1.1 The insulin-like growth factor (IGF) system The insulin-like growth factor (IGF) system has been shown to have an integral role in normal growth and development, and in the pathophysiology of various cancers. The IGF system is comprised of a series of circulating ligands (IGF-1, IGF-2), transmembrane receptor tyrosine kinases (IGF-1R, IGF-2R, and the insulin receptor (IR), high affinity lig...

BACKGROUND Alterations in the PI3K/Akt pathway are found in a wide range of cancers and the development of PI3K inhibitors represents a promising approach to cancer therapy. Constitutive PI3K activation, reflecting an intrinsic oncogenic deregulation of primary blast cells, is detected in 50% of patients with acute myeloid leukemia. However, the mechanisms leading to this activation are current...

Objective—IGF-1 stimulates cartilage repair but is not a practical therapy due to its short halflife. We have previously modified IGF-1 by adding a heparin-binding domain and have shown that this fusion protein (HB-IGF-1) stimulates sustained proteoglycan synthesis in cartilage. Here, we first examined the mechanism by which HB-IGF-1 is retained in cartilage. We then tested whether HB-IGF-1 pro...

1. Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) together with a truncated form of IGF-1 were purified to homogeneity from bovine colostrum. 2. Two forms of IGF-1 were totally resolved from IGF-2 in the purification by h.p.l.c. involving cation-exchange and reverse-phase columns. 3. The complete amino acid sequences for all three forms of IGF were determined. The sequence of bovine IGF-...