KOIZUMI Motoiki Sapporo Medical University, School of Medicine, clinical instructor, 医学部, 助手 (50244348)
SATO Noriyuki Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (50158937)
|Budget Amount *help
¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1995 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1994 : ¥1,200,000 (Direct Cost : ¥1,200,000)
In the previous studies, we reported Rb or p53 geen products could be bind with intracellular heat shock proteins in ovarian cancer cell lines, with some corelation with carcinogenesis in human cells.
In this studywe performed a immunohistochemical analysis of heat shock proteinp53 or Rb gene products in human ovarian cancerwhich showed p53 protein expression was associated with cancer progression, but Rb products and their phosphorylating enzyme cdc-2 was expressed in the early process of carcinogenesis. Further, by using newly produced anti-hap 73 monoclonal antibody (Hybridoma 13 : 737,1994), hap73 expressions were examined with ovarian tisuues ; negative for normal ovarial tissues, 36% of bening tumors, 77% of borderline tumors, and 68% in early stage ovarian cancer, 65% in advanced ovarian cancer. And Rb proteins were also expressd in the similar fashion, at borderline tumors most frequently. But, the frequency of p53 expression was increased with the grade of malignancies during c
arcinogenesis and progression. And as the prognostic factor, only p53 expression was associated with poor prognosis of ovarian cancer patients.
70kDa heat shock proteins overexpress in the process of carcinogenesis and may be expressed on the surface, as an important tumor-rejection antigen during hostimmune responses. We reported that one of the antigens expressed on the surface of H-ras transformed fibrosarcoma cell line, W31 from rat fetal fibroblast WFB was heat shock protein, especially hsc 73, and the cytotoxicity of CE3+4-8-T cell receptor alphabeta-killer (DNT) cells for W31 was recognized as the ligand of hsc73 with certain celluar nascent of mutant peptides from the tumor cell, and this immunologic reaction was also detected in the system of human ovarian cancer cell lines. Further analysis of these intracellular peptides were performed between rat fetal cells and W31 tumor cells, cytotoxicity included with peptides was inhibited with hsc73 antibody and proteinase treatment was blocked with this reaction. This means these peptides are very important in the immunoreaction of hsc73-ralated cytotoxicity in the process of tumor rejection. Less