Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

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Background: This study aims to investigate: (a) the putative association between the presence of microcalcifications and the expression of both epithelial-to-mesenchymal transition and bone biomarkers, (b) the role of microcalcifications in the breast osteoblast-like cells (BOLCs) formation, and (c) the association between microcalcification composition and breast cancer progression. Methods: We collected 174 biopsies on which we performed immunohistochemical and ultrastructural analysis. In vitro experiments were performed to demonstrate the relationship among microcalcification, BOLCs development, and breast cancer occurrence. Ex vivo investigations demonstrated the significant increase of breast osteoblast-like cells in breast lesions with microcalcifications with respect to those without microcalcifications. Results: In vitro data displayed that in the presence of calcium oxalate and activated monocytes, breast cancer cells undergo epithelial to mesenchymal transition. Also, in this condition, cells acquired an osteoblast phenotype, thus producing hydroxyapatite. To further confirm in vitro data, we studied 15 benign lesions with microcalcification from patients that developed a malignant condition in the same breast quadrant. Immunohistochemical analysis showed macrophages’ polarization in benign lesions with calcium oxalate. Conclusions: Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.

These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials.

Background In this study, we investigated the relationship between the expression of the main in situ markers of breast cancer and the presence of breast osteoblast-like cells (BOLCs). Methods We collected 100 breast biopsies. Serial paraffin sections were obtained from each biopsy to perform histological classifications and immunohistochemical analyses (RUNX2, RANKL, vimentin, TGFβ, Ki67, CD44, ER, PR and HER2). Results Linear regression analysis showed a positive and significant correlation between the number of BOLCs and the expression of EMT-related markers (vimentin and TGFβ), Ki67 and ER. Conversely, we observed an inverse correlation between the number of CD44-positive breast cancer cells and the BOLCs. No significant differences were observed between the number of BOLCs and the HER2 scores. Conclusions Morphological and molecular characterisation of BOLCs can lay the foundations towards understanding the biological basis of the formation of breast microcalcifications, and breast cancer metastasis to bone. The data here reported may be useful for the identification of breast lesions with high potential to develop bone metastasis.