"In addition to cancer, p53 mutations play important role in other proliferative disorders. For example, Prolapsus uteri in pelvic support disorders are common in elderly women. It has been suggested that alterations in collagen synthesis and collagen types are related to this connective tissue disorder. The studies have shown that higher proliferative activity in prolapsus fibroblasts may result from the decreased expression of p53 protein and may lead to a decrease in the synthesis and deposition of extracellular matrix components (Yamamoto et al., (2000) Mech. Ageing Dev. 115(3):175-87). Another proliferative disorder, moyamoya, is a progressive cerebrovascular occlusive disease. It has been suggested that moyamoya disease may result, at least in part, from an abnormal regulation of extracellular matrix metabolism that leads to increased steady state levels of elastin mRNA and elastin accumulation in the initial thickening (Yamamoto et al., (1997) Stroke 28(9):1733-8).
"`Reactive species` (RS) of various types are formed in vivo and many are powerful oxidizing agents, capable of damaging DNA and other biomolecules. Increased formation of RS can promote the development of malignancy, and the `normal` rates of RS generation may account for the increased risk of cancer development in the aged. Hence additional actions of RS must be important, possibly their effects on p53, cell proliferation, invasiveness and metastasis (Halliwell, (2007) Biochem. J. 401(1):1-11).
"Genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity (Matheu et al., (2007) Nature. 448(7151):375-9).
"Recent strategies have also turned to the p53 family member, p73, which like p53 is a potent inducer of death, but in contrast is rarely lost or mutated in tumors (Bell and Ryan (2007) Cell Cycle 6(16):1995-2000). p63 and p73, members of the p53 family, have been shown to be functionally distinct from p53. Based on gene sequence homologies, a p53 (TP53) gene family become apparent with the addition of the most recently identified p63 (TP73L; formerly TP63) and p73 (TP73) genes to the already known p53 (Kommagani et al., (2007) J. Biol. Chem. 282(41):29847-54). In addition to p73, p21 and p27 are other cell cycle proteins related to p53-mediated cell cycle arrest.
"Delivery of wild type p53 encoding nucleic acid using a nanoparticle formulation has been successfully demonstrated, however, this system has certain drawbacks. For example, it is difficult to ensure that enough p53 nucleic acid enters the cell to be subsequently encoded into sufficient levels of functional p53 protein to ameliorate the symptoms of proliferative disease. Additionally, it is unclear whether diseased cells are capable of transcribing and producing protein in an efficient manner. It is an objective the present invention to provide an improvement to existing methods for delivery of p53, or other proteins involved in cellular senescence, to cells."
Supplementing the background information on this patent, NewsRx reporters also obtained the inventor's summary information for this patent: "In accordance with the present invention, a method for inhibiting restenosis of a blood vessel (e.g., an artery or vein) comprising administering an effective amount of a protein containing nanoparticle via a blood vessel to a subject in need of treatment is provided. In a particular embodiment, the protein is selected from the group consisting of p21, p27, p53, p63, p73 or a functional fragment thereof. In another embodiment, the nanoparticle comprises a biodegradable polymer comprising a poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), polyallylamine, polyanhydride, polyhydroxybutyric acid, or a polyorthoester or a combination thereof. In still another embodiment, the nanoparticle comprises a targeting moiety. In a different embodiment of the invention, the nanoparticle comprises a plasticizer.
"In another aspect of the invention, a p53 protein nanoparticle formulation for sustained release of an effective amount of p53 protein said formulation comprising p53 protein, at least one biodegradable polymer, and an inert plasticizer are provided. In another aspect, the formulation further comprises an antioxidant, an anti-infective, an antiseptic, a steroid, a therapeutic peptide, an analgesic, an anti-inflammatory agent, an anticancer agent, a narcotic, an anesthetic, an antiangiogenic agent, a polysaccharide, a vaccine, an antigen, or a nucleic acid. In yet another aspect, the nanoparticle formulations also include a biodegradable polymer comprising a poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), polyallylamine, polyanhydride, polyhydroxybutyric acid, or a polyorthoester. In a further aspect, the nanoparticle formulation comprises a targeting moiety.
"The methods of the invention also include managing VSMC inflammation in a patient following angioplasty comprising administering to said patient a therapeutic agent in an effective amount to manage VSMC inflammation. In another embodiment, the therapeutic agent is a protein containing nanoparticle formulation. In yet another embodiment, the protein containing nanoparticle formulation contains a protein or protein fragment set forth in Table I or Table II.
"In another aspect of the invention, a protein containing nanoparticle formulation wherein said protein is selected from the group consisting of SEQ ID NO: 1-28 in a pharmaceutically acceptable carrier is provided.
"In yet another embodiment, a method of inhibiting inflammation in a patient following angioplasty is provided comprising administering to said patient a protein containing nanoparticle formulation comprising a protein or protein fragment selected from the group consisting of SEQ ID NO: 1-28."
For the URL and additional information on this patent, see: Labhasetwar, Vinod. Apoptosis-Modulating P53 Protein Therapy for Vascular Disorders and Nanoparticles Containing the Same. U.S. Patent Number 8507437, filed
Keywords for this news article include: Biotechnology, Genetics, Oncology, Apoptosis, Education, Inflammation, Nanoparticle, Therapeutics, Bioengineering, Nanotechnology, Cancer Vaccines, Cancer Gene Therapy, Extracellular Space, Extracellular Matrix, Emerging Technologies, Biodegradable Polymers,
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC
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