Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer.
Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer.
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DOI：
10.1186/bcr1678
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Howe LR
中科院分区：
文献类型：
--
作者：
Howe LR
许多人类癌症表现出前列腺素（PG）水平升高，这是由于环氧化酶-2 （COX-2）的上调，环氧化酶-2是类二十烷类生物合成的关键酶。COX-2在约40%的浸润性乳腺癌中过表达，在浸润前导管原位癌中过表达的频率更高，广泛的药理学和遗传学证据表明COX酶与肿瘤有关。流行病学分析表明，抑制cox的非甾体抗炎药对人类癌症有保护作用。补充实验研究已经证实，在啮齿动物乳腺癌模型中，传统的非甾体类抗炎药和选择性COX-2抑制剂都能抑制乳腺肿瘤的形成。此外，敲除Cox-2可减少乳腺肿瘤发生和血管生成，相反，转基因Cox-2过表达可诱导肿瘤形成。COX/PG信号作为化学预防靶点的效用已经通过随机对照临床试验确立。然而，这些研究也发现选择性COX-2抑制剂的使用增加了心血管风险。因此，目前的工作方向是寻找更安全的方法来对抗COX/PG信号以预防和治疗癌症，特别关注PGE2的调控和信号，因为PGE2是一种关键的致瘤性前列腺素。
Many human cancers exhibit elevated prostaglandin (PG) levels due to upregulation of cyclooxygenase-2 (COX-2), a key enzyme in eicosanoid biosynthesis. COX-2 over-expression has been observed in about 40% of cases of invasive breast carcinoma and at a higher frequency in preinvasive ductal carcinoma in situ tumors, Extensive pharmacologic and genetic evidence implicates COX enzymes in neoplasia. Epidemiologic analyses demonstrate a protective effect of COX-inhibiting nonsteroidal anti-inflammatory drugs with respect to human cancer. Complementary experimental studies have established that both conventional nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors suppress mammary tumor formation in rodent breast cancer models. Furthermore, knocking out Cox-2 reduces mammary tumorigenesis and angiogenesis, and, conversely, transgenic COX-2 over-expression induces tumor formation. The utility of COX/PG signaling as a target for chemoprevention has been established by randomized controlled clinical trials. However, these studies also identified increased cardiovascular risk associated with use of selective COX-2 inhibitors. Thus, current efforts are directed toward identifying safer approaches to antagonizing COX/PG signaling for cancer prevention and treatment, with a particular focus on PGE2 regulation and signaling, because PGE2 is a key protumorigenic prostanoid.
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影响因子：
50.3
作者：
Crawford, YG;Gauthier, ML;Tlsty, TD
通讯作者：
Tlsty, TD
COX-2表达与原位导管癌中的侵袭性表型有关。
影响因子：
8.8
作者：
Boland, G P;Butt, I S;Prasad, R;Knox, W F;Bundred, N J
通讯作者：
Bundred, N J
影响因子：
3.9
作者：
Chen, S;Zhou, D;Yang, C
通讯作者：
Yang, C
影响因子：
6.2
作者：
Denkert, C;Winzer, KJ;Hauptmann, S
通讯作者：
Hauptmann, S
影响因子：
158.5
作者：
Bertagnolli, Monica M.;Eagle, Craig J.;Hawk, Ernest T.
通讯作者：
Hawk, Ernest T.