1993 Fiscal Year Final Research Report Summary
Application of cytochrome P-450 of human fetal liber(P-450HFLa) as a tumor marker
| Project/Area Number |
03670768
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Chiba University |
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Principal Investigator |
OKAJIMA Yuko Dept. Obstet & Gynecol. Chiba Univ. Hastital Assistant., 医学部・附属病院, 助手 (10203978)
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| Co-Investigator(Kenkyū-buntansha) |
FUKASAWA Ichio Dept. Obstet & Gynecol. Chiba Univ. Hastital Instructor., 医学部・附属病院, 講師 (00189911)
INABA Noriyuki Dept. Obstet & Gynecol. Chiba Univ. Instructor., 医学部, 講師 (70114238)
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| Project Period (FY) |
1991 – 1993
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| Keywords | P-450HFLa / Immunohistochemistry / Immunoelectron microscopy / Pregnancy / Enzyme immunoassay / Onco-feto-placental antigen / Tumor marker / Gynecologic malignancies |
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| Research Abstract |
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
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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
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[Publications] Okajima Y, Inba N, Fukasawa I, Ota Y, Hirai Y, Sato N, Yamanoto G, Itabashi K, Kitada M, Kamataki T, Takamizawa H: "Immunohistochemical and immunoelictron mictoscopic study of cytochrme P-450 of human fetal livers (P-450HFLa) : Implications for an once-feto-placental enzyme" Asia-Oseania Journal of Obstetrics and Gynaecology. 19. 329-341 (1993)
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