The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer.

Background: The faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme.

Aim: To determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC.

Design And Setting: Patients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation.

Transport function and transcriptional regulation of a liver-enriched human organic anion transporting polypeptide 2B1 transcriptional start site variant.

Human organic anion transporting polypeptide 2B1 (OATP2B1) is a membrane transporter that facilitates the cellular uptake of a number of endogenous compounds and drugs. OATP2B1 is widely expressed in tissues including the small intestine, liver, kidney, placenta, heart, skeletal muscle, and platelets. It was recently shown that differential promoter usage in tissues results in expression of five OATP2B1 transcriptional start site variants that use distinct first exons but share common subsequent exons.

The discovery of benzanilides as c-Met receptor tyrosine kinase inhibitors by a directed screening approach.

A directed screen of a relatively small number of compounds, selected for kinase ATP pocket binding potential, yielded a novel series of hit compounds (1). Hit explosion on two binding residues identified compounds 27 and 43 as the best leads for an optimization program having reduced secondary metabolism, as measured by in vitro rat hepatocytes incubation, leading to oral bio-availability. Structure-activity relationships and molecular modeling have suggested a binding mode for the most potent inhibitor 12.

Small-molecule androgen receptor downregulators as an approach to treatment of advanced prostate cancer.

Chemical starting points were investigated for downregulation of the androgen receptor as an approach to treatment of advanced prostate cancer. Although prototypic steroidal downregulators such as 6a designed for intramuscular administration showed insufficient cellular potency, a medicinal chemistry program derived from a novel androgen receptor ligand 8a led to 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (10b), for which high plasma levels following oral administration in a preclinical model compensate for moderate cellular potency.

Pathogenesis of pain in chronic pancreatitis: ongoing enigma.

The pathogenesis of pain in chronic pancreatitis remains an enigma. The cause of pain is almost certainly multifactorial and may vary at different stages of the disease process. These factors may include the release of excessive oxygen-derived free radicals, tissue hypoxia and acidosis, inflammatory infiltration with influx of pain transmittent substances into damaged nerve ends, and the development of pancreatic ductal and tissue fluid hypertension due to morphological changes of the pancreas.