A non invasive method for obtaining rna from buccal mucosa epithelial cells for gene expression profiling
Novel method for increasing the selective localization of Photodynamic Therapy (PDT) dyes using the nuclear estrogen receptor (ER) as a target Invention: Photodynamic therapy (PDT) is an established method for the treatment of cancer. However, developing an effective method for selective targeting of PDT-dyes has proved difficult. The invention describes a novel method for significantly increasing selective localization of PDT dyes, and identifies specific compounds to be used. Introduction: Estrogen Receptor (ER) provides a viable target for the selective breast tumor delivery of drugs/toxins, because breast tumor cells express ER in higher levels than other tissues, particularly in the earlier stages of malignancy and under post-operative hormone-treatment. Therefore, conjugates of estrogen/anti- estrogen and toxins are viable candidates for selective tumor-delivery. However, such conjugates migrate into any cell that expresses ER (although to a higher extent to tumor cells due to the presence of significantly more copies of ER than normal cells expressing ER). Therefore, some selectivity is achieved, but not to the extent that is required for selective tumor cell-killing. The inventors hypothesized that (1) a synthetic conjugate of estradiol and a porphyrin might combine the high-affinity binding of estrogen for endogenous ER, and natural tumor localization property of porphyrin to localize the conjugate into tumor with much higher degree of selectivity than what is achievable with estrogen-mimics and porphyrins individually, and (2) such a process could effectively lower the concentration of porphyrin required for desired cell-killing. Therefore, there would be significantly less systemic photo-toxicity. Stage of Development: Proof of Principle Experiments strongly supported the hypotheses that ER containing breast tumor cells would selectively take up the estradiol-porphyrin conjugate, and such a process might lower the amount of porphyrin (in the form of conjugate) required for a selective cell killing. Specifically, experiments included: • Coupled chlorin e6, a known photo-toxin, to a derivative of C17-α-alkynylestradiol to make an estrogen-
porphyrin conjugate which bounds to ER in a specific and dose-dependent manner. Furthermore, this conjugate was taken up by ER-positive MCF-7 cells in a dose-dependent manner, but not the parent porphyrin i.e. chlorin e6-dimethyl ester, while there was low and dose-independent uptake of estrogen-chlorin e6 conjugate or chlorin e6-dimethyl ester by ER-negative MDA-MD-231 cells.
• In addition, exposure of ER containing MCF-7 cells, incubated with the conjugate, induced strong cell
killing. In contrast, cells (MCF-7 and MDA-MB-231) that were kept in the dark, or cells that did not contain ER (MDA-MB 231) showed very little cell death.
The invention is not limited to the estrogen receptor interaction system. This method of selective delivery might be adopted to target other nuclear receptors by coupling an appropriate ligand to a drug or toxin e.g. androgen and porphyrin for hormone-sensitive prostate cancer. Intellectual Property: US patent application under prosecution (US20030220313). No foreign rights available. Publications: James, DA et al. Synthesis and Estrogen Receptor Binding Affinity of A Porphyrin-Estradiol Conjugate for Targeted Photodynamic Therapy of Cancer. Bioorg. Med. Chem. Lett 9 (1999)2379-2384 Inventors: Rahul Ray, Scott Mohr and Narasimha Swamy OTT Contact: Catherine Ives Tel: (617) 358-4550 Fax: (617) 358-5001 em
Dronedarone This factsheet is intended to help those aﬀ ected Dronedarone has been shown to be eﬀ ective in by atrial ﬁ brillation understand the medication reducing the likelihood of recurrence of AF by dronedarone, with a brief introduction to how it around 25% in patients with paroxysmal AF (episodes which come and go on their own) and persistent AF (AF which will not revert
Bakgrund och syfte: Makularegistret startade under 2003 för att få en kontinuerlig uppföljning och kvalitetssäkring av behandling vid choroidal kärlnybildning, CNV, under gula fläcken i retina. Makuladegenerationer (eller sk åldersförändringar i gula fläcken (AMD)), är den vanligaste orsaken till synnedsättning hos personer äldre än 50 år i västvärlden. 30 % av personer ä