Basal secretion of ApoJ was two-fold greater in neonatal than adult glia. Responses to cytokines also differed by donor age. In adult glia, IL-6 increased ApoE secretion, but slightly decreased ApoJ. Both IL-1 beta and TNFalpha treatments increased ApoJ secretion from adult glia, with little effect on ApoE. In contrast to adult glia, neonatal ApoJ secretion did not respond to IL-1 beta, IL-6, or TNFalpha, and ApoE secretion from neonatal glia was slightly increased by IL-6. These differences may contribute to age-related neuroinflammatory processes, and are pertinent to the general use of neonatal-derived primary glia in models for neurodegenerative disease.

Aging↗