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RAMOT at Tel Aviv University Ltd. posted this:

Uterine fibroids (leiomyomas) are the most common benign tumors in women. They The Fibroids disrupt the functions of the uterus and cause excessive uterine bleeding, anemia, infertility, defective implantation of embryos, recurrent pregnancy loss, preterm labor, obstruction of labor, pelvic discomfort and urinary incontinence; they may mimic or mask malignant tumors. Nearly 70% of white women and more than 80% of black women will have had at least one fibroid by the time they reach 50 years of age; 15 - 30 percent of them will develop severe symptoms. Approximately 200,000 hysterectomies, 30,000 myomectomies, and thousands of selective uterine-artery embolizations and high-intensity focused ultrasound procedures are performed annually in the United States to remove or destroy uterine fibroids. The annual economic burden of these tumors is estimated to be between 5.9 and 34.4 billion US$. Uterine fibroids are monoclonal tumors that arise from the uterine smooth-muscle tissue (i.e., the myometrium). Histologically, fibroids are benign neoplasms composed of disordered smooth-muscle cells buried in abundant quantities of extracellular matrix. A striking feature of uterine fibroids is their dependency on the ovarian steroids estrogen and progesterone. Ovarian activity is essential for fibroid growth; most fibroids shrink after menopause. Gonadotropin-releasing-hormone (GnRH) analogues, which suppress ovarian activity and reduce circulating levels of estrogen and progesterone, shrink fibroids and reduce associated uterine bleeding. The unique vascular architecture of fibroids, consisting of an avascular core surrounded by a well-vascularized myometrium is caused, most likely, due to an angiogenic imbalance. Resarchers suggest that the perliminary tumor, which is small in size with a minimal intrinsic blood supply, may release angiogenic factors as vascular endothelial growth factor (VEGF) that lead to an increase in the vascular density of the surrounding myometrium. This may, in turn, give rise to capillary sprouts that vascularize the small fibroid, promoting its growth and enlargement. This increase in vascular density of myometrium may account for the symptoms of menorrhagia observed in women with fibroids. In addtion, the current medications for leiomyomas, such as GnRH and selective progesterone receptormodulators, have displayed suppressive effects on the expression of VEGF. Therefore, VEGF may be a potential target in the treatment of uterine fibroid Project ID : 10-2014-852

RAMOT at Tel Aviv University Ltd. posted this:

. monocytogenes is considered as one of the most promising bacterial vectors to be used as live attenuated vaccine since it has multiple advantages as a vaccine platform. Listeria signals to the innate immune system through multiple pathways, activating cell surface Toll-like receptors and intracellular Nod-like receptors. The antigens delivered by this vector behave as endogenous antigens, they are presented on the cell surface and generate cellmediated immune response, Moreover, Listeria can be repeatedly administered and it is easy to manufacture. Immunization with the bacterium Listeria monocytogenes induces a robust protective immune response mediated by cytotoxic lymphocytes that are efficient at killing infected cells upon reinfection. When L. monocytogenes enters a cell, it secretes the small molecule cyclic diadenosine monophosphate (c-di-AMP), which activates the host protein STING leading to a type I interferon response. Recently, it was shown that IFN-beta production as part of the type I interferon response is inversely correlated with adaptive immunity to Listeria. In the absence of STING signaling, mice restricted bacterial growth and maintained higher numbers of cytotoxic lymphocytes upon reinfection, whereas mice immunized in the presence of elevated levels of cdi- AMP were less protected. These results suggest that the inflammation induced by a bacterial pathogen can be detrimental to the development of adaptive immunity, which could provide new insights into vaccine development. Therefore, in agreement with the prediction that a strain of Listeria that doesn't induce type I interferon response might be a better immunizing strain we generated several mutants lacking sets of multi-drug resistance (MDR) transporters. With these mutants we illustrated for the first time that it is the cohort of MDR transporters that together contribute to type I interferon induction during infection and that c-di-AMP is involved in this phenotype. In light of these results we expect the ?mdr L. monocytogenes strains to be better potentiators of the adaptive immunity as antigen presentating platforms for live vaccine therapy Project ID : 10-2014-783