Unveiling heterogeneity: the pressing challenge to cancer diagnosis and therapy

Since the pioneering studies of Heppner and co-workers on mouse mammary cancer, the presence of heterogeneous phenotypes and genotypes within the cancer bulk has been clearly demonstrated in several types of malignancies. Different co-existing sub-populations, arising from both genetic and non-genetic variability and providing both heritable and non-heritable clones, give rise to an organized community in which not only cooperative but also conflicting interactions may set up. The resulting clonal crosstalk guarantees tumour growth, helping its spread through metastasis and the emergence of resistance to the commonly exploited anti-cancer treatments. Although aware of tumour heterogeneity, we are still far from understanding how different phenotypes and genotypes interact, thus allowing the whole community to survive therapeutic selection and/or suppression. This is why we failed so far to fine-tune a long-lasting, effective treatment for this kind of pathology. Accordingly, untangle tumour complexity is a basic and urgent challenge scientists should not work around anymore

Synthetic analogues of flavonoids as novel prototypes of food supplements

Flavonoids are ubiquitous in fruits and vegetables and show many functional effects, resulting from their ability to modulate key molecular mechanisms related to cardiovascular diseases and some types of cancer. They are present in relatively high amounts in the diet of both European and American population and their intake is highly recommended for preventive health purposes. However, despite endowed with intriguing activities, flavonoids possess significant drawbacks. Actually, their functional effects occur at high, non-physiological concentrations, seldom reached in the circulation, and a clear evidence of the relationship between flavonoids consumption and health benefits still lacks. Moreover, their low solubility and stability, coupled with unfavourable pharmacokinetics properties and the ability to modulate additional and unrelated molecular targets, limit their exploitability either as food supplements or even as drug candidates. Nevertheless, they represent an excellent and logical source of inspiration for medicinal chemists, who may design synthetic analogues to achieve safer and more effective compounds. Prompted by these considerations, we developed a number of synthetic analogues of flavonoids, to obtain novel anti-oxidant, anti-inflammatory compounds as viable agents exploitable in the management of vascular dysfunctions. When tested at a concentration fully consistent with their use in vivo, our derivatives turned out to be more effective than well known flavonoids in modulating platelet reactivity and regulating key inflammatory events involved in the remodelling of vessel walls. Accordingly, they may represent novel prototypes of food supplements, exploitable to enrich the efficacy of natural flavonoids compounds

Functional efficacy of food components and non-nutrient bioactives. A case study: Phaseolus vulgaris L.

Healthy diet is generally believed to have a major influence on both the prevention and development of chronic non-communicable diseases like obesity, diabetes, cardiovascular events, cancer, and osteoporosis. Actually, most food-derived macro and micronutrients, as well as phytochemicals, are able to regulate key metabolic pathways and modulate oxidative stress and inflammatory signalling. Accordingly, interventions designed for healthy eating have become a hot topic in nutritional research and the intake of a number of food is nowadays highly recommended to get and maintain physical and mental health.1 The potential of pulses to address nutritional needs, for example, has been recently acknowledged by UN General Assembly, which declared 2016 International Year of Pulses. Although recognizing their important role in healthy diet, the full set of benefits that pulse crops can offer has not been fully characterized yet, and this results in an intriguing research opportunity. To raise awareness about the important role of pulses in healthy diets and their contribution to nutrition, we focused our attention on Phaseolus vulgaris L. (Zolfino Landraces), a small, pale yellow Tuscan bean coming from the very small mountainous region of Pratomagno, between the provinces of Arezzo and Florence.2,3 This particular variety of bean differs from the other ones for the high content of flavonoids, known for their antioxidant and chelating properties. However, it contains also a number of amphiphilic compounds, represented by saponins, whose functional activities have not been thoroughly studied yet. Being characterized by a rigid hydrophobic group, connected via glycoside bonds to hydrophilic oligosaccharide chain, these compounds are acknowledge as natural surfactants able to exert beneficial effects on blood cholesterol levels. However, investigated in depth, saponins proved also to modulate the activity of aldose reductase, a key enzyme of glucose metabolism involved in long term diabetic complications, thus opening up a novel nutritional claim for this kind of pulse