Yazar "Yoshida, O" seçeneğine göre listele

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    p21WAF-1/CIP-1, a downstream regulator of functional p53 loss, in transitional cell carcinoma of urothelium
    (Karger, 2000) Özdemir, E; Kakehi, Y; Yoshida, O
    Objectives: The expression of p21(WAF-1/CIP-1), a downstream regulator of p53, is a universal cycline-dependent kinase inhibitor. The aim of this study is to determine whether p21 expression could be used as a prognostic marker in urothelial carcinomas. Methods: By use of immunohistochemistry, we examined the expression of p21(WAF-1/CIP-1) in 60 patients with urothelial carcinomas and compared the results with the status of nuclear p53 and mdm2 accumulation, expression of type IV collagen in the basement membranes and upregulation of metalloproteinases (MMP-1, MMP-2, MMP-9). Results: p21(WAF-1/CIP-1) immunoreactivity was observed in 51.7% of the tumors, and in only 39% of the tumors with functional p53 loss (nuclear accumulation of p53 and/or mdm2). p21(WAF-1/CIP-1) overexpression was not associated with grade and stage of the tumors and presence or absence of concomitant CIS, Moreover, p21(WAF-1/CIP-1) overexpression was not associated with upregulation of metalloproteinases or destruction of type IV collagen of basement membranes. Conclusions: Our results suggest that p21(WAF-1/CIP-1) expression is regulated by both p53-dependent and independent pathways and is not related to grade, stage or potential markers of invasion in urothelial carcinomas. Copyright (C) 2000 S. Karger AG. Basel.
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    Öğe
    Role of matrix metalloproteinase-9 in the basement membrane destruction of superficial urothelial carcinomas
    (Lippincott Williams & Wilkins, 1999) Özdemir, E; Kakehi, Y; Okuno, H; Yoshida, O
    Purpose: This study was conducted to clarify which matrix metalloproteinases (MMPs) play a key role in destruction of the underlying basement membrane (BM) of superficial urothelial carcinomas. Urine concentrations of MMP-9 and tissue inhibitors of matrix metalloproteinase-l (TIMP-1) were also measured. Materials and Methods: Overexpression of MMP-1, MMP-2 and MMP-9 was analyzed immunohistochemically in 60 patients with transitional cell carcinomas of the urothelium (41 were pTa or pis, 19 were pT(1-4)), and compared them with type IV collagen expression in tumor BM. In 33 of them, urine concentrations of MMP-9 and TIMP-1 were measured by one-step sandwich enzyme immunoassay. Results: Positive expression of MMP-1, MMP-2 and MMP-9 was found in 53%, 17%, and 65% of tumors, respectively. Only MMP-9 expression rates were increased with grades and stages (p = 0.03). In pTa and pis tumors, type IV collagen expression was reduced in 17 of 26 (65.4%), and it was associated with positive MMP-9 expression (p = 0.0283). MMP-9 was detected in all urine samples of urothelial cancer patients, while urine TIMP-1 was detectable in 18 of 33 patients. In 16 healthy volunteers, both of them were below detectable levels, Balance between urinary MMP-9 and TIMP-1 were particularly kept in superficial urothelial carcinomas with intact tumor BM. Tumor BM: status, however, was not associated with urinary MMP-9 or TIMP-1 levels. Conclusions: These results suggest that MMP-9 plays a key role in the invasion step of superficial urothelial carcinomas. Detection of urinary MMP-9 may become a new, non-invasive mean for the diagnosis of urothelial carcinomas.