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Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium, suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell selfpropel its migration and metastasis to the bone.-Silva, J., S. Dasgupta, G. Wang, K. Krishnamurthy, E. Ritter, and E. Bieberich. Lipids isolated from bone induce the migration of human breast cancer cells. The migration of cancer cells is a key factor in metastasis, which is a multistep event that involves the interaction of host and tumor tissue. Bone is the most common site to which breast cancer cells metastasize (1, 2). The mechanism underlying this specific metastatic behavior is not completely understood. Recently, we reported that oxygenated derivatives of cholesterol (oxysterols) synthesized and released by human osteoblast-like MG63 cells induce the migration of nonmetastatic human breast cancer MCF-7 cells (3). Bile acids, another species of oxygenated cholesterol, have long been implicated in the tumorigenesis of colorectal cancer (4, 5). Recent studies have shown that an increased concentration of bile acids in breast cyst fluid is indicative of a higher risk of developing breast cancer (6, 7). It remained to be elucidated, however, which cell signaling pathways for tumorigenesis and breast cancer cell migration are triggered by bile acids.The secondary bile acid deoxycholic acid or its salt deoxycholate (DC) is synthesized by intestinal bacteria and transported to the liver and other tissues by the serum (8-11). The specific enrichment of deoxycholic acid and other bile acids in breast cyst fluid shows that tissues other than liver can take up and accumulate bile acids from the serum (7,12,13). Bile acids bind to the nuclear receptor farnesoid X receptor (FXR) and activate a variety of genes involved in cholesterol metabolism and transport (14-17). FXR is expressed in colorectal tumor cells; however, it is not clear how bile acid-induced activation of FXR triggers cancerogenesis (18). In this study, we show for the first time that bone tissue and MG63 cells contain DC. We provide evidence that DC is taken up from the medium and can be released at a concentration that induces the mi...

Isolated fungal soft-tissue infections are uncommon but may cause severe morbidity or mortality among transplant recipients and other immunosuppressed patients. Twelve immunocompromised patients illustrating three patterns of infection were treated recently at the Duke University Medical Center. These groups comprised (I) locally aggressive infections, (II) indolent infections, and (III) cutaneous manifestations of systemic infection. Patient diagnoses included organ transplant, leukemia, prematurity, chronic obstructive pulmonary disease, and rheumatoid arthritis. Time from immunosuppression to biopsy ranged from 5.5 to 31 weeks. Organisms included Aspergillus, Rhizopus, Fusarium, Paecilomyces, Exophiala, and Curvularia. Patients presented with necrotic ulcerations or nodules. Surgical treatment ranged from radical debridement to excisional biopsy to none. Antifungal chemotherapy also was employed in some cases. The mortality rate was 33 percent, two patients dying without evidence of fungal infection. Six of the eight survivors cleared their infections. Necrotic skin lesions with surrounding erythema in this population call for prompt examination, biopsy, and culture. Group I lesions mandate radical excision with rapid intraoperative microscopic control and systemic antifungal medication. Group II requires surgical control with or without antifungal therapy. Group III requires systemic antifungal therapy for metastatic infection. In our opinion, treatment of fungal soft-tissue infection should be tailored to infection type and requires a team approach of surgeon and expert infectious disease consultation.

With appropriate planning and adherence to basic reconstructive surgical principles, correction of the buried penis can yield a high success rate.