Dorota Formanowicz

Atherosclerosis, a chronic inflammatory and oxidative stress-mediated disease impacting the arterial system, stands as a primary cause of morbidity and mortality worldwide. The complexity of this disease, driven by numerous factors, requires a thorough investigation of its underlying mechanisms. In our study, we explore the complex interplay between cholesterol homeostasis, macrophage dynamics, and atherosclerosis development using a Petri net-based model anchored in credible, peer-reviewed biological and medical research. Our findings underscore the significant role of macrophage colony-stimulating factor (M-CSF) inhibition in reducing atherosclerotic plaque formation by modulating inflammatory responses and lipid accumulation. Furthermore, our model highlights the therapeutic potential of targeting the C-X-C motif ligand 12 (CXCL12)/ C-X-C motif chemokine receptor type 4 (CXCR4) pathway to hinder hematopoietic stem and progenitor cells’ (HSPCs’) mobilization and plaque development. Based on the results obtained, which are in agreement with current studies, additional strategies are also proposed, such as decreasing M1 macrophage polarization for therapeutic gains, opening the door to future research and novel treatment approaches.

Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients initially diagnosed at the Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Center in Bydgoszcz, Poland. The probability of disease-free survival (DFS) and overall survival (OS) in relation to potential prognostic factors for the patients were determined using a Kaplan–Meier analysis, and univariate and multivariate Cox regression analyses evaluated the predictive factors of IBrC patients. The investigation of the potential prognostic model’s accuracy was analyzed using the ROC curve. Results: Patients with tumor size < 2 cm, Ki67 expression < 20%, luminal-A molecular subtype, and extra-dose brachytherapy boost administration displayed the most favorable prognosis according to breast cancer disease-free survival and overall survival. The estimated 5 year probability of DFS and OS rates in women with tumor diameter < 2 cm were 89% and 90%, respectively. In tumor diameter > 2 cm, the estimated 5 year probability of DFS was 73% and OS was 76%. Interestingly, the tumor diameter of 1.6 cm with a specificity of 60.5% and a sensitivity of 75% occurred as the best threshold point to differentiate patients with cancer recurrence from those without cancer progression. Conclusions: Our study provides essential information on the clinicopathological profile and future outcomes of early stage IBrC patients. Furthermore, the tumor diameter cut-off value of 1.6 cm discriminating between disease recurrence and those without disease progression patients represents an innovative direction for further research.