Chapter category: Cytokines/Growth Factors
Antisense and Triple Helix Strategies in Basic and Clinical Research: Challenge for Gene Therapy of Tumors Expressing IGF-I
The JNK Signaling Pathway
Edited by: Anning LinISBN: 1-58706-120-1
» Get more information about this book at landesbioscience.com «
Chapter authors:
L.C. UpeguiGonzalez, J.C. Francois, L.A. Trojan, A. Ly, R. Przewlocki, C. Malvy and J. Trojan
In prokaryotes and eukaryotes, genetic information is supported by doublestranded DNA, in which only one strand is usually transcribed in messenger RNA. Nevertheless, transcription could occur from both strands or from complementary strands, leading sometimes to the synthesis of complementary antisense and sense RNAs. For several years, it has been shown that natural antisense RNA which is transcribed from one strand could hybridize to the sense RNA. This natural physiological regulation represents the basis of the antisense approach to artificially inhibit gene expression of particular genes involved in human diseases. Using this antisense strategy, the translation of messenger RNA (sense RNA) can be blocked by binding of a complementary strand to mRNA. The achievement of this artificial regulation could be done using either plasmid constructs transcribing intracellular antisense RNA or short oligonucleotides delivered to cells via appropriate carriers. In the latter case, a specific ribonuclease (RNAse H) recognizes the oligonucleotide/mRNA hybrid and cleaves the RNA moiety, leading to a specific inhibition of translation. Several examples of both strategies, antisense RNA and antisense oligonucleotides, i.e., utilization of antisense RNA to inhibit the intracellular insulinlike growth factor I expression, are presented in relation to future applications in antitumor gene therapy. Gene therapy and gene immunotherapy provide new approaches for clinical trials. Among these are strategies using either antisense or triple helix technologies which lead to activation of the host immune system. In the latter technology the oligonucleotides that block gene expression are the triplehelix forming oligonucleotides (TFOs). They block transit of RNA polymerases by forming a triplehelical structure on DNA. These TFOs promise to be a new class of sequencespecific DNAbinding drugs which will target malignancies at the transcriptional level. TFOs may prove to be the basis for effective chemotherapy drugs for different cancers. Numerous cancers express IGF-I, a protein commonly associated with cellular normal and neoplastic growth and differentiation. IGF-I antisense RNA and IGF-I triple helix RNA-DNA strategies have been shown to induce the arrest and rejection of tumors in vivo such as rat glioma, mouse teratocarcinoma and rat and mouse hepatoma. These results have formed the basis for a gene therapy clinical trial for human primary glioblastoma (USA and Poland) and hepatocellular cancer (China).
Additional chapters from this book:
The Structure of the Type 1 Insulin-Like Growth Factor Receptor
Colin W. Ward, Thomas P. J. Garrett, Mei Lou, Neil M. McKern, Timothy E. Adams, Thomas C. Elleman, Peter A. Hoyne, Maurice J. Frenkel, Leah J. Cosgrove, George O. Lovrecz, Lindsay G. Sparrow, Lynne Lawrence and V. Chandana Epa
The type 1 insulin-like growth factor receptor (IGF-1R) is widely expressed across many cell types in fetal and postnatal tissues. Signalling through the IGF-1R is the principal pathway responsible ...
Insulin-Like Growth Factor Binding Proteins (IGFBPs) and Apoptosis
Claire M. Perks and J. M. P. Holly
A cell and by extracellular cues from soluble survival factors and from cell contacts with its extracellular environment. For many cell types the most prevalent and potent survival factor is IGF-I. ...
IGF-I, Insulin and Cancer Risk: Linking the Biology and the Epidemiology
Michael Pollak
Insulin and insulin-like growth factor signaling systems arose early in evolution and play key roles in regulating cellular proliferation and survival, energy utilization at both the cellular an...
The Role of the IGF System in Prostate Cancer
Charles T. Roberts, Jr.
An important aspect of the IGF system in postnatal human physiology is its involvement in tumorigenesis. This was hardly unexpected, based upon the demonstrated role of IGF-I, in particular, as ...
Laron Syndrome: Primary GH Insensitivity or Resistance
Zvi Laron
An up to-date description of the etiology, clinical and laboratory pathology of the Laron Syndrome (Primary GH resistance or insensitivity). is presented. Laron Syndrome is a unique model to stu...
Functional Relationships between Transforming Growth Factor-Beta and the Insulin-Like Growth Factor Binding Proteins
Susan Fanayan and Robert C. Baxter
Insulin-like growth factor binding proteins (IGFBPs) modulate cell functions through IGF-dependent and independent mechanisms. The IGFBPs are subject to complex regulation, both inhibitory and s...
The Insulin-Like Growth Factors in Mammary Development and Breast Cancer
Teresa L. Wood, Malinda A. Stull, Dawn Kardash-Richardson, Michael A. Allar and Aimee V. Loladze
Normal and abnormal growth of mammary or breast epithelium is coordinately controlled by circulating hormones and locally-produced growth factors. The insulin-like growth factors and their prima...
IGF1 and Brain Development
Carolyn A. Bondy, Wei-Hua Lee and Clara M. Cheng
During the course of brain development, insulin-like growth factor (IGF1) and the IGF1 receptor are most highly expressed by maturing projection neurons during a time of rapid process growth and...
IGF-Independent Effects of the IGFBP Superfamily
Gillian E. Walker, Ho-Seong Kim, Yong-Feng Yang and Youngman Oh
The proposed “insulin-like growth factor binding protein (IGFBP) superfamily” is said to consist of the high affinity binding proteins, IGFBP-1 to -6 and low affinity binding proteins (IGFBP-rel...
Diabetes
Tero Saukkonen and David B. Dunger
Insulin-like growth factor-I (IGF-I) has effects on insulin-stimulated glucose metabolism, increasing peripheral glucose disposal and decreasing hepatic glucose output, thus enhancing insulin se...
Insulin-Like Growth Factor-I Stimulation of Growth: Autocrine, Paracrine and/or Endocrine Mechanisms of Action?
A. Joseph D'Ercole
The relationship between the sites of insulin-like Growth factor-I (IGF-I) expression and the sites of its growth promoting actions have been debated for years. There is compelling evidence for ...
Insulin-Like Growth Factor II (IGF-II) and Non-Islet Cell Tumor Hypoglycemia (NICTH)
Naomi Hizuka, Izumi Fukuda, Yukiko Ishikawa and Kazue Takano
Extrapancreatic tumors associated with hypoglycemia (non-islet-cell tumor hypoglycemia, NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth fa...
Insulin-Like Growth Factor-I and the Kidney
Franz Schaefer and Ralph Rabkin
This review describes the multiple ways in which the kidney and the IGF-I system interact in both health and disease. IGF-I is an important physiological regulator of glomerular hemodynamics, re...
IGFs and Sarcomas
Fariba Navid and Lee. J. Helman
Insulin-like growth factors (IGFs) and their receptors exert their effects on a variety of sarcomas through autocrine, paracrine and endocrine mechanisms. In addition to regulating the proliferati...
IGFs and the Nervous System
Gina M. Gehrke, Gary Meyer and Eva L. Feldman
The insulin-like growth factors-I and -II (IGF-I and IGF-II) are neurotrophic factors with sequence homology to pro-insulin. Through the type I IGF receptor (IGF-IR), the IGFs mediate proliferat...
Epidemiologic Approaches to Evaluating Insulin-Like Growth Factor and Cancer Risk
Eva S. Schernhammer and Susan E. Hankinson
Epidemiologic studies that simply observe the natural cause of events often are referred to as observational studies. In contrast, studies in which the investigator intervenes to change some p...
Regulation of Insulin-Like Growth Factor-I Gene Expression
Xia Wang and Martin L. Adamo
Insulin-like growth factor-I (IGF-I) mRNAs is expressed in adults principally in liver, which secretes IGF-I to act as an endocrine growth factor. Liver IGF-I mRNAs are transcribed from multip...
IGF Action and Skeletal Muscle
David T. Kuninger and Peter S. Rotwein
The insulin-like growth factors, IGF-I and IGF-II, comprise a pair of structurally related, secreted proteins which control diverse cellular functions by regulating multiple signal transductio...
IGFs and Epithelial Cancer
Walter Zumkeller
Insulin-like growth factors (IGFs), IGF receptors and IGF-binding proteins (IGFBPs) are expressed in epithelial cancer. The IGF system is involved in the regulation of the proliferation of bot...
The IGF System in Breast Cancer
Janet L. Martin
Breast cancer remains one of the most common causes of mortality in women worldwide, despite intensive research aimed at identifying the factors involved in its establishment and progressio...
IGFBP-5, A Multifunctional Protein, Is an Important Bone Formation Regulator
Subburaman Mohan, Yousef Amaar and David J Baylink
Bone formation is essential to all aspects of bone physiology, including growth, remodeling, and repair. In terms of potential messenger molecules that regulate bone formation, recent studi...
The Role of Insulin-Like Growth Factor-1 and Extracellular Matrix Protein Interaction in Controlling Cellular Responses to this Growth Factor
David R. Clemmons
Insulin-like growth factor-I (IGF-I) is a small polypeptide growth factor that is ubiquitously present in physiologic fluids. IGF-I is a potent stimulant of extracellular matrix protein (ECM) ...
The Insulin-Like Growth Factor System and Bone
Thomas L. Clemens and Clifford J. Rosen
In the last several years, investigators have begun to unravel the role of insulin like growth factor-I (IGF-I), and its family of IGF binding proteins, in the building and maintenance of t...
Insulin-Like Growth Factor Binding Proteins (IGFBPs) and Apoptosis
C.M. Perks and J.M.P. Holly
Apoptosis is a physiologically regulated mode of cell death, which plays a critical role during development and maturation. Apoptosis is tightly controlled both within the cell and by extracel...
IGFBPs—Gene and Protein Structure
Leon A. Bach and Nigel J. Parker
IGF actions are regulated by a family of six high affinity binding proteins (IGFBPs), some of which also have IGF-independent actions. The IGFBPs have highly conserved N- and C-doma...
Insulin-Like Growth Factors in Critical Illness
Greet Van den Berghe
Low circulating levels of insulin-like growth factor-I (IGF-I) and alterations in IGF-binding proteins (IGFBP-s) mark the catabolic state of critical illness. The origin of these changes appear...
Insulin-Like Growth Factors and Hematological Malignancies
Anne J. Novak and Diane F. Jelinek
Immune cell development and homeostasis is a highly coordinated process influenced by a network of cells and soluble factors. The endocrine system, in particular the insulin-like growth factor...
Metabolic Effects of Insulin-Like Growth Factor I and Growth Hormone in vivo: A Comparison
Nelly Mauras
The metabolic effects of IGF-I are varied and remarkably similar in many respects to those of GH. IGF-I mediates some, but not all of the metabolic actions of GH in man. Both GH and IGF-I pote...
Structure and Function of the IGF-1 and Mannose 6-phosphate/IGF-2 Receptors
Susan L. Spence and Peter Nissley
The IGF-1 receptor (IGF1R) gene is transcriptionally regulated by growth factors and tumor repressors and encodes a 210 kDa ab chain which is proteolytically cleaved...
IGF-I Receptor Signaling in Health and Disease
Renato Baserga, Marco Prisco and Tina Yuan
The type 1 insulin-like growth factor (IGF-I) receptor is a tyrosine kinase receptor, conserved through evolution in metazoans, from C. elegans to mammals. It displays several functions, so...
The Molecular Basis of IGF-I Receptor Gene Expression in Human Cancer
Haim Werner
The insulin-like growth factor-I receptor (IGF-IR) has a central role in normal cellular proliferation as well as in transformation processes. Transcription factors have been ident...
Antisense and Triple Helix Strategies in Basic and Clinical Research: Challenge for Gene Therapy of Tumors Expressing IGF-I
L.C. UpeguiGonzalez, J.C. Francois, L.A. Trojan, A. Ly, R. Przewlocki, C. Malvy and J. Trojan
In prokaryotes and eukaryotes, genetic information is supported by doublestranded DNA, in which only one strand is usually transcribed in messenger RNA. Nevertheless, transcription could occur...
The Many Levels of Control of IGF-II Expression
P. Elly Holthuizen
The functions of IGF-II are very diverse. IGF-II plays a role in the development of the embryo, it is an important mitogenic factor for growing cells, it is involved in differentiation process...
