| 1. |
- Block, Keith I., et al.
(författare)
-
Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
-
Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
-
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.
|
|
| 2. |
- Liang, Y, et al.
(författare)
-
Mitigation of Type-I ELMs with n =2 Fields on JET
- 2012
-
Ingår i: 24th IAEA Fusion Energy Conference, 8-13 October 2012. ; , s. EX/P4-23-
-
Konferensbidrag (refereegranskat)abstract
- Recently, strong mitigation of Type-I Edge Localized Modes (ELMs) has been observed with application of the n = 2 field in high collisionality (nu^*_e=2.0) H-mode plasma on JET tokamak with ITER-like wall. In this experiment, the EFCC power supply system has been enhanced with a coil current up to 88kAt (twice than before). With an n = 2 field, the large type-I ELMs with frequency of ~ 45 Hz was replaced by the high frequency (few hundreds Hz) small ELMs. No density pump-out was observed during an application of the n = 2 field. The influence of the n = 2 field on the core and the pedestal electron pressure profiles is within the error bar and it can be neglected. During the normal type-I ELM H-mode phase, the maximal surface temperature (Tmax) on the outer divertor plate was overall increasing and associated with large periodical variation due to the type-I ELMs. However, during an application of the n = 2 field, Tmax was saturated and has only small variation in few degrees due to the small mitigated ELMs. Splitting of the outer strike point has been observed during the strong mitigation of the type-I ELMs.
|
|
