Disease relevance of AFP

• Intratumoral injection of AdV resulted in growth retardation and regression in a majority of established hepatomas, but with a much wider therapeutic index and less systemic toxicity using the AFP vector [1].
• Therefore, both TSG3 and TSG17 tumors were regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP-producing gastric carcinoma [2].
• At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p=0.05), p53 mutation (p=0.0004), liver cirrhosis (p=0.0094), large tumor (p=0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors [3].
• Our data show that some non-hepatoid AFP-producing gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP-producing gastric carcinomas [2].
• Gastric cancers producing alpha-fetoprotein (AFP) have a poor prognosis and a high incidence of liver metastasis [4].

Psychiatry related information on AFP

• Ataxia with oculomotor apraxia type 2 (AOA2) is a newly described autosomal recessive cerebellar ataxia (ARCA) defined by genetic location to 9q34 of three families sharing gait ataxia, oculomotor apraxia and/or elevated alpha-foetoprotein (AFP) levels [5].
• The reaction time with the AFP kit is 90 s [6].
• RESULTS: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration [7].
• This may influence the decision-making process when termination of pregnancy is considered in cases of high AF AFP and/or positive acetylcholinesterase [8].
• A workshop, held in May, 1978, at the National Institute of Child Health and Human Development, considered the quality control of reagents and assays for measuring alpha fetoprotein (AFP) in maternal serum and amniotic fluid for the antenatal screening and diagnosis of open neural tube defects [9].

High impact information on AFP

• We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP) [10].
• The second-trimester tests were various combinations of measurements of serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A in 77 affected and 385 unaffected pregnancies [11].
• BACKGROUND: Screening for trisomy 21 (Down's syndrome) by measuring maternal serum alpha-fetoprotein, chorionic gonadotropin, and estriol concentrations and then performing chorionic-villus sampling or amniocentesis identifies approximately 60 percent of fetuses with this disorder [12].
• In screening for Down's syndrome in the second trimester of pregnancy, the concentrations of alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, and intact human chorionic gonadotropin in material serum are widely used markers [13].
• The rate of detection of Down's syndrome was 53 percent and the false positive rate was 5 percent when alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, the maternal age were used together as predictors [13].

Chemical compound and disease context of AFP

• Vascular endothelial growth factor expression was observed in all four of the AFP-producing gastric cancers, whereas thymidine phosphorylase was not expressed in any of the AFP-producing gastric cancers [14].
• Prevention of N-methyl-N-nitrosourea-induced breast cancer by alpha-fetoprotein (AFP)-derived peptide, a peptide derived from the active site of AFP [15].
• The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase [16].
• Immunohistochemical expression of pi class glutathione S-transferase and alpha-fetoprotein in hepatocellular carcinoma and chronic liver disease [17].
• F9 embryonal carcinoma (EC) cells, cultured in suspension in medium containing 5 X 10(-8) M retinoic acid, aggregate and differentiate into embryoid bodies with an outer layer of visceral endoderm cells that synthesize and secrete alphafetoprotein (AFP) (Hogan, B. L. M., A. Taylor, and E. Adamson, 1981, Nature (Lond.). 291:235-237) [18].

Biological context of AFP

• This mechanism for p53-mediated repression of AFP gene expression may be active during hepatic differentiation and lost in the process of tumorigenesis [19].
• Immunohistochemical studies revealed that the AFP-binding protein(s) is expressed in blood vessels of chorionic villi from placentae of the second and the third but not of the first trimester during pregnancy [20].
• The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13 [21].
• CONCLUSIONS: These results suggest that AFP-producing gastric cancers have high malignant potential (high proliferative activity, weak apoptosis, and rich neovascularization) compared with that of AFP-negative gastric cancers [14].
• While the primitive lamphrey possesses a serum protein twice the size of mammalian albumin, the bony fishes, reptiles, and amphibians display two ALB-like molecules sharing amino acid sequence similarity to mammalian AFP [22].

Anatomical context of AFP

• Suppression of AFP gene transcription by ING was strongly dependent on AT-motifs that bind to the hepatocyte nuclear factor 1 (HNF1) transcription factor [23].
• These data indicate that AFP may act as a specific proangiogenic factor of endothelial cells within the fetomaternal unit during advanced stages in pregnancy [20].
• Furthermore, AFP enhances blood vessel formation in a chick chorioallantoic membrane assay in vivo [20].
• Interestingly, AFP has no proliferative or migratory effects on endothelial cells isolated from the umbilical vein in the absence of vascular endothelial growth factor [20].
• Using a primary monolayer culture system, we investigated the proliferative activity of human (h) cord blood (CB) and highly purified AFP. hAFP, purified from hCB by Cibacron blue and immunoaffinity chromatography was homogeneous on SDS-PAGE and silver stain [24].

Associations of AFP with chemical compounds

• Induction of p53 in response to actinomycin D or hypoxic stress decreases AFP expression [19].
• Like the founding family member p53, TA-p73 represses AFP expression by chromatin structure alteration, targeting reduction of acetylated histone H3 lysine 9 and increased dimethylated histone H3 lysine 9 levels [25].
• Alpha-fetoprotein (AFP) is a 65-kDa oncofetal glycoprotein found in fetal and maternal fluids during pregnancy [26].
• Here we comparatively analyze, in PBMCs from patients with AIDS and related syndromes, (1) changes in membrane fluidity, measured as the cholesterol/phospholipid ratio (CH/PL), and (2) changes in the expression of AFP receptors and of the alpha chain of IL-2 receptor (TAC antigen) [27].
• In an immunohistochemical analysis of 13 SpHCC tumors, cytokeratin CAM 5.2 and AFP were positive in 8 (62%) tumors and 3 (23%) tumors in both ordinary HCC and spindle cell components, respectively [28].
• Overall, downstaging HCC patients with high AFP is feasible and leads to similar intent-to-treat and post-transplant survivals to those of patients with AFP persistently low [29].
• Assessment of AFP response may be considered as an alternative to RECIST to capture sorafenib activity in HCC [30].

Physical interactions of AFP

• The present results provide strong evidence that AFP directly binds to CCR5 expressed by human primary macrophages and by transfected CCR5+ HeLa cells [31].
• We have isolated a full-length cDNA encoding a protein (ATBF1) that binds to an AT-rich motif in the human alpha-fetoprotein gene enhancer [32].
• Addition of the 2-F diminishes ER and AFP-binding affinities while augmenting the affinity for the SHBG [33].
• This strongly suggests that competition between NF-1 and HNF-1 for binding to their overlapping binding sites on the AFP promoter is critical for modulating its activity [34].
• Using solid-phase, chromatin-assembled AFP DNA templates and analysis of chromatin structure and transcription in vitro, we find that p53 binds DNA and alters chromatin structure at the AFP core promoter to regulate transcription [35].

Co-localisations of AFP

• After labeling KCl-treated human breast cancer cytosols with 125I, double immunodiffusion, immunoelectrophoresis, and autoradiography revealed that radiolabeled AFP codiffused and comigrated with alpha 1 electrophoretic mobility in a manner identical to that of added carrier cord serum AFP [36].

Regulatory relationships of AFP

• Western blot assay also demonstrated that AFP promoted the expression of mutative p53 and p21(ras) proteins, and the increased rate of those proteins was 13.0%, 39.9%, and 70.9%, as well as 35.2%, 102.6%, and 46.8% at 6, 12, and 24 h, respectively, as compared with the control [37].
• Treatment with MMC of AFP-gastric cancer cells enhanced their susceptibility to LAK-T cells and induced ATBF1 gene expression [38].
• These results indicate that the ability of extracellular matrix materials to enhance attachment and/or growth is different from that to enhance AFP and albumin production in HuH-6 and probably in HuH-7 [39].
• The targeted expression of the human interleukin-2/interferon alpha2b fused gene in alpha-fetoprotein-expressing hepatocellular carcinoma cells [40].
• Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation [41].
• This represents the first direct evidence that ZHX2 represses AFP [42].

Other interactions of AFP

• Interestingly, in most cases, there was no correlation between GPC3 and AFP values [43].
• These findings provide novel evidence that p33(ING1b) represses AFP transcription by at least two mechanisms, one of which includes p53 [23].
• Although individual family members display an approximate clock-like evolution, there are significant deviations-the rates of divergence for AFP differ by a factor of 7, the rates for ALB differ by a factor of 2 [44].
• When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls) [24].
• The characteristics, including metastatic potential, of 5 xenografts of alpha-fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined [2].

Analytical, diagnostic and therapeutic context of AFP

• Western blot analysis of proteins present in developmentally staged, liver nuclear extracts reveal a one-to-one correlation between activation of p53 protein and repression of AFP during hepatic development [19].
• This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy [3].
• Although the determination of AFP levels in maternal blood and amniotic fluid is widely used in the prenatal diagnosis of NTDs, demonstration of AFP in amniotic fluid cells by means of immunocytochemistry has not been described [45].
• The phylogeny of the AFP molecule should prove useful for investigators seeking markers for animal models of human diseases, serological cross-reactivity between AFP molecular species, identification of larval or fetal protein homologs of AFP, and provide strategies for biochemical purification and physiological studies [22].
• The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry [46].

References