Cytosolic phospholipase A2{alpha} and cancer: a role in tumor angiogenesis.
Cytosolic phospholipase A2{alpha} and cancer: a role in tumor angiogenesis.
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胞浆磷脂酶 A2{α} 和癌症：在肿瘤血管生成中的作用。
DOI：
10.1093/jnci/djq324
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Salvucci,Ombretta
中科院分区：
文献类型：
--
作者：
Tosato,Giovanna;Segarra,Marta;Salvucci,Ombretta
1378 Editorials| JNCI Vol. 102, Issue 18| September 22, 2010 production of eicosanoids (including prostaglandins, thromboxanes, and leukotrienes), which are biologically active lipids implicated in inflammation, cancer, and other cellular processes (2). cPLA2α also contributes to production of platelet-activating factor, another mediator of inflammation, which is formed from phospholipids generated from the release of arachidonic acid (3). The cPLA2α gene was mapped to human chromosome 1q25, proximal to the gene coding for cyclooxygenase-2, which is downstream of cPLA2α in the biochemical pathway of eicosanoid production (4). The promoter region of cPLA2α contains binding sites for the transcription factor nuclear factor kappa-B (5) and response elements for glucocorticoids and interferons (6)—all modulators of inflammation—raising the possibility of coordinated regulation of inflammation mediated by cPLA2α expression. Various cytokines and phosphorylation of signal transducer and activator of transcription 3 promote cPLA2α expression in smooth muscle cells (6), and activation of the Toll-like receptor 3 induces cPLA2α activation in myeloid cells (7). Mice that are genetically deficient in cPLA2α, which are generally healthy but less fertile than normal mice (8, 9), have been useful in confirming the central role of cPLA2α in the arachidonic acid pathway and in linking the enzyme to the pathogenesis of various disease states, particularly those involving inflammation. For example, cPLA2α-deficient mice are remarkably resistant to collagen-induced arthritis (10), anaphylaxis (9), acute respiratory stress syndrome (11), experimental autoimmune encephalomyelitis (12), and inflammation following reperfusion of hypoxic tissue (ischemia reperfusion injury)(8, 13).In view of the important role that inflammation plays in the development of some of the most prevalent human cancers (2, 14), it is not surprising that cPLA2α has been implicated in carcinogenesis. For example, mice that carry a germline mutation in the adenoma polyposis coli gene (Apc Min/+) and lack cPLA2α expression (cPLA2α J/J) develop statistically significantly fewer tumors in the small intestine compared with Apc Min/+ controls that express cPLA2α (15), and cPLA2α-deficient mice are substantially less likely than littermate controls that are not deficient in cPLA2α to develop urethane-induced lung tumors (16) and spontaneous lung metastasis from primary tumors (17). In this issue of the Journal, Linkous et al.(18) confirm a role for cPLA2α in tumor development and progression by using syngeneic glioblastoma and Lewis lung carcinomas cell lines injected subcutaneously in cPLA2α-deficient mice. Remarkably, the authors showed that none of the cPLA2α-deficient mice developed glioblastomas, whereas all of the control mice that expressed cPLA2α did, and that 50% of the cPLA2α-deficient mice experienced a regression of the Lewis lung carcinomas, whereas none of the control mice did. Because the experimental system used cPLA2α-deficient mice bearing tumors derived from tumor cell lines that were not cPLA2α deficient, the results implicate cPLA2α from the normal tumor microenvironment as an important mediator of tumor development and progression. How does cPLA2α expressed in the tumor microenvironment promote tumor development and progression? Cells in the tumor microenvironment and their products can exert diverse tumorpromoting effects: They can stimulate the proliferation and survival of malignant cells, facilitate dissemination of metastases,
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使用生长抑素评估一定肥胖范围内体内胰岛素抵抗的简化方法
影响因子：
7.7
作者：
M. Nagulesparan;P. Savage;R. Unger;P. Bennett
通讯作者：
P. Bennett
回复：“解释前瞻性观察研究中的多个逻辑回归系数”
影响因子：
5
作者：
B. Levin;J. Fleiss
通讯作者：
J. Fleiss
中度肥胖对健康的影响。
影响因子：
4.9
作者：
B. Larsson;P. Björntorp;G. Tibblin
通讯作者：
G. Tibblin
DOI：
10.1161/01.atv.5.4.311
发表时间：
1985
期刊：
Arteriosclerosis (Dallas, Tex.)
影响因子：
--
作者：
Stern,MP;Rosenthal,M;Haffner,SM
通讯作者：
Haffner,SM
影响因子：
105.7
作者：
LARSSON, B;SVARDSUDD, K;TIBBLIN, G
通讯作者：
TIBBLIN, G