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 E2-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.

Dads, Daughters, And Disney: The Historical Trajectory Of Fairy Tale Fathers And Daughters

In my thesis I use a historical approach to close readings of fairy tale texts and movies to study the evolution of fathers, daughters, and marriage within three landmark tales: ¿Cinderella,¿ ¿Sleeping Beauty,¿ and ¿Snow White.¿ Using the works of Giambattista Basile, Charles Perrault, Jacob and Wilhelm Grimm, and Walt Disney and his cohort of animators, I trace the historical trajectory of these three elements, analyzing both the ways they change and develop as history progresses as well as the ways they remain consistent. Through close and comparative readings of primary sources and films, I demonstrate the power structures and familial dynamics evident through the interactions of fathers and daughters. Specifically, I show that through the weakness and ineptitude of fairy tale fathers, fairy tale daughters are able to gain power, authority, and autonomy by using magic and marriage to navigate patriarchal systems. The work I have done is important because it explores how each tale is a product of the story before it and thus that in order for these tales to continue to survive the test of time, we must not only recognize the validity of the academic merit of the Disney stories, but also remember them and others as we forge new paths in the stories we use to teach both children and parents. Specifically, this work is important because it explores the historical trend evident in the evolving relationships between fathers and daughters. This relationship ultimately it reveals the deep underlying need for family within all of us.