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Fertility and Sterility Aug 2021To determine if high alpha-fetoprotein (AFP) level in vaginal blood collected on a sanitary pad can assist with detecting an active miscarriage.
OBJECTIVE
To determine if high alpha-fetoprotein (AFP) level in vaginal blood collected on a sanitary pad can assist with detecting an active miscarriage.
DESIGN
A prospective cohort study.
SETTING
Academic medical center.
PATIENT(S)
Five groups were evaluated: women with active miscarriage, pregnancy of unknown location, completed miscarriage or extrauterine pregnancy (EUP), ongoing pregnancy, and undergoing elective dilation and curettage (D&C).
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
For each patient, AFP level in the vaginal blood collected on a sanitary pad was quantified.
RESULT(S)
The vaginal blood AFP median levels (and their ranges) were 3.7 IU/mL (0.5-739.2) and 4,542 IU/mL (15.6-100,000) in the active miscarriage (n = 16) and the elective D&C (n = 24) groups, respectively. Alpha-fetoprotein was detected in all elective D&C and active miscarriage cases except in 1 case. In the ongoing pregnancy group (n = 35), only 2 of 35 specimens showed detectable AFP levels. In the pregnancy of unknown location (n = 12) and the completed miscarriage or EUP (n = 10) groups, no AFP was detected. Receiver operating characteristic analysis demonstrated 93.7% sensitivity and 97.8% specificity for the detection of an active miscarriage (cutoff 0.61 IU/mL; area under the curve 0.96).
CONCLUSION(S)
Alpha-fetoprotein can be extracted from vaginal blood collected on sanitary pads. A high level of vaginal AFP can assist with the same-day detection of an active miscarriage. This novel test is useful in differentiating active miscarriages from ongoing pregnancies, completed miscarriages, and EUPs and, therefore, it reduces uncertainty, anxiety level, and number of repeat office visits.
Topics: Abortion, Spontaneous; Adult; Female; Humans; Middle Aged; Pregnancy; Pregnancy Trimester, First; Vagina; Young Adult; alpha-Fetoproteins
PubMed: 33461753
DOI: 10.1016/j.fertnstert.2020.10.006 -
Biochimica Et Biophysica Acta Apr 2000Alpha-fetoprotein (AFP) is a major serum protein produced during fetal development. Experimental findings suggest that AFP has antiestrotrophic activity and that it can...
Alpha-fetoprotein (AFP) is a major serum protein produced during fetal development. Experimental findings suggest that AFP has antiestrotrophic activity and that it can be developed as a therapeutic agent to treat existing estrogen-dependent breast cancer or to prevent premalignant foci from developing into breast cancer. The antiestrotrophic activity of AFP was reported to be localized to a peptide consisting of amino acids 447-480, a 34-mer peptide termed P447. A series of parsings and substitutions of amino acids in the P447 sequence was intended to identify the shortest analog which retained antiestrotrophic activity. Peptides related to P447 were generated using solid phase peptide synthesis. Several shorter peptides, including an 8-mer called P472-2 (amino acids 472-479, peptide sequence EMTPVNPG), retained activity, whereas peptides shorter than eight amino acid residues were inactive. The dose-related antiestrotrophic activity of AFP-derived peptides was determined in an immature mouse uterine growth assay that measures their ability to inhibit estradiol-stimulated uterine growth. In this assay, the maximal inhibitory activities exhibited by peptide P472-2 (49%), by peptide P447 (45%), and by intact AFP (35-45%) were comparable. The octapeptide P472-2 was also active against estradiol-stimulated growth of T47D human breast cancer cells in culture. These data suggest that peptide P472-2 is the minimal sequence in AFP, which retains the antiestrotrophic activity found with the full-length molecule. The synthetic nature and defined structure of this 8-mer peptide suggest that it can be developed into a new drug which opposes the action of estrogen, perhaps including the promotional effects of estradiol in the development of human breast cancer.
Topics: Amino Acid Sequence; Animals; Body Weight; Breast Neoplasms; Cell Division; Cells, Cultured; Dose-Response Relationship, Drug; Drug Design; Estradiol; Estrogen Receptor Modulators; Female; Humans; Mice; Molecular Sequence Data; Oligopeptides; Organ Size; Peptides; Protein Structure, Secondary; Uterus; alpha-Fetoproteins
PubMed: 10727847
DOI: 10.1016/s0925-4439(00)00008-9 -
BMC Research Notes Nov 2023This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II...
OBJECTIVE
This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).
RESULTS
A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Vitamin K; Vitamins; Bayes Theorem; ROC Curve; Biomarkers; Biomarkers, Tumor
PubMed: 37932802
DOI: 10.1186/s13104-023-06600-y -
American Journal of Public Health Jun 1979
Topics: Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; alpha-Fetoproteins
PubMed: 87133
DOI: 10.2105/ajph.69.6.552 -
Developmental Biology Dec 2009The four members of the albumin gene family encode the serum transport proteins albumin, alpha-fetoprotein, alpha-albumin, and vitamin D-binding protein. These genes are...
The four members of the albumin gene family encode the serum transport proteins albumin, alpha-fetoprotein, alpha-albumin, and vitamin D-binding protein. These genes are transcribed primarily in the liver with each having a different pattern of developmental expression. The tight linkage of these genes, particularly that of albumin, alpha-fetoprotein and alpha-albumin, and their liver-specific expression, has led to the suggestion that these genes share common regulatory elements. To directly examine whether the alpha-fetoprotein enhancer region could regulate the albumin gene family, expression of these genes was monitored in mice in which this region was deleted by homologous recombination. Our data indicate that this enhancer region is required for alpha-fetoprotein and albumin activation early in liver development and alpha-fetoprotein reactivation during liver regeneration, but that albumin, alpha-albumin, and vitamin D-binding protein expression later in hepatic development is not affected by the absence of these enhancers. We also demonstrate that RNA polymerase II loading on the alpha-fetoprotein and albumin promoters is reduced in the absence of this enhancer region, indicating a direct role for these enhancers in the assembly of the RNA Polymerase II complex during liver development.
Topics: Albumins; Animals; Base Sequence; Chromatin Immunoprecipitation; DNA Primers; Enhancer Elements, Genetic; In Situ Hybridization; Liver; Liver Regeneration; Mice; Mice, Knockout; Promoter Regions, Genetic; RNA Polymerase II; alpha-Fetoproteins
PubMed: 19782060
DOI: 10.1016/j.ydbio.2009.09.026 -
Seminars in Cancer Biology Feb 2011The mouse alpha-fetoprotein (AFP) gene is abundantly expressed in the fetal liver, normally silent in the adult liver but is frequently reactivated in hepatocellular... (Review)
Review
The mouse alpha-fetoprotein (AFP) gene is abundantly expressed in the fetal liver, normally silent in the adult liver but is frequently reactivated in hepatocellular carcinoma. The basis for AFP expression in the fetal liver has been studied extensively. However, the basis for AFP reactivation during hepatocarcinogenesis is not well understood. Two novel factors that control postnatal AFP repression, Zhx2 and Zbtb20, were recently identified. Here, we review the transcription factors that regulate AFP in the fetal liver, as well as Zhx2 and Zbtb20, and raise the possibility that the loss of these postnatal repressors may be involved in AFP reactivation in liver cancer.
Topics: Animals; Carcinoma, Hepatocellular; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Microarray Analysis; Transcription Factors; Transcriptional Activation; alpha-Fetoproteins
PubMed: 21216289
DOI: 10.1016/j.semcancer.2011.01.001 -
PeerJ 2023The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal... (Comparative Study)
Comparative Study
Levels of PIVKA-II and alpha-fetoprotein in unresectable hepatocellular carcinoma compared to healthy controls and predictive values of both markers with radiological responses after loco-regional interventions.
BACKGROUND
The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal was to assess the roles of PIVKA-II and AFP in predicting radiological response after loco-regional therapy.
METHODS
This prospective cohort study enrolled consecutive samples of HCC patients and healthy controls. Venous blood samples were obtained at baseline and after interventions to determine serum levels of PIVKA-II and AFP using the chemiluminescent microparticle immunoassay method. Radiologic responses were determined based on the WHO criteria.
RESULTS
Fifty-four HCC patients (mean age 58.9 years, 49 males) and 40 healthy controls (mean age 33.5 years, 26 males) were recruited. The median serum levels of PIVKA-II and AFP in HCC . healthy controls were 988.4 . 24.2 mAU/ml and 13.6 . 1.7 ng/ml, respectively (both < 0.001). With ROC curve analysis, the area under the curve (AUC) for PIVKA-II was 0.95 95% CI [0.90-0.99], and for AFP it was 0.98, 95% CI [0.95-1.0]). The cut-off value for PIVKA-II was 41.4 mAU/ml, and AFP was 4.8 ng/ml. PIVKA-II levels correlated significantly with radiological responses ( = 0.64, = 0.02) but not AFP ( = 0.09, = 0.2).
CONCLUSION
PIVKA-II and AFP levels are distinctive between unresectable HCC and healthy controls. However, PIVKA-II, not AFP, can predict the radiological response after loco-regional therapy.
Topics: Adult; Humans; Male; Middle Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Liver Neoplasms; Prospective Studies
PubMed: 37780370
DOI: 10.7717/peerj.15988 -
World Journal of Gastroenterology Jan 2016Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria,... (Review)
Review
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor's biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as (18)F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Fluorodeoxyglucose F18; Humans; Liver Neoplasms; Liver Transplantation; Patient Selection; Positron-Emission Tomography; Prognosis; Protein Precursors; Prothrombin; RNA, Messenger; alpha-Fetoproteins
PubMed: 26755873
DOI: 10.3748/wjg.v22.i1.232 -
Biochemistry. Biokhimiia Jan 2000Alpha-fetoprotein (AFP) is the main component of mammalian fetal serum. It is synthesized by visceral endoderm of the yolk sac and by fetal liver. Immediately after... (Review)
Review
Alpha-fetoprotein (AFP) is the main component of mammalian fetal serum. It is synthesized by visceral endoderm of the yolk sac and by fetal liver. Immediately after birth AFP level in blood decreases dramatically. AFP synthesis is reactivated in liver tumors and germinogeneous teratoblastomas, in a lesser degree after chemical and mechanical liver injuries followed by regeneration (i.e., acute viral hepatitis). AFP blood level change is an important marker for liver tumors that is widely used in clinical practice. Therefore, the study of the molecular and cellular mechanisms participating in regulation of the oncoembryonal protein AFP is an important task. On various experimental models it has been shown that the expression is regulated mainly on the transcriptional level, the AFP gene having a 7 kb regulatory region upstream. Within this region a tissue-specific promoter, three independent enhancers, and a silencer that is at least partially responsible for AFP gene expression decrease in adult liver have been defined. Some ubiquitous and some tissue-specific transcription factors, including hepatocyte nuclear factors (HNFs), which mediate the transcription of most of the liver-specific genes, have been shown to bind to the promoter. However, the mechanisms determining drastic changes of AFP synthesis level in the course of ontogenesis and carcinogenesis remain incompletely clarified. Also, little is known about negative regulators of AFP gene expression in cells of non-hepatic origin and in adult liver.
Topics: Animals; Enhancer Elements, Genetic; Gene Expression Regulation, Neoplastic; Models, Biological; Models, Genetic; Nuclear Proteins; Promoter Regions, Genetic; Rats; Transcription Factors; Transcription, Genetic; alpha-Fetoproteins
PubMed: 10702646
DOI: No ID Found -
Viruses Apr 2022Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for... (Review)
Review
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6-8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis B virus; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; alpha-Fetoproteins
PubMed: 35458505
DOI: 10.3390/v14040775