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Search Results: 1 - 10 of 5148 matches for " Hugo Vankelecom "
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Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine
Van den broeck Anke,Gremeaux Lies,Topal Baki,Vankelecom Hugo
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-354
Abstract: Background Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC( like) phenotype. Methods Human PDAC samples were expanded in immunodeficient mice and first-generation xenografts analyzed for the presence of a Hoechst dye-effluxing SP using flow cytometry (FACS). To investigate chemoresistance of the SP, mice bearing PDAC xenografts were treated with gemcitabine and SP proportion determined. In addition, the SP and the main tumour cell population (MP) were sorted by FACS for RNA extraction to profile gene expression, and for culturing under sphere-forming conditions. Results A SP was identified in all PDAC samples, analyzed. This SP was more resistant to gemcitabine than the other tumour cells as examined in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the MP as analyzed in vitro by sphere-forming capacity. Conclusion We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer. Trial registration Clinicaltrials.gov NCT00936104
The Dark Side of EGFP: Defective Polyubiquitination
Mathijs Baens, Heidi Noels, Vicky Broeckx, Sofie Hagens, Sabine Fevery, An D. Billiau, Hugo Vankelecom, Peter Marynen
PLOS ONE , 2006, DOI: 10.1371/journal.pone.0000054
Abstract: Enhanced Green Fluorescent Protein (EGFP) is the most commonly used live cell reporter despite a number of conflicting reports that it can affect cell physiology. Thus far, the precise mechanism of GFP-associated defects remained unclear. Here we demonstrate that EGFP and EGFP fusion proteins inhibit polyubiquitination, a posttranslational modification that controls a wide variety of cellular processes, like activation of kinase signalling or protein degradation by the proteasome. As a consequence, the NF-κB and JNK signalling pathways are less responsive to activation, and the stability of the p53 tumour suppressor is enhanced in cell lines and in vivo. In view of the emerging role of polyubiquitination in the regulation of numerous cellular processes, the use of EGFP as a live cell reporter should be carefully considered.
Molecular markers associated with outcome and metastasis in human pancreatic cancer
Van den Broeck Anke,Vankelecom Hugo,Van Eijsden Rudy,Govaere Olivier
Journal of Experimental & Clinical Cancer Research , 2012, DOI: 10.1186/1756-9966-31-68
Abstract: Background Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Methods We performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e. good outcome (OS and DFS > 50 months, n = 7) versus bad outcome (OS < 19 months and DFS < 7 months, n = 10). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue (n = 11). Results The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components such as ITGB1 and EPHA2 were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/β-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with β-catenin being also highly upregulated in metastatic tissue. Conclusions Components of the integrin and ephrin pathways and EMT related genes, might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis.
Metabolic Impact of Adult-Onset, Isolated, Growth Hormone Deficiency (AOiGHD) Due to Destruction of Pituitary Somatotropes
Raul M. Luque,Qing Lin,José Córdoba-Chacón,Papasani V. Subbaiah,Thorsten Buch,Ari Waisman,Hugo Vankelecom,Rhonda D. Kineman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015767
Abstract: Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre+/?,iDTR+/? offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre?/?,iDTR+/? mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes.
The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis
Jasper Wouters, Marguerite Stas, Lies Gremeaux, Olivier Govaere, Anke Van den broeck, Hannelore Maes, Patrizia Agostinis, Tania Roskams, Joost J. van den Oord, Hugo Vankelecom
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076550
Abstract: Melanoma remains the most lethal skin cancer, mainly because of high resistance to therapy. Side population (SP) cells are found in many types of cancer and are usually enriched in therapy-resistant as well as tumorigenic cells. Here, we identified a Hoechst dye-effluxing SP in a large series of human melanoma samples representing different progression phases. The SP size did not change with disease stage but was correlated with the prognostic “Breslow’s depth” in the primary (cutaneous) tumors. When injected into immunodeficient mice, the SP generated larger tumors than the bulk “main population” (MP) melanoma cells in two consecutive generations, and showed tumorigenic capacity at lower cell numbers than the MP. In addition, the SP reconstituted the heterogeneous composition of the human A375 melanoma cell line, and its clonogenic activity was 2.5-fold higher than that of the MP. Gene-expression analysis revealed upregulated expression in the melanoma SP (versus the MP) of genes associated with chemoresistance and anti-apoptosis. Consistent with these molecular characteristics, the SP increased in proportion when A375 cells were exposed to the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating condition of hypoxia. In addition, the SP showed enhanced expression of genes related to cell invasion and migration, as well as to putative (melanoma) cancer stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected in a number of tumor cells in human melanomas, and in particular in clusters at the invasive front of the primary tumors. Together, our findings support that the human melanoma SP is enriched in tumorigenic and chemoresistant capacity, considered key characteristics of CSC. The melanoma SP may therefore represent an interesting therapeutic target.
Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
Anke Van den broeck, Hugo Vankelecom, Wouter Van Delm, Lies Gremeaux, Jasper Wouters, Joke Allemeersch, Olivier Govaere, Tania Roskams, Baki Topal
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073968
Abstract: In many types of cancers, a side population (SP) has been identified based on high efflux capacity, thereby enriching for chemoresistant cells as well as for candidate cancer stem cells (CSC). Here, we explored whether human pancreatic ductal adenocarcinoma (PDAC) contains a SP, and whether its gene expression profile is associated with chemoresistance, CSC and prognosis. After dispersion into single cells and incubation with Hoechst dye, we analyzed human PDAC resections specimens using flow cytometry (FACS). We identified a SP and main population (MP) in all human PDAC resection specimens (n = 52) analyzed, but detected immune (CD45+) and endothelial (CD31+) cells in this fraction together with tumor cells. The SP and MP cells, or more purified fractions depleted from CD31+/CD45+ cells (pSP and pMP), were sorted by FACS and subjected to whole-genome expression analysis. This revealed upregulation of genes associated with therapy resistance and of markers identified before in putative pancreatic CSC. pSP gene signatures of 32 or 10 up- or downregulated genes were developed and tested for discriminatory competence between pSP and pMP in different sets of PDAC samples. The prognostic value of the pSP genes was validated in a large independent series of PDAC patients (n = 78) using nCounter analysis of expression (in tumor versus surrounding pancreatic tissue) and Cox regression for disease-free and overall survival. Of these genes, expression levels of ABCB1 and CXCR4 were correlated with worse patient survival. Thus, our study for the first time demonstrates that human PDAC contains a SP. This tumor subpopulation may represent a valuable therapeutic target given its chemoresistance- and CSC-associated gene expression characteristics with potential prognostic value.
A Generalization of Cramer’s Rule  [PDF]
Hugo Leiva
Advances in Linear Algebra & Matrix Theory (ALAMT) , 2015, DOI: 10.4236/alamt.2015.54016
Abstract:

In this paper, we find two formulas for the solutions of the following linear equation \"\"\"\", where \"\" is a \"\" real matrix. This system has been well studied since the 1970s. It is known and simple proven that there is a solution for all \"\" if, and only if, the rows of A are linearly independent, and the minimum norm solution is given by the Moore-Penrose inverse formula, which is often denoted by \"\" ; in this case, this solution is given by \"\". Using this formula, Cramer’s Rule and Burgstahler’s Theorem (Theorem 2), we prove the following representation for this solution

\"\"

\"\", where \"\" are the row vectors of the matrix A. To the best of our knowledge and looking in to many Linear Algebra books, there is not formula for this solution depending on determinants. Of course, this formula coincides with the one given by Cramer’s Rule when \"\".

Gold nanoclusters as colloidal catalysts for oxidation of long chain aliphatic 1,2-diols in alcohol solvents
P. G. N. Mertens,I. F. J. Vankelecom,P. A. Jacobs,D. E. De Vos
Gold Bulletin , 2005, DOI: 10.1007/BF03215255
Abstract: Long chain aliphatic 1,2-diols like 1,2-hexanediol and 1,2-octanediol can be converted to the corresponding α-hydroxy-alkanoates with total chemoselectivity, in an oxidation catalyzed by an aqueous gold sol under O2 atmosphere. The sol is stabilized with poly(vinylalcohol), and the reaction is performed in alcohol solvents. Two methods are proposed for the efficient recycling of the colloidal Au catalyst. Firstly a solvent-resistant membrane filtration can be applied. As the membrane material, poly(dimethylsiloxane) is chosen. Secondly, in appropriate conditions, the reaction proceeds in the liquid biphasic mode, and the aqueous Au sol can be recycled by phase separation. Using either of both approaches, the colloidal stability and catalytic activity can be preserved over several recycles.
A Characterization of Semilinear Surjective Operators and Applications to Control Problems  [PDF]
Edgar Iturriaga, Hugo Leiva
Applied Mathematics (AM) , 2010, DOI: 10.4236/am.2010.14033
Abstract: In this paper we characterize a broad class of semilinear surjective operators given by the following formula where Z are Hilbert spaces, and is a suitable nonlinear function. First, we give a necessary and sufficient condition for the linear operator to be surjective. Second, we prove the following statement: If and is a Lipschitz function with a Lipschitz constant small enough, then and for all the equation admits the following solution .We use these results to prove the exact controllability of the following semilinear evolution equation , , where , are Hilbert spaces, is the infinitesimal generator of strongly continuous semigroup in the control function belong to and is a suitable function. As a particular case we consider the semilinear damped wave equation, the model of vibrating plate equation, the integrodifferential wave equation with Delay, etc.
Archaelogy, Paleoindian Research and Lithic Technology in the Middle Negro River, Central Uruguay  [PDF]
Hugo G. Nami
Archaeological Discovery (AD) , 2013, DOI: 10.4236/ad.2013.11001
Abstract: The Negro river is the most important inner fluvial course in Uruguay. Its basin, mainly the middle portion, has produced an unusual archaeological record characterized by a significant evidence of Paleoindian remains. Systematic archaeological research allowed conducting a number of field and laboratory activities. The identification of Paleoindian vestiges and buried sites was a significant focus of this investigation. The advances on surveys and excavations in Los Molles and Minas de Callorda sites are reported. Different dating methods yielded the first dates in the area and diverse technological analyses on lithic artifacts allow recognizing the existence of unreported techniques and reduction strategies. Functional studies with special attention to Paleo-South American vestiges permitted to identify diverse micro-wear clues. Finally, the role of river basins in the peopling of the eastern part of the southern cone and the hypothesis about the origin of the fishtail pattern is discussed.
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