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SCHU-03: Novel Biomarkers in Prostate Cancer Detection

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Page 1: SCHU-03: Novel Biomarkers in Prostate Cancer Detection

Sociedad Chilena deUrologıa Annual MeetingWednesday, November 191400-1730

SCHU-01VEGF165b, an Inhibitory SpliceVariant of VEGF165 in TransitionalCell Carcinoma of the Bladder: InVivo ExpressionGopi S1,2, H-Zadeh M1, Sen C2, Harper S2,Bates D2, Gillatt D1

1Department of Physiology, University ofBristol and Southmead Hospital, Bristol,UK; 2Microvascular Research Laborato-ries, University of Bristol and SouthmeadHospital, Bristol, UK

Introduction and Objectives: In theUK, bladder cancer is the fifth most com-mon cancer and second commonest uro-logical malignancy. Angiogenesis is essen-tial for tumor growth, survival andmetastasis. Vascular endothelial growthfactor (VEGF-A) is a key factor in mostsolid tumors, including bladder cancer.The VEGF165b family of splice isoforms isendogenous, anti-angiogenic and inhibitscolorectal tumor growth. The objective ofthis study is to determine the in vivo ex-pression of VEGF165b in bladder cancer.Materials and Methods: The establishedhuman bladder cancer cell line EJ28 weretransfected with pcDNA3, VEGF165,VEGF165b and both in tandem, and wasinstilled by intravesical injections in nudefemale mice, under general anaesthetic.The harvested tumor was fixed in 4% PFA.The tissue was stained using haematoxylinand eosin and viewed under light micro-scope to determine tumor uptake and in-filtration. The subcutaneous tumor injec-tions assessed tumor growth and volumeover 28 days. The in vitro growth of thetransfected cells studied the growth of thecell number.Results: The intravesical tumors showedthat the mean tumor area was reducedin VEGF165b expressing tumors comparedwith control, and inhibited growth ofVEGF165 expressing tumors. Tumor takewas less in VEGF165b expressing tumorsthan control, and VEGF165b inhibited tu-mor take of VEGF165 expressing tumors.The subcutaneous tumor growth demon-strated that VEGF165b significantly in-creased the doubling time of the tumors(two way ANOVA). The in vitro growthassay demonstrated that the VEGF165 ex-pressing cells grew at a faster rate.Conclusions: The in vivo models show

VEGF165 increases tumor growth com-pared to control. VEGF165b has an inhibi-tory effect on angiogenesis in establishedhuman bladder cancer cell lines grown inin vivo models.

SCHU-02The Role of Steroid Hormones inFemale Bladder Outlet Obstructionand in a Rat ModelShen Z2, Yu Y1, Zhou Y1, Zhou X1,Chen S1

1Department of Urology, The First Affili-ated Hospital, College of Medicine, Zhe-jiang University, Hangzhou, P.R., China;2Department of Urology, Rui Jin Hospi-tal, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai, P.R.,China.

Introduction and Objectives: To investi-gate whether steroid hormones includingestrogen, progesterone and testosteroneare related to female bladder outlet ob-struction (fBOO) and the effects of thesehormones on bladder morphology.Materials and Methods: In a prospectivestudy, 69 perimenopausal women withLUTS were evaluated by physical examina-tion, cystourethrography, and urodynamicstudies. They were divided into twogroups: fBOO (39 cases) or nBOO(29cases). Serum steroid hormone levelswere determined by radioimmunoassay.Biopsies were obtained from the bladderneck and the trigone; hormone receptors(ER, PR and AR) were assessed by immu-nohistochemistry. In the animal model a4-week study of 70 adult female Sprague-Dawley rats were divided into 7 groups: asham group, and 6 groups of oophorecto-mized rats as follows; without hormonereplacement therapy, with low-dose estra-diol, with high-dose estradiol, with pro-gesterone, with combined estradiol andprogesterone and with testosterone. Mea-surements of the weight and thickness ofthe bladder wall were done. Morphologi-cal changes of bladder tissues were evalu-ated by light and electron microscopy.Results: Serum estradiol levels werelower in the study group compared to thecontrol group, 19.8�14.2 and 23.7�15.8pg/ml, respectively. Conversely, testoster-one levels were significantly higher(72.4�37.5 ng/dl). The bladder biopsiesof fBBO patients showed decreased immu-nostaining for AR, ER and PR; this wasmore evident for AR in the trigone region(7.89% compared to 64.29% in control).The oophorectomized rats showed thin-ner bladder walls (0.97mm�0.11mm,p�0.05) and wide spaces between de-trussor muscle fascicles with collagen de-

posits; estrogen and testosterone treat-ments reversed these changes. Moreover,high-dose estrogen treatment resulted inthe development of many cytoplasmicvacuoles in detrussor cells.Conclusions: Our study supports a po-tential role for androgen therapy in fBOOpatients. The animal model showed therelevance of steroid hormones in preserv-ing bladder structures.

SCHU-03Novel Biomarkers in Prostate CancerDetectionJohnson E1, Smith S2, Probert C1,Ratcliffe N2, Persad R1

1Bristol Urological Institute, Bristol, UK;2University of the West of England, Bris-tol, UK

Introduction and Objectives: Prostatecancer screening remains contentiousmainly due to the lack of a definitivescreening test. The odour of urine is pro-duced by substances known as volatileorganic compounds (VOCs), which canbe detected by mass spectrometry. Weundertook a pilot study detecting VOCsemitted from urine, to determine whetherVOCs changed with the development ofprostate cancer.Materials and Methods: First-void urineand serum (PSA) samples were obtainedfrom 13 men with prostate cancer (me-dian 75.2yrs) and 24 age-matched controls(median 62.9yrs). The headspace abovepH-adjusted urine samples was extracted,for 20mins, using a carboxen/polydimeth-ylsiloxane solid phase micro-extractionfibre. VOCs were analysed by gas chroma-tography/mass spectroscopy.Results: VOCs emitted into the head-space under alkaline conditions werefound to be discriminating. The identifiedcompounds were analysed using forwardstepwise discriminant analysis: threeVOCs, when used together, gave 89% cor-rect classification of samples: sensitivi-ty�77%, specificity�96%.Conclusions: VOCs in urinary headspacechange with the development of prostatecancer. As controls were age-matched, itis likely that VOCs are uninfluenced bybenign prostate disease. Urinary VOCs areexciting potential new markers for pros-tate cancer and importantly are non-inva-sive and do not require a prior prostaticmassage.

SCHU-04Radical Retropubic or PerinealProstatectomy Worsens the Quality of

SOCIEDAD CHILENA DE UROLOGIA

UROLOGY 72 (Supplement 5A), November 2008 S3