High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors.

The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues. This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase. We conducted high-throughput screening assays to identify small molecules that inhibit NleB/SseK activity. Two compounds, 100066N and 102644N, both significantly inhibited NleB1, SseK1, and SseK2 activities. Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein. These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells. Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase. These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.

Prevalence of known prognostic factors in female breast carcinoma including oestrogen receptor, progesterone receptor and Her-2/neu status--a study in a tertiary care centre.

Breast cancer is second most common cancer in Indian women. It is often curable by various treatment modalities when detected in early stage. Prognosis and selection of therapy in breast cancer depends upon various factors including clinical parameters, histopathological subtype and molecular characteristics of primary tumour. The aim of this study was to determine the prevalence of different prognostics factors including immunohistochemical marker ie, oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Her-2/neu) status in female breast carcinoma in a tertiary care centre. In this study 80 females patients who were found to have carcinoma of breast by fine needle aspiration cytology (FNAC) and consequently confirmed by histopathology were followed up for one year. Immunohistochemical staining for molecular markers like oestrogen receptor (ER), progesterone receptor (PR) and Her-2/neu were done in selected 48 cases. Various clinical parameters, cytopathological and hispathological findings as well as immunohistochemical studies were correlated to know the prevalence of these important prognostic factors. It was found that majority of patients were under 50 years of age group with high parity status. Significant patients had breast lump > 4 cm in size. Infiltrating duct carcinoma not otherwise specified (NOS) was the most common histological type showing predominantly microscopic grade II as per Nottingham's Modification of Bloom Richardson grading system. Immunohistochemistry showed 75% ER positivity, 66.66% PR positivity and 25% Her-2/neu positivity.