| Nitric oxide(NO) is a simple-structured radical gas. Many biologic effects have been attributed to NO. NO plays a role in pathophysiological activities including carcinogenesis. Recent studies showed that NO have dual pro-tumor and anti-tumor actions depending on its concentration. NO may facilitate tumor progression through angiogenesis and vascular dilation in tumor; while at high concentration NO have cytotoxic effects on tumor cells. NO is synthesized from L-arginine by nitric oxide synthase(NOS). There are two classes of NOS, namely constitutive NOS(cNOS) and inducible NOS(iNOS), cNOS(including neuronal NOS (nNOS) and endothelial NOS (eNOS)) are constitutively expressed, and their activities depend on Ca++ and calmodulin. The speed of NO production by cNOS is low; while that of iNOS is relatively high. iNOS is independent of Ca++ and is induced by lipopolysaccharide, interleukin-lp and y-interferon. Recent studies have demonstrated elevated NOS (especially iNOS) expression and activities in prostate cancer, breast cancer and gynecological cancer. Levels of NOS activities correlated with the histological grade of malignancy in breast cancer and gynecological cancer. These indicate NOS may facilitate tumor progression. But the role of NOS and NO in tumorbiology is still unclear.Bladder cancer is the most common malignancy in genitourinary cancers in china and transitional cell carcinoma of the bladder accounts for more than 90% of bladder cancer. Angiogenesis is an absolute requirement for sustained bladder cancer growth and metastasis, and tumors larger than 1 to 2 mm require the induction and ingrowth of new capillaries. Microvessel density(MVD) reflects the quantitation of tumor associated neovascularity. An angiogenic role for NOS and NO in cancer development has been suggested, however information on the role of NOS and NO in bladder cancer angiogenesis is scanty. Therefore we investigated the distribution and expression of NOS in human transitional cell carcinoma of the bladder and its relationship with tumor microvessel density to explore the role of NOS in the angiogenesis and progression of transitional cell carcinoma of the bladder.Materials and methodsBladder tumor specimens were collected from 35 patients(27 male, 8 female) in the first affiliated hospital of Zhejiang University from 2000.4 to 2000.7. Histologic diagnosis revealed that all patients had TCC. Their histologic classification and staging were: 0^=8), G2(n=13) and G3(n=14); Tis.,(n=13), T2(n=12) and T3.4(n=10), respectively. 12 cases of a paraneoplastic mucosa and Scases of normal bladder mucosa were included in the study as control. All specimens were fixed in 10% formalin, embedded in paraffin and cut into 5-jim slices. We used streptavidin-biotin complex method for immunohistochemical detection of NOS and CD34 antigens to study the expression of nitric oxide synthase in TCC and its relationship with tumor microvessel density.Results1. Positive expression of nNOS was found in 26 out of 35 cases of TCC and the positive expression rate was 74.3%, while the positive expression rate in paraneoplastic mucosa and normal bladder mucosa was 83.3%(10/12) and 50.0%(4/8), respectively, no significant difference was found(,P>0.05). The expression of iNOS was as following(Table 1): The positive expression rate of iNOS in TCC, paraneoplastic mucosa and normal bladder mucosa was 85.7%(30/35), 66.7%(8/12) and 50.0%(4/8), respectively. There was significant difference among three groups(P< 0.05). A stronger expression of iNOS was observed in TCC compared with that in normal bladder mucosa(P < 0.05). But no significant difference was found between the expression of iNOS in TCC and that of paraneoplastic mucosa, so was paraneoplastic mucosa and normal bladder mucosa. The positive expression rate of eNOS in TCC, paraneoplastic mucosa and normal bladder mucosa was 42.9%(15/35), 58.3%(7/12) and 37.5%(3/8), respectively. There was no significant difference among three groups(P>0.05). No significant relationship was found between... |
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