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Purpose: BMS-275183 is an orally bioavailable taxane that has antitumor activity in preclinical cancer models. However, limited BMS-275183 studies have been performed in head and neck squamous cell carcinoma (HNSCC) cell lines. The purpose of this study is to identify the biological activity of BMS-275183 on HNSCC. Materials and Methods: Head and neck squamous cell carcinoma cell lines, HN6, HN12, and HN30, were exposed to BMS-275183. BMS-275183-induced growth suppression, cell-cycle arrest, and apoptosis were measured. Then, expression of selected proteins that were induced by BMS-275183 was determined by Western blot analysis. Results: BMS-275183 suppressed proliferation and induced G(2)M arrest and apoptosis in all HNSCC cell lines tested. BMS-275183 altered the expression of cell-cycle regulators, such as cyclin A and cyclin B1. The expression of E2F and p27 was decreased and increased, respectively, in all HNSCC cell lines. Cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) were increased in HN6 and HN12 cells. epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) expression were decreased by BMS-275183 in HN6 and HN30 cell lines, whereas phosphorylated epidermal growth factor receptor (pEGFR) was decreased in only HN6 cells. Conclusions: BMS-275183 induced cellular apoptosis, cell-cycle arrest, and altered gene expression in HNSCC via molecular pathways similar to other taxanes. These preclinical experiments suggest that BMS-275183 may be useful in treating HNSCC and that the aforementioned genes can potentially be used as surrogate end-point biomarkers. [ABSTRACT FROM AUTHOR]

Our purpose was to use endoscopically directed biopsies and scanning electron microscopy to quantify Helicobacter pylori biofilm density on the surface of human gastric mucosa in urease-positive and -negative patients. Participating patients underwent flexible esophago-gastro-duodenoscopies coupled with gastric mucosal biopsies. Rapid urease testing was performed on all specimens to determine the presence of H. pylori, followed by scanning electron microscopy to identify the existence of biofilms. Samples were then analyzed using Carnoy Image Analysis Software to determine percent biofilm coverage of the total surface area. These data were compared to control specimens that were urease negative. Of the patients who tested urease positive for H. pylori, the average percent of total surface area covered by biofilms was 97.3%. Those testing negative had an average surface area coverage of only 1.64%. These differences were determined to be statistically significant at the 0.0001 level. This study demonstrates that compared with controls, urease-positive specimens have significant biofilm formation, whereas urease-negative specimens have little to none. This was reflected in the significantly increased biofilm surface density in urease positive specimens compared with urease-negative controls. [ABSTRACT FROM AUTHOR]

The purpose of this study was to use endoscopically directed biopsies and scanning electron microscopy (SEM) to document the existence of Helicobacter pylori biofilms in human gastric mucosa. Patients underwent flexible esophagogastroduodenoscopies with three gastric mucosal biopsies. Rapid urease testing was performed to determine the presence or absence of H pylori. Urease-positive and urease-negative control specimens were imaged with SEM to obtain detailed images of gastric mucosa for the identification of biofilm colonies. Samples were obtained from patients who underwent esophagogastroduodenoscopies. Eleven were found to be H pylori positive and nine were H pylori negative. These were imaged at 500× and 1000× with electron microscopy. Dense, mature biofilms were present and attached to the cell surface of H pylori-positive specimens and were absent in urease-negative controls. Photomicrographs were obtained. Biofilms are complex microbiological ecosystems where sessile bacteria surround themselves in a protective matrix. This lifestyle affords protection, allows for growth in hostile environments, and alters host physiology. Many have hypothesized that H pylori infections resulting in gastric ulcers may be a manifestation of biofilms. Our investigation is the first to photographically document the existence of H pylori biofilms on human gastric mucosa. This elucidation of the ecology and pathophysiology of the mucosa of the organism is important to our understanding of a potential mechanism of this organism''s resistance to current therapy and how to better eradicate it in the future. [Copyright &y& Elsevier]