78 research outputs found
Nuclear physics and astrophysics of the r-process
Some nuclear and astrophysical aspects of the r-process are discussed.
Particular attention is paid to observations of abundances in metal-poor stars
and their implications for the astrophysical site and yield patterns of the
r-process. The effects of supernova neutrinos and related nuclear processes on
the yield patterns are explored. The uncertainties in the theoretical nuclear
input for the r-process are discussed and the need for experimental data is
emphasized.Comment: 10 pages, 5 figures, Invited Talk at the International Nuclear
Physics Conference (INPC2004
The Origin of the Heavy Elements: Recent Progress in the Understanding of the r-Process
There has been significant progress in the understanding of the r-process
over the last ten years. The conditions required for this process have been
examined in terms of the parameters for adiabatic expansion from high
temperature and density. There have been many developments regarding
core-collapse supernova and neutron star merger models of the r-process.
Meteoritic data and observations of metal-poor stars have demonstrated the
diversity of r-process sources. Stellar observations have also found some
regularity in r-process abundance patterns and large dispersions in r-process
abundances at low metallicities. This review summarizes the recent results from
parametric studies, astrophysical models, and observational studies of the
r-process. The interplay between nuclear physics and astrophysics is
emphasized. Some suggestions for future theoretical, experimental, and
observational studies of the r-process are given.Comment: typos in Eqs. (30) and (31) correcte
Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation
Safe approaches for camptothecin delivery: Structural analogues and nanomedicines
[EN] Twenty-(S)-camptothecin is a strongly cytotoxic molecule with excellent antitumor activity over a wide spectrum of human cancers. However, the direct formulation is limited by its poor water solubility, low plasmatic stability and severe toxicity, which currently limits its clinical use. As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines. In this review, we summarize recent advances in the design, synthesis and development of camptothecin molecular derivatives and supramolecular vehicles, following a systematic classification according to structure-activity relationships (structural analogues) or chemical nature (nanomedicines). A series of organic, inorganic and hybrid materials are presented as nanoplatforms to overcome camptothecin restrictions in administration, biodistribution, pharmacokinetics and toxicity. Nanocarriers which respond to a variety of stimuli endogenously (e.g., pH, redox potential, enzyme activity) or exogenously (e.g., magnetic field, light, temperature, ultrasound) seem the best positioned therapeutic materials for optimal spatial and temporal control over drug release. The main goal of this review is to be used as a source of relevant literature for others interested in the field of camptothecin-based therapeutics. To this end, final remarks on the most important formulations currently under clinical trial are provided. (C) 2016 Elsevier B.V. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects MAT2012-39290-C02-02 and SEV-2012-0267) is gratefully acknowledged. Dr. E.M. Rivero thanks the Cursol Foundation for a post-doctoral scholarship.Botella Asuncion, P.; Rivero-Buceta, EM. (2017). Safe approaches for camptothecin delivery: Structural analogues and nanomedicines. Journal of Controlled Release. 247:28-54. https://doi.org/10.1016/j.jconrel.2016.12.023S285424
Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma
Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models
Stimulus-dependent differences in signalling regulate epithelial-mesenchymal plasticity and change the effects of drugs in breast cancer cell lines
Barriers and gateways: a study of nursing students’ utilisation of learning support resources
Threat(s) and conformity deconstructed: Perceived threat of infectious disease and its implications for conformist attitudes and behavior
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