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: Background.Evidence has accumulated that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is involved in the regulation of the proliferation of breast tumor cells. For complete tumor suppression high hypercalcemic doses of 1,25-(OH)2D3 are needed. The aim of this study was to assess the effect of combined treatment of 1,25-(OH)2D3 at low doses and melatonin (MEL) on the proliferation of estrogen-responsive rat breast cancer cell line RM4.: Materials and methods.RM4 cell proliferation was assessed by [3H]thymidine uptake. The presence of TGF-β1 in serum-free conditioned medium was determined by inhibition antibody binding assay.: Results.In 17-βE cultured RM4 cells both MEL and 1,25-(OH)2D3 alone and in combination significantly reduced [3H]thymidine incorporation in a dose-related fashion. MEL by itself was ineffective in inhibiting the FCS-cultured RM4 cells, while 1,25-(OH)2D3 strongly inhibited [3H]thymidine incorporation. Meanwhile, MEL increased the sensitivity of the FCS-cultured RM4 cells to 1,25-(OH)2D3 in the combined regimen, from 20- to 100-fold. MEL significantly enhanced the TGF-β1 secretion from RM4 cells and vitamin D3 increased the TGF-β1 secretion in a dose-dependent manner, from 2- to 7-fold. Moreover, a further enhancement of the TGF-β1 release was obtained with the combined treatment, but only for low 1,25-(OH)2D3 concentrations. The addition of monoclonal anti-TGF-β1 antibody to the medium of RM4 cells exposed to vitamin D3 alone or in combination with MEL increased the [3H]thymidine uptake compared to the correspondent cells cultured without antibody.: Conclusions.Our data point to a potential benefit of combination therapy with 1,25-(OH)2D3 and MEL in the treatment of breast cancer and suggest that the growth inhibition could be related, at least in part, to the enhanced TGF-β1 secretion. [Copyright &y& Elsevier]

The growing demand for personalized medicine we are currently witnessing has given rise to more in-depth research in the field of biomarker discovery and, thus, in biological banks that hold the ability to process, collect, store, and distribute "high-quality" biological specimens. However, the notion of "specimen quality" is subject to change with technological advancements. In this perspective, we propose that the notion of sample quality should shift from a broad definition of "high-quality" to a "fit-for-purpose" concept more suitable for precision medicine studies. Digital twins are a digital replica of real entities. These are largely adopted in any digitalized domain and are currently finding applications in biomedicine. The adoption of digital twins for biosamples, proposed in this paper, can provide prompt information about the whole lifecycle of the physical twin (i.e., the biosample) and substantially extend the possible matching criteria between the available samples and the researchers' and physicians' requests. This fine-tuning matching could greatly contribute to improving the "fit-for-purpose" quality, not only for studies based on current needs, but also to improve the identification of the best available samples in future situations, determined by the evolution of technologies and biosciences. Assuming and exploiting a data-science view in our biobank perspective, the more (accurate) data there are available, the more information can be extrapolated from them, the more opportunities there are for matching future, currently unknown, needs. This should be a mandatory principle that the 'time machines' called biobanks should follow., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)