Abstract：
:The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Ras(mt). Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras(mt) is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Ras(mt) activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras(mt). Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras(mt) activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease.
journal_name
Int J Biol Scijournal_title
International journal of biological sciencesauthors
Logsdon CD,Lu Wdoi
10.7150/ijbs.15020subject
Has Abstractpub_date
2016-01-28 00:00:00pages
338-46issue
3issn
1449-2288pii
ijbsv12p0338journal_volume
12pub_type
杂志文章,评审abstract：:Background and aims: Dysfunction of the immune regulatory system plays a role in the pathogenesis of allergic rhinitis (AR). The underlying mechanism needs to be further investigated. Published data indicate that soluble CD83 (sCD83) has immune regulatory activities. This study aims to investigate the role of sCD83 in...
journal_title：International journal of biological sciences
pub_type： 杂志文章
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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更新日期：2010-08-03 00:00:00
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journal_title：International journal of biological sciences
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更新日期：2016-01-28 00:00:00
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journal_title：International journal of biological sciences
pub_type： 杂志文章,评审
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更新日期：2007-10-25 00:00:00
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journal_title：International journal of biological sciences
pub_type： 杂志文章
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更新日期：2012-01-01 00:00:00
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journal_title：International journal of biological sciences
pub_type： 杂志文章,评审
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更新日期：2009-09-04 00:00:00
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journal_title：International journal of biological sciences
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更新日期：2019-09-07 00:00:00
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journal_title：International journal of biological sciences
pub_type： 杂志文章
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更新日期：2011-04-15 00:00:00
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journal_title：International journal of biological sciences
pub_type： 杂志文章
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更新日期：2013-04-29 00:00:00
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journal_title：International journal of biological sciences
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更新日期：2016-12-07 00:00:00
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journal_title：International journal of biological sciences
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更新日期：2007-02-06 00:00:00
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
pub_type： 杂志文章,评审
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更新日期：2012-01-01 00:00:00
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journal_title：International journal of biological sciences
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更新日期：2017-07-18 00:00:00
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
pub_type： 杂志文章,评审
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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journal_title：International journal of biological sciences
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doi：10.7150/ijbs.5855
更新日期：2013-05-15 00:00:00
