Abstract
The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin‐2 (IL‐2) production and expression of IL‐2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL‐2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL‐2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL‐2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL‐2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL‐2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL‐2 production was restored to benign control levels. On the other hand, the expression of IL‐2 receptor remained unchanged even if PSK was given after completion of chemotherapy.
Keywords: PSK, Interleukin‐2, Human ovarian carcinoma, Combination chemotherapy
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REFERENCES
- 1).Jurin , M. and Suit , H. D.In vitro activity of lymphocytes and serum of C3H5/Bu mice during the growth of methylcholanthrene‐induced tumor and its regression following local irradiation . Cancer Res. , 34 , 672 – 678 ( 1974. ). [PubMed] [Google Scholar]
- 2).Paranjpe , M. S. and Boone , C. W.Kinetics of the anti‐tumor delayed hypersensitivity response in mice with progressively growing tumors: stimulation followed by specific suppression . Int. J. Cancer , 13 , 179 – 186 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 3).Sidkey , Y. A. and Auerbach , R.Lymphocyte‐induced angiogenesis in tumor‐bearing mice . Science , 192 , 1237 – 1238 ( 1976. ). [DOI] [PubMed] [Google Scholar]
- 4).Mills , G. B. and Paetkau , V.Generation of cytotoxic lymphocytes to syngeneic tumor by using co‐stimulator (interleukin 2) . J. Immunol. , 125 , 1897 – 1903 ( 1980. ). [PubMed] [Google Scholar]
- 5).Burger , C. J. , Elgert , K. D. and Farrar , W. L.Interleukin 2 (IL‐2) activity during tumor growth: IL‐2 production kinetics, absorption of and responses to exogenous IL‐2 . Cell Immunol. , 84 , 228 – 239 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 6).Moretta , A.Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning . Eur. J. Immunol. , 15 , 148 – 155 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 7).Ehrlich , C. E. , Einhorn , L. , Stehman , F. B. and Blessing , J.Treatment of advanced epithelial ovarian cancer using cisplatin, adriamycin, and cytoxan—the Indiana University experience . Clin. Obstet. Gynecol. , 10 , 325 – 335 ( 1983. ). [PubMed] [Google Scholar]
- 8).Vogl . S. E. , Pagano , M. , Kaplan , B. H. , Greenwald , E. , Arseneau , J. and Bennett , B.Cis‐platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with small tumor burden . Cancer , 51 , 2024 – 2030 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 9).Piver , M. S.Ovarian carcinoma. A decade of progress . Cancer , 54 , 2706 – 2715 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 10).Kikuchi , Y. , Asaji , T. , Kizawa , I. , Koyama , E. , Oomori , K. and Kato , K.The effect of cimetidine on natural killer cell activity and responsiveness to phytohemagglutinin of peripheral blood lymphocytes in patients with gynecologic malignancies . J. Natl. Def. Med. Coll. , 9 , 114 – 120 ( 1984. ). [Google Scholar]
- 11).Lotze , M. T. , Frana , L. W. , Sharrow , S. O. , Robb , R. J. and Rosenberg , S. A.In vivo administration of purified human interleukin 2. I. Half life and immunologic effects of the Jurkat cell line‐derived interleukin 2 . J. Immunol. , 134 , 157 – 166 ( 1985. ). [PubMed] [Google Scholar]
- 12).Dempsey , R. A. , Dinarello , C. A. , Mier , J. W. , Rosenwasser , L. J. , Allegretta , M. , Brown , T. E. and Parkinson , D. R.The differential effects of human leukocytic pyrogen/lymphocyte‐activating factor, T cell growth factor, and interferon on human natural killer activity . J. Immunol. , 129 , 2504 – 2510 ( 1982. ). [PubMed] [Google Scholar]
- 13).Boyum , A.Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and granulocytes by combining centrifugation and sedimentation at 1 g . Scand. J. Clin. Lab. Invest. , 21 , Suppl. 97 , 77 – 89 ( 1968. ). [PubMed] [Google Scholar]
- 14).Gillis , S. , Ferm , M. , Ou , W. and Smith , K.T cell growth factor: parameters of production in a quantitative microassay for activity . J. Immunol. , 120 , 2027 – 2032 ( 1978. ). [PubMed] [Google Scholar]
- 15).Gillis , S. and Smith , K. A.Long term cultures of tumor‐specific cytotoxic T cells . Nature , 268 , 154 – 156 ( 1977. ). [DOI] [PubMed] [Google Scholar]
- 16).Robb , R. J. , Munck , A. and Smith , K. A.T cell growth factor receptors. Quantitation, specificity and biological relevance . J. Exp. Med. , 154 , 1455 – 1474 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17).Lauria , F. , Far , R. , Cavo , M. , Raspadori , D. , Glubellino , M. C. , Tazzari , P. L. and Tura , S.Membrane phenotype and functional behavior of T lymphocytes in multiple mycloma: correlation with clinical stages of the disease . Clin. Exp. Immunol. , 56 , 653 – 658 ( 1984. ). [PMC free article] [PubMed] [Google Scholar]
- 18).Yron , I. , Schickler , M. , Fisch , B. , Pinkas , H. , Ovada , J. and Witz , I. P.The immune system during the precancer and the early cancer period. IL‐2 production by PBL from post‐menopausal women with and without endometrial carcinoma . Int. J. Cancer , 38 , 331 – 338 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 19).Wagner , H. and Röllinghoff , M.T‐T cell interactions during in vitro cytotoxic allograft responses. I. Soluble products from activated LY1+ T cells autonomously antigen primed LY23+ T cells to cell proliferation and cytolytic activity . J. Exp. Med. , 148 , 1523 – 1538 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20).Farrar , J. J. , Simon , P. L. , Koopman , W. J. and Fuller‐Bonar , J.Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell‐mediated immune responses . J. Immunol. , 121 , 1353 – 1360 ( 1978. ). [PubMed] [Google Scholar]
- 21).Hancock , E. J. , Kilburn , D. G. and Levy , J. G.Helper cells active in the generation of cytotoxicity to a syngeneic tumor . J. Immunol. , 127 , 1394 – 1397 ( 1981. ). [PubMed] [Google Scholar]
- 22).Yamada , K.Effects of PSK (Krestin) on interleukin production . Abstracts of the 14th International Congress of Chemotherapy , p . 332 ( 1985. ).
- 23).Akiyama , J. , Kawamura , T. , Gotohda , E. , Yamada , Y. , Hosokawa , M. , Kodama , T. and Kobayashi , H.Immunochemotherapy of transplanted KMT‐17 tumor in WKA rats by combination of cyclophosphamide and immunostimulatory protein‐bound polysaccharide isolated from Basidiomycetes . Cancer Res. , 37 , 3042 – 3045 ( 1977. ). [PubMed] [Google Scholar]
- 24).Mizushima , Y. , Yuhki , N. , Hosokawa , M. and Kobayashi , H.Diminution of cyclophosphamide‐induced suppression of antitumor immunity by an immunomodulator PS‐K and combined therapeutic effects of PS‐K and cyclophosphamide on transplanted tumor in rats . Cancer Res. , 42 , 5176 – 5180 ( 1982. ). [PubMed] [Google Scholar]