ABSTRACT
To explore the ability to use genetic fusions of transferrin as a carrier for brain targeting and delivery, a series of fusion proteins containing both human nerve growth factor (NGF) and human transferrin was produced in mammalian cells. A protein in which the hinge region from human IgG3 joined the carboxyl terminus of NGF and the amino terminus of transferrin formed a covalent homodimer, bound human transferrin receptor, and retained full NGF in PC12 cells. In contrast, proteins in which polypeptide dimerization was not induced or in which NGF was fused through its amino terminus had greatly reduced NGF activity. The ability to maintain both biologically active NGF and transferrin as part of a fusion protein may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.
Subject(s)
Blood-Brain Barrier , Brain/metabolism , Drug Delivery Systems , Nerve Growth Factors/biosynthesis , Nerve Growth Factors/pharmacology , Receptors, Transferrin/metabolism , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/pharmacology , Transferrin/administration & dosage , Drug Carriers , Enzyme-Linked Immunosorbent Assay , Humans , Polymerase Chain ReactionABSTRACT
Curative treatment of bladder cancer is limited to superficial tumors (Ta-T2). Advanced stages (T3a + T3b) can be treated only palliatively even when confined to the bladder (N0, M0). Nevertheless the differentiation between curable and incurable tumors is difficult. The classification of patients into the two different categories is usually done on the basis of tumor infiltration and lymph node involvement. In this retrospective study all available data of patients with bladder cancer were evaluated for their prognostic reliability in order to obtain a safe basis for further therapeutic approaches. The principal aim was to define parameters of reliable prognostic significance to prevent under- or overtreatment during the entire course of the disease.
