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The significance of placental and placental-like alkaline phosphatases in tumor biology and their potential use in clinical practice
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
1984 (English)Doctoral thesis, comprehensive summary (Other academic)Text
Abstract [en]

Placental alkaline phosphatase (PLAP) is a membrane bound enzyme normally synthesized by the syncytiotrophoblasts in the human placenta. Recent studies have indicated that trace amounts of placental-like alkaline phosphatases also are present in several normal organs like testes and endocervix. PLAP and PLAP-1ike enzymes are furthermore synthesized by some tumors and can be detected in sera of approximately 12 % of patients with any type of cancer, more often in patients with genital tumors. This synthesis has been considered to be ectopic.PLAP is known to be electrophoretically highly polymorphic. Both poly- and monoclonal antibodies were used to study this enzyme. One of the monoclonal antibodies was able to discriminate between different phenotypes of PLAP and thus immunochemical approaches to elucidate enzyme polymorphism were established.To evaluate the potential clinical use of PLAP as a tumor marker serum levels of the enzyme were measured by a radioimmunoassay in 100 patients with the testicular tumor seminoma. Elevated levels of PLAP were found in 43 % of the patients with primary tumors and in 75 % of the patients with recurrent or metastatic disease. After successful treatment of seminoma the PLAP levels decreased. This indicates that measuring PLAP give useful information during follow up of treatment of seminomas.The content of PLAP-like enzymes in seminoma tumors was determined in 13 typical seminomas. The levels, of enzyme found in the tumor tissue ranged from 870-13 404 ng/g wet weight, which should be compared to around 100 ng/g in normal testes. Analysis using monoclonal antibodies and enzyme inhibitors showed the PLAP-like enzymes present in seminomas to be similar to the enzymes in normal testes. This suggests that the increased expression of PLAP-like enzymes in seminomas results from an enhanced eutopic expression of enzymes found in normal testis.A sensitive catalytic assay was used to quantify enzyme levels in sera from women with malignant gynaecological tumors. In the group of patients with cervical carcinoma 68 % had values exceeding the normal limit. For patients with ovarian cancer and carcinoma of the breast the percentages were 35 and 23 respectively.Monoclonal and polyclonal antibodies against PLAP were evaluated for tumor immunolocalization of human PLAP-producing tumors in nude mice.The antibodies were labeled with "125j and injected into mice with tumors. The distribution of 25j_an-ti-PLAP in various tissues showed that the labeled antibodies were enriched in the tumors, with a mean concentration ratio of 7. This indicates that there is a potential use of PLAP in localizing tumors in humans.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1984. , 37 p.
Umeå University medical dissertations, ISSN 0346-6612 ; N.S., 129
Keyword [en]
Alkaline phosphatase, seminoma, eutopic, gynaecological tumors, immunolocalization
National Category
Chemical Sciences
URN: urn:nbn:se:umu:diva-118687OAI: diva2:923311
Public defence
1984-11-16, sal B, LUO, Umeå universitet, Umeå, 10:00

S. 1-37: sammanfattning, s. 39-88: 5 uppsatser

Available from: 2016-04-26 Created: 2016-03-29 Last updated: 2016-04-26Bibliographically approved

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