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Search Results: 1 - 10 of 5014 matches for " Gabriela Dontu "
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Breast cancer stem cell markers – the rocky road to clinical applications
Gabriela Dontu
Breast Cancer Research , 2008, DOI: 10.1186/bcr2130
Abstract: The cancer stem cell model, a concept initially proposed more than a century ago, has been revisited with increasing enthusiasm in the past decade. This model proposes that tumors, like normal tissues, are organized in a cellular hierarchy, in which 'cancer stem cells' are the only cells with unlimited proliferation potential and therefore capable of driving tumor growth and metastasis. The 'differentiated' cancer cells that account for the majority of the tumor population may have high proliferation potential, but it is not unlimited. It follows that eliminating these differentiated progenies while sparing the cancer stem cells will ultimately result in relapse. The other component of the stem cell model of carcinogenesis holds that stem and progenitor cells are the cells susceptible to transformation, owing to their long life and high proliferative capacity.A paradigm-shifting hypothesis, the cancer stem cell model could potentially be the foundation for new preventive and therapeutic strategies in cancer. However, concerns regarding the validity of this model have been expressed, mostly regarding its experimental validation. It has been brought to attention that xenografting cancer cells in immunosupressed animals, the gold standard for testing cancer stem cell properties in vivo, may select for cells adaptable to the animal host, therefore introducing an unavoidable bias. Experts in the field cautioned against oversimplified views that do not take into account the genetic variability and clonal evolution of cancer cells, including those of cancer stem cells.The efforts of numerous recent studies focused on testing the validity and universality of this model across tumor types of various tissues, and on exploring its clinical implications. In line with these directions, the recent study by Honeth and colleagues [1] aims to identify possible correlations between the representation of tumor-initiating cells and classic molecular and histoclinical parameters that cl
MicroRNAs: shortcuts in dealing with molecular complexity?
Gabriela Dontu, Emanuele de Rinaldis
Breast Cancer Research , 2010, DOI: 10.1186/bcr2455
Abstract: MicroRNAs are able to control complex programs by regulating the expression of hundreds of genes simultaneously. Since their discovery almost three decades ago, numerous alterations in miRNA expression with varying underlying mechanisms were associated with human malignancies [1]. The study by Shimono and colleagues now shows that certain miRNAs may control the molecular makeup of stemness, and may be a shared trait of stem cells from various origins: embryonal and adult stem cells, normal and malignant stem cells [2]. This molecular similarity between normal and malignant stem cells re-enforces the concept put forward by the cancer stem cell model, according to which stem cells and early progenitor cells are more susceptible to transformation than their differentiated counterparts [3]. This may be due in part to a molecular intracellular context that sustains self-renewal and/or high proliferative potential.Shimono and colleagues performed a comparative analysis of purified CD44+CD24-lin- cancer stem cell populations from three different breast cancers, which revealed differential expression of 37 miRNAs [2]. Among these, three clusters of miRNAs were consistently downregulated in an additional eight breast cancer samples: miRNA-183-96-182, miRNA-200c-141 and miRNA-200b-200a-429. The latter two clusters have the same seed sequence, suggesting that they may have overlapping targets. Remarkably, this downregulation appeared to be conserved in embryonal carcinoma cells (Tera-2 cells), in normal and malignant mammary stem cells of mouse origin defined by the CD24-CD49f+lin- phenotype [4], and in normal mammary stem/progenitor cells defined by the CD49f+EpCAMneg/lowCD31-CD45- phenotype [5]. When miRNA-200c levels were restored in any of these cells, they lost the ability to proliferate in vitro, as demonstrated by a dramatic decline in clonogenicity, and they lost the ability to proliferate in vivo, as demonstrated by an inability to generate tumors or normal outgrowths
Mammary stem cells, self-renewal pathways, and carcinogenesis
Suling Liu, Gabriela Dontu, Max S Wicha
Breast Cancer Research , 2005, DOI: 10.1186/bcr1021
Abstract: The mammary gland in humans and in other mammals is a dynamic organ that undergoes significant developmental changes during pregnancy, lactation, and involution. It is likely that the cellular repertoire of the human mammary gland is generated by a stem cell component. These stem cells have a unique capacity for self-renewal as well as for generating the three lineages that comprise the lobulo-alveolar structure of the adult gland: myoepithelial cells forming the basal layer of ducts and alveoli, ductal epithelial cells lining the lumen of ducts, and alveolar epithelial cells synthesizing milk proteins [1,2]. Under the regulation of systemic hormones, as well as local stromal epithelial interactions, these cells proliferate extensively, differentiate during each pregnancy and lactation, and undergo apoptosis during mammary involution [2]. It has been shown previously that a subset of the luminal epithelial cells could convert to myoepithelial cells in culture, signifying the possible existence of a progenitor cell [3]. Recently, Stingl and colleagues characterized the multipotent epithelial cells in the normal adult breast [4]. In their experimental system, two distinct types of human breast epithelial cell (HBEC) progenitor population could be distinguished on the basis of their differential expression of the MUC-1 glycoprotein CALLA/CD10 and epithelial-specific antigen (ESA). MUC-1+/CALLA-/ESA+ progenitors (luminal restricted progenitor, or alveolar progenitor) expressed typical luminal epitopes (keratin 8/18, keratin 19, MUC-1, and ESA) and showed low levels of expression of myoepithelial epitopes (keratin 14 and CD44v6). The second type of progenitor, MUC-1-to ±/CALLA± to +/ESA+(bipotent progenitor, or ductal progenitor), generated mixed colonies of both luminal and myoepithelial cells when seeded in two-dimensional and three-dimensional cultures. Furthermore, they suggested that the MUC-1+/CALLA-/ESA+ and the MUC-1-to ±/CALLA± to +/ ESA+ progenitors are candida
Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells
Gabriela Dontu, Kyle W Jackson, Erin McNicholas, Mari J Kawamura, Wissam M Abdallah, Max S Wicha
Breast Cancer Research , 2004, DOI: 10.1186/bcr920
Abstract: In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists.Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells.These studies suggest that Notch signaling plays a critical role in normal human mammary development by acting on both stem cells and progenitor cells, affecting self-renewal and lineage-specific differentiation. Based on these findings we propose that abnormal Notch signaling may contribute to mammary carcinogenesis by deregulating the self-renewal of normal mammary stem cells.Stem cells in adult tissues are characterized by their ability to undergo self-renewal and multilineage differentiation [1]. The elucidation of pathways that govern stem cell functions is essential for understanding normal development and organogenesis. Moreover, there is increasing evidence that defects in these pathways play an important ro
Stable One-Dimensional Periodic Wave in Kerr-Type and Quadratic Nonlinear Media
Roxana Savastru,Simona Dontu,Dan Savastru,Marina Tautan,Vasile Babin
Mathematical Problems in Engineering , 2012, DOI: 10.1155/2012/532610
Abstract: We present the propagation of optical beams and the properties of one-dimensional (1D) spatial solitons (“bright” and “dark”) in saturated Kerr-type and quadratic nonlinear media. Special attention is paid to the recent advances of the theory of soliton stability. We show that the stabilization of bright periodic waves occurs above a certain threshold power level and the dark periodic waves can be destabilized by the saturation of the nonlinear response, while the dark quadratic waves turn out to be metastable in the broad range of material parameters. The propagation of (1
Classic (Nonquantic) Algorithm for Observations and Measurements Based on Statistical Strategies of Particles Fields
D. Savastru,Simona Dontu,Roxana Savastru,Andreea Rodica Sterian
Advances in High Energy Physics , 2013, DOI: 10.1155/2013/876870
Journal of Plant Development , 2008,
Abstract: In this work was to establish the taxonomic and ecologic structure of algocenoses from different agricultural cultures and the conservation in situ” through the separation in pure cultures of trunks of nitrogen fixation algae that can be used in the process of soil fertility increase, as a source of nitrogen. It is worth studying the ecologic structure of algae communities, reflected by vital forms.
A free boundary problem describing the saturated-unsaturated flow in a porous medium. Part II. Existence of the free boundary in the 3D case
Gabriela Marinoschi
Abstract and Applied Analysis , 2005, DOI: 10.1155/aaa.2005.813
Abstract: We present an extension of the results given in the first part ofthis paper (2004) referring to the existence in the 3D case ofa free boundary between the saturated and unsaturated domains thatmay be evidenced during the water flow into a porous medium.
A free boundary problem describing the saturated-unsaturated flow in a porous medium
Gabriela Marinoschi
Abstract and Applied Analysis , 2004, DOI: 10.1155/s1085337504311127
Abstract: This paper presents a functional approach to a nonlinear model describing the complete physical process of water infiltration into an unsaturated soil, including the saturation occurrence and the advance of the wetting front. The model introduced in this paper involves a multivalued operator covering the simultaneous saturated and unsaturated flow behaviors and enhances the study of the displacement of the free boundary between these two flow regimes. The model resides in Richards' equation written in pressure form with an initial condition and boundary conditions which in this work express the inflow due to the rain on the soil surface on the one hand, and characterize a certain permeability corresponding to the underground boundary, on the other hand. Existence, uniqueness, and regularity results for the transformed model in diffusive form, that is, for the moisture of the soil, and the existence of the weak solution for the pressure form are proved in the 3D case. The main part of the paper focuses on the existence of the free boundary between the saturated and unsaturated parts of the soil, and this is proved, in the 1D case, for certain stronger assumptions on the initial data and boundary conditions.
Kernel convergence and biholomorphic mappings in several complex variables
Gabriela Kohr
International Journal of Mathematics and Mathematical Sciences , 2003, DOI: 10.1155/s0161171203303321
Abstract: We deal with kernel convergence of domains in ℂn which are biholomorphically equivalent to the unit ball B. We also prove that there is an equivalence between the convergence on compact sets of biholomorphic mappings on B, which satisfy a growth theorem, and the kernel convergence. Moreover, we obtain certain consequences of this equivalence in the study of Loewner chains and of starlike and convex mappings on B.
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