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COX-2抑制剂或能预防宫颈癌发病

2012-02-06 MedSci MedSci原创

非洲、加勒比海和拉丁美洲等发展中国家地区的女性被诊断有宫颈癌的几率非常高,并且其死亡率也一直居高不下。西半球HIV感染率最高的地区之一就是海地,同时海地也是世界上宫颈癌发生几率最高的地区。在海地,罹患侵袭性宫颈癌是感染HIV女性患者死亡的普遍原因。 最近,一项由纽约长老会医院/韦尔康奈尔医学中心的研究者联合纽约、海地和卡塔尔的癌症专家所进行的研究证实:非甾体抗炎药--阿司匹林对非洲、加勒比海以及

非洲、加勒比海和拉丁美洲等发展中国家地区的女性被诊断有宫颈癌的几率非常高,并且其死亡率也一直居高不下。西半球HIV感染率最高的地区之一就是海地,同时海地也是世界上宫颈癌发生几率最高的地区。在海地,罹患侵袭性宫颈癌是感染HIV女性患者死亡的普遍原因。

最近,一项由纽约长老会医院/韦尔康奈尔医学中心的研究者联合纽约、海地和卡塔尔的癌症专家所进行的研究证实:非甾体抗炎药--阿司匹林对非洲、加勒比海以及拉丁美洲的女性有相当大的帮助,阿司匹林能有效抑制已感染艾滋病毒(HIV)女性宫颈癌的发展。相关研究成果发表在Cancer Prevention Research杂志上。

在海地生活了7年,这项研究的领导者--丹尼尔-菲茨杰拉德教授一直致力于该国HIV感染病人的治疗。菲茨杰拉德与海地当地一家主要从事 HIV/AIDS临床服务、治疗和研究的权威机构GHESKIO合作一起开展了这项研究。菲茨杰拉德教授表示:许多HIV感染的年轻患者已经能通过接受抗病毒治疗控制HIV病情的发展,不接受抗病毒治疗的话,HIV感染的年轻患者只有慢慢随病情发展患上宫颈癌并最终死于宫颈癌。

许多炎性疾病慢慢会发展成肿瘤,如胃炎会恶化成胃癌等。该项研究发现HIV能和PGE2(通常在炎症时被激活)联合起来导致以下肿瘤的发生及发展,其中就包括宫颈癌。HIV感染女性罹患宫颈癌的风险是HIV阴性女性的5倍,据研究者称,这是因为HIV能增加患者宫颈癌组织中PGE2生成的量,PGE2生成过多会导致宫颈癌的发生。

基于上述研究结果,研究人员猜测运用COX-2分子抑制剂诱导PGE2降解或许能抑制HIV感染女性罹患宫颈癌。在已上市的COX-2分子抑制剂中最有效、廉价的就是--阿司匹林。

为了进一步研究阿司匹林等前列腺类物质抑制剂是否能降低HIV感染女性患宫颈癌的风险。研究人员将受试女性分成三组,分析了各组患者体内COX-2 和PEG-M的水平。结果发现13名未感染HIV和HPV的女性,其体内COX-2和PEG-M的水平是呈上升趋势的。18名感染HIV而未感染HPV的女性,COX-2和PEG-M的量也是增高的。而17位HIV和HPV均阴性的女性体内COX-2和PEG-M的量呈下降趋势。菲茨杰拉德教授认为这个发现表明:HIV是女性宫颈中COX-2和全身性PGE2增加的关键纽带。感染HIV和HPV的女性随病情发展被诊断患有宫颈癌的风险也增加。(生物谷 Bioon.com)

The Effect of HIV and HPV Coinfection on Cervical COX-2 Expression and Systemic Prostaglandin E2 Levels

Daniel W. Fitzgerald1,2,3, Karl Bezak3, Oksana Ocheretina1,3, Cynthia Riviere6, Thomas C. Wright5, et al.

Human immunodeficiency virus (HIV-1) infection causes chronic inflammation. COX-2–derived prostaglandin E2 (PGE2) has been linked to both inflammation and carcinogenesis. We hypothesized that HIV-1 could induce COX-2 in cervical tissue and increase systemic PGE2 levels and that these alterations could play a role in AIDS-related cervical cancer. Levels of cervical COX-2 mRNA and urinary PGE-M, a biomarker of systemic PGE2 levels, were determined in 17 HIV-negative women with a negative cervical human papilloma virus (HPV) test, 18 HIV-infected women with a negative HPV test, and 13 HIV-infected women with cervical HPV and high-grade squamous intraepithelial lesions on cytology. Cervical COX-2 levels were significantly associated with HIV and HPV status (P = 0.006 and 0.002, respectively). Median levels of urinary PGE-M were increased in HIV-infected compared with uninfected women (11.2 vs. 6.8 ng/mg creatinine, P = 0.02). Among HIV-infected women, urinary PGE-M levels were positively correlated with plasma HIV-1 RNA levels (P = 0.003). Finally, levels of cervical COX-2 correlated with urinary PGE-M levels (P = 0.005). This study shows that HIV-1 infection is associated with increased cervical COX-2 and elevated systemic PGE2 levels. Drugs that inhibit the synthesis of PGE2 may prove useful in reducing the risk of cervical cancer or systemic inflammation in HIV-infected women

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    2012-12-27 jklm09
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    2012-02-08 一闲
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