Search

Milk fat globule-epidermal growth factor-factor VIII (MFGE8), also called lactadherin or SED1, is a secreted integrin-binding protein that promotes elimination of apoptotic cells by phagocytes leading to tolerogenic immune responses, and vascular endothelial growth factor (VEGF)-induced angiogenesis: two important processes for cancer development. Here, by transcriptomic analysis of 228 biopsies of bladder carcinomas, we observed overexpression of MFGE8 during tumor development, correlated with expression of genes involved in cell adhesion or migration and in immune responses, but not in VEGF-mediated angiogenesis. To test whether MFGE8 expression was instrumental in bladder tumor development, or a simple consequence of this development, we used genetic ablation in a mouse model of carcinogen-induced bladder carcinoma. We showed that Mfge8 was also upregulated in mouse carcinoma, and that in its absence, Mfge8-deficient animals developed less advanced tumors. Angiogenesis was similar in carcinogen-treated Mfge8-expressing or -deficient bladders, thus ruling out a major role of the proangiogenic function of Mfge8 for its protumoral role. By contrast, the tumor-promoting role of Mfge8 was not observed anymore in mice devoid of adaptive immune system, and human tumors overexpressing MFGE8 where invaded with macrophages and regulatory T cells, thus suggesting that MFGE8/lactadherin favors development of bladder tumors at least partly by an immune system-dependent mechanism. Our observations suggest future use of MFGE8-inhibiting molecules as therapies of bladder carcinomas, and of a limited number of other human cancers, in which our analysis of public databases also revealed overexpression of MFGE8. [ABSTRACT FROM AUTHOR]

Purpose: To report our experience with mechanical thrombectomy in proximal deep vein thrombosis (DVT).Methods: Eighteen patients with a mean (+/- SD) age of 37.6 +/- 16.1 years who presented with DVT in the iliac and femoral vein (n = 3), inferior vena cava (n = 5), or inferior vena cava and iliac vein (n = 10), were treated with the Amplatz Thrombectomy Device after insertion of a temporary caval filter.Results: Successful recanalization was achieved in 15 of 18 patients (83%). Overall, the percentage of thrombus removed was 66 +/- 29%: 73 +/- 30% at caval level and 55 +/- 36% at iliofemoral level. Complementary interventions (seven patients) were balloon angioplasty (n = 2), angioplasty and stenting (n = 2), thrombo-aspiration alone (n = 1), thrombo-aspiration, balloon angioplasty, and permanent filter (n = 1), and permanent filter alone (n = 1). There was one in-hospital death. Follow-up was obtained at a mean of 29.6 months; three patients had died (two cancers, one myocardial infarction); 10 had no or minimal sequelae; one had post-phlebitic limb.Conclusion: Mechanical thrombectomy is a potential therapeutic option in patients presenting with proximal DVT. [ABSTRACT FROM AUTHOR]

The current therapeutic options for right atrial thrombi-surgical embolectomy and thrombolysis-are associated with high mortality and such patients often have contraindications to these therapeutic options. The purpose of this study was to evaluate the feasibility of endovascular right atrial embolectomy. Two patients with contraindications to thrombolysis and surgery were treated by a femoral approach. A catheter was placed in the right atrium, under fluoroscopic control, and a basket device was used to trap the thrombus. The location and extent of the thrombus was established before the procedure by transesophageal echocardiography (TEE) and the procedure was performed with TEE and fluoroscopy. Thrombi were withdrawn in the basket into the inferior vena cava (IVC) and a filter was inserted by a jugular approach and positioned in the IVC, just above the thrombi. The basket was removed leaving the thrombus below the filter. One patient died immediately after the procedure. In conclusion, endovascular extraction of right atrial thrombi may represent a potential therapeutic alternative, particularly in patients with contraindications to thrombolysis and surgery. [ABSTRACT FROM AUTHOR]