Role of thymidine phosphorylase in an in vitro model of human bladder cancer invasion

PURPOSE: It has been previously demonstrated that the angiogenic factor thymidine phosphorylase is elevated significantly in invasive bladder cancer. We report that it is not merely an incidental finding. Thymidine phosphorylase has a functional role in bladder cancer invasion. MATERIALS AND METHODS: The superficial bladder cancer cell line RT112 was transfected by retroviral techniques to generate the RT112-TP clone that expressed significantly elevated levels of thymidine phosphorylase, comparable to those of invasive human bladder cancers. The empty vector control RT112-EV was generated for comparison. Growth of these transfectants was examined using a new in vitro model of bladder cancer invasion based on de-epithelialized rat bladder and by assessing growth as xenografts in nude mice. The effect of 5-deoxy-5-fluorouridine, a prodrug activated by TP to produce 5-fluorouracil, was also examined. RESULTS: RT112-TP high thymidine phosphorylase expressing cells invaded into the stroma of the in vitro model but wild-type RT112 and RT112-EV cells did not. This invasion was abolished by 5-deoxy-5-fluorouridine. Invasion correlated with thymidine phosphorylase expression on immunohistochemical testing. There was also a significantly greater xenograft growth rate for RT112-TP than for RT112-EV, confirming the malignant growth advantage conferred by thymidine phosphorylase. CONCLUSIONS: We demonstrated that thymidine phosphorylase may have a functional role in bladder cancer invasion and the apparent advantage of thymidine phosphorylase expression to tumor cells can be exploited by therapies that utilize prodrugs such as 5-deoxy-5-fluorouridine, which is activated by thymidine phosphorylase and inhibited invasion in our model.     

Expression of macrophage inflammatory protein-1alpha (MIP-1alpha) in human endometrium throughout the menstrual cycle.

OBJECTIVE: To investigate the distribution and the role of macrophage inflammatory protein-1alpha (MIP-1alpha) in human endometrium during cyclic changes. SETTING: Department of Obstetrics and Gynaecology, Shiga University of Medical Science and University Hospital. MATERIALS: Eighteen endometrial tissue specimens surgically resected or biopsied from women with normal menstrual cycles, without hormonal disorder or endometrial diseases. METHODS: By immunohistochemistry, using monoclonal antibodies (lambda delta 78 for MIP-1alpha and CR3/43 for human leukocyte antigen-DR (HLA-DR)). RESULTS: Immunoreactivity for anti-MIP-1alpha was distributed diffusely in epithelial cells throughout the proliferative and secretory phases but was absent during menstruation due to degenerative or necrotic changes. HLA-DR was expressed in epithelial cells only in the late secretory phase and was not expressed in stromal cells. CONCLUSION: Immunohistochemical analysis showed the presence of MIP-1alpha in the endometrial epithelium. Expression of HLA-DR in epithelial cells was observed only in the late secretory phase, suggesting that accumulation of MIP-1alpha in epithelium occurred by self production and not via a receptor mediated pathway. MIP-1alpha was released from the denuded epithelium during menstruation and appeared to contribute to the accumulation of monocytes/macrophages into the endometrial cavity. MIP-1alpha has a number of biological effects other than monocytic chemotaxis, and some of these effects may be exerted in the endometrial tissue.     

Hemoptysis after coil embolization for pulmonary arteriovenous malformation: Histopathological confirmation of bronchial epithelium extension

Coil embolization is widely performed for pulmonary arteriovenous malformations (PAVMs). We describe herein 2 cases of hemoptysis during long-term follow-up after coil embolization for PAVMs. For both cases, lobectomy was performed and histopathological examinations revealed chronic inflammation and bronchial epithelium extension into the sac of the PAVM. In addition, we performed a systematic review of previous reports of hemoptysis after embolization for PAVMs.