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  • 1
    Language: English
    In: Cancer, 2019-08-01, Vol.125 (15), p.2693-2703
    Description: Background Desmoid tumors (DTs) are rare and understudied fibroblastic lesions that are frequently recurrent and locally invasive. DT patients often experience chronic pain, organ dysfunction, decrease in quality of life, and even death. Methods Sorafenib has emerged as a promising therapeutic strategy, which has led to the first randomized phase 3 clinical trial devoted to DTs. Concurrently, we conducted a comprehensive analysis of sorafenib efficacy in a large panel of desmoid cell strains to probe for response mechanism. Results We found distinctive groups of higher‐ and lower‐responder cells. Clustering the lower‐responder group, we observed that CTNNB1 mutation was determinant of outcome. Our results revealed that a lower dose of sorafenib was able to inhibit cell viability, migration, and invasion of wild‐type and T41A‐mutated DTs. Apoptosis induction was observed in those cells after treatment with sorafenib. On the other hand, the lower dose of sorafenib was not able to inhibit cell viability, migration, or invasion or to induce apoptosis in the S45F‐mutated DTs. The investigation of autophagy showed the dependency of S45F‐mutated DTs on this pathway as a part of cell survival mechanism. Significantly, when autophagy was inhibited genetically or pharmacologically in the S45F mutant cell strains, sensitivity to sorafenib was restored. Conclusions Our findings suggest that the response to sorafenib differs when comparing S45F‐mutated DTs and T41A‐mutated or wild‐type DTs. Furthermore, the combination of hydroxychloroquine and sorafenib enhances the antiproliferative and proapoptotic effects in S45F‐mutated DT cells, suggesting that profiling β‐catenin status could guide clinical management of desmoid patients who are considering sorafenib treatment. Sorafenib treatment is more effective in wild‐type and T41A‐mutated DT cell strains. The resistance observed in S45F‐mutated cells is driven by elevated basal autophagy and could be reversed by autophagy inhibition.
    Subject(s): Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Autophagy ; Autophagy - drug effects ; Cell migration ; Cell survival ; Cell viability ; Clustering ; Dependence ; Desmoid tumors ; Female ; Fibromatosis, Aggressive - drug therapy ; Humans ; Hydroxychloroquine ; Inhibition ; Lesions ; Life Sciences & Biomedicine ; Male ; Mutation ; Oncology ; Pain ; Patients ; Phagocytosis ; Pharmacology ; Profiling ; Quality of life ; Science & Technology ; Sorafenib ; Sorafenib - pharmacology ; Sorafenib - therapeutic use ; Therapeutic combination ; Tumors
    ISSN: 0008-543X
    E-ISSN: 1097-0142
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 2
    Language: English
    In: Journal of physical and chemical reference data, 2019-06, Vol.48 (2), p.23101
    Description: Accurate, empirical rovibronic energy levels, with associated uncertainties, are determined for the lowest seven electronic states of the 16O2 molecule using the MARVEL (Measured Active Rotational-Vibrational Energy Levels) algorithm. After careful analysis and validation of 30 671 rovibronic transitions (including 24 376 measured and 6295 artificial transitions), collected from 91 publications, 4279 empirical rovibronic energy levels are determined. The highly accurate empirical (MARVEL) energy database is then augmented with rovibronic energies obtained from accurate effective Hamiltonians for the lowest six electronic states, establishing a hybrid database containing 15 946 rovibronic energy levels. Based on this hybrid database, complete up to the first dissociation limit, 41 260 cm−1, an accurate temperature-dependent ideal-gas partition function, Qint(T), and some related thermochemical functions [isobaric heat capacity, Cpo(T), entropy, So(T), and (absolute) enthalpy, Ho(T)] are derived for 16O2 employing the direct-summation technique. All thermochemical functions are reported, in 1 K increments up to 5000 K, in the supplementary material to this paper.
    Subject(s): Data bases ; Energy ; Entropy ; Heat transfer ; Studies ; Superheroes ; Temperature
    ISSN: 0047-2689
    E-ISSN: 1529-7845
    Source: American Institute of Physics (AIP) Publications
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  • 3
    Language: English
    In: PloS one, 2017, Vol.12 (11), p.e0188859
    Description: Leiomyosarcoma (LMS) is a malignant soft tissue sarcoma (STS) with a dismal prognosis following metastatic disease. Chemotherapeutic intervention has demonstrated to have modest clinical efficacy with no curative potential in LMS patients. Previously, we demonstrated pan-HDAC inhibition to have a superior effect in various complex karyotypic sarcomas. In this study, our goal is to evaluate the therapeutic efficacy of mocetinostat alone and in combination with gemcitabine in LMS. Human leiomyosarcoma (LMS) cell lines were used for in vitro and in vivo studies. Compounds tested included the class I HDAC inhibitor, mocetinostat, and nucleoside analog, gemcitabine. MTS and clonogenic assays were used to evaluate the effect of mocetinostat on LMS cell growth. Cleaved caspase 3/7 analysis was used to determine the effects of mocetinostat on apoptosis. Compusyn software was used to determine in vitro synergy studies for the combination of mocetinostat plus gemcitabine. A LMS xenograft model in SCID mice was used to test the impact of mocetinostat alone, gemcitabine alone and the combination of mocetinostat plus gemcitabine. Mocetinostat abrogated LMS cell growth and clonogenic potential, and enhanced apoptosis in LMS cell lines. The combination of mocetinostat plus gemcitabine exhibited a synergistic effect in LMS cells in vitro. Similarly, mocetinostat combined with gemcitabine resulted in superior anti-LMS effects in vivo. Mocetinostat reduced the expression of gemcitabine-resistance markers RRM1, RRM2, and increased the expression of gemcitabine-sensitivity marker, hENT1, in LMS cells. LMS are aggressive, metastatic tumors with poor prognosis where effective therapeutic interventions are wanting. Our studies demonstrate the potential utility of mocetinostat combined with gemcitabine for the treatment of LMS.
    Subject(s): Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis - drug effects ; Benzamides - administration & dosage ; Biology and Life Sciences ; Cell Division - drug effects ; Cell Line, Tumor ; Chemotherapy, Combination ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Dosage and administration ; Drug Synergism ; Drug therapy ; Gemcitabine ; Humans ; Leiomyosarcoma ; Leiomyosarcoma - drug therapy ; Leiomyosarcoma - pathology ; Medicine and Health Sciences ; People and places ; Pyrimidines - administration & dosage ; Research and analysis methods ; Risk factors ; Usage
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 4
    Language: English
    In: European journal of international law, 2012-02-01, Vol.23 (1), p.97-119
    Description: In the dominant narrative of international law, historical events in space and time are made to fall along an invisible line of progress, from Westphalia in 1648 through the Bretton Woods and San Francisco conferences of 1944 and 1945 to the present day and continuing on through the future to a more just world. Against this, a counter-narrative has emerged which denies the possibility of such linear development and consigns international law to forever tracing an unending circular path between points of idealism and realpolitik. This article examines how international lawyers have created and continue to create these metaphysical geographies of international law. Drawing on the work of the French multi-disciplinary thinkers Gilles Deleuze and Felix Guattari, this article shows that both approaches, and indeed the very concept of international law, can at most only replicate and impose pre-conceived theories and that the imposition of such theories is contrary to the natural patterns of human consciousness. It urges us to see international law rather as but one manifestation of the ongoing struggle between efforts to impose unity on and to control human consciousness and the mind's efforts to break free of such restricting structures. [PUBLICATION ABSTRACT]
    Subject(s): Attorneys ; Congresses and Conventions ; Consciousness ; Evaluation ; France ; Geography ; Geography, Historical ; International Law ; Lawyers ; Metaphysics ; Narratives ; New York ; Space and Time ; Studies ; Usage
    ISSN: 0938-5428
    E-ISSN: 1464-3596
    Source: Hellenic Academic Libraries Link
    Source: Academic Search Ultimate
    Source: HeinOnline Law Journal Library
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: European journal of international law, 2014-03-01, Vol.25 (1), p.25-29
    Description: This article responds to Daniel Bethlehem's assertions that globalization is diminishing the importance of geography, and thereby challenging the Westphalian order on which international law is constructed. It contends that international law does not take geography as it is but actively creates and sustains a state-based geography. It argues that the challenges Bethlehem identifies are not new but are inherent in international law's efforts to impose a state-based order on a global world. The question is not whether international lawyers will respond to these challenges, but how they will respond. Will they follow Bethlehem in reinforcing a statist order, or will they place sovereignty of states in the service of the global human community?
    Subject(s): Attitudes ; Evaluation ; Geography ; Geography, Political ; Geopolitics ; GLOBALISATION ; Globalization ; INTERNATIONAL LAW ; Lawyers ; LEGAL PROFESSION ; Legal studies ; Services ; Social aspects ; Sovereignty ; Statism
    ISSN: 0938-5428
    E-ISSN: 1464-3596
    Source: Hellenic Academic Libraries Link
    Source: Academic Search Ultimate
    Source: HeinOnline Law Journal Library
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Oncogene, 2020-08, Vol.39 (34), p.5589-5600
    Description: Wnt/β-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations are associated with an aggressive phenotype in several of these tumor types and may be associated with therapeutic tolerance. Desmoid tumors typically have a stable genome with β-catenin mutations as a main feature, making these tumors an ideal model to study the changes associated with different types of β-catenin mutations. Here, we show that the apoptosis mechanism is deregulated in β-catenin S45F mutants, resulting in decreased induction of apoptosis in these cells. Our findings also demonstrate that RUNX3 plays a pivotal role in the inhibition of apoptosis found in the β-catenin S45F mutants. Restoration of RUNX3 overcomes this inhibition in the S45F mutants, highlighting it as a potential therapeutic target for malignancies harboring this specific CTNNB1 mutation. While the regulatory effect of RUNX3 in β-catenin is already known, our results suggest the possibility of a feedback loop involving these two genes, with the CTNNB1 S45F mutation downregulating expression of RUNX3, thus providing additional possible novel therapeutic targets for tumors having deregulated Wnt/β-catenin signaling induced by this mutation.
    Subject(s): Abdominal Neoplasms - genetics ; Abdominal Neoplasms - metabolism ; Abdominal Neoplasms - pathology ; Adenomatous Polyposis Coli - genetics ; Adenomatous Polyposis Coli - metabolism ; Adenomatous Polyposis Coli - pathology ; Apoptosis ; Apoptosis - genetics ; beta Catenin - genetics ; beta Catenin - metabolism ; Breast cancer ; Carcinogenesis ; Cell Line, Tumor ; Colorectal carcinoma ; Core Binding Factor Alpha 3 Subunit - genetics ; Core Binding Factor Alpha 3 Subunit - metabolism ; Down-Regulation ; Embryogenesis ; Fibromatosis, Aggressive - genetics ; Fibromatosis, Aggressive - metabolism ; Fibromatosis, Aggressive - pathology ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Genomes ; HEK293 Cells ; Homeostasis ; Humans ; Mutants ; Mutation ; Mutation, Missense ; Phenotypes ; Runx3 protein ; Therapeutic applications ; Therapeutic targets ; Tumors ; Wnt protein ; Wnt Signaling Pathway - genetics ; β-Catenin
    ISSN: 0950-9232
    E-ISSN: 1476-5594
    Source: Alma/SFX Local Collection
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  • 7
    Language: English
    In: Physical review. B, Condensed matter and materials physics, 2012-04, Vol.85 (15)
    Description: The modified Becke-Johnson exchange potential [F. Tran and P. Blaha, Phvs. Rev. Lett. 102. 226401 (20091 (http://dx.doi.org/10.1103/PhvsRevLett. 102.22640111 (TB-mBJ) yields very accurate electronic band structures and gaps for various types of semiconductors and insulators (e.g., sp semiconductors, noble-gas solids, and transition-metal oxides). However, the TB-mBJ potential has, for a few groups of solids, the tendency to underestimate the band gap. This has led us to examine the possibility to further improve over the original TB-mBJ potential by either reparametrizing its coefficients using a larger test set of solids or defining a parametrization for small-/medium-size band-gap semiconductors only. We also checked alternatives to the average of [white triangle down][rho]/[rho] in the unit cell for the determination of parameter c, which determines the amount of the screening contribution. Among these different possibilities, the best one seems to be a reparametrization of the coefficients, which leads to a much more balanced description of the band gaps.
    Subject(s): Balancing ; Band structure of solids ; Condensed matter ; Energy gaps (solid state) ; Exchange ; Insulators ; Oxides ; Semiconductors
    ISSN: 1098-0121
    E-ISSN: 1550-235X
    Source: Single Journals
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  • 8
    Language: English
    In: Physical review. B, 2017-08-01, Vol.96 (5)
    Description: The method based on fast Fourier transforms proposed by G. Román-Pérez and J. M. Soler [Phys. Rev. Lett. 103, 096102 (2009)], which allows for a computationally fast implementation of the nonlocal van der Waals (vdW) functionals, has significantly contributed to making the vdW functionals popular in solid-state physics. However, the Román-Pérez-Soler method relies on a plane-wave expansion of the electron density; therefore it cannot be applied readily to all-electron densities for which an unaffordable number of plane waves would be required for an accurate expansion. In this work, we present the results for the lattice constant and binding energy of solids that were obtained by applying a smoothing procedure to the all-electron density calculated with the linearized augmented plane-wave method. The smoothing procedure has the advantages of being very simple to implement, basis-set independent, and allowing the calculation of the potential. It is also shown that the results agree very well with those from the literature that were obtained with the projector augmented wave method.
    Subject(s): Electron density ; Electrons ; Fast Fourier transformations ; Fourier transforms ; Functionals ; Lattice parameters ; Mathematical analysis ; Plane waves ; Smoothing ; Solid state physics
    ISSN: 2469-9950
    E-ISSN: 2469-9969
    Source: Hellenic Academic Libraries Link
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  • 9
    Language: English
    In: ACS nano, 2011-04-26, Vol.5 (4), p.3003-3009
    Description: The optical properties and charge trapping phenomena observed on oxide nanocrystal ensembles can be strongly influenced by the presence of nanocrystal interfaces. MgO powders represent a convenient system to study these effects due to the well-defined shape and controllable size distributions of MgO nanocrystals. The spectroscopic properties of nanocrystal interfaces are investigated by monitoring the dependence of absorption characteristics on the concentration of the interfaces in the nanopowders. The presence of interfaces is found to affect the absorption spectra of nanopowders more significantly than changing the size of the constituent nanocrystals and, thus, leading to the variation of the relative abundance of light-absorbing surface structures. We find a strong absorption band in the 4.0−5.5 eV energy range, which was previously attributed to surface features of individual nanocrystals, such as corners and edges. These findings are supported by complementary first-principles calculations. The possibility to directly address such interfaces by tuning the energy of excitation may provide new means for functionalization and chemical activation of nanostructures and can help improve performance and reliability for many nanopowder applications.
    Subject(s): first-principles calculations ; metal oxide ; nanocrystals ; nanopowders ; optical absorption
    ISSN: 1936-0851
    E-ISSN: 1936-086X
    Source: Hellenic Academic Libraries Link
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  • 10
    Language: English
    In: Cancer cell international, 2018, Vol.18 (1), p.89-89
    Description: Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) is aggressive with recurrence in 80% and metastasis in 20% of patients. We previously found that miR-133a was significantly underexpressed in liposarcoma tissues. As this miRNA has recently been shown to be a tumor suppressor in many cancers, the objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS. Real-time PCR was used to evaluate expression levels of miR-133a in human DDLPS tissue, normal fat tissue, and human DDLPS cell lines. DDLPS cells were stably transduced with miR-133a vector to assess the effects in vitro on proliferation, cell cycle, cell death, migration, and metabolism. A Seahorse Bioanalyzer system was also used to assess metabolism in vivo by measuring glycolysis and oxidative phosphorylation (OXPHOS) in subcutaneous xenograft tumors from immunocompromised mice. miR-133a expression was significantly decreased in human DDLPS tissue and cell lines. Enforced expression of miR-133a decreased cell proliferation, impacted cell cycle progression kinetics, decreased glycolysis, and increased OXPHOS. There was no significant effect on cell death or migration. Using an in vivo xenograft mouse study, we showed that tumors with increased miR-133a expression had no difference in tumor growth compared to control, but did exhibit an increase in OXPHOS metabolic respiration. Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS.
    Subject(s): Adipocytes ; Apoptosis ; Biotechnology ; Brain tumors ; Cell cycle ; Cell death ; Cell growth ; Cell lines ; Cell migration ; Cell proliferation ; Chromosomes ; Colorectal cancer ; Dedifferentiated liposarcoma ; Glycolysis ; Kinetics ; Liposarcoma ; Mesenchyme ; Metabolism ; Metastases ; Metastasis ; MicroRNAs ; Migration ; miR-133a ; miRNA ; Oxidative metabolism ; Oxidative phosphorylation ; Pathogenesis ; Phosphorylation ; Primary Research ; Respiration ; Sarcoma ; Tissues ; Tumor suppressor genes ; Tumors ; Xenografts
    ISSN: 1475-2867
    E-ISSN: 1475-2867
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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