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COX-2特异性抑制剂可能无预防胃癌作用
目前认为，胃癌与Ｈｐ感染密切相关，Ｈｐ已被ＷＨＯ定为Ｉ类致癌原。研究发现，Ｈｐ感染后胃黏膜ＣＯＸ－２表达水平显著增高，ＰＧＥ２生成增多。有人推测，非选择性ＣＯＸ－２抑制剂通过抑制ＣＯＸ－２，减少前列腺素生成，降低黏膜增殖水平，起到预防肿瘤的作用，该推论已得到流行病学证实。但由于非选择性ＮＳＡＩＤ能诱发溃疡形成，且Ｈｐ感染也是致溃疡的重要因素，因而限制了其应用。Ｓｃｈｅｉｍａｎ等对ＣＯＸ－２特异性抑制剂对肿瘤的预防作用进行了研究。
该研究共纳入２６名健康志愿者（其中２０名为Ｈｐ感染者），受试者接受罗非昔布２５ ｍｇ／日，连续应用２周。采用内镜下活检评价ＰＧＥ２水平、炎症反应及增殖水平。
结果显示，罗非昔布对受试者胃黏膜ＰＧＥ２水平、炎症反应及增殖水平均无显著影响。研究者由此推测，Ｈｐ感染后增高的ＰＧＥ２主要产生于ＣＯＸ－１途径。另外，服用ＣＯＸ－２抑制剂的Ｈｐ感染者溃疡发生率并没有明显增加，也可用该推论解释。
该研究从另一方面也说明，ＣＯＸ－２特异性抑制剂在胃癌预防中的作用似乎并不确定。同ＣＯＸ－２特异性抑制剂相比，非选择性ＣＯＸ抑制剂能显著抑制Ｈｐ感染相关的胃黏膜ＰＧＥ２和增殖水平，故其可能具有预防胃癌发生的保护性作用。但目前不除外ＣＯＸ－２特异性抑制剂对特殊病变（如萎缩性胃炎、肠上皮化生）具有肿瘤预防的作用，这也是将来研究的方向。 Scheiman JM, Greenson JK, Lee J, Cryer B.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. jscheima@umich.edu
Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention.
Aliment Pharmacol Ther. 2003 Jun 15;17(12):1535-43.
Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. AIM: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. METHODS: Twenty infected (eight males, 12 females; age 38 +/- 1.8) and six uninfected (four males, two females; age 36 +/- 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. RESULTS: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, H. pylori score in body and antrum and mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. CONCLUSION: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.
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http://www.blackwell-synergy.com/Journals/member/institutions/issuelist.asp?journal=apt 用COX分类方法评价当今NSAIDs
COX理论的形成
２０世纪７０年代初发现，非甾体类抗炎药（ＮＳＡＩＤｓ）是通过抑制促使前列腺素（ＰＧ）生成的环氧合酶（ＣＯＸ）的途径，发挥抗炎作用的，但也由此引出了不良反应。
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作者:admin@医学,生命科学 2011-08-14 05:13
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