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다형성아교모세포종 환자에서 Cyclooxygenase-2 발현이 생존율에 미치는 영향
Impact of Cyclooxygenase-2 Expression on the Survival of Glioblastoma

최영민    (동아대학교 의과대학 방사선종양학교실   ); 김대철    (동아대학교 의과대학 병리학교실   ); 김기욱    (동아대학교 의과대학 신경외과학교실   ); 송영진    (동아대학교 의과대학 신경외과학교실   ); 이형식    (동아대학교 의과대학 방사선종양학교실   ); 허원주    (동아대학교 의과대학 방사선종양학교실   ); 최순섭    (동아대학교 의과대학 영상의학교실   ); 서수영    (동아대학교 의과대학 미생물학교실  );
  • 초록

    목적 :다형성아교모세포종 환자들에서 cyclooxygenase-2 (COX-2) 단백의 발현 정도와 생존율에 미치는 영향을 조사하고자 한다. 대상 및 방법: 1997년부터 2006년까지 다형성아교모세포종으로 수술 및 방사선치료를 받은 환자들 중에서, 의식 상태의 악화로 40 Gy 전에 방사선치료가 중단된 3명을 제외한 30명을 대상으로 하였다. 조직에서의 COX-2의 발현은 면역조직화학염색으로 검사하였다. 생존 분석과 성별, 나이, 활동도, 수술 정도, 방사선량, COX-2 발현 정도 등이 생존율에 미치는 영향을 Kaplan Meier 법과 log rank test로 분석 및 검증하였다. 결과: 중앙추적관찰기간은 13.3개월이었다( $6{\sim}83$ ). 전체 환자들에서 COX-2의 발현이 관찰되었고, 종양 세포의 75%이상에서 COX-2가 양성이었던 환자가 24명이었다. 종양 세포의 25%미만, 3명(10.0%); $25{\sim}50%$ , 1명(3.3%); $50{\sim}75%$ , 2명(6.7%); $75{\sim}100%$ , 24명(80.0%). 중앙생존기간이 13.5개월이었고, 2년 생존율은 17.5%없다. 수술 정도(50% 이상 종양 제거)와 방사선량(59 Gy 이상 조사)이 생존율에 유의하게 영향을 주었다(p 0.05), 2년 생존율은 각각 33.3%와 13.3%없다(p>0.05). 결론: 다형성아교모세포종에서의 COX-2 양성도는 높았지만, 다형성아교모세포종 환자들에서 COX-2 발현의 정도와 생존율 간에는 통계적인 유의성이 없었으므로, 향후 보다 많은 환자들을 대상으로 COX-2 발현 정도가 생존율에 미치는 영향에 대한 연구가 필요하다.


    Purpose: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). Materials and Methods: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: $44{\sim}65.1$ Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. Results: The median length of follow-up was 13.3 months (range: $6{\sim}83$ months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p 0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). Conclusion: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.


  • 주제어

    다형성아교모세포종 .   방사선치료 .   생존율.  

  • 참고문헌 (32)

    1. Lin MT, Lee RC, Yang PC, Ho FM, Kuo ML. Cyclooxygenase- 2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem 2001; 276:48997-49002 
    2. Chinery R, Coffey RJ, Graves-Deal R, et al. Prostaglandin J2 and 15-deoxy-delta12,14-prostaglandin J2 induce proliferation of cyclooxygenase-depleted colorectal cancer cells. Cancer Res 1999;59:2739-2746 
    3. Tomozawa S, Tsuno NH, Sunami E, et al. Cyclooxygenase- 2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer. Br J Cancer 2000;83:324-328 
    4. Kardosh A, Blumenthal M, Wang WJ, Chen TC, Schonthal AH. Differential effects of selective COX-2 inhibitors on cell cycle regulation and proliferation of glioblastoma cell lines. Cancer Biol Ther 2004;3:55-62 
    5. Nam DH, Park K, Park C, et al. Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib. Oncol Rep 2004;11:263-268 
    6. Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 1993;26:239-244 
    7. Cho JH, Lee CG, Kim KJ, et al. Radiation dose-escalation trial for glioblastomas with 3D-conformal radiotherapy. J Kor Soc Ther Radiol Oncol 2004;22:237-246     
    8. Kowalczuk A, Macdonald RL, Amidei C, et al. Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas. Neurosurgery 1997;41: 1028-1036 
    9. Bleehen NM, Stenning SP. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. Br J Cancer 1991;64:769-774 
    10. Chang CH, Horton J, Schoenfeld D, et al. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer 1983;52:997-1007 
    11. Sawaoka H, Kawano S, Tsuji S, Tsujii M, Murata H, Hori M. Effects of NSAIDs on proliferation of gastric cancer cells in vitro: possible implication of cyclooxygenase-2 in cancer development. J Clin Gastroenterol 1998;27(Suppl 1):S47-52 
    12. Kirschenbaum A, Liotta DR, Yao S, et al. Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase- 2 in the human fetal and adult male reproductive tracts. J Clin Endocrinol Metab 2000;85:3436-3441 
    13. Deininger MH, Weller M, Streffer J, Mittelbronn M, Meyermann R. Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo. Acta Neuropathol 1999;98: 240-244 
    14. Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 1979;5:1725-1731 
    15. Yasojima K, Schwab C, McGeer EG, McGeer PL. Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res 1999;830:226-236 
    16. Shono T, Tofilon PJ, Bruner JM, Owolabi O, Lang FF. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res 2001;61: 4375-4381 
    17. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001;95:190-198 
    18. Petersen C, Petersen S, Milas L, Lang FF, Tofilon PJ. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 2000;6: 2513-2520 
    19. Buccoliero AM, Caldarella A, Gheri CF, et al. Inducible cyclooxygenase (COX-2) in glioblastoma--clinical and immunohistochemical (COX-2-VEGF) correlations. Clin Neuropathol 2006;25:59-66 
    20. Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 1998;58: 362-366 
    21. Joki T, Heese O, Nikas DC, et al. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 2000;60: 4926-4931 
    22. Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res 2000; 6:135-138 
    23. Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 1993;11:371-386 
    24. Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 1989;16:1405-1409 
    25. Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000;60:1306-1311 
    26. Karim A, McCarthy K, Jawahar A, Smith D, Willis B, Nanda A. Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines. Anticancer Res 2005;25:675-679 
    27. Prayson RA, Castilla EA, Vogelbaum MA, Barnett GH. Cyclooxygenase-2 (COX-2) expression by immunohistochemistry in glioblastoma multiforme. Ann Diagn Pathol 2002; 6:148-153 
    28. Sandberg-Wollheim M, Malmstrom P, Stromblad LG, et al. A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4. Cancer 1991;68:22-29 
    29. Souhami L, Seiferheld W, Brachman D, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 2004;60:853-860 
    30. Kakiuchi Y, Tsuji S, Tsujii M, et al. Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Cancer Res 2002; 62:1567-1572 
    31. Pyo H, Choy H, Amorino GP, et al. A selective cyclooxygenase- 2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxy-genase-2. Clin Cancer Res 2001;7:2998-3005 
    32. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996 

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