Royal London Hospital

About: Royal London Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 4854 authors who have published 5081 publications receiving 168207 citations. The organization is also known as: London Infirmary & London Hospital.

Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients

Abstract: The clinical significance of detecting supposed tumour cell-derived mRNA transcripts in blood using the polymerase chain reaction (PCR) remains unclear. We have used a fully quantitative 5′-nuclease RT-PCR assay to screen for the expression of cytokeratins (ck) 19 and 20 and guanylyl cyclase C (GCC) in the peripheral blood of 21 healthy controls and 27 colorectal cancer patients. Expression of cytokeratin 19 and 20 mRNA was detected in 30% and 100% of samples, respectively, taken from healthy volunteers. There was no apparent difference in ck19 and ck20 mRNA transcription levels between controls and patients, or between patients with different Dukes' stages. While GCC mRNA was detected in only 1/21 control samples, it was expressed in approximately 80% of patients, although again there was no correlation between GCC levels and disease stage. Transcription levels of all three markers varied considerably between samples, even between samples taken from the same person at different times. We conclude that neither ck19 nor ck20 are reliable markers for the detection of colon epithelial cells in peripheral blood and that an evaluation of the usefulness of GCC awaits further longitudinal studies. © 1999 Cancer Research Campaign

Inflammatory bowel disease--a radical view.

Abstract: Although the aetiology of inflammatory bowel disease remains unknown, its pathogenesis is gradually being unravelled. Increasing attention has been focused recently on the role of free radicals, in both normal metabolism and defence against disease, and also in a wide variety of conditions, for example rheumatoid arthritis, diabetes mellitus, atherosclerosis, pancreatitis, and peptic ulcer, in which oxidant stress seems to exceed homeostatic mechanisms. Free radical activity may contribute to the pathogenesis of both inflammation and cancer. This review examines the evidence that abnormal oxidative metabolism is of central importance to active inflammatory bowel disease. The potential pathogenicity of free radicals has been emphasised by recent work which suggests that reactive oxygen metabolites are not just one of a number of mediators and cytokines involved in the inflammatory process in inflammatory bowel disease but many have a pivotal role by initiating the expression of genes controlling may other aspects of the inflammatory, immune, and acute phase response, by activation of the transcription factor NF-x,.5

Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity

Abstract: EKB-569 is an irreversible inhibitor of epidermal growth factor receptor (EGF-R) tyrosine kinase. It inhibits EGF-induced phosphorylation of EGF-R and the growth of tumors that overexpress EGF-R in animal models. In clinical trials, EKB-569 and all other EGF-R inhibitors cause skin rashes. To understand the latter phenomenon, the effect of EKB-569 on EGF-R as well as downstream signaling to phosphoinositide 3-kinase-protein kinase B (AKT), extracellular signal-regulated kinase 1 and 2 (ERK1/2), or signal transducer and activator of transcription 3 (STAT3) pathways were compared in tumor cell lines and normal human keratinocytes (NHEK) grown in tissue culture. Tumor cell lines that have high (A431 epidermoid and MDA-468 breast carcinomas) and low (MCF-7 breast carcinoma) expression of EGF-R were used. NHEK cells express at least 15-fold less EGF-R than A431 cells. EKB-569 was a potent inhibitor of proliferation in NHEK, A431, and MDA-468 cells (IC(50) = 61, 125, and 260 nM, respectively) but not MCF-7 cells (IC(50) = 3600 nM). EKB-569 was also a potent inhibitor of EGF-induced phosphorylated EGF-R (pEGF-R) in A431 and NHEK cells (IC(50) = 20-80 nM). The reduction in pEGF-R paralleled inhibition of phosphotyrosine-705 STAT3, while the inhibition of phosphorylated AKT and phosphorylated ERK1/2 occurred at higher concentrations of EKB-569 (75-500 nM) in both A431 and NHEK cells. The effects were specific because EKB-569 did not inhibit the nuclear factor-kappaB pathway. It is proposed that skin toxicity associated with EKB-569 is due to inhibition of EGF-R signaling. Downstream signal transduction markers, particularly the activation status of STAT3, may be useful surrogate markers to guide clinical development of EGF-R inhibitors.

Early radiological observations may predict the long-term survival of femoral hip prostheses

Abstract: We reviewed a consecutive series of 527 uninfected hip replacements in patients resident in the UK which had been implanted from 1981 to 1993. All had the same basic design of femoral prosthesis, but four fixation techniques had been used: two press-fit, one HA-coated and one cemented. Review and radiography were planned prospectively. For assessment the components were retrospectively placed into two groups: those which had failed from two years onwards by aseptic femoral loosening and those in which the femoral component had survived without revision or recommendation for revision. All available radiographs in both groups were measured to determine vertical migration and examined by two observers to agree the presence of radiolucent lines (RLLs), lytic lesions, resorption of the neck, proximal osteopenia and distal intramedullary and distal subperiosteal formation of new bone. We then related the presence or absence of these features and the rate of migration at two years to the outcome with regard to aseptic loosening and determined the predictive value of each of these variables. Migration of > or = 2 mm at two years, the presence of an RLL of 2 mm occupying one-third of any one zone, and subperiosteal formation of new bone at the tip of the stem were predictors of aseptic loosening after two years. There were too few lytic lesions to assess at two years, but at five years a lytic lesion > or = 2 mm also predicted failure. We discuss the use of these variables as predictors of femoral aseptic loosening for groups of hips and for individual hips. We conclude that if a group of about 50 total hip replacements, perhaps with a new design of femoral stem, were studied in this way at two years, a mean migration of < 0.4 mm and an incidence of < 10% of RLLs of 2 mm in any one zone would predict 95% survival at ten years. For an individual prosthesis, migration of < 2 mm and the absence of an RLL of < or = 2 mm at two years predict a 6% chance of revision over approximately ten years. If either 2 mm of migration or an RLL of 2 mm is present, the chances of revision rise to 27%, and if both radiological signs are present they are 50%. If at five years a lytic lesion has developed, whatever the situation at two years, there is approximately a 50% chance of failure in the following five years. Our findings suggest that replacements using a limited number of any new design of femoral prosthesis should be screened radiologically at two years before they are generally introduced. We also suggest that radiographs of individual patients at two years and perhaps at five years should be studied to help to decide whether or not the patient should remain under close review or be discharged from specialist follow-up.