Somavert
Stefania Spada, Gary Walsh in Directory of Approved Biopharmaceutical Products, 2004
Description: Pegvisomant, the active ingredient of Somavert, is a PEGylated recombinant analogue of human growth hormone (hGH). It has been engineered to introduce nine mutations into the hGH amino acid sequence. This analogue binds to the hGH cell surface receptor but does not trigger an intracellular response. As such, it effectively acts in an antagonistic fashion, reducing the effects of endogenous hGH. The molecule is PEGylated in υitro in order to increase its serum half-life. It is generally presented in lyophilized form, to be reconstituted prior to subcutaneous use.
Hemostatic Risk Factors for Atherothrombosis
P. K. Shah in Risk Factors in Coronary Artery Disease, 2006
Atherosclerosis predisposes to arterial thrombosis and thrombosis superimposed on a disrupted plaque is the proximate event that triggers acute ischemic syndromes and sudden death. A number of studies have focused on novel risk factors, predominantly related to hemostasis and coagulation, to identify a potential role for primary hemostatic abnormalities and cardiovascular risk. Fibrinogen, precursor of fibrin, is an important coagulation protein that plays an important role in plasma viscosity and platelet aggregation. Thrombomodulin is an endothelial cell surface receptor for thrombin that accelerates thrombin-induced activation of the natural anticoagulant protein C. The relationship between hemostatic factors and risk for arterial atherothrombosis, after correction for all known risk factors and confounding variables, is at best weak and at worst unconvincing. Inflammation is critically linked to various pathophysiologic events leading to initiation, progression, and destabilization of atherosclerosis. Several prospective studies have examined the relationship between FVII mediated pro-coagulant activity and atherothrombosis, but the results have been inconsistent.
Overview of Immune Tolerance Strategies
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Increased understanding of immune cell activation and regulation makes plausible the development of clinical strategies to control unwanted immune responses in a specific manner. The normal safeguards collectively termed immune tolerance refer to the immune system’s ability to control and prevent undesirable immune responses that lead to autoimmune diseases, asthma, or allergies, while still permitting protective immune responses to infection, vaccination, or tumor growth. The adaptive immune system, which consists of a vast repertoire of thymus-dependent T-lymphocytes and bone marrow-derived B-lymphocytes, achieves self tolerance both by eliminating dangerous cells that strongly recognize self tissues and by controlling those potentially self-reactive lymphocytes that escape deletion and are found throughout the body. Cell surface receptor molecules found on B- and T-lymphocytes determine the specificity of each cell by their ability to attach with lock-and-key accuracy to specific target molecules, termed antigens. T cell receptor molecules (TCR) bind to antigens comprised of short protein segments (peptides), derived from foreign or self proteins, that are held precisely in a pocket-like groove of self antigen presenting molecules, termed major histocompatibility complex (MHC) class I or MHC class II molecules. In this way, T cells recognize a complex of peptide-MHC molecules displayed on the surface of antigen presenting cells (APC). The B lymphocyte antigen receptor (BCR) is a membrane-bound immunoglobulin that recognizes antigen directly. Antigen binding by the TCR or BCR leads to aggregation of receptors on the cell surface, which brings together additional molecules within the cell to initiate a cascade of enzymatic reactions eventually leading to activation of genes in the nucleus. Gene activation determines how the cells respond to antigens; for example, by cell growth, secretion of factors, and activation of direct effector functions, such as the ability to destroy infected cells or secrete specific antibodies. Once activated, B cells release their immunoglobulin as antibodies that bind their antigens in blood or other tissues. Activated T cells may directly kill their target cells or help B cells to produce antibodies by direct cell-cell contact. They also produce soluble cytokines that mediate a variety of functions. 1
Targeted delivery of anti-cancer growth inhibitory peptides derived from human α-fetoprotein: review of an International Multi-Center Collaborative Study
Published in Journal of Drug Targeting, 2010
GJ Mizejewski, M Mirowski, P Garnuszek, M Maurin, BD Cohen, BJ Poiesz, GA Posypanova, VA Makarov, ES Severin, SE Severin
The α-fetoprotein derived growth inhibitory peptide (GIP) is a 34-amino acid peptide composed of three biologically active subfragments. GIP-34 and its three constituent segments have been synthesized, purified, and studied for biological activity. The GIP-34 and GIP-8 have been characterized as anticancer therapeutic peptides. An multicenter study was initiated to elucidate the means by which these peptide drugs could be targeted to tumor cells. The study first established which cancer types were specifically targeted by the GIP peptides in both in vitro and in vivo investigations. It was next demonstrated that radiolabeled peptide (125I GIP-34) is specifically localized to rodent breast tumors at 24 h post-injection. The radionuclide studies also provided evidence for a proposed cell surface receptor; this was confirmed in a further study using fluorescent-labeled GIP-nanobeads which localized at the plasma membrane of MCF-7 breast cancer cells. Finally, it was readily demonstrated that GIP conjugated to either fluorescein or doxorubicin (DOX) underwent tumor cell uptake; subsequently, DOX–GIP conjugates induced cytotoxic cell destruction indicating the utility of GIP segments as cancer therapeutic agents. Following a discussion of the preceding results, a candidate cell surface receptor family was proposed which correlated with previous published reports for a putative AFP/GIP receptor.
Effect of Tricylic Antidepressant Drugs on Lymphocyte Membrane Structure
Published in Journal of Immunopharmacology, 1984
Tricyclic antidepressant-induced perturbations of murine splenic lymphocyte membranes and cell surface concanavalin A receptor mobility have been investigated using the fluorescent probes diphenylhexatriene and fluorescein-conjugated concanavalin A. Results of these studies illustrate the possible relationship between tricyclic antidepressant-induced membrane perturbations and tricyclic antidepressant-induced suppression of the normal murine lymphocyte mitogen response. Tricyclic antidepressant effects on murine splenic lymphocyte membranes are dose-, time- and temperature dependent. Murine lymphocyte concanavalin A cell surface receptor mobility is not apparently altered by the tricyclic antidepressants.
Cellular Mechanism of Action of Botulinum Neurotoxin
Published in Journal of Toxicology: Toxin Reviews, 1986
Botulinum toxin (Botx) is the most potent toxin known. It is found as seven distinct serotypes (A-G). The toxin has a M.W. of approximately 150,000, but is usually found as two disulfide-linked chains, one of 100,000 and the other 50,000. The toxin acts presynaptically to block the release of acetylcholine and thereby induce paralysis. It is suggested that the toxin might act by the same general mechanism as other bacterial toxins, i.e. after binding to a cell surface receptor, it enters the cell and expresses some type of enzymatic action ultimately leading to the block of neurotransmitter release.
Related Knowledge Centers
- Cell Signaling
- Growth Factor
- Neurotransmitter
- Cytokine
- Hormone
- Receptor
- Cell