1731 REDUCTION OF PROSTATE CANCER INCIDENCE BY NAFTOPIDIL, AN α1 ADRENOCEPTOR ANTAGONIST AND...
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Source of Funding: None 1731 REDUCTION OF PROSTATE CANCER INCIDENCE BY NAFTOPIDIL, AN 1 ADRENOCEPTOR ANTAGONIST AND INHIBITOR OF TRANSFORMING GROWTH FACTOR- SIGNALING Daisuke Yamada*, Hiroaki Nishimatsu, Shintaro Kumano, Yoshikazu Hirano, Motofumi Suzuki, Tetsuya Fujimura, Hiroshi Fukuhara, Yutaka Enomoto, Haruki Kume, Yukio Homma, Tokyo, Japan INTRODUCTION AND OBJECTIVES: Quinazoline-based 1 adrenoceptor antagonists are known to inhibit prostate tumor growth via induction of apoptosis. We investigated the effect of a naphthalene- based 1 adrenoceptor antagonist, naftopidil, on prostate cancer inci- dence, apoptosis of prostatic cell and transforming growth factor- signaling. METHODS: Prescription records were linked to pathological data for men who continued naftopidil (n766) or tamsulosin (n1,015) for three months or longer between 2003 and 2010. Prostate cancer incidence was analyzed by Logrank test and Cox proportional hazards model. Apoptosis and cell cycle arrest were assessed by immunohistochemical detection of Bcl2 and p21, respectively. Interfer- ence with transforming growth factor- signaling was examined by Western blot analysis. RESULTS: Prostate cancer incidence was significantly lower in men who received naftopidil for three months or longer compared to tamsulosin (p0.035). Multivariate analysis confirmed decreased haz- ard ratio, 0.46, for naftopidil use (p0.013), which was more evident with longer administration. Immunohistochemical positivity for Bcl2, a marker for resistance to apoptosis, is less frequently detected in pros- tate cancer cells of men who received naftopidil compared to tamsulo- sin (p0.05). Naftopidil blocked Smad2 phosphorylation activated by transforming growth factor- in HeLa cells, with an IC50 of 3 M. CONCLUSIONS: Naftopidil reduced prostate cancer incidence possibly by inducing apoptosis preferentially in cancer cells and block- ing transforming growth factor- signaling. Source of Funding: Grant-in-Aid #21592066 (to H. N.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. 1732 SERUM PSA: EFFECT OF PHYSICAL EXERCISE IN MAN WITH ELEVATED PSA AND BENIGN PROSTATE HYPERPLASIA WITH NEGATIVE BIOPSIES Tillmann Loch*, Flensburg, Germany; Verena Lehmann, Saarbru ¨cken, Germany; Mathias Herrmann, Homburg, Germany; Wilfried Kindermann, Saarbr ¨cken, Germany INTRODUCTION AND OBJECTIVES: Cycling and other sport are assumed to influence PSA in serum. Controversial scientific results were the motivation to examine the influence of a standardized test on a cycling ergometer and a tread mill on PSA concentrations in men with elevated PSA levels and a benign prostate hyperplasia. METHODS: A total of 21 male volunteers (aged 615 years, tPSA 7.73.0 ng/ml and benign prostate hyperplasia with a prostate volume of 5418 ml) performed a 1 h cycling test on a cycling ergometer. A subgroup of 15 volunteers also performed a 1 h test on a treadmill. Blood samples were drawn before and several times after the cycling stress test up to 7 days afterwards (up to 120 min after the test on the treadmill) to determine total PSA (tPSA), complexed PSA (cPSA) and free PSA (fPSA). All men had prior C-TRUS evaluations with negative prostate biopsies and volumetry. RESULTS: The average increase in tPSA of 1.91.7 ng/ml (25%) after the cycling exercise test was significant. After the treadmill exercise the PSA increase was not as high, but with 1.01.0 ng/ml (12%) was also significant. On average the levels of PSA returned to the basic level 48 h after the cycling test, but in individual cases it took longer. fPSA showed the most noticeable increase after cycling with 92% on average. There was no correlation between increase in PSA and prostate volume. CONCLUSIONS: It should be considered that in men with BPH and PSA 4ng/ml a significant rise in PSA can be caused by physical activity, especially cycling. Men should abstain from physical exercise, especially from cycling for several days and at least for 24 h before PSA measurements are carried out. Source of Funding: None Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013 THE JOURNAL OF UROLOGY e711
Transcript of 1731 REDUCTION OF PROSTATE CANCER INCIDENCE BY NAFTOPIDIL, AN α1 ADRENOCEPTOR ANTAGONIST AND...
Source of Funding: None
1731REDUCTION OF PROSTATE CANCER INCIDENCE BYNAFTOPIDIL, AN �1 ADRENOCEPTOR ANTAGONIST ANDINHIBITOR OF TRANSFORMING GROWTH FACTOR-�SIGNALING
Daisuke Yamada*, Hiroaki Nishimatsu, Shintaro Kumano,Yoshikazu Hirano, Motofumi Suzuki, Tetsuya Fujimura,Hiroshi Fukuhara, Yutaka Enomoto, Haruki Kume, Yukio Homma,Tokyo, Japan
INTRODUCTION AND OBJECTIVES: Quinazoline-based �1adrenoceptor antagonists are known to inhibit prostate tumor growthvia induction of apoptosis. We investigated the effect of a naphthalene-based �1 adrenoceptor antagonist, naftopidil, on prostate cancer inci-dence, apoptosis of prostatic cell and transforming growth factor-�signaling.
METHODS: Prescription records were linked to pathologicaldata for men who continued naftopidil (n�766) or tamsulosin(n�1,015) for three months or longer between 2003 and 2010. Prostatecancer incidence was analyzed by Logrank test and Cox proportionalhazards model. Apoptosis and cell cycle arrest were assessed byimmunohistochemical detection of Bcl2 and p21, respectively. Interfer-ence with transforming growth factor-� signaling was examined byWestern blot analysis.
RESULTS: Prostate cancer incidence was significantly lower inmen who received naftopidil for three months or longer compared totamsulosin (p�0.035). Multivariate analysis confirmed decreased haz-ard ratio, 0.46, for naftopidil use (p�0.013), which was more evidentwith longer administration. Immunohistochemical positivity for Bcl2, amarker for resistance to apoptosis, is less frequently detected in pros-tate cancer cells of men who received naftopidil compared to tamsulo-sin (p�0.05). Naftopidil blocked Smad2 phosphorylation activated bytransforming growth factor-� in HeLa cells, with an IC50 of 3 �M.
CONCLUSIONS: Naftopidil reduced prostate cancer incidencepossibly by inducing apoptosis preferentially in cancer cells and block-ing transforming growth factor-� signaling.
Source of Funding: Grant-in-Aid #21592066 (to H. N.) fromthe Ministry of Education, Culture, Sports, Science andTechnology of Japan.
1732SERUM PSA: EFFECT OF PHYSICAL EXERCISE IN MAN WITHELEVATED PSA AND BENIGN PROSTATE HYPERPLASIA WITHNEGATIVE BIOPSIES
Tillmann Loch*, Flensburg, Germany; Verena Lehmann,Saarbrucken, Germany; Mathias Herrmann, Homburg, Germany;Wilfried Kindermann, Saarbrcken, Germany
INTRODUCTION AND OBJECTIVES: Cycling and other sportare assumed to influence PSA in serum. Controversial scientific resultswere the motivation to examine the influence of a standardized test ona cycling ergometer and a tread mill on PSA concentrations in men withelevated PSA levels and a benign prostate hyperplasia.
METHODS: A total of 21 male volunteers (aged 61�5 years,tPSA 7.7�3.0 ng/ml and benign prostate hyperplasia with a prostatevolume of 54�18 ml) performed a 1 h cycling test on a cyclingergometer. A subgroup of 15 volunteers also performed a 1 h test on atreadmill. Blood samples were drawn before and several times after thecycling stress test up to 7 days afterwards (up to 120 min after the teston the treadmill) to determine total PSA (tPSA), complexed PSA(cPSA) and free PSA (fPSA). All men had prior C-TRUS evaluationswith negative prostate biopsies and volumetry.
RESULTS: The average increase in tPSA of 1.9�1.7 ng/ml(25%) after the cycling exercise test was significant. After the treadmillexercise the PSA increase was not as high, but with 1.0�1.0 ng/ml(12%) was also significant. On average the levels of PSA returned tothe basic level 48 h after the cycling test, but in individual cases it tooklonger. fPSA showed the most noticeable increase after cycling with92% on average. There was no correlation between increase in PSAand prostate volume.
CONCLUSIONS: It should be considered that in men with BPHand PSA �4ng/ml a significant rise in PSA can be caused by physicalactivity, especially cycling. Men should abstain from physical exercise,especially from cycling for several days and at least for 24 h before PSAmeasurements are carried out.
Source of Funding: None
Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013 THE JOURNAL OF UROLOGY� e711
