Novel technologies for creating three-dimensional constructs with complex shapes would be highly useful in tissue engineering. In the present study, tubular structures were constructed using magnetic force. Magnetite nanoparticles in cationic liposomes were taken up by target cells. The magnetically labeled cells were seeded onto ultralow-attachment plates, and a magnet was placed under the wells. After 24 h of culture, the magnetically labeled cells formed a cell sheet. Subsequently, when a cylindrical magnet was rolled onto the cell sheet, the cell sheet was attracted to the magnet and formed a tube around it. The magnet was then removed, leaving behind a tubular structure. Two types of tissue were used to create tubular structures: urinary tissue, consisting of a monotypic urothelial cell layer; and vascular tissue, consisting of heterotypic layers of endothelial cells, smooth muscle cells, and fibroblasts. The present results suggest that this novel methodology using magnetite nanoparticles and magnetic force, which we have termed "magnetic force-based tissue engineering" (Mag-TE), is a promising approach to constructing tissue-engineered tubular structures.
Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P = 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P = 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.
The survival benefit of neoadjuvant chemotherapy (NAC) was assessed in patients with FIGO stage III or IV ovarian cancer, and the prognostic value of various therapeutic factors was determined. In patients treated for stage III or IV ovarian malignancies at the Department of Obstetrics and Gynecology of Nagoya University or related institutions between 1987 and 1996, 119 had a histologic diagnosis of serous cystadenocarcinoma. For this group, the long-term outcome was compared between 96 patients receiving conventional adjuvant chemotherapy following standard surgery and 23 patients treated with NAC, both followed by a second cytoreductive surgery. In a total of 29 patients with all histologic types of malignancy, the tumor response to NAC and survival were analyzed on the basis of histology, chemotherapy regimen, residual tumor size after the second cytoreductive operation, and the dose intensity of cisplatin. The long-term outcome (5-year survival rate) was better in patients treated with conventional adjuvant chemotherapy than in patients receiving NAC, although the difference was not significant. Overall survival did not differ significantly in relation to tumor histology or chemotherapy regimen. With respect to residual tumor size after the second surgery, patients with a residual tumor ≦ 2 cm in diameter had a significantly better prognosis than those with a residual tumor >2 cm. A better prognosis was also associated with a higher dose intensity of cisplatin, and patients treated at ≧ 18 mg/m2/week survived significantly longer than those receiving <18 mg/m2/week.
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