Kinya Yokota

Prognostic values of matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐2 expression in bladder cancer

Matrix metalloproteinase‐2 (MMP‐2), which degrades the extracellular matrix or the basement membrane, has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP‐2, its inhibitor (tissue inhibitor of metalloproteinase‐2 [TIMP‐2]), and its activator (membrane‐type matrix metalloproteinase‐1 [MT1‐MMP]) in tumor invasion or as a prognostic factor in patients with bladder carcinoma, the authors investigated the expression of MMP‐2, TIMP‐2, and MT1‐MMP in patients with bladder carcinoma.

Proteasomes and Antigen Processing

Publisher Summary This chapter discusses the recent findings related to the roles of proteasomes in the major histocompatibility complex (MHC) class I-restricted antigen-processing pathway. One of the most important responses in this antigen-specific immune system is to distinguish correctly non-self-antigens from self-antigens for selective elimination because deviation from this recognition would lead to a variety of opportunistic infections or autoimmune diseases. The chapter focuses on the roles of proteasomes and their regulators in antigen processing with special reference to the influence of γ-interferon (γ-IFN) on both the structure and the functions of the proteasome. Proteasomes play a central role in various biological processes, one of which is the generation of the peptides presented by MHC class I molecules to the circulating T lymphocytes. Proteasomes have been implicated as the processing enzyme for the generation of the ligand peptides for MHC class I receptors. Future studies should address how proteasome genes have evolved. Acquisition of the γ-IFN-responsive proteasomal and PA28 family genes may be related to that of multiple MHC and TAP genes during evolution. Studies on molecular evolution may provide new insight into the alternative roles of proteasome genes in immunity.

Prognostic Values of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 Expression in Bladder Cancer

BACKGROUND Matrix metalloproteinase-2 (MMP-2), which degrades the extracellular matrix or the basement membrane, has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-2, its inhibitor (tissue inhibitor of metalloproteinase-2 [TIMP-2]), and its activator (membrane-type matrix metalloproteinase-1 [MT1-MMP]) in tumor invasion or as a prognostic factor in patients with bladder carcinoma, the authors investigated the expression of MMP-2, TIMP-2, and MT1-MMP in patients with bladder carcinoma. METHODS Tissues obtained from 41 patients with bladder carcinoma were used for analysis. Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate dehydrogenase was examined by reverse transcriptase-polymerase chain reaction analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP expression and histologic findings or patient outcome were evaluated. RESULTS Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2< or = bladder tumors than in pT1a tumors (MMP-2: P < 0.0005; TIMP-2: P < 0.005). Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression, all were strongly associated with decreased survival (MMP-2: P < 0.0001; TIMP-2: P < 0.0001; and MT1-MMP: P < 0.005). Even within the radically cystectomized muscle invasive pT2< or = tumor group, patients with a high expression of any of these three genes had a worse prognosis than those with low expression (MMP-2: P < 0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). CONCLUSIONS MMP-2 and TIMP-2 are believed to contribute to the invasive properties of bladder carcinoma. The authors report that expression of MMP-2, TIMP-2, and MT1-MMP are useful prognostic indicators in patients with bladder carcinoma and may be helpful in designing treatment protocols.