Alpha Fetoprotein

Mercuric chloride (HgCl 2 ) has been shown to affect the male reproductive organs, and oxidative stress has been linked with hypospermatogenesis and with male infertility. However, the specific mode of impairment of spermatogenesis during HgCl 2 exposure has not yet been clarified fully. Because of the involvement of 17β-estradiol (E2) in the male reproductive tract and its putative role on spermatogenesis, the present study aimed to investigate the possibility that HgCl 2 -induced oxidative stress-mediated modulation of the E2 level exerts adverse effects on testicular steroidogenic and gametogenic activities. HgCl 2 treatment at 50 and 100 ppm for 90 days by continuous oral administration in the drink water resulted in significant dose-dependent fashion decrease in serum and testicular E 2 levels and an increase in testicular testosterone levels in dose-dependent manner, without statistical alteration in serum testosterone level among HgCl 2 exposed groups compared to the control. Cauda epididymal sperm count and motility were decreased significantly (p<0.01), in a dosedependent manner, in the HgCl 2 -treated groups, and qualitative examination revealed inhibition of spermatogenesis and the preferential loss of maturing and elongated spermatids. The seminiferous tubules were dilated in treated animals. When compared to the control, increase in lipid peroxidation due to toxic effects of HgCl2 was accompanied by significant reduction (p<0.01) in antioxidant enzymes activities, superoxide dismutase, catalase, and glutathione peroxidase of testes, implicating the presence of oxidative tissue damage. Furthermore, these tissue injuries caused functional impairment as evidenced with testicular elevated activity of lactate dehydrogenase. Unless oxidative stress can lead to cancer development, testis' tumor markers as beta human chorionic gonadotropin and alpha-fetoprotein levels have shown no significant differences in the HgCl 2 -exposed group compared with respect to the control. Large quantities of metal accumulated in the testis tissue are in agreement with the testis-activity failure verified in this tissue. These findings suggest that a decrease in E2 level after mercury exposure may render testis more susceptible to oxidative damage leading to its functional inactivation, thus providing new dimension to mechanisms underlying heavy metalinduced male infertility.

Ovarian cancer can be cured in up to 90% of cases if diagnosed early. CA125, the most studied ovarian cancer biomarker, exhibits poor sensitivity for detecting early disease stages and low specificity to malignancy. RECAF, the alpha-fetoprotein receptor, is a wide-spectrum oncofetal antigen with clinical potential for cancer diagnosis, screening, and monitoring. This study evaluated the performance of RECAF as a diagnostic tool and the sensitivity of a combination of RECAF and CA125 to detect early stages of ovarian cancer at a cutoff resulting in 100% specificity among healthy women. This retrospective case–control study was designed to measure the serum levels of RECAF and CA125 in normal individuals (n = 106) and cancer patients stages I/II (RECAF, n = 32; CA125, n = 35) and III/IV (RECAF, n = 49; CA125, n = 51). A competitive chemiluminescence assay was developed to measure the circulating RECAF. To eliminate any false positives, we classified as positive any patient with a RECAF or a CA125 value higher than their respective 100% specificity cutoff. We have shown that RECAF discriminated cancer and healthy donors better than CA125, particularly in the early stages (AUCRECAF = 0.96 and AUCCA125 = 0.805). CA125 sensitivity was lower in the early stages than in the advance stages; RECAF sensitivity was high at all stages. A combination of CA125 and RECAF detected three out of four early-stage patients, with no false positives. In conclusion, the combination of RECAF and CA125 serum values provides the specificity and the sensitivity necessary to screen for ovarian cancer and in particular, to detect early stages of the disease.

The risk of having a Down's syndrome term pregnancy was estimated using maternal age and the results of two maternal serum alpha-fetoprotein (AFP) tests carried out between 14 and 20 weeks gestation. The estimates of risk were derived from published data and the AFP results from nine affected and 14.5 unaffected pregnancies in which repeat testing had been carried out. Repeat AFP testing is unjustified in antenatal screening programmes for Down's syndrome, but if a second test happens to have been done, the appropriate estimate of risk that would be applicable when counselling individual patients depends on both results. For example a woman aged 3.5 years and 6 months with a first AFP level of 0.50 multiples of the normal median (MOM) was estimated to have a risk of 1 : 172. If a second test were donc on a fresh sample and the AFP level werc 0.80 MOM then the estimated risk would be 1:216 which is highcr than the estimated risk of 1:3.53 obtained if the second test were regarded as the only result. Estimates of risk are given for maternal serum AFP results in first and second tests ranging from 0.40 to 2-50 MOM.

Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture.FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2–4 fold lower (P < 0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P < 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space.Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA.Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.

Hepatocellular carcinoma (HCC) is the most recurrent hepatic malignancy and the third in the cancer-related casualties in the west. The frequently-documented causes of HCC are chronic liver infections by hepatitis B virus or hepatitis C virus, nonalcoholic fatty liver disease, cirrhosis, exposure to aflatoxins and tobacco smocking, etc. Clinical presentation of this fatal disease ranges from asymptomatic to upper abdominal pain or common health conditions like weight loss or lethargy. Among current surveillance strategy for suspected patients, liver imaging and serum alpha fetoprotein estimation has been regularly recommended. However, sensitivity of this diagnostic methodology especially in early detections, often suffers from compromised sensitivity and selectivity. Various image based and serological biomarkers for HCC has been introduced in recent decades with varied sensitivity as stand-alone or combined diagnostic protocol. The current article will review the status of HCC diagnosis with respect to common diagnostic protocol, and upcoming novel biomarkers.

A primary extragonadal germ cell tumor of the retroperitoneum was diagnosed in a 47-year-old man without elevated serum alpha-fetoprotein, human chorionic gonadotropin, or lactate dehydrogenase levels. The diagnosis was made by histologic analysis after resection. The patient responded well to a combination of cisplatin, etoposide, and ifosfamide, achieving a partial response with four cycles. Residual tumor resection revealed necrotic tissue only. The patient was alive and disease free 24 months after diagnosis. The diagnostic difficulties of this particular situation are discussed. UROLOGY 58: 281xv-281xviii, 2001.

Introduction: Testicular tumors can be classified as seminomatous and non-seminomatous germcell tumor (NSGCT) types. Mixed germ cell tumors contain more than one germ cell component and are much more common than any of the pure histologic forms representing 32%-60% of all germ cell tumors. The composition of these tumors varies. Here we present a rare case of a mixed germ cell tumor composed of seminoma, Yolk sack tumor and teratoma containing a sarcoma component of somatic type malignancy.

Background The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate. Methods A literature search identified potential markers for hepatocellular carcinoma. These markers were analysed and justification was provided for these factors' inclusion to (or exclusion from) the markers of hepatocellular carcinoma (HCC).

Given the tendency of a proportion of sacrococcygeal teratomas (SCT) to recur, we evaluated whether serial tumor marker measurements are helpful in the management of these children. Between 1985 and 2006, 32 children with SCT were followed up for 1-15 years, and a total of 344, 197, and 193 serial samples for serum alphafetoprotein (AFP), CA 125, and CA 19-9 were analyzed, respectively. Six children with neonatal SCT developed eight recurrences. Serum AFP was elevated in two of two children prior to diagnosis of malignant recurrences (yolk sac tumor and adenocarcinoma), and CA 125 was elevated in one third of mature and one third of immature recurrences. CA 19-9 remained within reference values in relation to recurrences of neonatal SCT. Taken together, serum CA 125 measurements may complement the use of serum AFP in the follow-up of SCT.

Background: Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors.

Objective This study was designed to investigate the relationship between the second trimester maternal serum markers and adverse pregnancy outcomes in healthy newborns. Materials and methods A total of 749 women who delivered in our institution with complete follow up and second-trimester triple marker test data available were included in the study. Women with multiple pregnancies, chronic diseases, diabetes mellitus, obesity, smokers and infants with chromosomal and congenital abnormalities were excluded. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated estriol (uE3) values were investigated in our cohort who developed preeclampsia (n = 28), gestational diabetes (GM) (n = 69), preterm labor-birth (n = 100), oligohydramnios (n = 37) and macrosomia (n = 59) by using receiver operating characteristic (ROC) curve analysis, with chi-square and Pearson’s correlation tests. Results Women with uE3 ≤ 1.26 MoM (P = 0.001, AUC = 0.666), HCG > 1.04 MoM (P = 0.032, AUC = 0.599) or AFP ≤ 0.69 MoM (P = 0.049, AUC = 0.600) values significantly developed oligohydramnios. Also, macrosomic infants were observed in women who had HCG values > 0.86 MoM (P = 0.047, AUC = 0.578). Patients with HCG > 1.04 MoM (P = 0.04, AUC = 0.565) and uE3 ≤0.88 MoM (P = 0.049, AUC = 0.571) developed GDM. HCG levels ≥2.5 or ≥3 MoM were significantly associated with the development of oligohydramnios [P = 0.005; OR = 4 (95% CI: 1.7–9.7)], [P = 0.008; OR = 4.9 (95% CI: 1.7–13.7)], respectively. When women with adverse (n = 237) and normal (n = 512) outcomes were compared there were significant differences in maternal serum AFP (1.40 ± 0.84 vs. 1.23 ± 0.75 MoM, P = 0.006) and uE3 values (1.38 ± 1.42 vs. 1.45 ± 0.98 MoM, P = 0.001). Conclusions Serum estriol, AFP or HCG values in triple test results may be associated with development of oligohydramnios, gestational diabetes and macrosomia in women with healthy and normal appearing fetuses.

Beckwith-Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alphafetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith-Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the diagnosis of an extremely aggressive hepatoblastoma. The latter was successfully treated with pre-surgical reductive chemotherapy, gross total mass resection, and subsequent chemotherapy. Based on this observation, the tumor surveillance routinely suggested every 3 months should be more intense and with closer time intervals in newborns with severe BWS phenotype. We suggest monitoring neonatal αFP every 20 days in such cases.

A sensitive and versatile methodology involving recordable compact disks as molecular screening surfaces and a standard optical CD/DVD drive as detector, is reported. Quantitative immunoanalysis, in microarray format, of a cancer marker (alpha-fetoprotein, AFP) and a selective herbicide (atrazine) on four types of audio-video disc was conducted. Enzyme or gold nanoparticle-labeled antibodies were used as tracers, forming a precipitate on the sensing disk surface. The principle of disk reading is based on capture of analog signals with the disk drive that were proportional to the darkness of the immunoreaction product. Detection limits for AFP (8.0 μg L −1 ) and for atrazine (0.04 μg L −1 ) were under the threshold needed to detect nonseminomatous testicular cancer, and below the maximum E.U. residue limit for drinking water, respectively. The described methodology improves the previous developments using CDs and highlights the enormous potential of immunoassay methods using standard audio-video disk surfaces in combination with the CD/DVD drive for clinical analysis, drug discovery, or high-throughput multiresidue screening applications.

Hereditary tyrosinemia type 1 (HT1) is an increasingly recognized inborn error of metabolism among Egyptian children. This study was undertaken to define the presenting clinical, biochemical and imaging features and outcome of 2-(2-motrp-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and liver transplantation in a cohort of Egyptian children diagnosed with HT1.

Presently, orthotopic liver transplant is the major therapeutic option for patients affected by primary liver diseases. This procedure is characterized by major invasive surgery, scarcity of donor organs, high costs, and lifelong immunosuppressive treatment. Transplant of hepatic precursor cells represents an attractive alternative. These cells could be used either for allogeneic transplantation or for autologous transplant after ex vivo genetic modification. We used stromal cells isolated from adipose tissue (AT-SCs) as platforms for autologous cell-mediated gene therapy. AT-SCs were transduced with lentiviral vectors expressing firefly luciferase, allowing for transplanted cell tracking by bioluminescent imaging (BLI). As a complementary approach, we followed circulating human α1-antitrypsin (hAAT) levels after infusion of AT-SCs overexpressing hAAT. Cells were transplanted into syngeneic mice after CCl(4)-induced hepatic injury. Luciferase bioluminescence signals and serum hAAT levels were measured at different time points after transplantation and demonstrate persistence of transplanted cells for up to 2 months after administration. These data, along with immunohistochemical analysis, suggest engraftment and repopulation of injured livers by transplanted AT-SCs. Moreover, by transcriptional targeting using cellular tissue-specific regulatory sequences, we confirmed that AT-SCs differentiate towards a hepatogenic-like phenotype in vitro and in vivo. Additionally, in transplanted cells reisolated from recipient animals' livers, we detected activation of the α-fetoprotein (AFP) promoter. This promoter is normally transcriptionally silenced in adult tissues but can be reactivated during liver regeneration, suggesting commitment towards hepatogenic-like differentiation of engrafted cells in vivo. Our data support AT-SC-mediated gene therapy as an innovative therapeutic option for disorders of liver metabolism.

With the advent of induced pluripotent stem cell (iPSC) technology, it is now feasible to generate iPSCs with a defined genotype or disease state. When coupled with direct differentiation to a defined lineage, such as hepatic endoderm (HE), iPSCs would revolutionize the way we study human liver biology and generate efficient "off the shelf" models of human liver disease. Here, we show the "proof of concept" that iPSC lines representing both male and female sexes and two ethnic origins can be differentiated to HE at efficiencies of between 70%-90%, using a method mimicking physiological relevant condition. The iPSC-derived HE exhibited hepatic morphology and expressed the hepatic markers albumin and E-cadherin, as assessed by immunohistochemistry. They also expressed alpha-fetoprotein, hepatocyte nuclear factor-4a, and a metabolic marker, cytochrome P450 7A1 (Cyp7A1), demonstrating a definitive endodermal lineage differentiation. Furthermore, iPSC-derived hepatocytes produced and secreted the plasma proteins, fibrinogen, fibronectin, transthyretin, and alpha-fetoprotein, an essential feature for functional HE. Additionally iPSC-derived HE supported both CYP1A2 and CYP3A4 metabolism, which is essential for drug and toxicology testing. Conclusion: This work is first to demonstrate the efficient generation of hepatic endodermal lineage from human iPSCs that exhibits key attributes of hepatocytes, and the potential application of iPSC-derived HE in studying human liver biology. In particular, iPSCs from individuals representing highly polymorphic variants in metabolic genes and different ethnic groups will provide pharmaceutical development and toxicology studies a unique opportunity to revolutionize predictive drug toxicology assays and allow the creation of in vitro hepatic disease models. (HEPATOLOGY 2009;50:000-000.) Abbreviations: ELISA, enzyme-linked immunosorbent assay; HE, hepatic endoderm; hESC, human embryonic stem cell; iPSC, induced pluripotent stem cell; MEF, mouse embryonic fibroblast; PBS, phosphate-buffered saline; PHH, primary human hepatocyte; From the

Background. Our aim was to assess the capability of Barcelona Clinic Liver Cancer (BCLC) staging system in allocating stage A patients to hepatic resection (HR) and the effect on survival. Methods. We enrolled 132 patients with hepatocellular carcinoma (HCC) amenable to HR. All patients underwent ultrasound (US)-guided anatomical resection (B2 segments) and then postoperative results were evaluated. Results. Results showed 95% of patients were Child A, 49% in BCLC A1, 21% in A2, 6% in A3, and 24% in A4. No 30-day mortality occurred. Overall survival got worse from A1 to A4 (P = 0.0271), while no differences were found in Childs A patients with or without portal hypertension (P = 0.1674). Multivariate analysis (Cox model) shows that only AFP (\20 ng/ml) was an independent predictor of survival: If the AFP is incorporated in BCLC staging system (all A1 and A2 patients with abnormal AFP levels were included in A3 subgroup), 5-year survival rate including normal AFP for A1 was 57% and for A2 was 65%, whereas the survival rates impaired in the worst candidates (5-year survival rate including AFP abnormal for A3 and A4 was 36%; P = 0.002). So, introducing AFP in BCLC classification it is possible to simplify the algorithm in only 2 classes, well-separated in survival curves (class 1 [AFP-]: 60%; class 2 [AFP?]: 37%; P = 0.0001). Conclusion. Our experience stressed the high value of BCLC system in staging of patients with HCC, but underlined that in selected patients (normal AFP) even A2 group may benefit from HR with a good survival.

This pictorial essay aims to show the clinical mimicry of hepatocellular carcinoma (HCC) and its diagnostic difficulty, and to create awareness among clinicians and radiologists of potential diagnostic pitfalls. A selected consecutive series of hepatectomies with proven HCC over a three- year period, identifying clinical presentation, blood results and imaging of patients with difficult preoperative diagnosis, was reviewed. The imaging

Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase activity (AChE) are described for gestational weeks 11-14 using rocket gel immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19) enzyme antigen immunoassay for AChE activity measurement. The normal ranges were established by the examination of 281 amniotic fluid samples from 281 normal pregnancies. AFP was found to increase from a median level of 14.0 MIUII at 11 weeks to a maximum at 13 weeks (median= 18.0 MIUII) (P<0.05), thereafter falling (not sidcant). No AChE test result exceeded 4.8 nkat/l. In addition, AFP and AChE values for three cases of fetal malformation, identified by the biochemical analyses of amniotic fluid, are given. These cases included two fetuses with a neural tube defect and one fetus with an abdominal wall defect. Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and AChE values were all high.

We systematically reviewed the evidence for determining the best radiological imaging for characterizing hepatocellular carcinoma (HCC) in cirrhotic patients in 997 articles between 1995 and 2001. We selected only prospective and retrospective cohorts of patients, excluding both case reports and studies without separate data on HCC. Only 29 studies, comprising 918 patients, fulfilled the inclusion criteria: 10 used the explanted liver as the reference standard of diagnosis. All except one, either found no statistically significant difference between imaging modalities or had no direct comparison of sensitivity between different modalities of imaging; 16 studies evaluated HCC among cirrhotic patients and had biopsy or imaging as the reference standard for diagnosis. However, no one imaging technique was shown to be superior. In two studies, data of a HCC subgroup was derived from the studies evaluating different kinds of focal hepatic lesions. No conclusion could be drawn because of the small sample size. One study addressed the issue of therapeutic impact. The evidence for choosing the best modality of imaging for characterizing HCC in cirrhotic patients is inadequate. Large multicentre studies with defined reference standards for diagnosis, and studies evaluating therapeutic impact are needed.

Alpha-fetoprotein (AFP) is a common tumoral marker in pediatric neoplasms; increased serum levels are usually encountered in tumors arising from tissues producing AFP during fetal life. However, elevation of such protein is rarely found in patients with Wilms tumor (WT). Three patients with WT and elevated serum AFP were studied over the course of the disease. One patient had left WT with invasion of aorto-caval lymph nodes and lung metastases. The second patient was referred to our center for abdominal recurrence of bilateral WT whereas the third showed right WT with inferior vena cava thrombosis. AFP levels demonstrated a trend parallel to decrease/increase of tumor size, with further elevation in patients with metastases. Elevated AFP serum levels in patients with WT could be related to peculiar histological features and serial dosage might be a useful diagnostic and prognostic test.

A case of pancreatoblastoma (PB) in a 2 month-old male infant with incomplete Beckwith-Wiedemann syndrome is presented. Clinical examination disclosed left hemihypertrophy, macroglossia, bilateral exophthalmos, and enlargement of the left testis. Imaging with ultrasound and computed tomography scan showed a well-defined, heterogeneous, and grossly cystic mass arising from the head of the pancreas. Serum alpha-fetoprotein (AFP) level was elevated. The tumor was completely resected, and the histological analysis showed PB. The patient's recovery was uneventful, and AFP returned to normal values after surgery. The child has been disease-free for 5 years, and his serum AFP remained within normal values. Six other examples of this association, PB, and Beckwith-Wiedemann syndrome are recorded in the literature. The risk of developing tumor in this syndrome (complete and incomplete form) increases when hemihypertrophy is present, and the need for routine screening examination is warranted. Beckwith-Wiedemann syndrome was suggested to be a favorable biological marker for survival in children who have intraabdominal tumors. D

Objective : This paper aims to highlight the clinical features, investigations and treatment of retroperitoneal teratomas condition. Methods : 12 patients (8 females and 4 males, age range-2 months to 14 yrs) of retroperitoneal teratoma admitted to the department of Pediatric Surgery, King George Medical University, Lucknow between 1980 and 2004 were studied. Investigations included hematology, plain X-ray of the abdomen, intravenous urography, ultrasound, computerised tomography (CT) of the abdomen (after 1990, 8 patients), and serum alpha-fetoprotein assay (after 1991, 6 patients, preoperatively). All patients underwent surgery. Serum alpha-fetoprotein assay was used during follow-up to detect recurrence. Results : Majority of the tumors were left pararenal in location. In two patients there was bilateral involvement. In all except one, the tumor could be excised easily preserving the kidneys. In one child with a massive cystic tumor with bilateral involvement, the tumor was marsupialised in the first stage and excised subsequently. One child died postoperatively, the other 11 children are well and there has been no tumor recurrence on follow-up. Conclusions : Retroperitoneal teratomas are uncommon lesions in children mostly arising in close relation to the kidneys. The majority are benign but complete excision is necessary for cure. Even large tumors with bilateral involvement of the retroperitoneum can be excised while preserving adjacent organs. Serum alphafetoprotein assay is a reliable method of detecting recurrence. [Indian J Pediatr 2006; 73 (3) : 221-223]

In order to differentiate whether slight alpha-fetoprotein (AFP) increases observed in any patient are due to germ cell tumours (GCT) or to liver diseases (including hepatotoxicity of chemotherapy), we measured the binding ratio of the AFP to concanavalin A (ConA). A total of 218 serum samples were studied: 102 samples from 72 GCT patients and 116 from patients with liver diseases. Considering a cut-off vahte to be a ConA binding ratio of 15%, we distinguished AFP produced by GCT (> 15%) from AFP produced by tumoral and non-tumoral liver diseases (~15%) with a sensitivity of 98% and specificity of 100%. The difference between mean ConA binding ratios was statistically sign&ant (P < 0.0001). We did not distinguish AFP produced by tumoral and non-tumoral liver diseases. ConA binding ratio may be a sensitive index to distinguish whether an increase of AFP concentration as low as 15 U/ml in a GCT patient during the follow-up is produced by the tumour or by liver dysfunction (including hepatotoxicity of chemotherapy).

The aim of this prospective study was to verify normal serum AFP (alpha-fetoprotein) levels in jaundiced breastfed infants with indirect hyperbilirubinemia. Methods: The study was conducted in clinically jaundiced breastfed infants, 20, or more, days old, referred to our outpatient ambulatory. Inclusion criteria were: birth at term after a physiologic pregnancy, with an Apgar score N 7 at 1 and 5 min, no evidence of congenital anomalies or diseases, direct bilirubin b 1 mg/dl, normal values of α-1-antitrypsin, glucose-6-phosphate dehydrogenase, thyroid stimulating hormone, triiodothyronine, tyroxine, and normal growth. 30 non-jaundiced breastfed infants age-weight-matched, were used as control group. Results: 98 jaundiced breastfed infants satisfied inclusion criteria. Their mean serum concentration of AFP was significantly higher than control infants (3548 vs 1095 ng/ml, p b 0.001). Serum AFP levels of jaundiced infants were directly associated with serum indirect bilirubin and γ-glutamyltranspeptidase concentrations. Conclusions: The most probable explanation of elevated AFP in jaundiced breastfed infants may be the presence in human milk of one or more factors which affect hepatocyte growth and/or function. Based on our finding we demonstrated that in jaundiced breastfed infants normal range of serum AFP levels are higher than previously published data for healthy infants. Our data can be useful for a right interpretation of AFP levels in breastfed infants with prolonged jaundiced and may be used to avoid unnecessary investigations.

Learning Objectives After completing this course, the reader will be able to: Discuss the basic epidemiology of pediatric CNS GCTs.Perform the diagnostic workup and full evaluation that is necessary when evaluating a patient with a suspected CNS GCT.Select among the different therapeutic alternatives employed in treating children with a CNS GCT. CME This article is available for continuing medical education credit at CME.TheOncologist.com Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressu...

Anencephaly is a lethal embryological malformation of the central nervous system in which the brain and the cranial vault are grossly malformed due to defect in the neurulation process1.  It can be detected during the pregnancy with ultrasonography and maternal serum alpha-fetoprotein (MSAFP ). We present a rare case of a 19 year old primipara , with no antenatal care, who delivered postdate by cesarean section , an anencephalous female child with cleft lip and palate .This case insists on the relevance of antenatal examination and care for early diagnosis and appropriate management during pregnancy.

Alpha-fetoprotein (AFP)-producing gastric cancer (AFP-GC) is a highly malignant variant of adenocarcinoma with aberrant hepatocellular phenotype. A detailed understanding of the regulation of its liver phenotype is lacking. Liver-enriched nuclear factors (LENFs) are implicated in the transcriptional regulation of AFP in the fetal liver. To investigate the regulatory role of LENFs in AFP-GCs, the expression of LENFs including CCAAT/enhancer binding protein (C/EBP)-β, C/EBP-α, hepatocyte nuclear factor (HNF)-1α, HNF-1β and HNF-4α was investigated in 3 cell lines of AFP-GC and 7 cell lines of control GC. The liver activating protein (LAP), an activating isoform of C/EBP-β, was predominantly expressed in AFP-GCs, whereas the liver inhibitory protein (LIP), an inhibitory isoform of C/EBP-β, predominated in the control GCs. HNF-1α was relatively suppressed in AFP-GCs. HNF-4α was expressed in one of three AFP-GC cell lines. C/EBP-α and HNF-1β were expressed at the same levels in both cell types of GC. AFP-GCs expressed a set of hepatocyte-related proteins (e.g., transferrin and albumin) while they still retained the several glandular cell-related proteins (e.g., MUC2). The induction of LIP reduced transferrin expression and induced CEA expression in an AFP-GC line. Collecting these results, it was suggested that the contribution of LENFs, especially isoforms of C/EBP-β, is possibly important in phenotypic regulation of AFP-GCs.

AIM: To investigate the antitumor activities of tachyplesin on human hepatocellular carcinoma (HCC) cells. METHODS: Tachyplesin, isolated from acid extracts of Chinese horseshoe crab (Tachypleus tridentatus) hemocytes, was used to treat the human HCC cell line SMMC-7721. Effects of tachyplesin on the proliferation of SMMC-7721 cells were measured with trypan blue dye exclusion test and HE staining. The morphology and

pregnancies. Perhaps a United Kingdom collaborative study should begin to investigate the reasons for such wide population variance in the reports for the median multiple of the median for Down's affected pregnancies. Until such studies are carried out, screening for Down's syndrome based on low maternal serum a fetoprotein concentration is premature.

The levels of a-fetoprotein mRNA in mice are determined by at least two trans-acting, unlinked genes, raf and Rif. raf determines the basal levels of a-fetoprotein mRNA in adult mice, while Rifdetermines its degree of inducibility during liver regeneration. To determine whether these regulatory loci affect other structural genes, we screened a murine fetal liver cDNA library for clones containing mRNA sequences that decrease after birth. One such clone, termed pHl9, was identified, and its mRNA was shown to be under

The value of determination of maternal serum of alpha-fetoprotein (MSAFP) concentration in i he second trimester is well established. In addition to open neural tube defects, pregnancies associated with elevated second-trimester MSAFP have been shown to be at increased risk for a variety of problems, including low birth weight, preterm delivery, and pregnancy-induced hypertension (PIH). We evaluated the potential usefulness of MSAFP in the early third trimester. MSAFP concentration was determined in over 200 women at the time of glucose screening. Results were analysed with regard to gestational age at sampling, maternal weight, race, diabetes, and presence of twins. MSAFP was twice as high in twin gestation, but not affected by race or the presence of diabetes. In contrast to levels in early gestation, third-trimester MSAFP does not appear to be predictive of preterm delivery, low birth weight, or PIH.

0~-Fetoprotein (AFP) is an oncofetal antigen believed to play an important role in normal development and carcinogenesis but very little is known about such a role. We have investigated here the role of AFP in neural retina development by selectively neutralising AFP in vitro. AFP has been immunohistochemically located in different cells and layers of the retina during its development, 4-day-old embryos being the earliest developmental stage when AFP is detected in the growing ganglion cell layer. Sevenday-retinae treated with antibodies to AFP in organ culture for 3 days did not continue to develop in the same way that they do in the egg. Neither the plexiform layers nor the buds of photoreceptor cells were observed after this culture period. In contrast, 7-day retinae cultured in the presence of non-immune serum developed in a manner similar to retinae in ovo. We present here the first evidence, derived by selectively blocking AFP in vitro with specific antibodies for an essential role of AFP in the normal development of the chick retina.

OBJECTIVE: Maternal plasma is an accessible biological fluid for investigating proteins modulated during fetal development and maintenance of pregnancy. Here we present demographics and pilot data from our ongoing ''Plasma Pregnancy Proteome'' study to identify (a) preclinical biomarkers for adverse outcomes such as PROM and preeclampsia and (b) proteins reflecting changes in fetal and maternal physiology during development.

Aberrant expression of the alpha-fetoprotein (AFP) gene is characteristic of a majority of hepatocellular carcinoma cases and serves as a diagnostic tumor-specific marker. By dissecting regulatory mechanisms through electromobility gel shift, transient-transfection, Western blot, and in vitro transcription analyses, we find that AFP gene expression is controlled in part by mutually exclusive binding of two trans-acting factors, p53 and hepatic nuclear factor 3 (HNF-3). HNF-3 protein activates while p53 represses AFP transcription through sequence-specific binding within the previously identified AFP developmental repressor domain. A single mutation within the DNA binding domain of p53 protein or a mutation of the p53 DNA binding element within the AFP developmental repressor eliminates p53-repressive effects in both transient-transfection and cell-free expression systems. Coexpression of p300 histone acetyltransferase, which has been shown to acetylate p53 and increase specific DNA ...

Background  We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE. Methods  We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence. Results  Of 199 patients, 139