The identification of new predictive biomarkers and therapeutic target for tailored therapy in breast cancer onset and progression is an interesting challenge. OLR-1 gene encodes the cell membrane receptor LOX-1 (lectin-like oxidized low-density lipoprotein receptor). We have recently identified a novel alternative OLR-1 isoform, LOX-1Δ4, whose expression and functions are still not clarified. In the present paper, we demonstrated that LOX-1 is overexpressed in 70% of human breast cancer (n = 47) and positively correlated to the tumor stage and grade (p < 0.01). Observations on LOX-1 and its splice variant Δ4 pointed out a different expression pattern correlated to breast cancer phenotypes. Overexpressing LOX-1 and LOX-1Δ4 in vitro, we obtained a strong enhancement of proliferative rate and a downregulation of cell death-related proteins. In addition, we observed a strong modulation of histone H4 acetylation and Ku70, the limiting factor of DNA double-strand breaks repair machinery implied in apoptosis inhibition and drug resistance acquisition. Moreover, LOX-1Δ4 overexpression is able to increase proliferation in a non-tumorigenic epithelial cell line, MCF12-F, acting as an oncogene. Altogether, these results suggest that LOX-1 may acts as a molecular link among metabolism, inflammation and cancer, indicating its potential role as biomarker and new molecular target, representing an attractive and concrete opportunity to improve current strategies for breast cancer tailored therapy.
Renal cell carcinoma (RCC) represents around 3% of all cancers, within which clear cell RCC (ccRCC) are the most common type (70–75%). The RCC disease regularly progresses asymptomatically and upon presentation is recurrently metastatic, therefore, an early method of detection is necessary. The identification of one or more specific biomarkers measurable in biofluids (i.e., urine) by combined approaches could surely be appropriate for this kind of cancer, especially due to easy obtainability by noninvasive method. OLR1 is a metabolic gene that encodes for the Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), implicated in inflammation, atherosclerosis, ROS, and metabolic disorder-associated carcinogenesis. Specifically, LOX-1 is clearly involved in tumor insurgence and progression of different human cancers. This work reports for the first time the presence of LOX-1 protein in ccRCC urine and its peculiar distribution in tumoral tissues. The urine samples headspace has also been analyzed for the presence of the volatile compounds (VOCs) by SPME-GC/MS and gas sensor array. In particular, it was found by GC/MS analysis that 2-Cyclohexen-1-one,3-methyl-6-(1-methylethyl)- correlates with LOX-1 concentration in urine. The combined approach of VOCs analysis and protein quantification could lead to promising results in terms of diagnostic and prognostic potential for ccRCC tumors.
Frailty fractures place a significant socioeconomic burden on the health care system. The Italian Society of Orthopaedics and Traumatology (SIOT) is proceeding to fracture liaison service (FLS) model accreditation in several Italian Fracture Units (FUs), which provides a multidisciplinary approach for the management of the fragility fracture patient. Introduction Osteoporosis and the resulting fragility fractures, particularly femoral fractures, place significant socioeconomic burdens on the health care system globally. In addition, there is a general lack of awareness of osteoporosis, resulting in underestimation of the associated risks and suboptimal treatment of the disease. The fracture liaison service (FLS) represents an exemplary model of post-fracture care that involves a multidisciplinary approach to the frail patient through the collaboration of multiple specialists. The purpose of this article is to highlight the path undertaken by the Italian Society of Orthopaedics and Traumatology (SIOT) for the purpose of certification of numerous FLS centers throughout Italy. Methods SIOT is proceeding with international FLS accreditation in several Italian Fracture Units (FUs), following the creation of a model that provides specific operational and procedural steps for the management of fragility fractures throughout the country. FUs that decide to join the project and implement this model within their facility are then audited by an ACCREDIA-accredited medical certification body. ResultsThe drafted FLS model, thanks to the active involvement of a panel of experts appointed by SIOT, outlines a reference operational model that describes a fluid and articulated process that identifies the procedure of identification, description of diagnostic framing, and subsequent initiation of appropriate secondary prevention programs for fractures of individuals who have presented with a recent fragility fracture of the femur. Conclusion Accreditation of this prevention model will enable many facilities to take advantage of this dedicated diagnostictherapeutic pathway for the purpose of fracture prevention and reduction of associated health and social costs.
Cigarette smoking has a negative impact on the skeletal system, as it reduces bone mass and increases fracture risk through its direct or indirect effects on bone remodeling. Recent evidence demonstrates that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. Moreover, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation between the daily number of cigarettes smoked and years of exposure has been shown, even though the underlying mechanisms are not fully understood. It is also well known that smoking causes several medical/surgical complications responsible for longer hospital stays and a consequent increase in the consumption of resources. Smoking cessation is, therefore, highly advisable to prevent the onset of bone metabolic disease. However, even with cessation, some of the consequences appear to continue for decades afterwards. Based on this evidence, the aim of our review was to evaluate the impact of smoking on the skeletal system, especially on bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Since smoking is a major public health concern, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention.
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