Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular expression of PSA in breast secretions, cells and tissues of healthy and diseased females. Although several studies have strongly suggested that the molecular forms of PSA seem to represent a potential tool for the risk assessment of breast cancer, recent reports have yielded conflicting results. Although several studies have suggested new biological function(s) for PSA in breast physiopathology, more studies are needed to enlist PSA unequivocally as an additional weapon in the anticancer armoury in breast cancer diagnostics

Current Issues, Challenges, and Future Perspectives in Clinical Laboratory Medicine

none2no: Laboratory medicine has undergone a profound evolution in organizational, methodological, and cultural terms in recent decades [...].openMannello, Ferdinando; Plebani, MarioMannello, Ferdinando; Plebani, Mari

Erythropoietin and its receptor in breast cancer: putting together the pieces of the puzzle

none2noopenMANNELLO F.; TONTI GAMannello, Ferdinando; Tonti, GAETANA ANNA MARI

The MMPs Genes Polymorphisms: Potential Role in Pharmacogenomics and Target Therapy

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Single-Cell Analysis: from Innovative Omics to Target Therapy

Copyright: © 2012 Mannello F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. To date, most of cell biology studies were performed on cell clusters, considering that all cells belonging to a peculiar cell type were identical. The renewed interest in cell-to-cell variation and its characterization enriched the concept of cellular heterogeneity, so far use, especially referred to cancer phenotypization [1]

Do Circulating Histones Represent the Missing Link among COVID-19 Infection and Multiorgan Injuries, Microvascular Coagulopathy and Systemic Hyperinflammation?

none5no: Several studies shed light on the interplay among inflammation, thrombosis, multi-organ failures and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Increasing levels of both free and/or circulating histones have been associated to coronavirus disease 2019 (COVID-19), enhancing the risk of heart attack and stroke with coagulopathy and systemic hyperinflammation. In this view, by considering both the biological and clinical rationale, circulating histones may be relevant as diagnostic biomarkers for stratifying COVID-19 patients at higher risk for viral sepsis, and as predictive laboratory medicine tool for targeted therapies.openLigi, Daniela; Maniscalco, Rosanna; Plebani, Mario; Lippi, Giuseppe; Mannello, FerdinandoLigi, Daniela; Maniscalco, Rosanna; Plebani, Mario; Lippi, Giuseppe; Mannello, Ferdinand

Chronic venous disease - Part II: Proteolytic biomarkers in wound healing

open5sìVenous leg ulcers (VLU) are characterized by sustained proteolytic microenvironment impairing the healing process. Wound fluid (WF) reflect the biomolecular activities occurring within the wound area; however, it is unclear if WF from different healing phases have different proteolytic profiles and how VLU microenvironment affects the wound healing mechanisms. We investigated the proteolytic network of WF from distinct VLU phases, and in WF- and LPS-stimulated THP-1 monocytes treated with glycosaminoglycan sulodexide, a well known therapeutic approach for VLU healing. WF were collected from patients with VLU during inflammatory (Infl) and granulating (Gran) phases. WF and THP-1 supernatants were analyzed for nine matrix metalloproteinases (MMP) and four tissue inhibitors of metalloproteinases (TIMP) by multiplex immunoassays. Our results demonstrated that: 1) WF from Infl VLU contained significantly increased concentrations of MMP-2, MMP-9, MMP-12, TIMP-1, and TIMP-2 compared to Gran WF; 2) WF from Gran VLU showed significantly increased levels of MMP-1, MMP-7, MMP-13, and TIMP-4 compared to Infl WF; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several MMP compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 significantly down-regulated the release of several MMPs. Our study provides evidence-based medicine during treatment of patients with VLU. WF from Infl and Gran VLU have different MMP and TIMP signatures, consistent with their clinical state. The modulation of proteolytic pathways in wound microenvironment by glycosaminoglycan sulodexide, provide insights for translating research into clinical practice during VLU therapy.openLigi, Daniela; Mosti, Giovanni; Croce, Lidia; Raffetto, Joseph D; Mannello, FerdinandoLigi, Daniela; Mosti, Giovanni; Croce, Lidia; Raffetto, Joseph D; Mannello, Ferdinand