The phenotypic reversion of cancer: Experimental evidences on cancer reversibility through epigenetic mechanisms (Review).

Different experimental models reveal that malignant cancer cells can be induced to change their phenotype into a benign one. This phenotypic transformation, confirmed both and , currently is known as 'tumor reversion'. This evidence raises a radical question among current cancer models: Is cancer reversible? How do genetic and epigenetic alterations hierarchically relate? Understanding the mechanisms of 'tumor reversion' represents a key point in order to evolve the actual cancer models and develop new heuristic models that can possibly lead to drugs that target epigenetic mechanisms, for example epigenetic drugs.

Technological grandparents: how communication technologies can improve the well-being of the elderly?

The ageing of the population is one of the most significant social transformations that the twenty first century is showcasing and a challenge that impacts society at large. The elderly, inasmuch as everybody else, are confronted with continuous transformations that are induced by technology, although they seldom benefit from the opportunities that technology entails. The digital divide amongst various segments of the population is often age-related and due to different reasons, including biological, psychological, social and financial ones.

Is Cancer Reversible? Rethinking Carcinogenesis Models-A New Epistemological Tool.

A growing number of studies shows that it is possible to induce a phenotypic transformation of cancer cells from malignant to benign. This process is currently known as "tumor reversion". However, the concept of reversibility hardly fits the current cancer models, according to which gene mutations are considered the primary cause of cancer.

Reuniting philosophy and science to advance cancer research.

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer.

Thinking in 3 dimensions: philosophies of the microenvironment in organoids and organs-on-chip.

Organoids and organs-on-a-chip are currently the two major families of 3D advanced organotypic in vitro culture systems, aimed at reconstituting miniaturized models of physiological and pathological states of human organs. Both share the tenets of the so-called "three-dimensional thinking", a Systems Physiology approach focused on recapitulating the dynamic interactions between cells and their microenvironment. We first review the arguments underlying the "paradigm shift" toward three-dimensional thinking in the in vitro culture community.

Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine.

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still far from becoming a reality, these studies highlight the role of physical and biological constraints (e.

Breaking down calcium timing in heterogenous cells populations.

Calcium controls a large number of cellular processes at different scales. Decades of studies have pointed out the importance of calcium signaling in regulating differentiation, apoptosis, mitosis and functions such as secretion, muscle contraction and memory. The space-time structure of calcium signaling is central to this complex regulation.

Scientific Practice in Modeling Diseases: Stances from Cancer Research and Neuropsychiatry.

In the last few decades, philosophy of science has increasingly focused on multilevel models and causal mechanistic explanations to account for complex biological phenomena. On the one hand, biological and biomedical works make extensive use of mechanistic concepts; on the other hand, philosophers have analyzed an increasing range of examples taken from different domains in the life sciences to test-support or criticize-the adequacy of mechanistic accounts. The article highlights some challenges in the elaboration of mechanistic explanations with a focus on cancer research and neuropsychiatry.

Co-emergence and Collapse: The Mesoscopic Approach for Conceptualizing and Investigating the Functional Integration of Organisms.

The fall of reductionist approaches to explanation leaves biology with an unescapable challenge: how to decipher complex systems. This entails a number of very critical questions, the most basic ones being: "What do we mean by 'complex'?" and "What is the system we should look for?" In complex systems, constraints belong to a higher level that the molecular one and their effect reduces and constrains the manifold of the accessible internal states of the system itself. Function is related but not deterministically imposed by the underlying structure.

Cancer and intercellular cooperation.

The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing.

Conceptual Challenges in the Theoretical Foundations of Systems Biology.

In the last decade, Systems Biology has emerged as a conceptual and explanatory alternative to reductionist-based approaches in molecular biology. However, the foundations of this new discipline need to be fleshed out more carefully. In this paper, we claim that a relational ontology is a necessary tool to ground both the conceptual and explanatory aspects of Systems Biology.

The role of coherence in emergent behavior of biological systems.

In his research activity, Emilio Del Giudice explored the possibility to move towards a unified view of some long-range dynamics in nature, ranging from quantum field theory in physics up to biology. Such a view is adopted in this contribution by discussing a mathematical model for synchronized electrical behavior of pancreatic beta cells. The stochasticity is a fundamental component of the physiological synchronized behavior of this system.

Why network approach can promote a new way of thinking in biology.

This work deals with the particular nature of network-based approach in biology. We will comment about the shift from the consideration of the molecular layer as the definitive place where causative process start to the elucidation of the among elements (at any level of biological organization they are located) interaction network as the main goal of scientific explanation. This shift comes from the intrinsic nature of networks where the properties of a specific node are determined by its position in the entire network (top-down explanation) while the global network characteristics emerge from the nodes wiring pattern (bottom-up explanation).

Breaking down levels of biological organization.

Understanding biological behaviours implies explaining the organization of living beings. Cancer compromises the normal structure and function of tissues, cells, and genes so that it appears as a multilevel phenomenon. The biology of cancer is thus giving us interesting insights on the organization of a biological system and its hierarchical phenomenology.

Hierarchies and causal relationships in interpretative models of the neoplastic process.

The aim of this paper is to present a critical analysis of the kind of biological systems identified in the main explanatory theories of cancer (i.e. Somatic Mutation Theory and Tissue Organization Field Theory) and how references to the hierarchical organization of these biological systems are used in their explanatory arguments.

Gene therapy and enhancement for diabetes (and other diseases): the multiplicity of considerations.

Gene therapy has reached the forefront of studies and research over the last 30 years because of its potential for curing, treating, and preventing diseases associated with DNA mutations. Type 1 and type 2 diabetes are two examples of very common polygenic and multifactorial diseases. The huge amount of scientific literature on this topic reflects a growing general interest in the possibilities of altering our genetic heritage and thus controlling the onset of diseases associated with mutations and relative risk factors.

The neoplastic process and the problems with the attribution of function.

Within the reductionist paradigm that has dominated the cancer research scene over the past 50 years, the definition of cancer and the explanation of its origin have always been given at the molecular genetic level. The neoplastic process is thus commonly explained as the accumulation of somatic mutations in certain genes that thus give rise to tumor cells, with consequent assignment of function to those genes involved. Nevertheless, the search for an essential definition of this disease has shifted attention from molecular components toward the functional properties of the tumor itself, which seems to present specific capabilities, emerging over the course of the disease, so that the functional test is always required to test the properties of certain genes to give tumors.

Towards an integrated view of the neoplastic phenomena in cancer research.

Cancer research has been at the forefront of biomedical activity in recent decades, and advances in molecular biology have provided a growing amount of information on the mechanisms involved in the etiopathogenesis of tumors. Nevertheless, despite these advances, the complexity of cancer is more evident, especially as different levels of phenomena are considered to explain the heterogeneity of the neoplastic process. A synthetic analysis of advances in cancer research illustrates these changes.

Germline APC mutation on the beta-catenin binding site is associated with a decreased apoptotic level in colorectal adenomas.

Germline mutations in APC tumor suppressor gene are responsible for familial adenomatous polyposis (FAP). A major role of these genetic changes is the constitutive activation of beta-catenin-Tcf-4 mediated transcription of nuclear target genes, but other cellular functions can be misregulated. To assess how different APC mutations can drive the early steps of colonic tumorigenesis, we studied the effect of 10 different germline-truncating alterations on the phenotype of the corresponding adenomas.