The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
Urethral injury is a common complication of pelvic trauma that, if undiagnosed, may lead to significant long-term morbidity. Segments of the urethra that are near the pubic rami and the puboprostatic ligaments are particularly vulnerable. Although computed tomography is commonly used for the initial imaging evaluation of patients with polytrauma, urethral injury is better assessed and classified by using urethrography. Complete urethral imaging is especially important at presentation because the insertion of a transurethral bladder catheter may exacerbate an existing injury (eg, cause a partial urethral tear to become a complete transection). However, even for radiologists who are familiar with standard technique, urethrography after pelvic trauma may be particularly challenging because the patient is immobile or a surgical fixation device or indwelling urethral catheter is present. Various methods may used to overcome these difficulties and ensure that optimal images are obtained so that a correct diagnosis can be made without additional imaging evaluations.
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