Sadahito Shin

Biological and Immunological Properties of Human Hepatocyte Growth Factor from Plasma of Patients with Fulminant Hepatic Failure.

We have recently purified human hepatocyte growth factor (hHGF), a heterodimer with molecular weight of about 83,000, from plasma of patients with fulminant hepatic failure (Gohda, E. et al., J. Clin. Invest. 81, 414-419, 1988). Biological and immunological properties of hHGF were examined. Out of the well-known growth factors tested, only epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated DNA synthesis of adult rat hepatocytes in primary culture. hHGF enhanced the DNA synthesis at less than one-tenth of the molar concentrations of EGF and TGF-alpha. Half-maximal stimulations by hHGF, EGF and TGF-alpha were observed at 30, 400 and 900 pM, respectively. Maximal stimulation by TGF-alpha, however, was greater than those caused by hHGF and EGF. The effect of hHGF was additive with the maximal effects of EGF and TGF-alpha. Anti-hHGF antiserum was prepared in a rabbit by injecting with purified hHGF. This antiserum recognized nonreduced hHGF, but not reduced hHGF. The antiserum for hHGF did not inhibit growth-promoting activity of EGF, that was neutralized by incubation with anti-EGF antiserum. The activity of hHGF was completely inhibited by anti-hHGF antiserum, but not by anti-EGF antiserum. hHGF did not show any cross-reactivity to anti-EGF antiserum as measured by enzyme immunoassay for EGF. Thus, biological and immunological properties of hHGF are different from those of EGF and TGF-alpha.

Development and Characterization of a Novel Anti-fucosylated Antigen Monoclonal Antibody YB-2 and Its Usefulness in the Immunohistochemical Diagnosis of Colorectal Cancer

A novel monoclonal antibody, YB‐2 was obtained after immunization of mice with fucosylated antigens isolated from human saliva. The antibody was demonstrated to react with Y (Fucα1→2Gal‐ β1→4[Fucα1→3]GlcNAcβ),Leb(Fucα1→2Galβ1→3[Fucα→4]GlcNAcβ)andHtype2 (Fucα→2Gal‐βl→4GlcNAcβ) antigens, but not with H type 1 (Fucα→2Galβ1→3GlcNAcβ), Le→ (Galβ1→3[Fucα1→4]GlcNAcβ), X (Galβ1→4[Fucα1→3]GlcNAcβ) or with non‐fucosylated antigens. Inhibition assays of YB‐2 antibody with such reactive antigens showed that YB‐2 antibody preferentially reacted with Y antigen. Formalin‐fixed and paraffin‐embedded sections prepared from normal and malignant colorectal tissues were examined immunohistochemically with YB‐2. The positive rates of staining with YB‐2 antibody were 88.6% in malignant and 12.0% in normal tissues. The expression of fucosylated antigens detected by YB‐2 antibody seemed to be correlated with survival among patients with primary colorectal cancer. Therefore, YB‐2 antibody could be useful as an immunochemical tool for diagnosis and evaluation of the prognosis of colorectal cancer.

Abnormal high level of proteasomes in sera from patients with hepatoma.

プロテアソームは,同一分子内に複数の蛋白分解活性を有する多機能プロテアーゼ複合体である.著者らは,ヒト肝から精製したプロテアソームのモノクローナル抗体を作成し,これを用いて肝硬変,転移性肝癌および肝細胞癌症例の血清プロテアソームを測定した.その結果,肝細胞癌症例(n=20)の血清プロテアソーム値は,対照群(n=50)のみならず肝硬変症例(n=8)に対しても有意に高値を示した.また,転移性肝癌症例(n=6)も対照群に対して有意に高値を示した.血清プロテアソーム値と,α-fetoprotein (α-FP)値およびCEA値の間には相関関係を認めず,血清プロテアソームとα-FPを組み合わせることにより肝細胞癌症例で高い陽性率が得られた.肝細胞癌および転移性肝癌症例に肝切除を行い腫瘍部を摘出すると,血清プロテアソーム値は低下した.これらの結果から,血清プロテアソームは,肝癌の診断およびその治療効果の判定に有用であることが示された.