Insulin-like growth factor (IGF) I is a polypeptide hormone important in normal growth and development. Although IGF-I is a mitogen for many cancer cell lines, previous work has suggested that autocrine production of IGF-I is uncommon in cancers of epithelial origin. In this study, expression of IGF-I, its binding proteins, and its receptor were examined in ovarian cancer cell lines and tissues...

Cytokines had originally been thought to be glycoproteins functioning largely in hematolymphopoiesis and immune reaction. In the 1990s, there have been an increasing number of reports showing that cytokines also play important roles in other organs and tissues, including the nervous system. Now the concepts of the nervous system as an immunologically privileged site have been significantly modi...

Thalidomide (Thd), a potent teratogen, was shown to have therapeutic potential in cancer, primarily in multiple myeloma (MM), yet its mechanism of action has not been elucidated. It was recently suggested that its teratogenicity is derived from interference in expression of genes regulated by GC-rich promoters by blocking the binding of SP1 transcription factor to its motif. We explored the val...

We report a boy with pseudohypoparathyroidism (PHP), hypothyroidism and low growth hormone (GH) values with no response to growth hormone releasing hormone (GHRH). He presented at age 17 mo because of developmental delay. He had the typical features (short stature, obesity, round face, brachydactyly) of Albright's hereditary osteodystrophy (AHO) and the biochemical profile of PHP; low serum cal...

The IGFI receptor promotes malignant progression and has been recognized as a target for cancer therapy. Clinical trials with anti-IGFIR antibodies provided evidence of therapeutic efficacy but exposed limitations due in part to effects on, and the compensatory function of, the insulin receptor system. Here, we report on the production, characterization, and biologic activity of a novel, IGF-ta...

Insulin-like growth factor (IGF-1) is a potent mitogen and an anti-apoptotic agent which is regulated by insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 carries IGF-1 through the bloodstream to the target tissues and protects it from proteolytic degradation. IGFBP-3 reduces tumorigenic potential of colon cancer cells in vitro. IGFBP3 may inhibit target cells directly. In the pre...

Vitamin D3 and metformin are widely used in humans for regulating mineral metabolism and as an antidiabetic drug, respectively; and both of them have been shown to have chemopreventive effects against various tumors. This study was designed to investigate the potential synergistic chemopreventive effects of vitamin D3 and metformin against the development of early colon neoplasia in two models....

Insulin-like growth factor (IGF)-I and IGF-II are important mitogen and IGF binding protein-3 (IGFBP-3) exerts opposite effects. However, the results of epidemiological studies on cancer influence are somewhat controversial, and mainly from Western countries. In the present study, we therefore examined associations of serum IGF-I, IGF-II and IGFBP-3 with colorectal cancer risk among participant...

Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay ...

Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the s...