Human Alphafetoprotein 1956–1978

Adinolfí, Matteo

doi:10.1007/978-1-4615-8276-2_3

Cited by 8 publications

(4 citation statements)

References 203 publications

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“…AFP is present in very small anounts (0.06 iig/ml) in the serum of normal adult rats and humans but at a very high concentrations (as much as 10,000 pg/ml) in the serum of fetal and hepatoma-bearing animals (for reviews see ref. [1][2][3]. A useful application of these findings has been the development of a serological test for the diagnosis of primary liver cancer in humans (4).…”

Section: Introductionmentioning

confidence: 99%

Hormonal modulation of α-fetoprotein gene expression in newborn rat livers

Chiu¹,

Massari²,

Schwartz³

et al. 1981

Nucl Acids Res

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Suppression of serum alpha-fetoprotein (AFP) levels in glucocorticoid treated newborn rats was investigated. Daily intraperitoneal injection of 2 micrograms/g body weight of dexamethasone into newborn rats greatly reduced the concentration of AFP in the serum and liver cytosol. In contrast, this treatment stimulated liver ornithine decarboxylase activity. The reduction in AFP levels is not due to a change of distribution of AFP molecular variants, inhibition of secretion of synthesized AFP by the liver or disruption of liver polysomes. Glucocorticoids decrease the AFP levels in hormone-treated rats by supressing the synthesis of AFP. The size of AFP polysomes isolated from the livers of dexamethasone-treated rats were as large as those from normal rats. However, the amount of AFP-producing polysomes in hormone-treated rat liver is only 14% of the controls. By hybridization assays, it was found that dexamethasone treated livers contained decreased amounts of AFP mRNA sequences in liver cytoplasmic and nuclear RNAs. The decreased amounts of AFP mRNA sequences in hormone-treated liver are caused by both a decrease in the rate of AFP mRNA transcription and in AFP mRNA stability.

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Section: Introductionmentioning

confidence: 99%

Hormonal modulation of α-fetoprotein gene expression in newborn rat livers

Chiu¹,

Massari²,

Schwartz³

et al. 1981

Nucl Acids Res

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“…Newlands Received 25 April 1983;accepted 19 June 1983 The normal serum concentration of AFP has been variously quoted as <20 ku 11 (Javadpour, 1980); usually <16kul1-and always <40kul1- (Pearson et al, 1979); <30kul-' (Catalona, 1979) and <20 ku 1- (Adinolfi, 1979).…”

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confidence: 99%

Problems of interpretation of serum concentrations of alpha-foetoprotein (AFP) in patients receiving cytotoxic chemotherapy for malignant germ cell tumours

Newlands¹,

Dent²,

Mitchell³

et al. 1983

Br J Cancer

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Summary Serial determinations of serum alpha-foetoprotein (AFP) concentrations are well established in monitoring the response to therapy of malignant germ cell tumours. Using a radioimmunoassay (RIA) with a sensitivity down to 2 kuI-1 the majority (57%) of 28 patients with non-AFP producing germ cell tumours had measurable immunologically-reactive AFP in their serum while on treatment. Follow-up for 11-43 months (mean 27) without evidence of tumour activity indicated that this immunologically-reactive AFP was unlikely to be produced by tumour. In patients where the initial serum AFP was raised prior to chemotherapy the AFP concentration did not fall to the normal range at the end of the treatment in 16 (32%) of 41 patients. Follow-up of these patients for 9-48 months (mean 27) has resulted in 5 (12%) relapses in this group. Serum AFP >20 ku I1 three months after stopping chemotherapy was a good indicator of residual active tumour and 4 (57%/) of 7 patients in this group relapsed. The production of detectable serum AFP is probably related to the type of chemotherapy used and only 7 (14%) of 51 patients treated for gestational choriocarcinoma had detectable AFP concentrations while on cytotoxic chemotherapy. The problem of interpretation of serum AFP concentration in patients with malignant germ cell tumour stresses the need to determine whether there are differences between AFP produced by germ cell tumours and that produced at other sites as a basis for a sensitive assay system able to discriminate between them.AFP is a glycoprotein with a molecular weight of 70K daltons. It is produced in several physiological and disease states and is a normal component of human foetal serum. It is produced in certain liver diseases, notably hepatocellular carcinoma (McIntire et al., 1972) and in situations where there is hepatic regeneration (Bloomer et al., 1973;Elgort et al., 1973;Masopust et al., 1968; Waldmann et al., 1974).AFP is now used routinely with human chorionic gonadotrophin (hCG) in the diagnosis of anaplastic germ cell tumours and in monitoring their response to therapy and follow-up. The production of AFP by germ cell tumours is closely associated with the histological finding of yolk sac or embryonal elements (N0rgaard-Pedersen et al., 1975;Kurman et al., 1977;Talerman et al., 1977;Grigor et al., 1977). A high serum concentration of AFP in the absence of liver disease or pregnancy is likely to be due to an anaplastic germ cell tumour or some other AFP-producing tumour. When present the serum concentration of AFP correlates well with the body burden of AFP-producing cells. However, with more intensive and successful chemotherapy in the management of patients with metastatic germ cell tumours, this has raised problems of interpretation since AFP concentrations above the normal range may not reflect residual tumour.Correspondence: E.S. Newlands Received 25 April 1983; accepted 19 June 1983 The normal serum concentration of AFP has been variously quoted as <20 ku 11 (Javadpour, 1980); usually <16kul1-and alw...

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“…However, expression of the AFP gene is reactivated by cell proliferation during liver regeneration, and in certain hepatocellular carcinomas. The AFP gene can also be induced in other oncogenic states, such as in hepatoid adenocarcinomas occurring in tissues other than the liver, and in teratoblastomas [Abelev, 1968;Adinolfi, 1979;Ruoslahti, 1979;Tilghman, 1985;Chen et al, 1996, and refs therein]. Therefore, the AFP gene provides an excellent model to study transcriptional regulation during mammalian development and oncogenic transformation.…”

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Identification of a Cis-acting element in the rat ?-fetoprotein gene and its specific binding proteins in F9 cells during retinoic acid-induced differentiation

et al. 1999

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Mouse F9 embryonic teratocarcinoma stem cells can be induced to differentiate into visceral endoderm. Following retinoic acid (RA) treatment, alpha-fetoprotein (AFP), a differentiation marker, is expressed and secreted. The mechanism by which RA regulates AFP expression during differentiation is not clear. The relatively late induction of AFP indicates that the AFP gene may not be a primary target of RA activity during F9 cell differentiation. In this study, a CAT reporter plasmid containing the rat AFP 5'-regulatory region (-7040 to +7) adjacent to the CAT gene (pAFPCAT) was stably transfected into F9 cells and used to delineate a cis-acting element which associates with AFP gene activation. Similar spatial and temporal expression patterns between the transcriptional activity of the recombinant AFP gene and the endogenous AFP gene demonstrate that this stably transfected F9 system can be used to dissect both cis-elements and trans-acting factors responsible for RA-induced AFP expression. Using a series of deletion mutants of the pAFPCAT, the region between -2611 to -1855 was found to be important in AFP-induction. Subsequent analysis identified a functional sequence (-1905 to -1891, 5'-ACTAAAATGGAGACT-3') that differentially binds nuclear proteins from undifferentiated and differentiated F9 cells. This sequence, designed as differentiation-associated sequence (DAS) for its unique binding of a nuclear protein (DAP-II) that appears during RA-induced F9 differentiation, acts as a regulatory protein factor in AFP gene activation.

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Human Alphafetoprotein 1956–1978

Cited by 8 publications

References 203 publications

Hormonal modulation of α-fetoprotein gene expression in newborn rat livers

Hormonal modulation of α-fetoprotein gene expression in newborn rat livers

Problems of interpretation of serum concentrations of alpha-foetoprotein (AFP) in patients receiving cytotoxic chemotherapy for malignant germ cell tumours

Identification of a Cis-acting element in the rat ?-fetoprotein gene and its specific binding proteins in F9 cells during retinoic acid-induced differentiation

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