Sauter Edward R, Schlatter Lisa, Hewett John, Koivunen Debra, Flynn John T
Department of Surgery, University of Missouri-Columbia, One Hospital Drive, Room M588, Columbia, MO 65212, USA.
Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1745-50.
Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E(2) (PGE(2)) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE(2) production in cancerous tissue.
OBJECTIVE/HYPOTHESIS: We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE(2) would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE(2) levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma.
To determine if PGE(2) concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout).
NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control.
PGE(2) concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE(2) levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE(2) concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE(2) concentrations after celecoxib administration.
PGE(2) can be measured in NAF. PGE(2) levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE(2) concentrations in NAF and plasma.
环氧化酶（COX-1、COX-2和COX-3）可将花生四烯酸转化为前列腺素、前列环素、血栓素及其他羟基脂肪酸。其中，前列腺素E2（PGE2）具有促进肿瘤生长的活性。COX-2同工型是癌组织中参与PGE2生成的主要酶。
目的/假设：我们对乳腺癌风险增加的女性给予COX-2抑制剂塞来昔布（200毫克，每日两次）。我们的假设是，PGE2会在乳腺乳头抽吸液（NAF）中分泌，NAF中的水平会高于相应血浆中的水平，且塞来昔布会降低NAF（反映乳腺组织类花生酸生成减少）和血浆中的PGE2水平。
确定在服用两周塞来昔布后，NAF和血浆中的PGE2浓度是否会降低，然后在停药两周后（洗脱期）恢复到基线水平。
在塞来昔布治疗前、服用塞来昔布两周后以及洗脱期两周后收集NAF和血浆。每位女性作为自身对照。
使用两种测量技术在样本中均可检测到NAF和血浆中的PGE2浓度。平均而言，NAF中PGE2水平比匹配血浆中的高81倍。从技术角度来看，根据所使用的检测技术（放射免疫分析与化学发光免疫分析），在相似液体中测量的PGE2浓度存在差异。服用塞来昔布后，PGE2浓度没有显著降低。
PGE2可在NAF中测量。与匹配的血浆样本相比，PGE2水平在NAF中更为集中。每日两次服用200毫克塞来昔布似乎不会显著降低NAF和血浆中的PGE2浓度。
