1,720,996 research outputs found
Stem cell distribution and MGMT expression in glioblastoma: Role of intratumoral hypoxic gradient
No full textL-Proline as a modulator of ectodermal differentiation in ES cells. Focus on "L-Proline induces differentiation of ES cells: a novel role for an amino acid in the regulation of pluripotent cells in culture
No full textThe development of cell therapeutics from embryonic stem (ES) cells will require technologies that direct cell differentiation to specific somatic cell lineages in response to defined factors. The initial step in formation of the somatic lineages from ES cells, differentiation to an intermediate, pluripotent primitive ectoderm-like cell, can be achieved in vitro by formation of early primitive ectoderm-like (EPL) cells in response to a biological activity contained within the conditioned medium MEDII. Fractionation of MEDII has identified two activities required for EPL cell formation, an activity with a molecular mass of 100 M l-proline and some l-proline-containing peptides resulted in changes in colony morphology, cell proliferation, gene expression, and differentiation kinetics consistent with differentiation toward a primitive ectoderm-like cell. This activity appeared to be associated with l-proline since other amino acids and analogs of proline did not exhibit an equivalent activity. Activation of the mammalian target of rapamycin (mTOR) signaling pathway was found to be necessary but not sufficient for l-proline activity; addition of other activators of the mTOR signaling pathway failed to alter the ES cell phenotype. This is the first report describing a role for amino acids in the regulation of pluripotency and cell differentiation and identifies a novel role for the imino acid l-proline
Effects of phytochemicals on thyroid function and their possible role in thyroid disease
No full textAbout 1 of 10 women, particularly those older than 60 years of age, shows some degree of thyroid hormone deficiency. Thyroid diseases are generally characterized by perturbations of thyroid signaling homeostasis. The most common examples of thyroid diseases include hypothyroidism, hyperthyroidism, and several types of thyroid cancers. Phytochemicals have been shown to have either beneficial or detrimental effects on thyroid function. Some flavonoids have been reported to affect the expression and the activity of several thyroid-related enzymes and proteins, and for this reason some concerns have been raised about the possible thyroid-disruptive properties of foods enriched in these substances. On the other hand, the beneficial effects of some plant-derived compounds, such as myricetin, quercetin, apigenin, rutin, genistein, and curcumin, and their possible role as adjuvants for the treatment of thyroid cancers have been described. Here, the role of phytochemicals in thyroid signaling modulation and their possible beneficial or detrimental effects on thyroid disease risk are discussed
Role of environmental chemicals, processed food derivatives, and nutrients in the induction of carcinogenesis
No full textIn recent years it has been hypothesized that cancer stem cells (CSCs) are the actual driving force of tumor formation, highlighting the need to specifically target CSCs to successfully eradicate cancer growth and recurrence. Particularly, the deregulation of physiological signaling pathways controlling stem cell proliferation, self-renewal, differentiation, and metabolism is currently considered as one of the leading determinants of cancer formation. Given their peculiar, slow-dividing phenotype and their ability to respond to multiple microenvironmental stimuli, stem cells appear to be more susceptible to genetic and epigenetic carcinogens, possibly undergoing mutations resulting in tumor formation. In particular, some animal-derived bioactive nutrients and metabolites known to affect the hormonal milieu, and also chemicals derived from food processing and cooking, have been described as possible carcinogenic factors. Here, we review most recent literature in this field, highlighting how some environmental toxicants, some specific nutrients and their secondary products can induce carcinogenesis, possibly impacting stem cells and their niches, thus causing tumor growt
Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes.
No full textHuman neural precursor proliferation and potency is limited by senescence and loss of oligodendrocyte potential. We found that in vitro expansion of human postnatal brain CD133(+) nestin(+) precursors is enhanced at 5% oxygen, while raising oxygen tension to 20% depletes precursors and promotes astrocyte differentiation even in the presence of mitogens. Higher cell densities yielded more astrocytes regardless of oxygen tension. This was reversed by noggin at 5%, but not 20%, oxygen due to a novel repressive effect of low oxygen on bone morphogenetic protein (BMP) signaling. When induced to differentiate by mitogen withdrawal, 5% oxygen-expanded precursors generated 17-fold more oligodendrocytes than cells expanded in 20% oxygen. When precursors were expanded at 5% oxygen and then differentiated at 20% oxygen, oligodendrocyte maturation was further enhanced 2.5-fold. These results indicate that dynamic control of oxygen tension regulates different steps in fate and maturation and may be crucial for treating neurodegenerative diseases
Rheumatoid arthritis research in the 21st century: Limitations of traditional models, new technologies, and opportunities for a human biology-based approach
No full textRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease characterized by progressive bone and cartilage destruction, functional impairment, and long-term disability. Although RA has been described in the medical literature for over two hundred years, its etiology and pathophysiology are insufficiently understood. The current treatment of RA is mainly empirical or based on drugs that interfere with generic steps of the immune response, with limited efficacy and/or significant side effects. Much of RA research has been traditionally based on animals and simplistic in vitro models, which have been shown to poorly recapitulate human RA etiopathogenesis and drug responses. A revolution in science and technology has produced a new generation of more relevant and predictive tools. These tools, which include patient-derived cells, innovative 3D cell culture systems, computational analyses and models, together with omics and large-scale epidemiological studies represent novel and exciting approaches to enhance and forward RA research in a human biology-based perspective. After considering some pitfalls and flaws of traditional models, in this review we discuss novel tools applicable to design human-oriented RA research, while fostering the need for a more holistic and preventative approach to the disease. Our goal is to stimulate discussion, both at scientific and public level, on the need to explore new avenues in RA research and to support a paradigm-shift from animal-based towards human biology-based systems to better understand human pathophysiology and to develop more effective targeted therapies for personalized treatment and prevention
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The three-layer concentric model of glioblastoma: Cancer stem cells, microenvironmental regulation, and therapeutic implications
No full textTumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called hypoxic niche plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development. Copyright © 2011 Luca Persano et al
Inhibition of PI3K Signalling Selectively Affects Medulloblastoma Cancer Stem Cells
Full text linkMedulloblastoma is the most common malignant brain tumor of childhood. Although survival has slowly increased in the past years, the prognosis of these patients remains unfavourable. In this context, it has been recently shown that the intracellular signaling pathways activated during embryonic cerebellar development are deregulated in MDB. One of the most important is PI3K/AKT/mTOR, implicated in cell proliferation, survival, growth, and protein synthesis. Moreover, a fraction of MDB cells has been shown to posses stemlike features, to express typical neuronal precursor markers (Nestin and CD133), and to be maintained by the hypoxic cerebellar microenvironment. This subpopulation of MDB cells is considered to be responsible for treatment resistance and recurrence. In this study, we evaluated the effects of PI3K/AKT pathway inhibition on primary cultures of MDB and particularly on the cancer stem cell (CSC) population (CD133(+)). PI3K inhibition was able to counteract MDB cell growth and to promote differentiation of stemlike MDB cells. Moreover, PI3K/AKT pathway suppression induced dramatic cell death through activation of the mitochondrial proapoptotic cascade. Finally, analysis on the stem cells fraction revealed that the MDB CSC population is more sensitive to PI3K targeting compared to the whole cancerous population and its nonstem cell counterpart
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