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- 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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- Guha Sarkar, T., et al.
(författare)
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Cross-correlation of the H I 21-cm signal and Lyα forest: a probe of cosmology : H I 21-cm signal and Lyα
- 2011
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 410:2, s. 1130-1134
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Tidskriftsartikel (refereegranskat)abstract
- Separating the cosmological redshifted 21-cm signal from foregrounds is a major challenge. We present the cross-correlation of the redshifted 21-cm emission from neutral hydrogen (HI) in the post-reionization era with the Ly-alpha forest as a new probe of the large scale matter distribution in the redshift range z=2 to 3 without the problem of foreground contamination. Though the 21-cm and the Ly-alpha forest signals originate from different astrophysical systems, they are both expected to trace the underlying dark matter distribution on large scales. The multi-frequency angular cross-correlation power spectrum estimator is found to be unaffected by the discrete quasar sampling, which only affects the noise in the estimate. We consider a hypothetical redshifted 21-cm observation in a single field of view 1.3 degrees (FWHM) centered at z=2.2 where the binned 21-cm angular power spectrum can be measured at an SNR of 3 sigma or better across the range 500 < l < 4000 . Keeping the parameters of the 21-cm observation fixed, we have estimated the SNR for the cross-correlation signal varying the quasar angular number density n of the Ly-alpha forest survey. Assuming that the spectra have SNR ~5 in pixels of length 44 km/s, we find that a 5 sigma detection of the cross-correlation signal is possible at 600 < l < 2000 with n=4 deg^{-2}. This value of n is well within the reach of upcoming Ly-alpha forest surveys. The cross-correlation signal will be a new, independent probe of the astrophysics of the diffuse IGM, the growth of structure and the expansion history of the Universe.
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