Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Prospective Study for Korean Red Ginseng Extract as an Immune Modulator Following a Curative Gastric Resection in Patients with Advanced Gastric Cancer

진행성 위암 환자에서 수술 후 홈삼엑기스에 의한 면역 조절자 역할에 관한 전향적 연구

  • Suh, Sung-Ock (Department of Surgery, College of Medicine, Korea University) ;
  • Kim, Jin (Department of Surgery, College of Medicine, Korea University) ;
  • Cho, Min-Young (Department of Surgery, College of Medicine, Korea University)
  • 서성옥 (고려대학교 의과대학 외과학교실) ;
  • 김진 (고려대학교 의과대학 외과학교실) ;
  • 조민영 (고려대학교 의과대학 외과학교실)
  • Published : 2004.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of this study was to evaluate prospectively the impact of the red ginseng extract on circulating interleukin (IL) 2 and 10 in advanced gastric cancer during chemotherapy after operative treatment. Analysis of circulating IL-2 and 10 was performed in 50 patients with advanced gastric adenocarcinoma who underwent a curative surgery or with an unresectable gastric adenocarcinoma by using ELISA and monoclonal antibodies at preoperative day 1, postoperative months 1, and 3. Twenty-five patients as the control group, twenty-six patients as the non-ginseng (NG) group, and twenty-four patients as the ginseng (G) group were eligible in this study. All plasma IL-2 of the NG and G groups was significantly lower an that of the control group on preoperative 1 day. These values of the G group were more increase than these of the NG group during the postoperative chemotherapy. The mean value of serum IL-10 of the control group (0.608pg/ml) was significantly lower than that of the advanced gastric cancer patients including the NG (12.015 pg/ml) and G group (9.409 pg/ml) (p＜0.001). These values of the G group were reduced progressively during the postoperative chemotherapy. The mesh value of the G group were only close to that of the control group on postoperative months 3 (p=0.003). The number of patients who were enrolled in this study was relatively small to fully evaluate the immunologic effects of the red ginseng extract on circulating IL-2 and 10. Despite this limitation, these results suggest that the post-operative intake of the red ginseng extract have potential to improve earlier anti-cancer immunity with recovering IL-2 and reducing IL-10 from the depressed IL-2 and elevated IL-10 by gastric cancer during the postoperative chemotherapy. This study will be based on the future study to evaluate the anti-immunity of the red ginseng extract.

본 연구는 근치적 위절제 및 림프절 절제와 혹은 절제불가능 환자에서 항암화학요법 치료를 받는 위암환자에서 홍삼액기스 투여군에서 비록 각군의 대상 개체의 표본수가 적음에도 불구하고 홍삼엑기스 투여군에서 항암 cytokine으로 알려진 IL-2가 위암 대조군에 비하여 높게 나타나고 숙주의 항암 면역기능을 저해하는 cytokine인 IL-10은 수술 후 1개월에 홍삼엑기스 투여군에서 위암 대조군에 보다 그 감소비가 높게 나타났으며, 수술 후 3개월에는 홍삼엑기스 투여군에서만 건강 대조군 값에 접근하는 결과를 보여 보조 항암 화학요법 기간에서 홍삼엑기스의 투여는 위암 환자에서의 숙주의 항암 면역 억제의 현상을 빠른 시간 내에 회복시킬 수 있는 효과가 있는 것으로 보여진다. 대단위 개체를 포함하는 지속적인 추가 연구의 필요성이 절실하며 이러한 추가 연구가 진행 된다면 홍삼엑기스의 위암환자에서의 항암 면역기능의 역할을 임상적으로 증명 할 수 있으리라고 기대 된다.

Keywords

References

  1. Yun, T. K. and Choi, S. Y. : Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol. Biomarkers Prev. 4, 401-408 (1995)
  2. Yun, T. K. and Choi, S. Y. : Non-organ specific cancer prevention of ginseng: a prospetive study in Korea. Int. J. Epidemiol. 27, 359-364(1998) https://doi.org/10.1093/ije/27.3.359
  3. Singh, V. K., Agarwal, S. S. and Gupta, B. W. : Immunomodulatory activity of Panax Ginseng extract. In Proceedings of the 4th International Ginseng Symposium. Korean Ginseng Research Institute. p. 225-232 (1984)
  4. Singh, V. K., Agarwal, S. S. and Gupta, B. M. : Immunomodulatory activity of Panax ginseng extract. Planta Med. 50(6), 462-465 (1984) https://doi.org/10.1055/s-2007-969773
  5. Yun, T. K. : Experimental and epidemiological evidence of the cancer-preventive effects of panax ginseng C. A. meyer. Nutr. Rev. 54, 71-81 (1996) https://doi.org/10.1111/j.1753-4887.1996.tb03822.x
  6. Lee, Y. S., Chung, I. S. and Lee, I. R. : Activation of multiple effectors pathways of immune system by the antineoplastic immuno-stimulator acidic polysaccharide ginsan isolated from Panax ginseng. Anticancer Res. 17, 323-331 (1997)
  7. Park, J. H., Byun, J. Y., Kim, B. K. and Kim, I. C. : Recurrent gastric cancer after curative surgery. J. Korean Cancer Assoc. 30, 488-496 (1998)
  8. Sulitzeanu, D. : Immunosuppressive factors in human cancer. Adv. Cancer Res. 60, 247-267 (1993) https://doi.org/10.1016/S0065-230X(08)60827-1
  9. Moy, M. P., Holmes, E. C. and Golub, S. M. : Depression of NK cytotoxic activity in lymphocytes infiltrating human pulmonary tumors. Cancer Res. 45, 57-60 (1985)
  10. Pawelec, G., Zeuthen, J. and Kiessling, R. : Escape from host-amtitumor immunity. Crit. Rev. Oncog. 8(2-3), 111141 (1997)
  11. Chousib, S. Asselin-Paturel, C., Mami-Chouaib, F., Caig-nard, A. and Blay, J. Y. : The host-tumor immune conflict: from immunosuppression to resistance and destruction. Immunol. Today 18, 493-497 (1997) https://doi.org/10.1016/S0167-5699(97)01115-8
  12. Prehn, R.T. : Tumor immunogenicity: how far can it be pushed? Proc. Natl. Acad. Sci. USA 90, 4332-4333 (1993) https://doi.org/10.1073/pnas.90.10.4332
  13. Schondorf, T., Engel, H., Kurbacher, C.M., Brenne, V., Kolhagen, M. and Gohringh J. : Immunologic features of tumorinfiltrating lymphocytes and peripheral blood lymphocytes in ovarian cancer patients. J. Soc. Gynecol. Investig. 5, 102-107 (1998) https://doi.org/10.1016/S1071-5576(97)00112-3
  14. Yoong, K. F. and Adams, D. H. : Interleukin 2 restores CD3-zeta chain expression but fails to generate tumour-specific lytic activity in tumour-infiltrating lymphocytes derived from human colorectal hepatic metastases. Br. J. Cancer 77, 1072-1081 (1998) https://doi.org/10.1038/bjc.1998.179
  15. Moore, K. W., Ogarra, A., de Waal Malefyt, R., Vieira, P. and Mos-mann, T. R. : Interleukin-10. Annu. Rev. Immunol. 11, 165-190 (1993) https://doi.org/10.1146/annurev.iy.11.040193.001121
  16. de Waal Malefyt, R., Haanen, J., Spits, H., Roncarolo, M. G., Velde, A. T. and Figdor, C. : Interleukin-10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T-cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J. Exp. Med. 174, 915924(1991) https://doi.org/10.1084/jem.174.4.915
  17. Oppenheim, J. and Fujiwara, H. : The role of cytolines in cancer. Cytokine Growth Factor Rev. 7, 279-288 (1996) https://doi.org/10.1016/S1359-6101(96)00025-1
  18. Romagnani, S. : Lymphokine production by human T cells in disease states. Annu. Rev. Immunol. 12, 227-257 (1994) https://doi.org/10.1146/annurev.iy.12.040194.001303
  19. Mosmann, T. R. and Sad, S. : The expanding universe of T-cell subsets : Th1, Th2 and more. Immunol. Today 17, 138-146 (1996) https://doi.org/10.1016/0167-5699(96)80606-2
  20. Street, D., Kaufmann, A. M., Vaughan, A., Fisher, S. G., Munter, M. and Schrechkenberger, C. : Inter-gamma enhances susceptibility of cervical cancer cells to lysis by tumor-specific cytotoxic T cells. Gynecol. Oncol. 65, 265-272 (1997) https://doi.org/10.1006/gyno.1997.4667
  21. Lowes, M. A., Bishop, G. A., Crotty, K., Barnetson, R. S. and Halliday, G. M. : T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. J. Invest. Dermatol. 108, 914-919 (1997) https://doi.org/10.1111/1523-1747.ep12292705
  22. Hauang, M., Wang, J., Lee, P., Sharma, S., Mao, J. T. and Meissner, H. : Human non-small cell lung cancer express a type 2 cytokine pattern. Cancer Res. 55, 3847-3853 (1995)
  23. Qin, Z., Noffz, G., Mohaupt, M. and Blankenstein, T. : Interleulin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells. J. Immunol. 159, 770-776 (1997)
  24. Avradopoulos, K., Mehta, S., Blakinton, D. and Wanebo, H. J. : Inter-leukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck. Ann. Surg. Oncol. 4, 184-190 (1997) https://doi.org/10.1007/BF02303803
  25. Fortis, C., Foppi, M., Gianotti, L., Galli, L., Citterio, G. and Conson-nio, G. : Increased interleukin-10 serum levels in patients with solid tumours. Cancer Lett. 24(104), 15 (1996)
  26. Gianotti, L., Fortis, C., Braga, M., Gentilini, O., Vignali, A., Di Carlo, V. : Radical oncologic surgery affects the circulatory levels of interleukin 10. J. Surg. Oncol. 66, 244-247 (1997) https://doi.org/10.1002/(SICI)1096-9098(199712)66:4<244::AID-JSO4>3.0.CO;2-B
  27. De Vita, F., Orditura, M., Galizia, G., Romano, C., Infusino, S., Auriemma, A., Lieto, E. and Catalano, G. : Serum Inter-leukin-10 levels in patients with advanced gastrointestinal malignancies. Cancer 86, 1936-1943 (1999) https://doi.org/10.1002/(SICI)1097-0142(19991115)86:10<1936::AID-CNCR9>3.0.CO;2-9
  28. Tsubono, M., Nio, Y., Shiraishi, T., Morimoto, H., Tseng, C.C., Kawabata, K., Masai, Y., Fukumoto, M. and Tobe, T. : Increased number of suppressor T-cells and impaired IL-2 mediated T-cell function in peripheral blood of gastric cancer patients. J. Clin. Lab. Immunol. 33(3), 107-115 (1990)
  29. Sugiyama, Y., Sakata, K., Saji, S., Takao, H. and Hamuro, J. : Effects of serum immunosuppressive factors on antitumor cytotoxicity of interleukin 2-induced lymphocytes. J. Surg. Oncol. 35(4), 223-229 (1987) https://doi.org/10.1002/jso.2930350403
  30. Yun, Y. S., Lee, Y. S., Jo, S. K. and Jung, I. S. : Inhibition of autochthonous ginseng as an immunomodulator. Planta Med. 59. 521-524 (1993) https://doi.org/10.1055/s-2006-959752