Angeliki Sarandakou

Tumor Markers In Biological Fluids Associated With Pregnancy

Proteins that are expressed by both malignant and healthy fetal tissues are recognized as oncofetal. These antigens are associated with cell proliferation and differentiation and are produced in high concentrations in pregnancy and malignancy. Their biological role in malignancy is the suppression of the hosts immune system, while in pregnancy they affect the maternal immune response, generating maternal tolerance toward the embryo. This review describes the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell carcinoma antigen (SCC), cancer antigen 15-3 (CA 15-3), mucin-like carcinoma-associated antigen (MCA), tissue polypeptide-specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), and prostate-specific antigen (PSA) in maternal serum (MS), umbilical cord serum (UC), and amniotic fluid (AF) and outlines their roles in the assessment of pregnancy and malignancy. All antigens studied, except CA 15-3, are oncofetal. The presence of considerable concentrations of AFP, hCG, CEA, CA125, SCC, MCA, TPS, CA 19-9, and PSA in AF during pregnancy may be attributed to their involvement in biological functions associated with fetal development, differentiation, and maturation. MS CEA, CA 15-3, and CA 19-9, in contrast to all the others, are not influenced significantly by pregnancy and thus remain reliable tumor markers in monitoring malignancy in pregnant patients.

Vascular Endothelial Growth Factor and Placenta Growth Factor in Intrauterine Growth-Restricted Fetuses and Neonates

The angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are respectively up- and downregulated by hypoxia. We aimed to study circulating levels of the above factors in intrauterine growth restriction (IUGR) and to correlate their levels with the customized centiles of the infants. The study included 25 IUGR and 25 appropriate for gestational age (AGA) full-term, singleton infants and their mothers. Maternal (MS), fetal (UC), and neonatal day 1 (N1) and 4 (N4) blood was examined. MS and N1 PlGF, as well as UC VEGF levels correlated with the customized centiles of the infants (r= 0.39, P=.007, r=0.34, P=.01, and r= -0.41, P=.004, resp). Furthermore, UC, N1, and N4 VEGF levels were higher in girls (r=0.36, P=.01, r=0.33, P=.02, and r=0.41, P=.005 resp). In conclusion, positive and negative correlations of examined factors with the customized centiles of the infant could rely on placental function and intrauterine oxygen concentrations-both being usually lower in IUGR cases-while higher VEGF levels in girls should possibly be attributed to the stimulating action of estrogens.

Age-related differentiations of Th1/Th2 cytokines in newborn infants

OBJECTIVE: To evaluate age-related differentiation of immune response in newborns by measuring serum concentrations of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) during the perinatal period. SUBJECTS AND METHODS: Fifty-seven healthy term neonates, their mothers and 25 healthy adults (controls) age-matched to the mothers were included in the study. Cytokine concentrations were measured in the umbilical cord (UC), and in first-day (1N) and fifth-day (5N) neonatal samples, compared with those in maternal serum (MS) and control serum samples. RESULTS: Serum IL-2 concentrations in the UC were markedly elevated compared with those in MS and controls (p < 0.0001), decreasing significantly thereafter up to 5N (p < 0.001). IL-4 serum concentrations did not differ significantly between the UC, 1N and 5N samples; they were, however, markedly elevated compared with those in MS (p < 0.001, p < 0.0007 and p < 0.0001, respectively) and controls (p < 0.05, p < 0.01 and p < 0.006, respectively). IFN-gamma serum concentrations were significantly lower in the UC compared with those in controls (p < 0.04), increasing significantly up to 5N (p < 0.03). Both IFN-gamma/IL-2 and IFN-gamma/IL-4 ratios increased significantly in 5N, compared with those in the UC (p < 0.001 and p < 0.03). CONCLUSION: Our findings indicate a differential cytokine balance at birth with enhanced expression of IL-2 and IL-4 against IFN-gamma. However, a regularization of immune response seems to proceed quickly during the early neonatal life.

Cytokine concentrations during the first days of life

OBJECTIVEnTo evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period.nnnSUBJECTS AND METHODSnForty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults.nnnRESULTSnIL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life.nnnCONCLUSIONnOur findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.

Soluble Fas Concentrations in the Follicular Fluid and Oocyte-Cumulus Complex Culture Medium From Women Undergoing In Vitro Fertilization: Association With Oocyte Maturity, Fertilization, and Embryo Quality

Objective: Because soluble Fas (sFas) inhibits Fas-mediated apoptosis by preventing death signal transduction, we determined sFas concentrations in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) from women undergoing in vitro fertilization (IV) in order to associate its concentrations with oocyte maturity, fertilization, and embryo quality. Methods: We studied 82 follicles from 11 healthy women (mean age, 35.4 ± 3.8 years) using a long protocol for IVF treatment. Individual FF and matched CM samples were immediately centrifuged at 4C and sFas concentrations were determined by sandwich enzyme-linked immunosorbent assays. Results: sFas concentrations were significantly higher in FF than in CM (P <.0001) and when oocytes were mature rather than immature (P <.002). Of 70 mature and 12 immature oocytes, 56 (80%) and two (16.6%), respectively, were fertilized. sFas concentrations in CM were significantly lower when mature oocytes were fertilized versus nonfertilized (P <.005). sFas concentrations in FF and CM were significantly related in an inverse manner to embryo quality (P = .004 and P = .0002, respectively). Conclusion: FF and CM from women undergoing IVF contain sFas. The latter has anti-apoptotic properties and levels are higher: in FF when oocytes are mature and in CM when oocytes are nonfertilized. Furthermore, FF and CM sFas concentrations are negatively correlated with embryo quality.

Soluble Fas antigen and soluble Fas ligand in early neonatal life

BACKGROUNDnAfter birth, apoptosis rates might slow down, compared to those in utero. Thus, factors, attenuating the apoptotic process, like the soluble forms of Fas/FasL system, may increase. AIM-STUDY DESIGN: Soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations were measured in maternal serum (MS), umbilical cord (UC) and neonatal serum in the first (1N) and fifth (5N) days after birth in order to evaluate the alterations of these molecules during the early neonatal period.nnnSUBJECTS AND METHODSnSoluble molecules were estimated in 35 healthy, appropriate for gestational age, full-term neonates, their mothers and in 25 healthy, nonpregnant women, age-matched to the mothers (controls), using enzyme immunoassays.nnnRESULTSnsFas concentrations in MS (p < 0.01), UC (p < 0.0001), 1N (p < 0.0003) and 5N (p < 0.02) were lower than those in controls. Neonatal sFas concentrations showed a significant increase from UC to 5N (p < 0.001). In contrast, sFasL concentrations were significantly elevated in all neonatal samples (UC, 1N and 5N) compared to those in MS and controls (p < 0.0001), showing also a significant elevation from UC to 5N (p < 0.0001).nnnCONCLUSIONnOur results demonstrate increasing serum concentrations of the soluble molecules sFas and sFasL during the first days after birth, indicating possibly a gradual decrease of apoptosis in early neonatal life.

Inflammatory cytokines and their soluble receptors during delivery and early life.

Term labor may affect inflammatory cytokine concentrations in the mother, fetus, and neonate. Inflammatory cytokines are potent factors of acute-phase response. Inducing prostaglandin biosynthesis, they cause changes in myometrium (1) and dilatation of the cervix, leading finally to labor. It may be possible that procedures controlling infection are relatively alike with those, which regulate the procedure of normal parturition (2). Cytokines influence physical immunity of the fetus–neonate by means of various actions – e.g. bone marrow cell maturation, involvement in phagocytosis, and expression of adhesion molecules (3). Neonatal defense is of paramount importance during the critical period of transition from the normally sterile intrauterine environment to the extrauterine one, characterized by exposure to multiple antigenic stimuli. Therefore, cytokines express a leading role in the perinatal period being present in maternal and fetal tissues (2). We studied serum concentrations of interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a), as well as their soluble receptors – sIL6R, sTNF RI, and sTNF RII – during the perinatal period and early life. Cytokine and their receptor concentrations were measured by means of ELISA in 57 samples of maternal serum (MS), umbilical cord (UC), and neonatal serum in the first day and the fifth day after birth (Table I). Sera from 45 healthy adults (controls) were also analyzed. IL-1b and IL-6 concentrations in MS and in all neonatal samples – UC, 1N, and 5N – were significantly elevated, compared to those in control samples (P< 0.0001). MS and UC concentrations depended significantly on the mode of delivery, being higher in vaginal delivery than that in elective cesarean section (P< 0.03, P< 0.0005). TNF-a concentrations in UC, 1N, and 5N samples were significantly higher than those in MS and controls, presenting a continuous increase from UC to 5N, whereas MS concentrations did not differ from controls. sIL-6R, sTNF RI, and sTNF RII concentrations in all studied samples were 3–4 orders of magnitude greater than the corresponding cytokine concentrations. Concentrations in all neonatal samples were significantly higher than those in MS and in controls. sIL-6R concentrations in MS did not differ from controls, whereas both sTNF RI and sTNF RII MS concentrations were significantly higher than those in controls. Only sTNF RI values in UC showed a dependence on the mode of delivery (P< 0.01).