49 research outputs found

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    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

    Update on Biomarkers for the Detection of Endometriosis

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    Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium

    Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

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    Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS

    Multiplex immunoassays in endometriosis: An array of possibilities

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    Multiplex immunoassays range from small-scaled multiplex sandwich ELISAs in a planar or bead-based format to the more expanded antibody arrays employing direct sample labeling. The plethora of data generated from these arrays could be of great interest to understand a complex disorder such as endometriosis. Multiplex immunoassay analysis may provide information on disease pathology and may lead to improved, timely diagnosis. Until now, the use of multiplex immunoassays has been limited in endometriosis. With the constant development of multiplex technologies, future studies should focus on implementing these techniques, and combining them with multivariate statistical analysis. In this review, we provide an overview of multiplex immunoassay methods used in endometriosis studies and the data sets acquired by these methodologies. These data and future studies might provide novel insights for biomarker discovery and investigation of the pathogenesis in endometriosis.status: publishe

    Technical Verification and Assessment of Independent Validation of Biomarker Models for Endometriosis

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    There is a great need for a noninvasive diagnosis for endometriosis. Several biomarkers and biomarker panels have been proposed. Biomarker models consisting of CA-125, VEGF, Annexin V, and glycodelin/sICAM-1 were previously developed by our group. The objective of our current study was to assess the impact of technical and biological variability on the performance of those previously developed prediction models in a technical verification and a validation setting. The technical verification cohort consisted of peripheral blood plasma samples from a subset of the patients included in the original study of Vodolazkaia et al. (99 women with and 37 women without endometriosis). The validation study was done in plasma samples of an independent patient cohort (170 women with and 86 women without endometriosis). Single immunoassays were used for CA-125, VEGF-A, sICAM-1, Annexin V, and glycodelin. Statistical analyses were done using univariate and multivariate (logistic regression) approaches. The previously reported prediction models for endometriosis had a low performance in both the technical verification and validation setting. New prediction models were developed, which included CA-125, Annexin V, and sICAM-1, but CA-125 was the only marker that was retained in the models across the technical verification and validation study. Overall, successful validation of a biomarker model depends on several factors such as patient selection, collection methods, assay selection/handling, stability of the marker, and statistical analysis and interpretation. There is a need for standardized studies in large, well-defined patient cohorts with robust assay methodologies.status: publishe
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