| 1. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Ge, Jing, et al.
(författare)
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Bringing light into the dark triplet space of molecular systems
- 2015
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 17:19, s. 13129-13136
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Tidskriftsartikel (refereegranskat)abstract
- A molecule or a molecular system always consists of excited states of different spin multiplicities. With conventional optical excitations, only the (bright) states with the same spin multiplicity of the ground state could be directly reached. How to reveal the dynamics of excited (dark) states remains the grand challenge in the topical fields of photochemistry, photophysics, and photobiology. For a singlet-triplet coupled molecular system, the (bright) singlet dynamics can be routinely examined by conventional femtosecond pump-probe spectroscopy. However, owing to the involvement of intrinsically fast decay channels such as intramolecular vibrational redistribution and internal conversion, it is very difficult, if not impossible, to single out the (dark) triplet dynamics. Herein, we develop a novel strategy that uses an ultrafast broadband white-light continuum as a excitation light source to enhance the probability of intersystem crossing, thus facilitating the population flow from the singlet space to the triplet space. With a set of femtosecond time-reversed pump-probe experiments, we report on a proof-of-concept molecular system (i.e., the malachite green molecule) that the pure triplet dynamics can be mapped out in real time through monitoring the modulated emission that occurs solely in the triplet space. Significant differences in excited-state dynamics between the singlet and triplet spaces have been observed. This newly developed approach may provide a useful tool for examining the elusive dark-state dynamics of molecular systems and also for exploring the mechanisms underlying molecular luminescence/photonics and solar light harvesting.
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| 3. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 4. |
- Wang, Zongwei, et al.
(författare)
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Broad targeting of angiogenesis for cancer prevention and therapy
- 2015
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; S1044-579X:15, s. 00002-00004
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Forskningsöversikt (refereegranskat)abstract
- Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature - is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies.
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| 5. |
- Wu, Bo, et al.
(författare)
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Visible-Light Photoexcited Electron Dynamics of Scandium Endohedral Metallofullerenes : The Cage Symmetry and Substituent Effects
- 2015
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:27, s. 8769-8774
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Tidskriftsartikel (refereegranskat)abstract
- Endohedral metallofullerenes (EMFs) have become an important class of molecular materials for optoelectronic applications. The performance of EMFs is known to be dependent on their symmetries and characters of the substituents, but the underlying electron dynamics remain unclear. Here we report a systematic study on several scandium EMFs and representative derivatives to examine the cage symmetry and substituent effects on their photoexcited electron dynamics using ultrafast transient absorption spectroscopy. Our attention is focused on the visible-light (530 nm as a demonstration) photoexcited electron dynamics, which is of broad interest to visible-light solar energy harvesting but is considered to be quite complicated as the visible-light photons would promote the system to a high-lying energy region where dense manifolds of electronic states locate. Our ultrafast spectroscopy study enables a full mapping of the photoinduced deactivation channels involved and reveals that the long-lived triplet exciton plays a decisive role in controlling the photoexcited electron dynamics under certain conditions. More importantly, it is found that the opening of the triplet channels is highly correlated to the fullerene cage symmetry as well as the electronic character of the substituents.
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