Learn More
Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming gammaH2AX, is an early cellular response to the induction of DNA double-strand breaks. Detection of this phosphorylation event has emerged as a highly specific and sensitive molecular marker for monitoring DNA damage initiation and resolution. Further, analysis of gammaH2AX foci has(More)
BACKGROUND Dysphagia is associated with numerous medical conditions and the major intervention to avoid aspiration in people with dysphagia involves modifying the diet to thickened fluids. This is associated with issues related to patient quality of life and in many cases non-compliance leading to dehydration. Given these concerns and in the absence of(More)
Double-strand breaks arise frequently in the course of endogenous - normal and pathological - cellular DNA metabolism or can result from exogenous agents such as ionizing radiation. It is generally accepted that these lesions represent one of the most severe types of DNA damage with respect to preservation of genomic integrity. Therefore, cells have evolved(More)
Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter(More)
Given the widespread use of radiotherapy in cancer, there has been a longstanding interest in the development of chemical compounds that can modify cellular responses to ionizing radiation. Additionally, recent terrorism threats suggesting attacks with 'dirty bombs' containing combinations of radioactive isotopes with conventional explosives, has increased(More)
Previous studies have described UVA-induced DNA strand breakage at the binding sites of iodinated DNA minor groove binding bisbenzimidazoles. The DNA breakage, presumably mediated by the carbon-centred ligand radical produced by photodehalogenation, was also shown to be cytotoxic. The earlier studies included a comparison of three ligand isomers, designated(More)
We show the efficacy of a therapeutic strategy that combines the potency of a DNA-binding photosensitizer, UV(A)Sens, with the tumor-targeting potential of receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in the minor groove of DNA and excited by UV(A) irradiation, induces cytotoxic lesions attributed to(More)
Oropharyngeal dysphagia, typically associated with older adults, represents a spectrum of swallowing disorders with potentially serious complications and a negative impact on quality of life. A major complication of dysphagia is caused by aspiration, predominantly of thin liquids, which may cause aspiration pneumonia. Given that thin liquids are typically(More)
Airway epithelial damage and repair represents a novel therapeutic target in asthma and chronic obstructive pulmonary disease. An established mouse model of airway epithelial damage involves the Clara cell cytotoxicity of parenterally administered naphthalene, an important environmental toxicant with genotoxic and carcinogenic potential. The objective of(More)