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The aim of this work was to explore the biomarkers associated with epithelial to mesenchymal transition (EMT) and mineralization processes as new prognostic factors across different breast cancer phenotypes. To this end, 133 breast biopsies, including benign and malignant lesions, with or without microcalcifications, were retrospectively collected. Immunohistochemical analysis was performed to evaluate the expression of vimentin, BMP-2, BMP-4, RANKL, Runx2, OPN, PTX3, and SDF-1, while Kaplan—Meier plots were used to assess their prognostic impact on overall survival in a dataset of 2976 breast cancer patients. The expression of vimentin, BMP-2, BMP-4, and SDF-1 was significantly higher in malignant lesions compared to benign ones, regardless of the presence of microcalcifications. Notably, these markers showed no correlation with traditional prognostic factors, such as tumor grade or hormone receptor status. The bioinformatics analysis provided valuable insights into the possible prognostic and therapeutic significance of BMP-2, BMP-4, SDF-1, and vimentin in breast cancer. In fact, all these biomarkers impact on the overall survival in specific molecular breast cancer types. In addition, high expression of SDF-1 and vimentin is able to predict the response to chemotherapy. The findings here reported suggest that vimentin, BMP-2, BMP-4, and SDF-1 could be independent prognostic biomarkers in breast cancer, providing insights beyond traditional clinical factors. [ABSTRACT FROM AUTHOR]

Environmental pollution poses a significant risk to public health, as demonstrated by the bioaccumulation of aluminum (Al) in colorectal cancer (CRC). This study aimed to investigate the potential mutagenic effect of Al bioaccumulation in CRC samples, linking it to the alteration of key mediators of cancer progression, including immune response biomarkers. Aluminum levels in 20 CRC biopsy samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The results indicated that Al bioaccumulation occurred in 100% of the cases. A correlation between Al levels and tumor mutation burden was observed. Furthermore, RNA sequencing revealed a significant association between Al concentration and the expression of the immune checkpoint molecule CTLA-4. Although correlations with PD-1 and PD-L1 were not statistically significant, a trend was observed. Additionally, a correlation between Al levels and both the presence of myeloid cells and IFNγ expression was detected, linking Al exposure to inflammatory responses within the tumor microenvironment. These findings suggested that Al can play a role in CRC progression by promoting both genetic mutations and immune evasion. Given the ubiquitous presence of Al in industrial and consumer products, dietary sources, and environmental pollutants, these results underscored the need for stricter regulatory measures to control Al exposure. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition." The correction addresses errors in Figure 6 and Figure 5 of the original publication. The corrected figures are provided in the document. The authors assure that the scientific conclusions of the article remain unaffected. [Extracted from the article]

Simple Summary: Cholangiocarcinoma is a highly aggressive cancer that originates from the bile ducts. Traditional treatments have limited effectiveness, necessitating the exploration of new approaches. Recent studies have highlighted the importance of programmed cell death mechanisms, including apoptosis, ferroptosis, pyroptosis, and necroptosis, in the development and progression of cholangiocarcinoma. Targeting these cell death pathways may increase the susceptibility of cholangiocarcinoma cells to chemotherapy and immunotherapy. However, further research is necessary to fully understand the intricacies of programmed cell death in cholangiocarcinoma and potentially identify effective therapeutic strategies. Cholangiocarcinoma is a highly aggressive cancer arising from the bile ducts. The limited effectiveness of conventional therapies has prompted the search for new approaches to target this disease. Recent evidence suggests that distinct programmed cell death mechanisms, namely, apoptosis, ferroptosis, pyroptosis and necroptosis, play a critical role in the development and progression of cholangiocarcinoma. This review aims to summarize the current knowledge on the role of programmed cell death in cholangiocarcinoma and its potential implications for the development of novel therapies. Several studies have shown that the dysregulation of apoptotic signaling pathways contributes to cholangiocarcinoma tumorigenesis and resistance to treatment. Similarly, ferroptosis, pyroptosis and necroptosis, which are pro-inflammatory forms of cell death, have been implicated in promoting immune cell recruitment and activation, thus enhancing the antitumor immune response. Moreover, recent studies have suggested that targeting cell death pathways could sensitize cholangiocarcinoma cells to chemotherapy and immunotherapy. In conclusion, programmed cell death represents a relevant molecular mechanism of pathogenesis in cholangiocarcinoma, and further research is needed to fully elucidate the underlying details and possibly identify therapeutic strategies. [ABSTRACT FROM AUTHOR]

Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb. [ABSTRACT FROM AUTHOR]

The main aim of this preliminary in vitro study was to evaluate both the uptake of [99Tc]Sestamibi into prostate cancer cells and the relationship among [99Tc]Sestamibi bioaccumulation, cancer cells proliferation and apoptosis. An in vitro study in which PC3 prostate cancer cell line was cultured with increasing doses of decayed sestamibi has been developed. Specifically, PC3 cells were incubated with three different concentrations of [99Tc]Sestamibi: 10 µg/mL, 1 µg/mL, and 0.1 µg/mL Expression of apoptotic caspase-3 and AIF, as well as the ultrastructure of PC3 cells, were evaluated at T0 and after 24, 48, 72, and 120 h following [99Tc]Sestamibi incubation. Data here reported showed the bioaccumulation of sestamibi in prostate cancer cells. As concern the cancer cell homeostasis, the treatment of PC3 cells with [99Tc]Sestamibi strongly influenced the cells proliferation. Indeed, a significant reduction in the number of mitosis was observed. Noteworthy, the accumulation of sestamibi in prostate cancer cells was associated with the appearance of morphological signs of apoptosis. The increase in AIF and caspase 3 expression in prostate cancer cells treated with 10 µg/mL of [99Tc]Sestamibi confirmed that this radiopharmaceutical can trigger the apoptosis. To the best of our knowledge, this preliminary study reported for the first time in vitro data about the uptake of sestamibi in prostate cancer cells. The evidence about the accumulation of sestamibi in prostate cancer cells and its role in the apoptosis process could open new clinical perspectives on the use of this radiopharmaceutical in both the diagnosis and treatment of prostate cancers. [ABSTRACT FROM AUTHOR]