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Obstetrics and Gynecology May 1978Elevation above the normal range of alpha-fetoprotein (AFP) concentration in amniotic fluid occurs in the presence of certain fetal anomalies. The value of a new method...
Elevation above the normal range of alpha-fetoprotein (AFP) concentration in amniotic fluid occurs in the presence of certain fetal anomalies. The value of a new method for radioimmunoassay of APF in amniotic fluid was tested by an analysis of 486 samples taken by amniocentesis at various stages of pregnancy. The normal range of concentrations during pregnancy was established by 348 samples from healthy women with normal pregnancies. This was compared with the levels found in the presence of various fetal malformations--Rh-isoimmunization, maternal diabetes, chromosomal anomalies, and fetal death in utero. The findings and their implications are discussed.
Topics: Amniotic Fluid; Female; Fetal Diseases; Gestational Age; Humans; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; alpha-Fetoproteins
PubMed: 77515
DOI: 10.1097/00006250-197805000-00016 -
The Journal of International Medical... Oct 2018Objectives This study aimed to examine a simple, effective, time-saving, and low-cost protein microarray method for detecting serum alpha-fetoprotein (AFP) and AFP-L3...
Objectives This study aimed to examine a simple, effective, time-saving, and low-cost protein microarray method for detecting serum alpha-fetoprotein (AFP) and AFP-L3 levels. Methods Serum samples from patients with hepatocellular carcinoma (HCC) (n = 33) and control subjects (n = 39) were collected and evaluated for the presence of AFP using a novel protein microarray. Glycoprotein (including AFP-L3) was enriched from crude samples by a Hotgen Biotech glycosyl capture spin column and then detected by protein microarray. An electrochemiluminescence immunoassay (ECLIA) was used to validate the measured values. Results Neither AFP levels lower than 20 ng/mL in the HCC group nor AFP levels higher than 20 ng/mL in the control group were found when tested by the ECLIA and protein microarray. The kappa test showed good consistency in the diagnostic performance of measuring serum AFP levels and the percentage of AFP-L3 in total AFP by the ECLIA and protein microarray. Protein microarray had advantages of smaller sample size required, low cost, and convenience compared with the ECLIA. Conclusion The protein microarray assay that was developed in the present study shows potential as an economic and convenient technique for detecting AFP and AFP-L3 levels in serum samples from patients with HCC.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Protein Array Analysis; alpha-Fetoproteins
PubMed: 30111217
DOI: 10.1177/0300060518789304 -
Biomeditsinskaia Khimiia 2005Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized tumor marker. This review summarizes data on structure and function of AFP with emphasis... (Review)
Review
Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized tumor marker. This review summarizes data on structure and function of AFP with emphasis on human AFP, which is intensively investigated. During the last decade multiple functionally important sites of human AFP have been revealed or predicted by searching of similarity between primary structures of AFP and other proteins or their DNA sequences. A number of peptides derived from human AFP have been studied by different teams of investigators. These peptides were obtained by limited proteolysis of AFP or synthesized using solid phase chemistry. Study of biological (physiological) activities of these peptides allows determining biologically active sites of alpha-fetoprotein and constructing its structural and functional map. Biomodulating properties of these peptides make them a potential basis for design of drugs for different purposes including using in anticancer therapy. Conformational changes in AFP molecule have been intensively studied for the last few years and sufficient conformational mobility of AFP with the ability to form molten globule form (MGF) despite its stability in solution has been demonstrated. Native molecule of AFP may contain cryptic biologically active sites, which are not available for ligand binding. These sites become open and available for interaction after changes in conformation of AFP molecule. Study of conformational changes of AFP under different conditions allows understanding molecular mechanisms of its functioning. This review describes and analyses data obtained, mainly, during the last few years on study of conformational states of alpha-fetoprotein and relationship between conformational changes of AFP and its biological activity. Biochemical, biophysical and functional characterislics of some well-studied peptide fragments of AFP and their structural and functional mapping are presented.
Topics: Animals; Humans; Peptides; Protein Conformation; alpha-Fetoproteins
PubMed: 15945348
DOI: No ID Found -
Japanese Journal of Cancer Research :... Apr 1993In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various...
In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.
Topics: Female; Humans; Immunohistochemistry; Liver Neoplasms; Male; Mesonephroma; Neoplasms; Neoplasms, Germ Cell and Embryonal; alpha-Fetoproteins
PubMed: 7685750
DOI: 10.1111/j.1349-7006.1993.tb00144.x -
Clinica Chimica Acta; International... Feb 1989An antibody-lectin enzyme immunoassay (EIA) technique was developed for the analysis of sugar chains of serum alpha-fetoprotein in various liver diseases. The...
An antibody-lectin enzyme immunoassay (EIA) technique was developed for the analysis of sugar chains of serum alpha-fetoprotein in various liver diseases. The anti-'alpha-fetoprotein'-IgG was coated on a microtiter plate and then treated with periodic acid. A serum sample was added to the plate and then a 'peroxidase'-conjugated lectin was added. The amount of lectin bound to the sugar chain of the 'alpha-fetoprotein' was estimated from the 'peroxidase' activity. The 'peroxidase' activities of 4 different lectins, LCA, Con A, LCA and EPHA, were compared. The LCA/'wheat germ agglutinin' activity ratio and LCA/EPHA activity ratio were increased in liver diseases and LCA/'wheat germ agglutinin' ratio showed a statistically significant difference between the chronic hepatitis and the liver cirrhosis groups (p less than 0.05). Furthermore, when serum samples were pretreated with sialidase, a statistically significant difference was observed in the LCA/EPHA and LCA/Con A ratios between the chronic hepatitis and the hepatoma groups (p less than 0.05). These results indicated that low sialylation at the non-reduced end of the sugar chains of 'alpha-fetoprotein' occurs in liver cirrhosis and that high fucosylation at the reduced end of N-acetylglucosamine residue of 'alpha-fetoprotein' occurs in hepatomas.
Topics: Antibodies; Biomarkers; Carbohydrates; Enzyme-Linked Immunosorbent Assay; Humans; Lectins; Liver Diseases; alpha-Fetoproteins
PubMed: 2465850
DOI: 10.1016/0009-8981(89)90160-5 -
Cerebellum (London, England) Jun 2024ARV1 mutation is known to present as developmental and epileptic encephalopathy (DEE)-38. However, the phenotypic spectrum has been expanding ever since it was reported...
ARV1 mutation is known to present as developmental and epileptic encephalopathy (DEE)-38. However, the phenotypic spectrum has been expanding ever since it was reported in 2016. Along with seizures and developmental delay, other unique clinical features include ophthalmological abnormalities and movement disorders in the form of ataxia and dystonia, especially in those with missense mutation. These manifestations closely mimic ataxia telangiectasia. Elevation of alpha-fetoprotein levels is an important investigative marker in the diagnosis of ataxia telangiectasia and ataxia with oculomotor apraxia syndromes. ARV1 can also be associated with increased alpha-fetoprotein. There are no reports evaluating alpha-fetoprotein levels in cases with ARV1 mutation, which is significant in the context of ocular abnormalities with ataxia. We report a case of ARV1 mutation presenting with ataxia, ocular abnormalities, and elevated alpha-fetoprotein levels, thus mimicking autosomal recessive cerebellar ataxias. This study provides a comprehensive literature review of the cases reported so far, thus expanding the understanding of the spectrum of presentation, and helps in correlating the clinical picture with the underlying causative genetic mutation. ARV1 gene is another example of one gene with phenotypic pleiotropy. Though presentation with DEE is common, a few, especially those with missense mutations, can present with ataxia and ocular abnormalities. All cases presenting with ataxia who have increased alpha-fetoprotein levels and seizures should be tested for the ARV1 gene, when testing for ataxia genes is negative. The underlying genetic mechanism can explain the varying clinical manifestations of the ARV1 gene.
Topics: Humans; alpha-Fetoproteins; Female; Male; Cerebellar Ataxia; Mutation, Missense
PubMed: 37749428
DOI: 10.1007/s12311-023-01606-5 -
Annals of the New York Academy of... Aug 1975
Topics: Amniotic Fluid; Animals; Body Weight; Female; Fetal Proteins; Gestational Age; Humans; Immunoelectrophoresis; Infant, Newborn; Liver; Molecular Weight; Pregnancy; Species Specificity; Vitelline Membrane; alpha-Fetoproteins
PubMed: 54039
DOI: 10.1111/j.1749-6632.1975.tb25397.x -
Tumour Biology : the Journal of the... 1996Recently, evidence was obtained that the ability to take up alpha-fetoprotein (alpha-FP), which is characteristic of fetal cells, may be required both in vivo and in...
Recently, evidence was obtained that the ability to take up alpha-fetoprotein (alpha-FP), which is characteristic of fetal cells, may be required both in vivo and in vitro by different types of human and animal tumor cells via expression of specific alpha-FP receptors. Mammary gland carcinomas belong to this class of tumor. In some neoplasms, expression of alpha-FP receptors is concomitant with activation of the alpha-FP gene and synthesis of the protein, suggesting that an autocrine alpha-FP/alpha-FP-receptor pathway is operational in these tumors. In the present work, 18 human breast cancer biopsy specimens were subjected to in situ hybridization with a human alpha-FP cDNA probe. Positive labeling for alpha-FP mRNA transcripts was seen in 8 of the specimens. Surprisingly, strong positive signals were seen in stromal fibroblasts and lymphocytes infiltrating tumor nests and in adipocytes adjacent to tumor areas, while the malignant cells themselves were hardly labeled. This suggest paracrine stimulation of the alpha-FP gene, probably as a result of epithelial-mesenchymal interactions. Pathological implications arise from the ability of alpha-FP to regulate growth, either alone or synergistically with other growth factors, as well as its ability to enhance fatty acid entry into proliferating cells.
Topics: Breast Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; RNA, Messenger; alpha-Fetoproteins
PubMed: 8792856
DOI: 10.1159/000217992 -
Life Sciences 1999Although the biological functions of alpha-fetoprotein ( AFP ) have been extensively studied, little is known about its effect on tumor cell growth. Our previous work...
Although the biological functions of alpha-fetoprotein ( AFP ) have been extensively studied, little is known about its effect on tumor cell growth. Our previous work has found that human AFP significantly stimulates the growth of mouse hepatoma cells in vitro. The purpose of the present study is to observe the effect of AFP on the proliferation of human hepatoma cells in vitro. Using a MTT- microculture tetrazolium assay, we found that the proliferation of human hepatoma cells was enhanced by in vitro treatment of AFP. However, the same concentrations of AFP had no effect on HL - 60 human leukemia cell proliferation, indicating that the human hepatoma cell proliferation - promoting role of AFP was not simply due to non-specific addition of exogenous protein and the proliferation enhancement of AFP showed certain tumor cell specificity. On the other hand, the growth stimulation of AFP could be diminished by rabbit anti - human AFP antibody. The anti- AFP antibody alone suppressed the growth of BEL - 7404 human hepatoma cells, not affecting HL - 60 cell proliferation. BEL - 7404 cell proliferation was not inhibited by normal rabbit immunoglobulins to demonstrate the specificity of anti-AFP effect. Taken together, it is concluded that AFP enhances the proliferation of human hepatoma cells in vitro, and this effect is seemingly mediated by an AFP/receptor autocrine pathway.
Topics: Antibodies; Autocrine Communication; Carcinoma, Hepatocellular; Cell Division; HL-60 Cells; Humans; Tumor Cells, Cultured; alpha-Fetoproteins
PubMed: 10027738
DOI: 10.1016/s0024-3205(98)00529-3 -
The Journal of Physical Chemistry. B May 2014The abundance of α-fetoprotein (AFP), a natural protein produced by the fetal yolk sac during pregnancy, correlates with lower incidence of estrogen receptor positive...
The abundance of α-fetoprotein (AFP), a natural protein produced by the fetal yolk sac during pregnancy, correlates with lower incidence of estrogen receptor positive (ER+) breast cancer. The pharmacophore region of AFP has been narrowed down to a four amino acid (AA) region in the third domain of the 591 AA peptide. Our computational study focuses on a 4-mer segment consisting of the amino acids threonine-proline-valine-asparagine (TPVN). We have run replica exchange molecular dynamics (REMD) simulations and used 120 configurational snapshots from the total trajectory as starting configurations for quantum chemical calculations. We optimized structures using semiempirical (PM3, PM6, PM6-D2, PM6-H2, PM6-DH+, PM6-DH2) and density functional methods (TPSS, PBE0, M06-2X). By comparing the accuracy of these methods against RI-MP2 benchmarks, we devised a protocol for calculating the lowest energy conformers of these peptides accurately and efficiently. This protocol screens out high-energy conformers using lower levels of theory and outlines a general method for predicting small peptide structures.
Topics: Antineoplastic Agents; Breast Neoplasms; Molecular Dynamics Simulation; Peptides; Protein Structure, Secondary; Thermodynamics; alpha-Fetoproteins
PubMed: 24702603
DOI: 10.1021/jp500017b