16 research outputs found
Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer
Background: Early detection of ovarian cancer could significantly improve patient outcomes. Cancer antigen 125 (CA 125) is elevated in sera from approximately 60% of patients with earlyâstage (I/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigenâautoantibody (AgâAAb) complexes have received relatively little attention. /
Methods: Luminexâbased immunoassays were used to measure human epididymis protein 4 (HE4), antiâHE4 autoantibody, and HE4 AgâAAb complexes in sera from patients with earlyâ (n = 73) and lateâstage ovarian cancers (n = 49) at the time of diagnosis and from asymptomatic women with (n = 15) or without ovarian cancer (n = 212) enrolled in the Normal Risk Ovarian Cancer Screening Study. /
Results: At 98% specificity for healthy, asymptomatic women, 7% of patients with earlyâstage (I/II) ovarian cancer and 4% of patients with lateâstage (III/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 AgâAAb complexes were detected in sera from 38% of earlyâstage cases and 31% of lateâstage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 AgâAAb complexes and CA 125 levels in earlyâstage ovarian cancer (P < .001). CA 125 detected 63% of cases, and a combination of CA 125 and HE4 AgâAAb complexes detected 81%. Complementarity was also observed in ROC curves for an independent validation set with 69 earlyâstage patients (P = .039). HE4 AgâAAb complexes were detected in serial preclinical serum samples from women destined to develop ovarian cancer: they correlated with CA 125 but did not provide a lead time. /
Conclusions: HE4 AgâAAb complexes could complement CA 125 in detecting a higher fraction of earlyâstage ovarian cancers
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference