Tzu Chi Medical Journal
Volume 20, Issue 2 , Pages 119-124, June 2008

Association Between Positive iNOS mRNA Expression and Recurrence-free Survival Among Patients with Non-muscle-invasive Bladder Cancer

  • Chih-Ming Lu

      Affiliations

    • Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    • Department of Urology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
    • ,
  • Allen W. Chiu

      Affiliations

    • Department of Health, Taipei City Government, Taipei, Taiwan
    • Corresponding Author InformationCorresponding author. Department of Health, Taipei City Government, 1, Shi Fu Road, Taipei, Taiwan
    • ,
  • Yu-Lun Huang

      Affiliations

    • Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
    • ,
  • Ying-Huei Lee

      Affiliations

    • Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan
    • ,
  • Ying-Chin Ko

      Affiliations

    • Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Received 14 September 2007; received in revised form 13 November 2007; accepted 28 November 2007.

Article Outline

Abstract 

Objective

Nitric oxide synthase is the key enzyme of the conversion of L-arginine to L-citrulline and nitric oxide. We conducted a study to investigate the association between positive inducible nitric oxide synthase (iNOS) mRNA expression and recurrence of bladder cancer.

Materials and Methods

Seventy-one patients with primary non-muscleinvasive bladder cancer were enrolled in this study. Tumor tissues were harvested during transurethral resection of bladder tumors. All operations were performed at the same hospital. Recurrence-free patients were followed up for at least 1 year unless tumors recurred during that time. The median intervals of follow-up were 34 months in the recurrence-free group and 12 months in the recurrence group. iNOS mRNA was detected using the RT-PCR-based method.

Results

Bladder cancer patients with positive iNOS mRNA expression had a higher recurrence risk (18.7% vs. 2.6%; p = 0.04). After adjusting for other risk factors, a statistical significance remained (p = 0.04; hazards ratio = 13.27; 95% CI = 1.07–164.36). The patients also had reduced recurrence-free survival (p = 0.019).

Conclusion

The positive expression of iNOS mRNA may be a useful prognostic indicator of bladder cancer.

Keywords:  Bladder cancer , Inducible nitric oxide synthase , Messenger RNA , Recurrence , Reverse transcriptase polymerase chain reaction

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References 

  1. Department of Health  . In: Health and Vital Statistics, Volume 1: General Health Statistics . Taipei: Department of Health, Executive Yuan, R.O.C.; 2003;p. 102–103
  2. Chen CJ , Chuang YC , Lin TM , Wu HY . Malignant neoplasms among residents of a blackfoot diseaseendemic area in Taiwan: higharsenic artesian well water and cancers . Cancer Res . 1985;45:5895–5899
  3. Chen CJ , Chuang YC , You SL , Lin TM , Wu HY . A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan . Br J Cancer . 1986;53:399–405
  4. Van der Meijden AP . Bladder cancer . Br Med J . 1988;317:1366–1369
  5. Palacios M , Knowles RG , Palmer RM , Moncada S . Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands . Biochem Biophy Res Commun . 1989;165:802–809
  6. Nathan C , Xie QW . Regulation of biosynthesis of nitric oxide . J Biol Chem . 1994;269:13725–13728
  7. Nathan C , Xie QW . Nitric oxide synthase: roles, tolls and controls . Cell . 1994;78:915–918
  8. Bhagat K , Vallance P . Nitric oxide 9 years on . J R Soc Med . 1996;89:667–673
  9. MacMicking J , Xie QW , Nathan C . Nitric oxide and macrophage function . Annu Rev Immunol . 1997;15:323–350
  10. Lin Z , Chen S , Ye C , Zhu S . Nitric oxide synthase expression in human bladder cancer and its relation to angiogenesis . Urol Res . 2003;31:232–235
  11. Swana HS , Smith SD , Perrotta PL , Saito N , Wheeler MA , Weiss RM . Inducible nitric oxide synthase with transitional cell carcinoma of the bladder . J Urol . 1999;161:630–634
  12. Sandes EO , Faletti AG , Riveros MD , et al.   Expression of inducible nitric oxide synthase in tumoral and nontumoral epithelia from bladder cancer patients . Nitric Oxide . 2005;12:39–45
  13. Epstein JI , Amin MB , Reuter VR , Mostofi FK . The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee . Am J Surg Pathol . 1998;22:1435–1448
  14. Chisholm GD , Hindmarsh JR , Howatson AG , et al.   TNM (1978) in bladder cancer: use and abuse . Br J Urol . 1980;52:500–505
  15. Messing EM , Catalona W . Urothelial tumors of the urinary tract . In:  Walsh PC ,  Retik AB editor. Campbell's Urology . 7thedition. Philadelphia: WB Saunders; 1998;p. 2327–2410
  16. Chiu AW , Huang YL , Huan SK , et al.   Potential molecular marker for detecting transitional cell carcinoma . Urology . 2002;60:181–185
  17. Thomsen LL , Lawton FG , Knowles RG , Beesley JE , Riveros-Moreno V , Moncada S . Nitric oxide synthase activity in human gynecological cancer . Cancer Res . 1994;54:1352–1354
  18. Thomsen LL , Miles DW , Happerfield L , Bobrow LG , Knowes RG , Moncada S . Nitric oxide synthase activity in human breast cancer . Br J Cancer . 1995;72:41–44
  19. Kloth T , Bloch W , Volberg C , Engelmann U , Addicks K . Selective expression of inducible nitric oxide synthase in human prostate carcinoma . Cancer . 1998;82:1897–1903
  20. Moochhala S , Chhatwal VJ , Chan ST , Ngoi SS , Chia YW , Rauff A . Nitric oxide synthase activity and expression in human colorectal cancer . Carcinogenesis . 1996;17:1171–1174
  21. Jansson OT , Morcos E , Brundin L , et al.   The role of nitric oxide in bacillus Calmette-Guerin mediated antitumour effects in human bladder cancer . Br J Cancer . 1998;78:588–592
  22. Shochina M , Fellig Y , Sughayer M , et al.   Nitric oxide synthase immunoreactivity in human bladder carcinoma . Mol Pathol . 2001;54:248–252
  23. Wolf H , Haeckel C , Roessner A . Inducible nitric oxide synthase expression in human urinary bladder cancer . Virchows Arch . 2000;437:662–666
  24. Eijan AM , Piccardo I , Riveros MD , et al.   Nitric oxide in patients with transitional bladder cancer . J Surg Oncol . 2002;81:203–208
  25. Wink DA , Mitchell JB . Nitric oxide and cancer: an introduction . Free Radic Biol Med . 2003;34:951–954
  26. Thomsen LL , Miles DW . Role of nitric oxide in tumour progression: lessons from human tumours . Cancer Metastasis Rev . 1998;17:107–118
  27. Xie K , Fidler IJ . Therapy of cancer metastasis by activation of the inducible nitric synthase . Cancer Metastasis Rev . 1998;17:55–75
  28. Oh BR , Nakajima K , Ahn KY , Ryu SB , Park YI , Dahiya R . Nitric oxide synthase gene and protein expression are upregulated by Bacille Calmette-Guerin in the rat bladder . Eur Urol . 2001;39:349–356
  29. Morcos E , Jansson OT , Adolfsson J , Kratz G , Wiklund NP . Endogenously formed nitric oxide modulates cell growth in bladder cancer cell lines . Urology . 1999;53:1252–1257
  30. Wenzel U , Kuntz S , De Sousa UJ , Daniel H . Nitric oxide suppresses apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions . Int J Cancer . 2003;106:666–675
  31. Morbidelli L , Chang CH , Douglas JG , Granger HJ , Ledda F , Ziche M . Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium . Am J Physiol . 1996;270:H411–H415
  32. Morbidelli L , Donnini S , Ziche M . Role of nitric oxide in the modulation of angiogenesis . Curr Pharm Des . 2003;9:521–530
  33. Moncada S , Higgs A . The L-arginine nitric oxide pathway . N Engl J Med . 1993;329:2002–2012
  34. Knowles RG , Moncada S . Nitric oxide synthases in mammals . Biochem J . 1994;298:249–258
  35. Ehsan A , Sommer F , Schmidt A , et al.   Nitric oxide pathways in human bladder carcinoma. The distribution of nitric oxide synthases, soluble guanylyl cyclase, cyclic guanosine monophosphate, and nitrotyrosine . Cancer . 2002;95:2293–2301
  36. Becker Y . Success and failure of dendritic cell (DC) anticancer activity may be modulated by nitric oxide synthetase (NOS) gene expression: a hypothesis . In Vivo . 1993;7:285–288
  37. Carroll PR . Urothelial carcinoma: cancers of the bladder, ureter, and renal pelvis . In:  Tanagho EA ,  McAninch JW editor. Smith's General Urology . 15th edition. New York: McGraw-Hill; 2000;p. 365

PII: S1016-3190(08)60021-X

doi:10.1016/S1016-3190(08)60021-X

Tzu Chi Medical Journal
Volume 20, Issue 2 , Pages 119-124, June 2008

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