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Microcalcifications (MCs) are important disease markers for breast cancer. Many studies were conducted on their characterization in female breast cancer (FBC), but no information is available on their composition in male breast cancer (MBC). Raman spectroscopy (RS) is a molecular spectroscopy that can rapidly explore the biochemical composition of MCs without requiring any staining protocol. In this study, we optimized an algorithm to identify the mineral components present in MCs from Raman images. The algorithm was then used to study and compare MCs identified on breast cancer pieces from male and female patients. In total, we analyzed 41 MCs from 5 invasive MBC patients and 149 MCs from 13 invasive FBC patients. Results show that hydroxyapatite is the most abundant type of calcium both in MBC and FBC. However, some differences in the amount and distribution of calcium minerals are present between the two groups. Besides, we observed that MCs in MBC have a higher amount of organic material (collagen) than FBC. To the best of our knowledge, this study provides the first overview of the composition of MCs present in MBC patients; and suggests that these patients have specific features that differentiate them from the previously studied FBC. Our result support thus the need for studies designed explicitly to the understanding of MBC.

Microcalcifications (MCs) are important disease markers for breast cancer. Many studies were conducted on their characterization in female breast cancer (FBC), but no information is available on their composition in male breast cancer (MBC). Raman spectroscopy (RS) is a molecular spectroscopy technique that can explore the biochemical composition of MCs rapidly and without requiring any staining protocol. We here compared, by Raman spectroscopy, the MCs identified on breast cancer pieces from male and female patients. In this study, we used Raman spectroscopy to analyse 41 microcalcifications from 5 invasive MBC patients and 149 MCs from 14 invasive FBC patients. Our findings show that hydroxyapatite is the most abundant type of calcium both in MBC and FBC. However, some differences in the amount and distribution of calcium minerals are present between the two groups. Besides, we observed that MCs in MBC have a higher amount of organic material (collagen) than FBC.This study provides the first overview of the composition of microcalcifications present in MBC and suggests that they have several specific features. Our result support the need for studies specifically designed to the understanding of MBC.

Background: Conduction disturbances after transcatheter aortic valve replacement (TAVR) are often transient. Limited data exist on anatomic factors predisposing to pacemaker dependency after TAVR. We sought to assess the rate and the possible predictors of pacemaker dependency after TAVR. Methods: Consecutive patients undergoing pacemaker implantation up to 30 days after TAVR between May 2014 and September 2019 were included. Baseline electrocardiographic, computed tomography, and procedural characteristics were collected, including valve implantation depth and membranous septum length, an anatomic surrogate of the distance between the aortic annulus and the His bundle. Pacemaker dependency at 30 days and 1 year and all-cause mortality during follow-up were evaluated. Results: Of 728 TAVR patients, 112 (53.5% men; median age, 81 years) underwent pacemaker implantation after TAVR. Of these, 44.6% (50 of 112) were pacemaker dependent at 30 days and 46.7% (36 of 77) at 1 year. By multivariate analysis, independent predictors of 30-day pacemaker dependency included left ventricular outflow tract calcifications under the left coronary cusp (odds ratio, 5.69 [95% CI, 1.45–22.31]; P =0.013) and a difference between membranous septum length and implantation depth (ΔMSID) ≥3 mm (odds ratio, 7.58 [95% CI, 2.07–27.78]; P =0.002). Conversely, membranous septum length and implantation depth alone were not associated with pacemaker dependency (odds ratio, 0.79 [95% CI, 0.60–1.05]; P =0.11 and odds ratio, 1.11 [95% CI, 0.99–1.24]; P =0.08). At a median follow-up of 28.1 (11.7–48.6) months, pacemaker-dependent patients did not show a worse survival ( P =0.26). Conclusions: Less than half of the patients undergoing pacemaker implantation after TAVR are pacemaker-dependent at midterm follow-up. ΔMSID ≥3 mm and the presence of left ventricular outflow tract calcifications under the left coronary cusp, but not membranous septum length nor implantation depth alone, are predictive of long-term pacemaker dependency after TAVR, thus influencing device selection and programming.

Background The effectiveness of therapies for chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries adults, can be improved via a deeper understanding of its molecular abnormalities. Whereas the isoforms of the eukaryotic elongation factor 1A (eEF1A1 and eEF1A2) are implicated in different tumors, no information are available in CLL. Methods eEF1A1/eEF1A2 amounts were quantitated in the lymphocytes of 46 CLL patients vs normal control (real time PCR, western blotting). eEF1A1 role in CLL was investigated in a cellular (MEC-1) and animal model of CLL via its targeting by an aptamer (GT75) or a siRNA (siA1) delivered by electroporation (in vitro) or lipofection (in vivo). Results eEF1A1/eEF1A2 were elevated in CLL lymphocytes vs control. eEF1A1 but not eEF1A2 levels were higher in patients which died during the study compared to those surviving. eEF1A1 targeting (GT75/siA1) resulted in MEC-1 viability reduction/autophagy stimulation and in vivo tumor growth down-regulation. Conclusions The increase of eEF1A1 in dead vs surviving patients may confer to eEF1A1 the role of a prognostic marker for CLL and possibly of a therapeutic target, given its involvement in MEC-1 survival. Specific aptamer/siRNA released by optimized delivery systems may allow the development of novel therapeutic options.

Eukaryotic elongation factor 1A (eEF1A), a protein involved in protein synthesis, has two major isoforms, eEF1A1 and eEF1A2. Despite the evidences of their involvement in hepatocellular carcinoma (HCC), the quantitative contribution of each of the two isoforms to the disease is unknown. We depleted the two isoforms by means of siRNAs and studied the effects in three different HCC cell lines. Particular care was dedicated to select siRNAs able to target each of the two isoform without affecting the other one. This is not a trivial aspect due to the high sequence homology between eEF1A1 and eEF1A2. The selected siRNAs can specifically deplete either eEF1A1 or eEF1A2. This, in turn, results in an impairment of cell vitality, growth and arrest in the G1/G0 phase of the cell cycle. Notably, these effects are quantitatively superior following eEF1A1 than eEF1A2 depletion. Moreover, functional tests revealed that the G1/G0 block induced by eEF1A1 depletion depends on the down-regulation of the transcription factor E2F1, a known player in HCC. In conclusion, our data indicate that the independent targeting of the two eEF1A isoforms is effective in reducing HCC cell growth and that eEF1A1 depletion may result in a more evident effect.