Application of cytochrome P-450 of human fetal liber(P-450HFLa) as a tumor marker

人胎儿细胞色素P-450(P-450HFLa)作为肿瘤标志物的应用

基本信息

批准号：
03670768
负责人：
OKAJIMA Yuko
金额：
$ 1.22万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

Cytochrome P-450 of human fetal livers(P-450HFLa) was demonstrated by the immunoperoxidase techniquw in tissue samples as follows ; human fetal organs, and cynomolgus placenta, and gynecologic organs which were obtained from 40 patients gynecologic malignancies and 32 patients with benign diseases.P-450HFLa was clearly localized in the cytoplasm and membranes of hepatocytes, and the fact was cofirmed immunoelectron micro-scopically. In addition. semiquantitative assay of staining intensity demonstrated that this tended to decrease with adbancing age.These findings suggest that hepatic P-450HFLa synthesis is inversely proportional to age, and that this enzyme is one of the differentia-tion antigens.P-450HFLa was also detected immunohistochemically in other fetal organs. The present study thus confirms that P-450HFLa is not specific to the liber and is ubiquitous even in the fetus. Marked positive stanining for P-450HFLa was demonstrated in villous syncytiotropho-blasts. In contrast, nop … More ositive staining was found in the cynomolgus monkey placenta, unlike the case for many other plactal antigens. These findings lead to the tentative conclusion that P-450HFLa is a fetoplacental enzyme peculiar to humans.P-450HFLa was denonstrated to occur very frequently in gynecologic malignancies. the mean positivity rate for all gynecologic malignancies was 85%, while the rate was gelow 25% for benign gyne-cologic diseases, indicating that P-450HFLa is the one of the onco-teto-placental enzymes.We established an enzyme immunoassay for P-450HFLa by utilizing the avidin-biotin-peroxidase reaction, and determined that the normal range was >3.0 units/ml. In weeks 4-42 of pregnancy, the P-450HFLa level ranged from 0 to 38 units/ml. It rose during the first tri-mester, fell during the second trimester, and the increased again during the third trimester. After delivery, the serum P-450HFLa con-centration immediately returned to the nonpregnant level. The posi-tivity rate was 0% in patients with benign ovarian neoplasms, 71% in thosw with endometriosis, and 10% in those with uterine myoma. The positivity rate was 100% in patients with both ovarian and endometrial carcinoma. In patients with cervical carcinoma, the positivity rate was 78%, but the absolute values were not markedly raised in comparison with those in healthy nonpregnant woman. The present study suggests that this enzyme could be used as a new screening marker for gynecologic malignancy in patients without endometriosis, but would be inadequate as a monitoring marker because of the amall difference between normal and pathological level. Less

采用免疫过氧化物酶技术对取自40例妇科恶性肿瘤和32例良性疾病的人胎儿器官、食蟹猴胎盘和妇科器官样本中的人胎儿肝脏细胞色素P-450（P-450HFLa）进行了检测； .P-450HFLa明确定位于肝细胞的细胞质和细胞膜，这一事实得到证实此外，半定量染色显示其强度随着年龄的增长而降低。这些结果表明，肝脏 P-450HFLa 的合成与年龄成反比，并且该酶是分化抗原之一。 .P-450HFLa 也在其他胎儿器官中进行了免疫组织化学检测，因此本研究证实 P-450HFLa 对自由体不具有特异性。甚至在胎儿中也普遍存在 P-450HFLa 的显着阳性染色，而在食蟹猴胎盘中发现了 nop 阳性染色，这与许多其他胎盘抗原的情况不同。初步结论P-450HFLa是人类特有的胎儿胎盘酶。P-450HFLa是研究表明，所有妇科恶性肿瘤的平均阳性率为 85%，而良性妇科疾病的阳性率为 25%，这表明 P-450HFLa 是肿瘤性胎盘肿瘤之一。我们利用亲和素-生物素-过氧化物酶反应建立了 P-450HFLa 的酶免疫测定法，并确定正常范围为>3.0单位/毫升，在怀孕第4-42周，P-450HFLa水平范围为0至38单位/毫升，在妊娠中期上升，在妊娠中期下降，然后再次上升。妊娠晚期，卵巢良性患者血清 P-450HFLa 浓度立即恢复至非妊娠水平，阳性率为 0%。子宫内膜异位症患者的阳性率为 71%，子宫肌瘤患者的阳性率为 100%，而宫颈癌患者的阳性率为 78%。与健康非孕妇相比，该酶没有显着升高，本研究表明，这种酶可以用作未患妇科恶性肿瘤的新筛查标志物。子宫内膜异位症，但由于正常水平和病理水平之间的差异较小，因此不足以作为监测标志物。