Antiestrogenic and anticancer activities of peptides derived from the active site of alpha-fetoprotein.

Cyclo[EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER(+) human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep might form a dynamically stable putative Type I beta-turn, and thus be biologically active without additional amino acids. The studies presented in this paper were performed to determine whether TOVN and other small analogs of AFPep would inhibit estrogen-stimulated cancer growth and exhibit a broad effective-dose range. These peptides contained nine or fewer amino acids, and were designed to bracket or include the putative pharmacophoric region (TOVN) of AFPep. Biological activities of these peptides were evaluated using an immature mouse uterine growth inhibition assay, a T47D breast cancer cell proliferation assay, and an MCF-7 breast cancer xenograft assay. TOVN had very weak antiestrogenic activity in comparison to AFPep's activity, whereas TOVNO had antiestrogenic and anticancer activities similar to AFPep. OVNO, which does not form a putative Type I beta-turn, had virtually no antiestrogenic and anticancer activities. A putative proteolytic cleavage product of AFPep, TOVNOGNEK, significantly inhibited E(2)-stimulated growth in vivo and in vitro over a wider dose range than AFPep or TOVNO. We conclude that TOVNO has anticancer potential, that TOVNOGNEK is as effective as AFPep in suppressing growth of human breast cancer cells, and that it does so over a broader effective-dose range.

Fluorescence analysis with quantum dot probes for hepatoma under one- and two-photon excitation.

A new class of fluorescent probe produced by conjugating semiconductor quantum dots (QDs) with protein molecule is proposed as an alternative to conventional organic labels. However the fluorescence characteristics of the QD bioconjugates are not clear while they are excitied with one- or two-photon laser pulse. We synthesized specific immunofluorescent probes by linking QDs to alpha fetoprotein (AFP) antibody for specific binding alpha-fetoprotein -an important marker for hepatocellular carcinoma cell lines, and archived specific fluorescence detection with the QDs-Anti-AFP in nude mice. Then, we have analyzed the fluorescence characteristics of QDs-Anti-AFP and original QDs both under one- and two-photon excitations. The results demonstrated that QDs-Anti-AFP's fluorescent spectral and lifetime haven't varied much from that of original QDs. Moreover, QDs-Anti-AFP have exhibited higher fluorescence efficiency than QDs under two-photon examination.

Utilidad de la alfafetoproteína sérica materna como parámetro de riesgo del embarazo / Utility of maternal serum alpha-fetoprotein as a risk marker of the pregnancy

Objetivos: Demostrar que las embarazadas con valores elevados, sin justificación aparente, de alfafetoproteína sérica tienen un riesgo mayor de resultados perinatales adversos.Sujetos y métodos: Se estudiaron 43.424 gestantes desde el segundo trimestre del embarazo hasta el parto. Se calculó el riesgo relativo entre los valores de alfafetoproteína en suero materno (AFPSM) y los resultados perinatales siguientes: partos pretérminos, muertes fetales anterior y posterior a la semana 28 de gestación, y recién nacidos con bajo peso.Resultados: Se estudió la influencia de las concentraciones de AFPSM sobre 4 resultados perinatales adversos, observándose en todos ellos una diferencia significativa entre el grupo de gestantes considerado control (AFPSM 2,5 MDM). Se observó un mayor riesgo relativo en las gestantes con muerte fetal anterior a la semana 28 de gestación.Conclusiones: Se ha comprobado que existe una relación entre los valores elevados de AFPSM y el riesgo de un resultado perinatal adverso. Sin embargo, la AFPSM no se puede considerar un marcador de cribado adecuado, por su baja sensibilidad, para seleccionar gestantes con un riesgo elevado de un resultado adverso. (AU)

Alpha-fetoprotein derived synthetic peptides: assay of an estrogen-modifying regulatory segment.

This study describes the estrogen bioassay of a synthetic peptide fashioned after an amino acid sequence from human alpha-fetoprotein (HAFP). The synthetic peptide (P149), modeled after a portion of the estrogen binding pocket of rat/human AFP chimeras, was produced via F-MOC solid phase chemistry. Bioassay of P149 in the estrogen-sensitive immature rodent uterus demonstrated an anti-estrogenic (40-50% inhibitory) activity in the 23 h but not the 3-4 h uterine response. In contrast to purified HAFP, incubation of the peptide with estrogen was not a prerequisite for inhibitory activity. The estrogen-dependent increase in uterine thrombin and tissue factor, as determined by an enzymatic esterase assay, was inhibited by 30% in rat uterine cytosols. In an in vitro bioassay of estrogen-induced focus formation in MCF-7 human breast cancer cultures, focus development was inhibited by 70% following peptide exposure. The mechanism of the AFP-derived peptide inhibition of estrogen-dependent growth remains to be determined.