Translating molecular medicine into clinical tools: doomed to fail by neglecting basic preanalytical principles

This commentary discusses a study on measurements of matrix metalloproteinase 9 (MMP-9) in serum of pseudoxanthoma elasticum patients recently published in Journal of Molecular Medicine. This study can be considered the typical "obstacle" to effective translational medicine as previously documented in JTM journal. Although serum has been frequently proven as inappropriate sample for determining numerous circulating MMPs, among them MMP-9, there are over and over again studies, as in this case, that measure MMP-9 in serum. Comparative measurements in serum and plasma samples demonstrated higher concentrations for MMP-9 in serum due to the additional release from leukocytes and platelets following the coagulation/fibrinolysis process. From this example it can be concluded that translating basic research discoveries into clinical tools needs a more intensive exchange between basic biomedical research and clinical scientists already in an early stage. Otherwise a lost of translation, as discussed in JTM journal, seems to be inevitable

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

Are matrix metalloproteinases the missing link?

none3openMANNELLO F; TONTI G.A.; PAPA SMannello, Ferdinando; Tonti, GAETANA ANNA MARIA; Papa, Stefan

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

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Spatial and Temporal Variability in Snow Properties and Firn Volume Across the Juneau Icefield in Southeast Alaska

Glaciers are important freshwater resources which have far reaching impacts on a range of local to global systems and processes, including ecosystems and societies. As global climate continues to change, the response of glaciers has largely been reductions in ice mass and widespread retreat. A high degree of accumulation and ablation occurs in the near surface which is exposed to the atmosphere. The Juneau Icefield (JIF) has, up until the mid-2010s, historically responded climate change anomalously where its main drainage, Taku Glacier (here forward referred to its native name T’aakú Kwáan Sít’i), has been advancing while all other JIF outlet glaciers have been retreating for years. In this thesis, I quantify and compare snow water equivalent (SWE) of the annual accumulation between 2012 (pre-retreat) and 2021 (during retreat) with repeated 400 MHz common-offset ground-penetrating radar (GPR) surveys across the southern portion of the Juneau Icefield which includes T’aakú Kwáan Sít’i and its main tributaries. Because these calculations require assumptions of radio wave velocity which depends on liquid water content and density, both properties that can vary spatially and temporally, I quantify this variability with ground-truthed measurements to determine bulk relative permittivity in the annual accumulation. From this, I determine the range of liquid water content in the snowpack. I additionally quantify the difference in firn thickness and volume across JIF over this time period from the same GPR dataset and begin to investigate the potential causes of this change. The SWE in 2012 ranged between 42-688 cm water equivalent (cm w.e.) and in 2021 between 15-570 cm w.e. The depth-density relationship is relatively consistent across JIF, so I conclude that variability in liquid water content is the likely driver for variability in derived relative permittivity. Between 2012 and 2021, JIF experienced widespread firn thinning that resulted in an approximate reduction of firn volume by 51.3 percent. This difference in firn thickness was most highly correlated with marine proximity and elevation. From the investigation into glacier velocity, it is likely that the observed firn thinning was not due to dynamic thinning and was likely a result of increased ablation, decreased accumulation, or increased densification rates. These decadal-scale observations have implications for the future health of JIF and for interpretations of GPR data in temperate glacier environments. First, such a drastic decrease in firn volume reduces the mass influx to glacier ice and its ability to store short-term melt water while also potentially increasing JIF’s susceptibility to contributing more to global sea-level rise. Second, the variability in relative permittivity across the study site suggests potential for high uncertainty in depth (30.5-54.1%) and SWE (32.2-56.2%) calculations due to spatial and, likely, temporal variability in liquid water content when using GPR to determine both variables in a temperate environment

Effects of Blood Collection Methods on Gelatin Zymography of Matrix Metalloproteinases

none1noopenMANNELLO F.Mannello, Ferdinand