No abstract available.
Adenocarcinoma ; Cervix Uteri* ; Cystadenocarcinoma, Mucinous ; Female

Fibronectin(Fn) is a large, multidomain glycoprotein, which exists in a soluble form in plasma and an insoluble fibrillar form in extracellular matrices. Fn affects many aspects of cellular responses. However, it is not known whether Fn could activate macrophages for the tumor cell killing. We report that Fn induces the tumoricidal activity of macrophages for murine bladder tumor(MBT-2) cell. Tumoricidal activity was determined by 3[H]-thymidine uptake of MBT-2 cell. Fn alone had no effect, whereas recombinant interferon- r(IFN- r) weakly induced the tumoricidal activity of macrophages for MBT-2 cells. However combination of Fn with recombinant IFN-r synergized to activate macrophages to kill MBT-2 cells in a dose dependent manner. At this point nitric oxide(NO) was secreted by activated macrophages, and the secretion of NO and tumoricidal activity of macrophage were inhibited in the presence of NG-monomethyl- L-arginine(NGMMA), a competitive inhibitor of NO synthase(NOS). Fn has various cell binding sites. The Arg-Gly-Asp(RGD) sequence present in the central cell binding domain of Fn is the prototype of these sites. Engineered fibronectin(eFn) is formed by RGD-rich sequence. Combination of eFn, instead of Fn, with recombinant IFN- T resulted in more powerful activation of macrophage in tumor cell killing than Fn. In conclusion, our results demonstrate that Fn acts as a modulator of macrophage activation for tumor cell killing induced by IFN-r via a process involving L-arginine dependent NO production. Especially, RGD sequence of Fn has important role for tumoricidal activity of macrophage. Although the precise mechanism of Fn to promote NO synthesis induced by IFN-r remains to be further elucidated, Fn-mediated macrophage adhesion by specialized cell surface receptors and activation of intracellular signals might be important in the development of macrophage activation.
Arginine ; Binding Sites ; Extracellular Matrix ; Fibronectins* ; Glycoproteins ; Homicide ; Macrophage Activation ; Macrophages* ; Nitric Oxide ; Plasma ; Receptors, Cell Surface ; Urinary Bladder

Transforming growth factor-B1(TGF-B1) has many fundamental biological processes including cell growth, extracellular matrix deposition and degradation, and inflammatory responses. TGF-B1 is released by platelet and inflammatory cells, and it affects all phases of wound healing after injury. It contributes to the regulation of fibroblast chemotaxis and proliferation, and also controls the synthesis and degradation of extracellular matrix necessary for tissue repair. Clinically, scar tissue formation and subsequent stricture after urethral injury frequently results in troublesome problems to urologists. In the phase I study of this report, we intended to how the histological changes and the involvement of TGF-B1 in the formation of stricture in injured urethrae of rats. We injured urethrae of 24 adult male Sprauge-Dawley rats(200-250 g.) by urethrotome and Dormia basket and then observed histological changes and analysed TGF-f, mRNA levels of the injured urethrae by Northern blot. Northern b1ot analysis showed that TGF-t, mRNA was much expressed on day 1,3,5 after injury. Fibroblasts and deposition of extracellular matrix were markedly increased on day 5. Reepithelialization was completed and urethral lumen was narrowed on day 10. In the phase II study, we tried to know that antisense TGF-B1 oligodeoxynucleotides(ODNs) could inhibit TGF-B1 expression and the formation of stricture in injured urethrae of rats. We injured urethrae of rats and treated the urethral injury with the application of antisense TGF-B1 ODNs. Northern blot analysis showed that TGF-B1 mRNA was little expressed in the urethrae treated with the antisense on day 1,3 after injury. Comparing to the antisense-nontreated urethrae, the antisense-treated urethrae showed decrease of submucosal thickening and maintained normal sized urethral lumens on day 14, 21 after injury. In conclusion, increase of TGF-B1 mRNA in injured urethrae of rats suggests that TGF-B1 could play an important role in repair mechanism. With application of antisense TGF-B1 ODNs in injured urethrae of rats, the expression of TGF-B1 can be inhibited and also the formation of stricture prevented.
Adult ; Animals ; Biological Processes ; Blood Platelets ; Blotting, Northern ; Chemotaxis ; Cicatrix ; Constriction, Pathologic* ; Extracellular Matrix ; Fibroblasts ; Humans ; Male ; Oligodeoxyribonucleotides* ; Rats* ; RNA, Messenger ; Transforming Growth Factor beta1* ; Urethra ; Urethral Stricture ; Wound Healing