Recent reports from other collaborators in this program as well as other investigators have shown that crude clinical pharmaceutical preparations of hCG approved for human injection inhibit the growth of Kaposi's Sarcoma (KS) cells in tissue culture as well as Kaposi tumors in both animal models and human patients. Factors contained within these hCG preparations are potential therapeutic reagents for patient treatment. Virtually any protein in the circulation can appear in the urine even at trace concentrations. The pharmaceutic forms of hCG for human use are produced from the urine of pregnant women but are only 35% hCG by weight. We have shown that anti-KS factors similar in size on gel filtration to those present in such clinical grades on crude hCG appear in higher concentrations in raw urine form women in the first trimester of pregnancy. During pregnancy, a wide variety of growth factors are secreted both by mother and fetus. None of the known factors tested exhibit the anti-KS activities found in commercial preparations of hCG, hCG subunits and the hCG beta core. The hypothesis of this project is that the factors responsible for these anti-KS effects (name hCG associated factors or HAF) are proteins or peptides in blood which are excreted into the urine during early pregnancy or other states. These proteins are distinct from hCG, hCGbeta, or hCGbeta core. In order to test this hypothesis, the following aims are proposed: 1. Isolate the anti-KS (HAF) proteins from the urine of women in early pregnancy in collaboration with project 1. 2. To chemically characterize the isolated HAF molecules by primary structural analysis and develop immunoassays to them. 3. To determine the precise chronological pattern of HAF excretion in early pregnancy and to investigate whether other physiological states lead to excretion of HAF to help understand the natural functions of these molecules.
|Pati, Shibani; Foulke Jr, James S; Barabitskaya, Oxana et al. (2003) Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat. J Virol 77:5759-73|
|Guo, Hong-Guang; Sadowska, Mariola; Reid, William et al. (2003) Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse. J Virol 77:2631-9|
|Birken, S; Gawinowicz, M A; Maydelman, Y et al. (2001) Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production. J Endocrinol 171:131-41|
|Birken, S; Kovalevskaya, G; O'Connor, J (2001) Immunochemical measurement of early pregnancy isoforms of HCG: potential applications to fertility research, prenatal diagnosis, and cancer. Arch Med Res 32:635-43|
|Pati, S; Cavrois, M; Guo, H G et al. (2001) Activation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrine model of Kaposi's sarcoma pathogenesis. J Virol 75:8660-73|