1,721,059 research outputs found
Tumor and the microenvironment: a chance to reframe the paradigm of carcinogenesis?
Full text linkThe somatic mutation theory of carcinogenesis has eventually accumulated an impressive body of shortfalls and paradoxes, as admittedly claimed by its own supporters given that the cell-based approach can hardly explain the emergence of tissue-based processes, like cancer. However, experimental data and alternatives theories developed during the last decades may actually provide a new framework on which cancer research should be reframed. Such issue may be fulfilled embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation and assuming radically different premises as well as new methodological frameworks. Within that perspective, the tumor microenvironment cannot be merely considered akin to new "factor" to be added to an already long list of "signaling factors"; microenvironment represents the physical-biochemical support of the morphogenetic field which drives epithelial cells towards differentiation and phenotype transformation, according to rules understandable only by means of a systems biology approach. That endeavour entails three fundamental aspects: general biological premises, the level of observation (i.e., the systems to which we are looking for), and the principles of biological organization that would help in integrating and understanding experimental data. © 2014 Mariano Bizzarri and Alessandra Cucina
SMT and TOFT. Why and how they are opposite andi incompatible paradigms
No full textThe Somatic Mutation Theory (SMT) has been challenged on its fundamentals
by the Tissue Organization Field Theory of Carcinogenesis (TOFT).
However, a recent publication has questioned whether TOFT could be a valid
alternative theory of carcinogenesis to that presented by SMT. Herein we critically
review arguments supporting the irreducible opposition between the two theoretical
approaches by highlighting differences regarding the philosophical, methodological
and experimental approaches on which they respectively rely. We conclude that
SMT has not explained carcinogenesis due to severe epistemological and empirical
shortcomings, while TOFT is gaining momentum. The main issue is actually to
submit SMT to rigorous testing. This concern includes the imperatives to seek
evidence for disproving one’s hypothesis, and to consider the whole, and not just
selective evidence
Reversibilità ed irreversibilità della trasformazione neoplastica: ipotesi per un nuovo paradigma
No full textcarcinogenesis, systems biolog
Theoretical aspects of Systems Biology
No full textThe natural world consists of hierarchical levels of complexity that range from subatomic particles and
molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a
whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e.
where self-organization processes take place. In the past, biological research has focused on questions
that could be answered by a reductionist program of genetics. The organism (and its development) was
considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm
is now underway and it is likely that such a process will lead to a conceptual revolution emerging from
the ashes of reductionism. This revolution implies the search for general principles on which a cogent
theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is
imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no
means Systems Biology could be considered a ‘simple’ ‘gradual’ extension of Molecular Biolog
The conceptual foundations of Systems Biology. An introduction.
No full textSystems Biology is more than just a sum up of different sciences, given that Systems Biology deals with ‘systems’, and it is concerned with the complex, emergent properties that arise from the relationship between molecules, cells and tissues. Functional properties are not yet in the ‘molecules’, instead they ‘emerge’ from a self-organized process, which shape geometrically the living structure into a system, characterized by hierarchical levels. Interaction among them lead to both top- and down-ward causation. Thus, nowadays Biology is facing a crisis — or is it an opportunity — reminiscent of the state of biology in pre-double-helix time. Time is gone for Biology to “concern itself with the great ‘nonreductionist’ 19th century biological problems that molecular biology left untouched: e.g. the nature of the complex organization of the living matter. Precisely, Systems Biology affords that task
Beyond the oncogene paradigm: Understanding complexity in cancerogenesis
No full textIn the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a ‘system biology disease’. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences (rules and constraints) outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted dru
Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease
No full textINTRODUCTION:
Inositol and its derivatives comprise a huge field of biology. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates in its free form, with its isomers or its phosphate derivatives, to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response.
AREAS COVERED:
Bioavailability, safety, uptake and metabolism of inositol is discussed emphasizing the complexity of interconnected pathways leading to phosphoinositides, inositol phosphates and more complex molecules, like glycosyl-phosphatidylinositols.
EXPERT OPINION:
Besides being a structural element, myo-inositol exerts unexpected functions, mostly unknown. However, several reports indicate that inositol plays a key role during phenotypic transitions and developmental phases. Furthermore, dysfunctions in the regulation of inositol metabolism have been implicated in several chronic diseases. Clinical trials using inositol in pharmacological doses provide amazing results in the management of gynecological diseases, respiratory stress syndrome, Alzheimer's disease, metabolic syndrome, and cancer, for which conventional treatments are disappointing. However, despite the widespread studies carried out to identify inositol-based effects, no comprehensive understanding of inositol-based mechanisms has been achieved. An integrated metabolomics-genomic study to identify the cellular fate of therapeutically administered myo-inositol and its genomic/enzymatic targets is urgently warranted
Anticancer Effects of Grape Seed Extract on Human Cancers: A Review
No full textGrape seed extract (GSE) is a complex mixture of several compounds, mostly represented by polyphenols
and phenolic acids. Their consumption is safe and is recognized to exert several and meaningful health benefits.
In particular, grape-related anti-tumoral activity encompasses a wide array of biological mechanisms and cellular
targets, eventually leading to inhibition of cell growth and to enhanced apoptosis in several cancer cell lines, including
lung, colon, breast, bladder, leukemia and prostate tumors. Those effects are likely modulated at the molecular
level through selectively modulating the redox balance and displaying anti-oxidant as well as pro-oxidant actions,
according to the specific context. GSE-related anti-cancer activity mostly relies on the induced increase in reactive
oxygen species, followed by the orchestrated down- and up-regulation of several key-molecular pathways, including
MAPK kinases, PI3K/Akt, NF-kB, cytoskeleton proteins and metalloproteinases. Promising results obtained in vitro as
well as on animal studies suggest that GSE may have a great relevance as source of potential new pharmacological
molecules, and could represent an important opportunity for clinical research
Cross talk between inflammatory cytokines and granulocyte-macrophage colony-stimulating factor in transplant vasculopathy
No full textstudio sui fattori che portano al rigetto dei trapint
Molecular mechanisms of melatonin's inhibitory actions on breast cancers
No full textMelatonin is involved in many physiological functions and it plays an important role in many pathological processes as well. Melatonin has been shown to reduce the incidence of experimentally induced cancers and can significantly inhibit the growth of some human tumors, namely hormone-dependent cancers. The anticancer effects of melatonin have been observed in breast cancer, both in in vivo with models of chemically induced rat mammary tumors, and in vitro studies on human breast cancer cell lines. Melatonin acts at different physiological levels and its antitumoral properties are supported by a set of complex, different mechanisms of action, involving apoptosis activation, inhibition of proliferation, and cell differentiation
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