11. |
- Liu, Meng, 1976, et al.
(författare)
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Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
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Tidskriftsartikel (refereegranskat)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
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12. |
- Mangles, S. P. D., et al.
(författare)
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Self-injection threshold in self-guided laser wakefield accelerators
- 2012
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Ingår i: Physical Review Special Topics. Accelerators and Beams. - 1098-4402. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- A laser pulse traveling through a plasma can excite large amplitude plasma waves that can be used to accelerate relativistic electron beams in a very short distance-a technique called laser wakefield acceleration. Many wakefield acceleration experiments rely on the process of wave breaking, or self-injection, to inject electrons into the wave, while other injection techniques rely on operation without self-injection. We present an experimental study into the parameters, including the pulse energy, focal spot quality, and pulse power, that determine whether or not a wakefield accelerator will self-inject. By taking into account the processes of self-focusing and pulse compression we are able to extend a previously described theoretical model, where the minimum bubble size k(p)r(b) required for trapping is not constant but varies slowly with density and find excellent agreement with this model.
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