The development of the sequencing technologies allowed the generation of huge amounts of molecular data from a single cancer specimen, allowing the clinical oncology to enter the era of the precision medicine. This massive amount of data is highlighting new details on cancer pathogenesis but still relies on tissue biopsies, which are unable to capture the dynamic nature of cancer through its evolution. This assumption led to the exploration of non-tissue sources of tumoral material opening the field of liquid biopsies. Blood, together with body fluids such as urines, or stool, from cancer patients, are analyzed applying the techniques used for the generation of omics data. With blood, this approach would allow to take into account tumor heterogeneity (since the circulating components such as CTCs, ctDNA, or ECVs derive from each cancer clone) in a time dependent manner, resulting in a somehow “real-time” understanding of cancer evolution. Liquid biopsies are beginning nowdays to be applied in many cancer contexts and are at the basis of many clinical trials in oncology.

Background: this study aims to investigate the possible association among the histopathologic features of carotid plaque instability, the presence of micro- or macrocalcifications, the expression of in situ inflammatory biomarkers, and the occurrence of the major risk factors in this process in a large series of carotid plaques. Methods: a total of 687 carotid plaques from symptomatic and asymptomatic patients were collected. Histological evaluation was performed to classify the calcium deposits in micro or macrocalcifications according to their morphological features (location and size). Immunohistochemistry was performed to study the expression of the main inflammatory biomarkers. Results: results here reported demonstrated that calcifications are very frequent in carotid plaques, with a significant difference between the presence of micro- and macrocalcifications. Specifically, microcalcifications were significantly associated to high inflamed unstable plaques. Paradoxically, macrocalcifications seem to stabilize the plaque and are associated to a M2 macrophage polarization instead. Discussion: the characterization of mechanisms involved in the formation of carotid calcifications can lay the foundation for developing new strategies for the management of patients affected by carotid atherosclerosis. Data of this study could provide key elements for an exhaustive evaluation of carotid plaque calcifications allowing to establish the risk of associated clinical events.

In the last decade, several studies have reported an unexpected and seemingly paradoxical inverse correlation between BMI and incidence of cardiovascular diseases. This so called “obesity paradox effect” has been mainly investigated through imaging methods instead of histologic evaluation, which is still the best method to study the instability of carotid plaque. Therefore, the purpose of our study was to evaluate by histology the role of obesity in destabilization of carotid plaques and the interaction with age, gender and other major cerebrovascular risk factors. A total of 390 carotid plaques from symptomatic and asymptomatic patients submitted to endarterectomy, for whom complete clinical and laboratory assessment of major cardiovascular risk factors was available, were studied by histology. Patients with a BMI ≥ 30.0 kg/m2 were considered as obese. Data were analyzed by multivariate logistic regression and for each variable in the equation the estimated odds ratio (OR) was calculated. Unstable carotid plaque OR for obese patients with age < 70 years was 5.91 (95% CI 1.17–29.80), thus being the highest OR compared to that of other risk factors. Unstable carotid plaque OR decreased to 4.61 (95% CI 0.54–39.19) in males ≥ 70 years, being only 0.93 (95% CI 0.25–3.52) among women. When obesity featured among metabolic syndrome risk factors, the OR for plaque destabilization was 3.97 (95% CI 1.81–6.22), a significantly higher value compared to OR in non-obese individuals with metabolic syndrome (OR = 1.48; 95% CI 0.86–2.31). Similar results were obtained when assessing the occurrence of acute cerebrovascular symptoms. Results from our study appear to do not confirm any paradoxical effect of obesity on the carotid artery district. Conversely, obesity is confirmed to be an independent risk factor for carotid plaque destabilization, particularly in males aged < 70 years, significantly increasing such risk among patients with metabolic syndrome.

The identification of individual or clusters of predictive genetic alterations might help in defining the outcome of cancer treatment, allowing for the stratification of patients into distinct cohorts for selective therapeutic protocols. Neuroblastoma (NB) is the most common extracranial childhood tumour, clinically defined in five distinct stages (1–4 & 4S), where stages 3–4 define chemotherapy-resistant, highly aggressive disease phases. NB is a model for geneticists and molecular biologists to classify genetic abnormalities and identify causative disease genes. Despite highly intensive basic research, improvements on clinical outcome have been predominantly observed for less aggressive cancers, that is stages 1,2 and 4S. Therefore, stages 3–4 NB are still complicated at the therapeutic level and require more intense fundamental research. Using neuroblastoma as a model system, here we herein outline how cancer prediction studies can help at steering preclinical and clinical research toward the identification and exploitation of specific genetic landscape. This might result in maximising the therapeutic success and minimizing harmful effects in cancer patients.