Malignancy is a common and dreaded complication following organ transplantation. The high incidence of neoplasm and its aggressive progression, which are associated with immunosuppressive therapy, are thought to be due to the resulting impairment of the organ recipient's immune-surveillance system. Here we report a mechanism for the heightened malignancy that is independent of host immunity. We show that cyclosporine (cyclosporin A), an immunosuppressant that has had a major impact on improving patient outcome following organ transplantation, induces phenotypic changes, including invasiveness of non-transformed cells, by a cell-autonomous mechanism. Our studies show that cyclosporine treatment of adenocarcinoma cells results in striking morphological alterations, including membrane ruffling and numerous pseudopodial protrusions, increased cell motility, and anchorage-independent (invasive) growth. These changes are prevented by treatment with monoclonal antibodies directed at transforming growth factor-beta (TGF-beta). In vivo, cyclosporine enhances tumour growth in immunodeficient SCID-beige mice; anti-TGF-beta monoclonal antibodies but not control antibodies prevent the cyclosporine-induced increase in the number of metastases. Our findings suggest that immunosuppressants like cyclosporine can promote cancer progression by a direct cellular effect that is independent of its effect on the host's immune cells, and that cyclosporine-induced TGF-beta production is involved in this.
We evaluated the efficacy of ethanolamine oleate (EO) as a sclerosing agent for a symptomatic hepatic or renal cyst. Seven patients with symptomatic hepatic (n = 3) or renal cysts (n = 4) were treated by sclerotherapy with EO. The cyst size in the greater diameter ranged from 6 to 13 cm. The cyst was punctured under ultrasound guidance, and after all of the cyst's content was aspirated, an iodized contrast agent was injected to check the absence of communication between the cyst and biliary tree, urinary tract, or vessels. Then, the solution of ethanolamine oleate-iopamidol mixture (EOI) of 10% of the volume of the cyst's content was injected via catheter. After 30 min, the injected EOI was aspirated completely before catheter removal. A follow-up computed tomography scan was performed at 1 and 3 months after treatment. The volume of the cyst and its reduction rate was calculated. In addition, symptoms and complications were assessed. The volume of the cyst ranged from 64 to 636 ml (mean: 328 ml) before treatment. Three months after treatment, it ranged from 2 to 50 ml (mean: 15ml) and the reduction rate of the cyst's volume was more than 90% on average. Symptoms caused by the cyst disappeared in all cases and no major complication was encountered. Although two patients had a low-grade fever after sclerotherapy, it was easily controlled. It is suggested that the sclerotherapy with EO might be a safe, effective, well-tolerated treatment for symptomatic hepatic or renal cysts.
Gelatin sponge (GS) is one of the most widely used embolic agents in interventional procedures. There are four commercially available GS products in Japan; however, the endovascular use of Gelfoam and Spongel is off-label, and Gelpart can only be used for hepatic artery embolization and Serescue can only be used for hemostasis of arterial bleeding. GS has been used for a variety of clinical indications, mainly tumor embolization and stopping massive arterial bleeding. The optimal size and preparation procedure of GS particles differs slightly for each clinical indication. In addition, there is a risk of ischemic and/or infectious complications associated with GS embolization in various situations. Therefore, radiologists should be familiar with not only the preparation and handling of GS particles, but also the disadvantages and potential risks, in order to perform GS embolization safely and effectively.
Our results suggest that PLLA bioabsorbable stents seems to be useful for implantation in the biliary system with further investigation.
The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 microg/ml for the cisplatin-HAI group, 1.23 microg/ml for the cisplatin-GS-TACE group, and 12.65 microg/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 microg/ml for the cisplatin-HAI group, 1.13 microg/ml for the cisplatin-GS-TACE group, and 1.09 microg/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.
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