3/30/2017 0 Comments Tareo DietL-nucleotides; alpha- nucleotides; modified base nucleotide; phosphorodithioate linkage; tAreo-pentofuranosyl nucleotide; acyclic.Patent WO2. 00. 20. A2 - Ribozyme based treatment of female reproductive diseases NUCLEIC ACID BASED MODULATION OF FEMALE REPRODUCTIVE DISEASESAND CONDITIONSThis patent application claims priority from Sandberg et al, USSN 6. November 3. 0, 2. Each of these applications is hereby incorporated by reference herein in it's entirety including the drawings and tables. Technical Field Of The Invention. This invention relates to methods and reagents for the treatment of diseases or conditions relating to the levels of expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor(s). Specifically, the instant mvention features nucleic- acid based molecules and methods that modulate the expression of vascular endothelial growth factor and/or vascular endothelial growth factor receptors, such as VEGFR1 and or VEGFR2, that are useful in preventing, treating, controlling and/or diagnosing disorders and conditions related to angiogenesis, including but not limited to cancer, tumor angiogenesis, or ocular indications such as diabetic retinopathy, or age related macular degeneration, proliferative diabetic retinopathy, hypoxia- induced angiogenesis, rheumatoid arthritis, psoriasis, wound healing, endometriosis, endometrial carcinoma, gynecologic bleeding disorders, irregular menstrual cycles, ovulation, premenstrual syndrome (PMS), and menopausal dysfunction. Background Of The Invention. The following is a discussion of relevant art, none of which is admitted to be prior art to the present invention. Neufeld et al, 1. Prog. VEGF- induced neovascularization is implicated in various pathological conditions such as tumor angiogenesis, or ocular indications such as diabetic retinopathy, or age related macular degeneration, proliferative diabetic retinopathy, hypoxia- induced angiogenesis, rheumatoid arthritis, psoriasis, wound healing and others. VEGF, an endothelial cell- specific mitogen, is a 3. Da glycoprotein with a wide range of activities that include promotion of angiogenesis, enhancement of vascular- permeability and others. VEGF belongs to the platelet- derived growth factor (PDGF) family of growth factors with approximately 1. A and B chain of PDGF at the amino acid level. Additionally, VEGF contains the eight conserved cysteine residues common to all growth factors belonging to the PDGF family (Neufeld et al, supra). VEGF protein is believed to exist predominantly as disulfide- lihked homodimers; monomers of VEGF have been shown to be inactive (Plouet et al, 1. EMBO J. 8, 3. 80. VEGF exerts its influence on vascular endothelial cells by binding to specific high- affinity cell surface receptors. Covalent cross- linking experiments with 1. TARO/ TARO ROOT - HEALTH BENEFITS AND USES: TARO AND BEEF CURRY RECIPE. The National Library of Australia's Copies Direct service lets you purchase higher quality, larger sized photocopies or electronic copies of newspapers pages. Clicking on the Order now button below will open the ordering form. Search the history of over 284 billion web pages on the Internet. The-mediterranean-diet.com. Kreuzfahrten-zentrale.de. Tareo.pl; Tarbeo.pl; Tarceo.pl; Tardeo.pl; Tareeo.pl; Tarfeo.pl; Targeo.pl. One of the shortcuts many people use to follow the Paleo diet is to consume only those items that are safe to eat when raw. If you follow this doctrine, then no, you cannot consume taro or many other starchy tubers. The present invention concerns methods and reagents useful in modulating EGFR gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. I- labeled VEGF protein have led to the identification of three high molecular weight complexes of 2. Da presumed to be VEGF and VEGF receptor complexes (Vaisman et al, 1. J Biol. Based on these studies VEGF- specific receptors of 1. Da molecular mass were predicted. In endothelial cells, receptors of 1. Da have been identified. The VEGF receptors belong to the superfamily of receptor tyrosine kinases (RTKs) characterized by a conserved cytoplasmic catalytic kinase domain and a hydrophilic kinase sequence. The extracellular domains of the VEGF receptors consist of seven immunoglobulin- like domains that are thought to be involved in VEGF binding functions. The two most abundant and high- affinity receptors of VEGF are flt- 1 (VEGFR1) (fins- like tyrosine kinase) cloned by Shibuya et al, 1. Oncogene 5, 5. 19 and KDR (VEGFR2) (kinase- insert- domain- containing receptor) cloned by Terman et al, 1. Oncogene 6, 1. 67. The murine homolog of KDR, cloned by Mathews et al, 1. Proc. Sci, USA, 8. KDR and is termed as flk- 1 (fetal liver kinase- 1). The high- affinity binding of VEGF to its receptors is modulated by cell surface- associated heparin and heparin- like molecules (Gitay- Goren et al, 1. J. In addition, a number of studies have demonstrated that VEGF is both necessary and sufficient for neovascularization. Takashita et al, 1. J. 9. 3, 6. 62, demonstrated that a single injection of VEGF augmented collateral vessel development in a rabbit model of ischemia. VEGF also can induce neovascularization when injected into the cornea. The invention relates to compositions and methods to inhibit gene expression. In particular, the invention provides co-therapies comprising oligonucleotides plus other therapies to treat cancer. Cultural Anthropology/Print version: Wikis: Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of. Expression of the VEGF gene in CHO cells is sufficient to confer tumorigenic potential to the cells. Kim et al, supra and Millauer et al, supra used monoclonal antibodies against VEGF or a dominant negative form of VEGFR2 receptor to inhibit tumor- induced neovascularization. During development, VEGF and its receptors are associated with regions of new vascular growth (Millauer et al., 1. Cell 7. 2, 8. 35; Shalaby et al., 1. J. Furthermore, transgenic mice lacking either of the VEGF receptors are defective in blood vessel formation and these mice do not survive; VEGFR2 appears to be required for differentiation of endothelial cells, while VEGFRl appears to be required at later stages of vessel formation (Shalaby et al., 1. Nature 3. 76, 6. 2; Fung et al., 1. Nature 3. 76, 6. 6). Thus, these receptors apparently need to be present to properly signal endothelial cells or their precursors to respond to vascularization- promoting stimuli. Increasing evidence suggests that the VEGF family may also be involved with both the etiology and maintenance of peritoneal endometriosis. Peritoneal endometriosis is a significant debilitating gynecological problem of widespread prevalence. It is now generally accepted that the pathogenesis of peritoneal endometriosis involves the implantation of exfoliated endometrmm. Maintenance of exfoliated endometrial tissue is dependent upon the generation and maintenance of an extensive blood supply both within and surrounding the ectopic tissue. Endometriosis is a disease affecting an estimated 7. Endometriosis is a leading cause of infertility, chronic pelvic pain and hysterectomy. Endometriosis can be characterized when endometrial tissue (the tissue inside the uterus which builds up and is shed each month during menses) is found outside the uterus, in other areas of the body. The endometrial tissue can respond to hormonal commands each month and break down and bleed. However, unlike the endometrium, these tissue deposits have no way of leaving the body. The result is internal bleeding, degeneration of blood and tissue shed from the growths, inflammation of the surrounding areas, expression of irritating enzymes and formation of scar tissue. In addition, depending on the location of the growths. Endometrial tissue has even been found lodged in the skin and at other extrapelvic locations like the arm, leg and even brain. Currently, the presence of Endometriosis can only be confirmed through surgery such as laparoscopy, but can be suspected based on symptoms, physical findings and diagnostic tests. Endometriosis can be treated in many different ways, both surgically and medically. Most commonly, surgery will be performed during which the disease will be excised, ablated, fulgarated, cauterized or otherwise removed, and adhesions will also be freed. Surgeries include but are not limited to laparoscopy; laparotomy; presacral and uterosacral and various levels of hysterectomies, where some or all of the reproductive organs are removed. Often, this method will only relieve the symptoms associated with growths on the reproductive organs, not the bowels or kidneys and related areas where Endometriosis can be present. There are several drugs used to treat Endometriosis that are utilized either alone or in combination with surgery. These include contraceptives, Gn. RH agonists, and/or synthetic hormones. Gn. RH agonists are commonly used on women in all stages of the disease and may sometimes have serious side affects. Gn. RH (gonadotropin releasing hormone) analogues are classified into 2 groups: agonists and antagonists. Agonists are commonly used in the treatment of Endometriosis by suppressing the manufacture of follicle stimulating hormone (FSH) and luteinizing hormone (LH), common hormones required in ovulation. When they are not secreted, the body will go into . However, these are again only stop- gap measures that can be utilized only for short term intervals. Once the body returns to it's normal state, the Endometriosis will again begin to implant itself. Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis (Donnez et al, 1. Hum. Reprod., 1. 3, 1. Endometrial growth and repair after menstruation are associated with profound angiogenesis. Abnormalities in these processes result in excessive or unpredictable bleeding patterns and are common in many women. It is therefore important to understand which factors regulate normal endometrial angiogenesis. Vascular endothelial growth factor (VEGF) is an endothelial cell- specific mitogen that plays an important role in normal and pathological angiogenesis (Fasciani et al, 2. Mol. Reprod., 6, 5. Sharkey et al, 2. J. Sources of this factor include the eutopic. Important to its etiology is the correct peritoneal environment in which the exfoliated endometrium is seeded and implants. Established ectopic tissue is then dependent on the peritoneal environment for its survival, an environment that supports angiogenesis. The increasing knowledge of the involvement of the VEGF family in endometriotic angiogenesis raises the possibility of novel approaches to its medical management, with particular focus on the anti- angiogenic control of the action of VEGF (Mc. Laren, 2. 00. 1, Hum. Update, 6, 4. 5- 5. Pavco et al, International PCT Publication No. WO 9. 7/1. 56. 62, describes methods and reagents for treating diseases or conditions related to levels of vascular endothelial growth factor receptor. Robinson, International PCT Publication No.
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