2,672 research outputs found
Hepatocellular Carcinoma as a Paradigm for a Systemic Evolutionary Approach to Cancer
No full textThe systemic evolutionary theory of cancer pathogenesis posits that cancer is generated by the de-emergence of the eukaryotic cell system and by the reappearance of its ancestral subsystems, the archaea (genetic material and cytoplasm) and the prokaryote (mitochondria), which operate autonomously or uncoordinatedly. This unpaired coordination can be caused by changes in the eukaryote environment, mainly inflammation, damage to mitochondrial DNA or to mitochondrial membranes by viruses, chemicals, hydrogenated fatty acids in foods, and damage to nuclear DNA controlling mitochondria energy production or metabolic pathways including glycolysis. Here, we propose that an “energy package” is constantly required by the cell to maintain its differentiated status. When the energy flow works normally, the two subsystems, the archaea and the prokaryote, are perfectly integrated and there is no prevalence of one system on the other, so that cellular differentiation is maintained. However, as a consequence of a long-lasting injury (e.g. chronic inflammation), the energy at tissue level is restricted and this may cause, over time, the gradual decoupling of the two subsystems with the “prokaryote” subsystem that becomes predominant. The cirrhotic liver represents a paradigmatic scenario whereby this process may occur, due to altered vascular bed, fibrosis and reduction of the oxygen availability. The prevalence of the “prokaryote” subsystem may explain the metabolic alterations seen in liver cancer cells as well as the capacity for proliferation and invasion, especially toward areas of major oxygen availability (e.g. arterialization of portal vein in the liver). This approach highlights the notion that tissue integrity is essential for the proper flow and availability of energy for the maintenance of cellular homeostatic functions
Plasma cholesterol and lipoprotein levels in relation to tumor aggressiveness and survival in HCC patients
No full textAbstract
Background and Aims: Hepatocellular carcinoma is associated with several chronic liver diseases, especially chronic hepatitis B virus, hepatitis C virus, and alcoholism. It is increasingly appreciated that obesity/metabolic syndrome is also associated with chronic liver disease and subsequent hepatocellular carcinoma. Methods: We retrospectively investigated the serum lipid profiles in a large hepatocellular carcinoma cohort, associated predominantly with the hepatitis B virus, hepatitis C virus, alcohol or nonalcoholic steatohepatitis. The cohort was examined both as a whole, as well as stratified by etiology. Results: We found significant associations between parameters of hepatocellular carcinoma biology such as maximum tumor diameter, portal vein thrombosis, tumor multifocality or alpha-fetoprotein levels and individual lipid components, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and body mass index. In a final multiple linear regression model considering all lipid variables together, only high-density lipoprotein cholesterol was significantly associated with the tumor Tumor Aggressiveness Index. High-density lipoprotein cholesterol was found to have a statistically higher hazard ratio for death than low high-density lipoprotein cholesterol levels (Cox). On examination by etiological group, alpha-fetoprotein levels were significantly higher in patients with hepatitis C virus compared to those with alcohol or nonalcoholic steatohepatitis, but maximum tumor diameter, tumor multifocality and portal vein thrombosis were similar across etiological groups. Nonalcoholic steatohepatitis patients had significantly less cirrhosis than other groups and hepatitis B virus patients had significantly higher cholesterol and low-density lipoprotein cholesterol levels than hepatitis C virus patients. Conclusions: This is the first report, to our knowledge, of a relationship between serum lipid parameters and indices of hepatocellular carcinoma growth, invasion and aggressiveness, as well as with survival
MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma
No full textSorafenib is the only approved systemic treatment for advanced hepatocellular carcinoma patients and all the recently published randomized controlled trials on new systemic drugs have been unsuccessful. This is likely due to a lack of understanding of tumor progression, molecular drivers, and liver toxicity, as well as flaws in trial design. An important signaling pathway in hepatocarcinogenesis is the MEK cascade involved in various cellular responses, including adaptation and survival. A key role in this cascade is played by MEK, of which MEK 1/2 represent the prototypes and an interesting target for new oncological drugs. This review analyzes recent developments and future perspectives on the role of MEK inhibitors in hepatocellular carcinoma treatment
Phase-Function Normalization in the 3-D Discrete-Ordinates Solution of Radiative Transfer – PART I: Conservation of Scattered Energy and Asymmetry Factor
No full textThe conditions for which conversation of scattered energy and phase-function asymmetry factor after discrete-ordinates methods (DOM) directional discretization for 3-D radiative transfer in anisotropic scattering media breaks down are examined. Directional discretization in anisotropic scattering media is found to alter the scattering asymmetry factor—a second-type of ‘‘false scattering.’’ Phase-function normalization which conserves scattered energy alone cannot correct this problem, and conservation of the asymmetry factor is simultaneously required. A normalization technique developed by the authors, which was successfully tested in 2-D asymmetric cylindrical-coordinate radiative transfer analysis, is intensively examined and validated with benchmark problems in 3-D Cartesian coordinates. In Part I of this study, the degree of anisotropy for which normalization is necessary to conserve these inherent quantities is presented for various phase-function approximations and discrete quadrature sets.Peer reviewed
Phase-Function Normalization in the 3-D Discrete-Ordinates Solution of Radiative Transfer – PART II: Benchmark Comparisons
No full textRadiative transfer in a cubic enclosure, subject to varying conditions, is determined using the discrete-ordinates method (DOM) with the two normalization techniques introduced in Part I of this study. Their predictions are compared with Monte Carlo simulations. For all cases, false scattering due to directional discretization cannot be corrected when the old technique, which solely conserves scattered energy, is implemented; and thus, signifi- cant discrepancies exist when compared to Monte Carlo results. The new technique, which conserves both scattered energy and the asymmetry factor, is able to retain original scatter- ing properties after directional discretization, leading to improved accuracy when compared to Monte Carlo. In addition, a parametric study is presented to gauge the impact of asym- metry-factor conservation on media with various optical properties. Finally, the impact of normalization is investigated for both ultrafast radiative transfer and ballistic incidence with varying incident angle.Peer reviewed
Is this an author I see before me? 'Anonymous' and the interminable Shakespeare question
No full textWas Shakespeare a fraud? In a departure from his usual blockbuster fare, director Roland Emmerich proposes in 'Anonymous' that the relatively obscure Edward de Vere, the Earl of Oxford, was the true author of the Bard's oeuvre. Brian McFarlane considers a controversy that is seemingly without end, and discusses the relevance of authorship to the plays of Shakespeare - and to contemporary cinema
Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro
No full textProtein Biomarkers in the Management of Hepatocellular Carcinoma: Novel Combinatory Approaches
No full textSeveral serum biomarkers have been proposed for diagnosis and assessment of prognosis in hepatocellular carcinoma (HCC) but none has entered routine clinical practice despite achieving reasonably high values for sensitivity, specificity and area under the ROC curve. After reviewing some of these we show how the performance of individual biomarkers may be enhanced by combining several different biomarkers in rigorously developed and validated statistical models. In such models the constituent biomarkers are considered as continuous variables rather than, as in conventional clinical practice, dichotomised with the application of cut-off points. This approach maximises the information extracted from the available data. We illustrate this concept with reference to the ‘GALAD’ model for diagnosis and the ‘BALAD’ model for prognosis both of which improve the utility of the individual constituent biomarkers
The reception of Norwegian-South African musical interactions : a study of selected musical collaborations from the 19th century to the present
No full textIncludes bibliographical references (leaves 166-186).This research project investigates the perception of Norwegian-South African musical interactions. It is an in depth study of four recent cases of musical collaboration between Norwegian and South African musicians with an emphasis on the Norwegian musicians perception of "the Other". Furthermore, it is an investigation into the fusion of music within these collaborations by assessing the discernible "South African flavour" and "Norwegian flavour" and an analysis of how they fuse
Poems by Tomaž Šalamun Translated by Brian Henry
No full textMercy Viva Italia, World Champions, 1982 I and You
Tomaž Šalamun (1941-2014) published more than 50 books of poetry in Slovenia. Translated into over 25 languages, his poetry received numerous awards, including the Jenko Prize, the Prešeren Prize, the European Prize for Poetry, and the Mladost Prize. In the 1990s, he served for several years as the Cultural Attaché for the Slovenian Embassy in New York, and later held visiting professorships at various universities in the U.S.
Brian Henry is the author of eleven books of poetry, most recently Permanent State (Threadsuns, 2020), and the prose book Things Are Completely Simple: Poetry and Translation (Parlor, 2022). He has translated Tomaž Šalamun’s Woods and Chalices (Harcourt, 2008), Aleš Debeljak’s Smugglers (BOA Editions, 2015), and five books by Aleš Šteger. His work has received numerous honors, including two NEA fellowships, the Alice Fay di Castagnola Award, a Howard Foundation fellowship, and the Best Translated Book Award
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