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Published in: International Urology and Nephrology 6/2012

01-12-2012 | Urology - Original Paper

Blood and tissue nitric oxide and malondialdehyde are prognostic indicators of localized prostate cancer

Authors: Meltem Ozlen Dillioglugil, Haluk Mekık, Bahar Muezzinoglu, T. Alp Ozkan, Cennet Gural Demir, Ozdal Dillioglugil

Published in: International Urology and Nephrology | Issue 6/2012

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Abstract

Objectives

Our objective was to examine blood and tissue levels of nitric oxide (NO) and malondialdehyde (MDA), and their correlations with well-known prognostic indicators [total prostate-specific antigen (tPSA),  %free/total PSA (%f/t PSA), pathological stage (pT), and Gleason sum] in patients who had radical retropubic prostatectomy (RRP) for localized prostate cancer (PCa) without metastasis.

Patients and methods

Preoperatively 31 patients’ bloods were obtained for determination of NO, MDA, fPSA, tPSA, and  %f/tPSA ratios. Tissues were obtained from RRP specimens for determination of NO and MDA. Gleason sum was assigned for each patient, and pT was determined according to 2002 TNM staging system. pTs were as follows: 10 pT2a, 7 pT2b, 8 pT2c, 4 pT3a, and 2 pT3b. Gleason sum of the PCa in the RRP specimens was as follows: 5 in 1, 6 in 14, 7 in 14, and 9 in 2 patients.

Results

There were strong correlations between blood and tissue levels of NO (r = 0.83, p < 0.001) and MDA (r = 0.63, p < 0.001), between serum NO and plasma MDA (r = 0.88, p < 0.001), and finally between tissue NO and tissue MDA (r = 0.83, p < 0.001). There was also a significant (p < 0.05) relationship between all well-known prognostic indicators of PCa (tPSA,  %f/tPSA, Gleason sum, and pT) and blood and tissue NO and MDA levels, with single exception of correlation between tissue MDA and Gleason sum (p = 0.073).

Conclusion

Clinically appropriate correlations shown in this study indicates that NO and MDA may be used for prognostic assessment of localized PCa, especially if supported with other well-designed studies including higher number of patients through multi-institutional collaboration.
Literature
1.
go back to reference Ames BN (1989) Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun 7(3–6):121–128PubMedCrossRef Ames BN (1989) Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun 7(3–6):121–128PubMedCrossRef
2.
go back to reference McCall MR, Frei B (1999) Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 26(7–8):1034–1053PubMedCrossRef McCall MR, Frei B (1999) Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 26(7–8):1034–1053PubMedCrossRef
3.
go back to reference Nanni S, Benvenuti V, Grasselli A et al (2009) Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer. J Clin Invest 119(5):1093–1098PubMedCrossRef Nanni S, Benvenuti V, Grasselli A et al (2009) Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer. J Clin Invest 119(5):1093–1098PubMedCrossRef
4.
go back to reference Yossepowitch O, Pinchuk I, Gur U et al (2007) Advanced but not localized prostate cancer is associated with increased oxidative stress. J Urol 178(4 Pt 1):1238–1243PubMedCrossRef Yossepowitch O, Pinchuk I, Gur U et al (2007) Advanced but not localized prostate cancer is associated with increased oxidative stress. J Urol 178(4 Pt 1):1238–1243PubMedCrossRef
5.
go back to reference Baltaci S, Orhan D, Gögüs C et al (2001) Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma. BJU Int 88(1):100–103PubMedCrossRef Baltaci S, Orhan D, Gögüs C et al (2001) Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma. BJU Int 88(1):100–103PubMedCrossRef
6.
go back to reference Reschner A, Harlin H, Laven B et al (2009) Expression of immunomodulating genes in prostate cancer and benign prostatic tissue. Anal Quant Cytol Histol 31(2):74–82PubMed Reschner A, Harlin H, Laven B et al (2009) Expression of immunomodulating genes in prostate cancer and benign prostatic tissue. Anal Quant Cytol Histol 31(2):74–82PubMed
7.
go back to reference Lim HW, Hong S, Jin W et al (2005) Up-regulation of defense enzymes is responsible for low reactive oxygen species in malignant prostate cancer cells. Exp Mol Med 37(5):497–506PubMed Lim HW, Hong S, Jin W et al (2005) Up-regulation of defense enzymes is responsible for low reactive oxygen species in malignant prostate cancer cells. Exp Mol Med 37(5):497–506PubMed
8.
go back to reference Almushatat AS, Talwar D, McArdle PA et al (2006) Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response in patients with prostate cancer. Int J Cancer 118(4):1051–1053PubMedCrossRef Almushatat AS, Talwar D, McArdle PA et al (2006) Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response in patients with prostate cancer. Int J Cancer 118(4):1051–1053PubMedCrossRef
9.
go back to reference Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36(8 Pt 1):1440–1443PubMed Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36(8 Pt 1):1440–1443PubMed
10.
go back to reference Yoshioka T, Kawada K, Shimada T et al (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 135(3):372–376PubMed Yoshioka T, Kawada K, Shimada T et al (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 135(3):372–376PubMed
12.
go back to reference Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMed
13.
go back to reference Miyake H, Hara I, Kamidono S et al (2004) Oxidative DNA damage in patients with prostate cancer and its response to treatment. J Urol 171(4):1533–1536PubMedCrossRef Miyake H, Hara I, Kamidono S et al (2004) Oxidative DNA damage in patients with prostate cancer and its response to treatment. J Urol 171(4):1533–1536PubMedCrossRef
14.
go back to reference Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142(2):231–255PubMedCrossRef Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142(2):231–255PubMedCrossRef
15.
go back to reference Tribble DL, Aw TY, Jones DP et al (1987) The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology 7(2):377–386PubMedCrossRef Tribble DL, Aw TY, Jones DP et al (1987) The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology 7(2):377–386PubMedCrossRef
16.
go back to reference Kanko M, Ozden M, Maral H et al (2006) Effect of clopidogrel on nitric oxide levels in an ischemia reperfusion model. J Cardiovasc Pharmacol 48(1):797–801PubMedCrossRef Kanko M, Ozden M, Maral H et al (2006) Effect of clopidogrel on nitric oxide levels in an ischemia reperfusion model. J Cardiovasc Pharmacol 48(1):797–801PubMedCrossRef
17.
18.
go back to reference Akyol O, Herken H, Uz E et al (2002) The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsychopharmacol Biol Psychiatry 26(5):995–1005PubMedCrossRef Akyol O, Herken H, Uz E et al (2002) The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsychopharmacol Biol Psychiatry 26(5):995–1005PubMedCrossRef
19.
go back to reference Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6(7):521–534PubMedCrossRef Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6(7):521–534PubMedCrossRef
20.
go back to reference Wink DA, Vodovotz Y, Laval J et al (1998) The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19(5):711–721PubMedCrossRef Wink DA, Vodovotz Y, Laval J et al (1998) The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19(5):711–721PubMedCrossRef
21.
go back to reference Klotz T, Bloch W, Volberg C et al (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82(10):1897–1903PubMedCrossRef Klotz T, Bloch W, Volberg C et al (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82(10):1897–1903PubMedCrossRef
22.
go back to reference Gradini R, Realacci M, Ginepri A et al (1999) Nitric oxide synthases in normal and benign hyperplastic human prostate: immunohistochemistry and molecular biology. J Pathol 189(2):224–229PubMedCrossRef Gradini R, Realacci M, Ginepri A et al (1999) Nitric oxide synthases in normal and benign hyperplastic human prostate: immunohistochemistry and molecular biology. J Pathol 189(2):224–229PubMedCrossRef
23.
go back to reference Aaltomaa SH, Lipponen PK, Viitanen J et al (2000) The prognostic value of inducible nitric oxide synthase in local prostate cancer. BJU Int 86(3):234–239PubMedCrossRef Aaltomaa SH, Lipponen PK, Viitanen J et al (2000) The prognostic value of inducible nitric oxide synthase in local prostate cancer. BJU Int 86(3):234–239PubMedCrossRef
24.
go back to reference Catalona WJ, Partin AW, Slawin KM et al (1998) Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. JAMA 279(19):1542–1547PubMedCrossRef Catalona WJ, Partin AW, Slawin KM et al (1998) Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. JAMA 279(19):1542–1547PubMedCrossRef
Metadata
Title
Blood and tissue nitric oxide and malondialdehyde are prognostic indicators of localized prostate cancer
Authors
Meltem Ozlen Dillioglugil
Haluk Mekık
Bahar Muezzinoglu
T. Alp Ozkan
Cennet Gural Demir
Ozdal Dillioglugil
Publication date
01-12-2012
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 6/2012
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-012-0221-1

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